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Guo C, Wan L, Li C, Wen Y, Pan H, Zhao M, Wang J, Ma X, Nian Q, Tang J, Zeng J. Natural products for gastric carcinoma prevention and treatment: Focus on their antioxidant stress actions in the Correa's cascade. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2024; 123:155253. [PMID: 38065034 DOI: 10.1016/j.phymed.2023.155253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/26/2023] [Revised: 11/15/2023] [Accepted: 12/01/2023] [Indexed: 01/17/2024]
Abstract
BACKGROUND Correa's cascade is a pathological process beginning from gastritis to gastric precancerous lesions, and finally to gastric carcinoma (GC). While the pathogenesis of GC remains unclear, oxidative stress plays a prominent role throughout the entire Correa's cascade process. Studies have shown that some natural products (NPs) could halt and even reverse the development of the Correa's cascade by targeting oxidative stress. METHODS To review the effects and mechanism by which NPs inhibit the Correa's cascade through targeting oxidative stress, data were collected from PubMed, Embase, Web of Science, ScienceDirect, and China National Knowledge Infrastructure databases from initial establishment to April 2023. NPs were classified and summarized by their mechanisms of action. RESULTS NPs, such as terpenoid, polyphenols and alkaloids, exert multistep antioxidant stress effects on the Correa's cascade. These effects include preventing gastric mucosal inflammation (stage 1), reversing gastric precancerous lesions (stage 2), and inhibiting gastric carcinoma (stage 3). NPs can directly impact the conversion of gastritis to GC by targeting oxidative stress and modulating signaling pathways involving IL-8, Nrf2, TNF-α, NF-κB, and ROS/MAPK. Among which polyphenols have been studied more and are of high research value. CONCLUSIONS NPs display a beneficial multi-step action on the Correa's cascade, and have potential value for clinical application in the prevention and treatment of gastric cancer by regulating the level of oxidative stress.
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Affiliation(s)
- Cui Guo
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Lina Wan
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Chengen Li
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Yueqiang Wen
- School of Basic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China
| | - Huafeng Pan
- Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China
| | - Maoyuan Zhao
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Jundong Wang
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources,Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
| | - Qing Nian
- Department of Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu 610072, China.
| | - Jianyuan Tang
- Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
| | - Jinhao Zeng
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China; Department of gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China.
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Rodrigues SD, da Silva MLS, Martins LZ, Gomes SEB, Mariani NAP, Silva EJR, Kushima H, Mattos BR, Rizzi E, Dias-Junior CA. Pregnancy hypertension-associated endothelial dysfunction is attenuated by isoflurane anesthesia: Evidence of protective effect related to increases in nitric oxide. Life Sci 2023; 331:122039. [PMID: 37648198 DOI: 10.1016/j.lfs.2023.122039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 08/14/2023] [Accepted: 08/21/2023] [Indexed: 09/01/2023]
Abstract
AIMS Pregnancy hypertension-induced endothelial dysfunction associated with impairment of nitric oxide (NO) bioavailability and hemodynamic derangements is a challenging for urgent procedures requiring maternal anesthesia. The volatile anesthetic isoflurane has demonstrated NO-associated protective effects. However, this isoflurane-induced effect is still unclear in pregnancy hypertension. Therefore, the present study examined the potential protective effects of isoflurane anesthesia on endothelial dysfunction and hemodynamic changes induced by hypertensive pregnancy associated with fetal and placental growth restrictions. MATERIALS AND METHODS Animals were distributed into four groups: normotensive pregnant rats (Preg), anesthetized pregnant rats (Preg+Iso), hypertensive pregnant rats (HTN-Preg), and anesthetized hypertensive pregnant rats (HTN-Preg+Iso). Systolic and diastolic pressures, mean arterial pressure (MAP), heart rate, fetal and placental weights, vascular contraction, endothelium-derived NO-dependent vasodilation, and NO levels were assessed. The vascular endothelial growth factor (VEGF) levels and endothelial NO synthase (eNOS) Serine (1177) phosphorylation (p-eNOS) expression were also examined. KEY FINDINGS Isoflurane produced more expressive hypotensive effects in the HTN-Preg+Iso versus Preg+Iso group, with respective reductions in MAP by 50 ± 13 versus 25 ± 4 mmHg (P < 0.05). Also, HTN-Preg+Iso compared to the HTN-Preg group showed (respectively) preventions against the weight loss of the fetuses (4.0 ± 0.6 versus 2.8 ± 0.6 g, P < 0.05) and placentas (0.37 ± 0.06 versus 0.30 ± 0.06 mg, P < 0.05), hyper-reactive vasocontraction response (1.8 ± 0.4 versus 2.8 ± 0.6 g, P < 0.05), impaired endothelium-derived NO-dependent vasodilation (84 ± 8 versus 50 ± 17 %, P < 0.05), reduced VEGF levels (147 ± 46 versus 25 ± 13 pg/mL, P < 0.05), and decreased p-eNOS expression (0.24 ± 0.07 versus 0.09 ± 0.05 arbitrary units, P < 0.05). SIGNIFICANCE Isoflurane anesthesia protects maternal endothelial function in pregnancy hypertension, and possibly endothelium-derived NO is involved.
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Affiliation(s)
- Serginara David Rodrigues
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Maria Luiza Santos da Silva
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Laisla Zanetoni Martins
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Sáskia Estela Biasotti Gomes
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Noemia A P Mariani
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Erick J R Silva
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Hélio Kushima
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil
| | - Bruna Rahal Mattos
- Unit of Biotechnology, University of Ribeirao Preto (UNAERP), Ribeirao Preto 14096-900, SP, Brazil
| | - Elen Rizzi
- Unit of Biotechnology, University of Ribeirao Preto (UNAERP), Ribeirao Preto 14096-900, SP, Brazil
| | - Carlos Alan Dias-Junior
- Department of Biophysics and Pharmacology, Institute of Biosciences, Sao Paulo State University (UNESP), Botucatu, 18618-689, SP, Brazil.
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Rocha TLA, Borges TF, Rodrigues SD, Martins LZ, da Silva MLS, Bonacio GF, Rizzi E, Dias-Junior CA. Sevoflurane and isoflurane anesthesia induce redox imbalance, but only sevoflurane impairs vascular contraction. Fundam Clin Pharmacol 2023; 37:937-946. [PMID: 37085979 DOI: 10.1111/fcp.12901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2023] [Revised: 02/28/2023] [Accepted: 04/11/2023] [Indexed: 04/23/2023]
Abstract
Volatile anesthetics may cause vascular dysfunction; however, underlying effects are unclear. The aim of the present study was to investigate whether sevoflurane and isoflurane affect vascular function, nitric oxide (NO) bioavailability, and biomarkers of oxidative stress and inflammation. Wistar rats were divided into three experimental groups: Not anesthetized (control group) or submitted to anesthesia with isoflurane (Iso group) or sevoflurane (Sevo group). Hemodynamic parameters were monitored during anesthesia, and blood gas values and biochemical determinants were analyzed. Isometric contractions were recorded in aortic rings. Vasoconstriction induced by potassium chloride (KCl) and phenylephrine (Phe) were measured. No differences in hemodynamic parameters and blood gasses variables were observed. Impaired KCl and Phe-induced contractions were observed in endothelium-intact aorta of Sevo compared to Iso and Control groups. Redox imbalance was found in Sevo and Iso groups. Reduced NO bioavailability and increased activity of matrix metalloproteinase 2 (MMP-2) were observed in Sevo, but not in the Iso group. While reduced IL-10 and IL-1β were observed in Sevo, increases in IL-1β in the Iso group were found. Sevoflurane, but not isoflurane, anesthesia impairs vasocontraction, and reduced NO and cytokines and increased MMP-2 activity may be involved in vascular dysfunction after sevoflurane anesthesia.
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Affiliation(s)
- Thalita L A Rocha
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
| | - Teubislete F Borges
- Department of Anesthesiology, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
| | - Serginara D Rodrigues
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
| | - Laisla Z Martins
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
| | - Maria L S da Silva
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
| | - Gisele F Bonacio
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo, Brazil
| | - Elen Rizzi
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo, Brazil
| | - Carlos A Dias-Junior
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University, UNESP, Botucatu, Sao Paulo, Brazil
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Matos Leitão M, Euclides Silva-Filho S, Arena AC, Heredia-Vieira SC, Cardoso CAL, Kassuya CAL. Antinociceptive and anti-inflammatory properties of aqueous extract obtained from Serjania marginata Casar leaves. JOURNAL OF ETHNOPHARMACOLOGY 2023; 304:116018. [PMID: 36496043 DOI: 10.1016/j.jep.2022.116018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/14/2022] [Revised: 11/28/2022] [Accepted: 12/02/2022] [Indexed: 06/17/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Serjania marginata Casar (Sapindaceae Family) Leaves are popularly used against abdominal pain. Antiulcer properties of S. marginata were scientifically described, however rare studies showed the antinociceptive effects of this plant. AIM OF STUDY In this study, we investigated the antinociceptive and anti-inflammatory effects of aqueous extract obtained from Serjania marginata leaves (AESM) in nociception/inflammation models. MATERIAL AND METHODS AESM was analyzed in FIA-ESI-IT-MS and Mass spectrometer LTQ XL. AESM oral administration (p.o.) (30, 100 and 300 mg/kg), dexamethasone subcutaneous injection (1 mg/kg, s.c.) and morphine (5 mg/kg, s.c.) were tested against the acetic acid-induced nociception, carrageenan-induced acute inflammatory paw edema/hyperalgesia, formalin-induced nociception and carrageenan-induced pleurisy in Swiss mice. RESULTS Flavonoids rutin was detected in the phytochemical analysis of this extract. Oral treatment of AESM 300 mg/kg significantly reduced the number of acetic acid-induced abdominal writhing. AESM (100 and 300 mg/kg) significantly inhibited formalin-induced nociception, mechanical hyperalgesia and paw edema in carrageenan-model. Furthermore, AESM significantly inhibited leukocyte migration and protein exudation in the carrageenan-induced pleurisy test. CONCLUSION This study confirms the antinociceptive, and anti-inflammatory activity of AESM, which may explain, in part, the popular use of this plant as a natural antinociceptive agent. This pharmacological action can be caused by flavonoids such as rutin and other compounds present in AESM.
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Affiliation(s)
- Maicon Matos Leitão
- Federal University of Grande Dourados, Faculty of Health Sciences, Dourados, Mato Grosso do Sul State, Brazil; School of Health Sciences, Unigran Capital University Center, Campo Grande, Mato Grosso do Sul State, Brazil.
| | - Saulo Euclides Silva-Filho
- Pharmaceutical Sciences, Food and Nutrition College, Federal University of Mato Grosso Do Sul, Campo Grande, Mato Grosso do Sul State, Brazil.
| | - Arielle Cristina Arena
- Department of Structural and Functional Biology, Institute of Biosciences of Botucatu, São Paulo State University, Botucatu, São Paulo State, Brazil.
| | - Silvia Cristina Heredia-Vieira
- Environment and Regional Development Postgraduate Program, Anhanguera-Uniderp University, Campo Grande, Mato Grosso do Sul State, Brazil.
| | - Cláudia Andrea Lima Cardoso
- Center of Studies in Natural Resources, State University of Mato Grosso do Sul, Dourados, Mato Grosso do Sul State, Brazil.
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Boeing T, Monteiro Magalhães de Oliveira B, Aldana-Mejía JA, Vidal Ccana-Ccapatinta G, Venzon L, Judah Cury B, Santos França TC, de Souza P, Roman Junior WA, Mota da Silva L, Kenupp Bastos J. Brazilian Red Propolis Accelerates Gastric Healing and Reduces Gastric Submucosal Layer Inflammation in Ultrasound-Monitored Rats. Chem Biodivers 2023; 20:e202200992. [PMID: 36445831 DOI: 10.1002/cbdv.202200992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/28/2022] [Accepted: 11/29/2022] [Indexed: 11/30/2022]
Abstract
Propolis has been used for the treatment of gastric disturbances in folk medicine, nevertheless, the gastric healing effects of Brazilian red propolis have not been unveiled. This study aimed to assess the gastric healing effect of the hydroalcoholic extract of red propolis (HERP) in the acetic acid-induced ulcer model. Rats under acetic acid-induced-ulcer were treated with HERP (100 mg/kg, p.o.) twice a day for seven days. Histological changes, oxidative stress, and inflammatory parameters were analyzed in the gastric tissue. Moreover, the gastric wall thickness was measured by ultrasound. The in vitro cytotoxicity of HERP and cellular migration of fibroblasts were evaluated. The treatment with HERP promoted gastric healing, reducing gastric wall thickness, macroscopic lesion area, and histopathological damages compared to the vehicle. Moreover, HERP reduced oxidative stress and inflammation in the gastric tissue but did not change mucin or collagen levels. HERP did not show signs of toxicity either in vivo or in vitro. HERP displayed a healing effect in vivo by reducing oxidative stress and inflammation. These data contribute to validating the popular use of this product in the treatment of gastric disorders and advance scientific knowledge in the search for new drugs for the management of gastric ulcers.
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Affiliation(s)
- Thaise Boeing
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | | | - Jennyfer Andrea Aldana-Mejía
- School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
| | - Gari Vidal Ccana-Ccapatinta
- School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
| | - Larissa Venzon
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | - Benhur Judah Cury
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | - Tauani Caroline Santos França
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | - Priscila de Souza
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | - Walter Antônio Roman Junior
- Postgraduate Program in Health Sciences, Universidade Comunitária da região de Chapecó (UNOCHAPECÓ), Chapecó, Santa Catarina, Brazil
| | - Luísa Mota da Silva
- Postgraduate Program in Pharmaceutical Sciences (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, Santa Catarina, Brazil
| | - Jairo Kenupp Bastos
- School of Pharmaceutical Sciences of Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, São Paulo, Brazil
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Cury BJ, Boeing T, Somensi LB, Campos A, Cechinel-Filho V, de Souza P, da Silva LM. Dimethyl Cardamonin from Fruits of Campomanesia reitziana D. Legrand Promotes Gastroprotection and Gastric Healing Effects in Rodents. Chem Biodivers 2022; 19:e202200727. [PMID: 36251014 DOI: 10.1002/cbdv.202200727] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Accepted: 10/17/2022] [Indexed: 12/27/2022]
Abstract
Campomanesia reitziana D. Legrand (Myrtaceae) displays antiulcer properties when given to rodents. The major active chemical components of C. reitziana are chalcones, including 4',6'-dihydroxy-2'-methoxy-3',5'-dimethylchalcone or dimethyl cardamonin (DMC); therefore, we hypothesized that this compound could have antiulcer effects and the present study aimed to evaluate its gastroprotective and gastric healing properties. DMC was isolated from the fruits of C. reitziana, and its gastroprotective effect was evaluated by ethanol and indomethacin-induced gastric ulcer models in mice (0.1 mg/kg, i.p. and 1 and 3 mg/kg, p.o.). Oxidative stress and inflammatory parameters were analyzed in the gastric tissue. Moreover, its gastric healing effect was evaluated in rats. In addition, the compound's mode of action was evaluated in vivo and in vitro by measuring H+ -K+ -ATPase activity. Finally, the cytotoxic potential of DMC was tested in fibroblasts and human gastric adenocarcinoma cells. The DMC reduced the ethanol-induced gastric ulcer in mice by 77 %, increased the adhered mucus, and reduced lipoperoxides levels. The block of nonprotein sulfhydryls (NP-SH) compounds by pretreatment with N-ethylmaleimide (NEM), the inhibition of nitric oxide synthase with Nω-nitro-L-arginine methyl ester hydrochloride (L-NAME), or the antagonism of α2 receptor using yohimbine reversed the gastroprotective effects of DMC. Furthermore, DMC reduced the acidity of gastric content in pylorus-ligated rats but did not change H+ , K+ -ATPase (isolated from rabbit) activity in vitro. DMC reduced the lesion area in acetic acid-induced ulcers and decreased myeloperoxidase activity. DMC did not change the viability of fibroblast cells (L929) but reduced the viability of human gastric adenocarcinoma cells (AGS). The results confirmed that DMC could significantly enhance the gastric healing process and prevent ulcers due to improving protective factors on the gastric mucosa and reducing gastric acid secretion.
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Affiliation(s)
- Benhur Judah Cury
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Thaise Boeing
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Adriana Campos
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Valdir Cechinel-Filho
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Priscila de Souza
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
| | - Luisa Mota da Silva
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Rua Uruguai, 458, Centro, 88302-901, Itajaí, Santa Catarina, Brazil
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Green chromatography as a novel alternative for the quality control of Serjania marginata Casar. Leaves. Microchem J 2022. [DOI: 10.1016/j.microc.2022.107671] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Meurer M, de Oliveira BMM, Cury BJ, Jerônimo DT, Venzon L, França TCS, Mariott M, Silva-Nunes R, Santos AC, Roman-Junior WA, Oliveira RG, Arunachalam K, Santin JR, Benvenutti L, Souza P, Aldana-Mejía JA, da Silva L. Extract of Tagetes erecta L., a medicinal plant rich in lutein, promotes gastric healing and reduces ulcer recurrence in rodents. JOURNAL OF ETHNOPHARMACOLOGY 2022; 293:115258. [PMID: 35378194 DOI: 10.1016/j.jep.2022.115258] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 02/09/2022] [Accepted: 03/29/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in South America to treat several ailments. Despite reports that T. erecta flowers are used in folk medicine to treat gastrointestinal diseases, there is no study regarding its gastric healing effects. AIM OF THE STUDY The effect of dry extract of T. erecta L. (DETe) in gastric healing and gastric ulcer recurrence was evaluated, contributing to the validation of the antiulcer potential of this medicinal plant. METHODS Rats were treated orally with vehicle (1 ml/kg), omeprazole (20 mg/kg), or DETe (3, 30 or 300 mg/kg) for 7 days, twice a day. The lesion area was evaluated, and the levels of reduced glutathione (GSH) and lipoperoxides (LOOH) and the activity of the superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and myeloperoxidase (MPO) were measured. The ulcer recurrence was evaluated in mice and induced by interleukin (IL)-1β (1 μg/kg, i.p). The recurred area, gastric wall thickness, GSH and cytokines levels, MPO and N-acetylglucosaminidase (NAG) activities were measured. RESULTS DETe accelerated the healing of gastric ulcers only at 300 mg/kg, reducing the ulcerated area by 66%. In parallel, DETe reduced LOOH levels, SOD, CAT and MPO activities, while increasing GST activity and mucin amount. In the recurrence model, DETe reduced the lesion area by 94%, and in parallel decreased the gastric wall thickness and TNF levels, while increasing IL-10 amount. CONCLUSIONS Corroborating the popular use of T. erecta, DETe favors the antioxidant system and reduce gastric inflammation, accelerating the gastric healing process and reducing the ulcer recurrence.
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Affiliation(s)
- Mariane Meurer
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Beatriz M M de Oliveira
- Postgraduate Program in Health Sciences, Community University of Chapecó Region, Chapecó, SC, 89809-900, Brazil
| | - Benhur J Cury
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Daniele T Jerônimo
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Larissa Venzon
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Tauani C S França
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Marihá Mariott
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Ruan Silva-Nunes
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Ana C Santos
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Walter A Roman-Junior
- Postgraduate Program in Health Sciences, Community University of Chapecó Region, Chapecó, SC, 89809-900, Brazil
| | - Ruberlei G Oliveira
- Postgraduate Program in Master's Degree in Sciences Applied to Hospital Care Júlio Müller University Hospital, Federal University of Mato Grosso, Cuiabá, Brazil
| | - Karuppusamy Arunachalam
- Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China
| | - José Roberto Santin
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Larissa Benvenutti
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Priscila Souza
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Jennyfer A Aldana-Mejía
- Postgraduate Program in Pharmaceutical Sciences, University of São Paulo, Campus Ribeirão Preto, Ribeirão Preto, Brazil
| | - Luisa da Silva
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil.
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Toxic Potential of Cerrado Plants on Different Organisms. Int J Mol Sci 2022; 23:ijms23073413. [PMID: 35408775 PMCID: PMC8998518 DOI: 10.3390/ijms23073413] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Revised: 10/25/2021] [Accepted: 10/27/2021] [Indexed: 12/04/2022] Open
Abstract
Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products.
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Ventura AS, Corrêa Filho RAC, Spica LN, Silva ACF, Araújo AMDE, Cardoso CAL, Jerônimo GT, Povh JA. Toxicological, biochemical and morphophysiological effects of Serjania erecta leaf aqueous extract on Piaractus mesopotamicus. AN ACAD BRAS CIENC 2021; 93:e20190479. [PMID: 34495195 DOI: 10.1590/0001-3765202120190479] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2019] [Accepted: 07/27/2019] [Indexed: 11/21/2022] Open
Abstract
This study was carried out to determine the toxicity and biochemical and morphophysiological changes caused by Serjania erecta leaf aqueous extract in pacu (Piaractus mesopotamicus). For acute toxicity testing (CL50-4h), pacu juveniles were exposed during 4 h to Serjania erecta aqueous extract concentrations of 2.5, 12.5, 25, 50, 100, and 150 µg mL-1, which were added directly to the water in the tanks. In the control group, the animals were kept in water free from aqueous extract. CL50-4 h was estimated at 57.43 µg mL-1. After exposure to the aqueous extract, the highest (P<0.05) glucose concentration and the lowest (P<0.05) plasma sodium level were when the fish were exposed to the S. erecta concentration of 50 µg mL-1. Mortality occurred at S. erecta extract levels higher than 50 μg mL-1, and all fish died at concentrations greater than 100 μg mL-1. In addition, exposure to this extract caused severe histological changes in the gills and liver with higher prevalence of necrosis (30.2%), and fatty degeneration (77.4%) respectively. At the concentrations tested here, S. erecta aqueous extract causes morphofunctional alterations in this fish species.
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Affiliation(s)
- Arlene S Ventura
- Universidade Federal de Mato Grosso do Sul (FAMEZ), Faculdade de Medicina Veterinária e Zootenia, Av. Sen. Filinto Müller, 2443, 79070-900 Campo Grande, MS, Brazil.,Universidade Federal da Grande Dourados, Faculdade de Ciências Agrárias (FCA), Rodovia Dourados/Itahum, Km 12, Unidade II, Caixa Postal 364, 79804-970 Dourados, MS, Brazil
| | - Ruy A C Corrêa Filho
- Universidade Federal de Mato Grosso do Sul (FAMEZ), Faculdade de Medicina Veterinária e Zootenia, Av. Sen. Filinto Müller, 2443, 79070-900 Campo Grande, MS, Brazil
| | - Louise N Spica
- Universidade Federal de Mato Grosso do Sul (FAMEZ), Faculdade de Medicina Veterinária e Zootenia, Av. Sen. Filinto Müller, 2443, 79070-900 Campo Grande, MS, Brazil
| | - Ana Cremilda F Silva
- Universidade Federal de Mato Grosso do Sul (FAMEZ), Faculdade de Medicina Veterinária e Zootenia, Av. Sen. Filinto Müller, 2443, 79070-900 Campo Grande, MS, Brazil
| | - Andrea M DE Araújo
- Universidade Federal da Grande Dourados, Faculdade de Ciências Agrárias (FCA), Rodovia Dourados/Itahum, Km 12, Unidade II, Caixa Postal 364, 79804-970 Dourados, MS, Brazil
| | - Claudia A L Cardoso
- Universidade Estadual de Mato Grosso do Sul, Centro de Estudos em Recursos Naturais (CERNA), Cidade Universitária de Dourados, Rodovia Itahum, Km 12, s/n, 79804-970 Dourados, MS, Brazil
| | - Gabriela T Jerônimo
- Universidade Federal do Amazonas (UFAM), Av. Rodrigo Otávio, 6200, 69080-900 Manaus, AM, Brazil
| | - Jayme A Povh
- Universidade Federal de Mato Grosso do Sul (FAMEZ), Faculdade de Medicina Veterinária e Zootenia, Av. Sen. Filinto Müller, 2443, 79070-900 Campo Grande, MS, Brazil
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11
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Serpeloni JM, Specian AFL, Ribeiro DL, Tuttis K, Heredia-Vieira SC, Vilegas W, Martínez-López W, Varanda EA, de Syllos Cólus IM. Selective anticancer effects of Serjania marginata Casar. extract in gastric cells are mediated by antioxidant response. ENVIRONMENTAL TOXICOLOGY 2021; 36:1544-1556. [PMID: 33885224 DOI: 10.1002/tox.23151] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/03/2021] [Revised: 03/17/2021] [Accepted: 04/11/2021] [Indexed: 06/12/2023]
Abstract
Gastric cancer is the fifth most common malignancy worldwide. Serjania marginata Casar. (SM) displays anti-inflammatory properties and has been used to treat gastrointestinal disorders. In the current study, we examined whether the hydroethanolic extract of SM leaves exerted cytotoxic, mutagenic, and protective effects in non-tumor gastric epithelium cells (MNP01) and gastric adenocarcinoma cells (ACP02) in vitro and analyzed whether its action was selective. Initially, cell viability (MTT assay), cell cycle kinetics (flow cytometry), and cell proliferation (total protein content) were analyzed. In addition, genomic instability (cytokinesis-block micronucleus cytome assay), anti/pro-oxidant status (CM-H2 DCFDA probe), and transcriptional expression (RT-qPCR) of genes related to cell cycle, cell death, and antioxidant defense were also evaluated. The SM extract was cytotoxic toward MNP01 and ACP02 cells at concentrations greater than 300 and 100 μg·ml-1 , respectively, and decreased protein content only toward ACP02 cells at 200 μg ml-1 . In ACP02 cells, the SM extract at 100 μg·ml-1 associated with doxorubicin (DXR; 0.2 μg ml-1 ) clearly promoted cell cycle arrest at the G2/M phase. The extract alone was not mutagenic to either cell type and reversed DXR-induced DNA damage and H2 O2 -induced oxidative stress in MNP01 cells. The gene expression experiments showed that SM hydroethanolic extract exerts an antioxidant response via NFE2L2 activation in non-tumor gastric cells, and cell cycle arrest (G2/M) in ACP02 gastric cancer cells via the TP53 pathway. The selective action of SM indicates that it is a promising therapeutic agent to treat gastric diseases and merits further studies.
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Affiliation(s)
- Juliana Mara Serpeloni
- Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil
| | - Ana Flavia Leal Specian
- Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil
| | - Diego Luis Ribeiro
- Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil
| | - Katiuska Tuttis
- Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil
| | | | - Wagner Vilegas
- Experimental Campus of São Vicente, São Paulo State University (UNESP), São Vicente, Brazil
| | - Wilner Martínez-López
- Epigenetics and Genomic Instability Laboratory, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay
| | - Eliana Aparecida Varanda
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, Brazil
| | - Ilce Mara de Syllos Cólus
- Department of General Biology, Center of Biological Sciences, State University of Londrina (UEL), Londrina, Brazil
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Zanatta AC, Vilegas W, Edrada-Ebel R. UHPLC-(ESI)-HRMS and NMR-Based Metabolomics Approach to Access the Seasonality of Byrsonima intermedia and Serjania marginata From Brazilian Cerrado Flora Diversity. Front Chem 2021; 9:710025. [PMID: 34295876 PMCID: PMC8290060 DOI: 10.3389/fchem.2021.710025] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Accepted: 06/24/2021] [Indexed: 11/24/2022] Open
Abstract
Seasonality is one of the major environmental factors that exert influence over the synthesis and accumulation of secondary metabolites in medicinal plants. The application of the metabolomics approach for quality control of plant extracts is essentially important because it helps one to establish a standard metabolite profile and to analyze factors that affect the effectiveness of the medicinal plants. The Brazilian Cerrado flora is characterized by a rich diversity of native plant species, and a number of these plant species have been found to have suitable medicinal properties. Some of these plant species include Byrsonima intermedia and Serjania marginata. To better understand the chemical composition of these plant species, we conducted a study using the state-of-the-art techniques including the HPLC system coupled to an Exactive-Orbitrap high resolution mass spectrometer with electrospray ionization interface UHPLC-(ESI)-HRMS and by NMR being performed 2D J-resolved and proton NMR spectroscopy. For the analysis, samples were harvested bimonthly during two consecutive years. UHPLC-(ESI)-HRMS data were preprocessed and the output data uploaded into an in-house Excel macro for peak dereplication. MS and NMR data were concatenated using the data fusion method and submitted to multivariate statistical analysis. The dereplication of LC-HRMS data helped in the annotation of the major compounds present in the extracts of the three plant species investigated allowing the annotation of 68 compounds in the extracts of B. intermedia (cinnamic acids, phenolic acids derived from galloyl quinic and shikimic acid, proanthocyanidins, glycosylated flavonoids, triterpenes and other phenols) and 81 compounds in the extracts of S. marginata (phenolic acids, saponins, proanthocyanidins, glycosylated flavonoids among other compounds). For a better assessment of the great number of responses, the significance of the chemical variables for the differentiation and correlation of the seasons was determined using the variable importance on projection (VIP) technique and through the application of the false discovery rate (FDR) estimation. The statistical data obtained showed that seasonal factors played an important role on the production of metabolites in each plant species. Temperature conditions, drought and solar radiation were found to be the main factors that affected the variability of phenolic compounds in each species.
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Affiliation(s)
- Ana C. Zanatta
- Laboratory of Phytochemistry, Institute of Chemistry, Department of Biochemistry and Organic Chemistry, São Paulo State University (UNESP), Araraquara, Brazil
- Laboratory of Bioprospecting of Natural Products, Institute of Biosciences, São Paulo State University (UNESP), São Vicente, Brazil
| | - Wagner Vilegas
- Laboratory of Bioprospecting of Natural Products, Institute of Biosciences, São Paulo State University (UNESP), São Vicente, Brazil
| | - RuAngelie Edrada-Ebel
- Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom
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13
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Bueno G, Chavez Rico SL, Périco LL, Ohara R, Rodrigues VP, Emílio-Silva MT, Assunção R, Machado da Rocha LR, Nunes DS, Besten MA, Heiden G, Lima Camargo AC, Justulin LA, Hiruma-Lima CA. The essential oil from Baccharis trimera (Less.) DC improves gastric ulcer healing in rats through modulation of VEGF and MMP-2 activity. JOURNAL OF ETHNOPHARMACOLOGY 2021; 271:113832. [PMID: 33460758 DOI: 10.1016/j.jep.2021.113832] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 12/12/2020] [Accepted: 01/11/2021] [Indexed: 06/12/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Baccharis trimera (Less.) DC known as "carqueja" in Brazil has been acknowledged as a medicinal plant in folk medicine for the treatment of stomach aches and gastrointestinal disorders. AIM OF THE STUDY The present study aimed to evaluate the gastroprotective and healing effects of essential oil from B. trimera (EOBT) against gastric ulcer lesions caused by absolute ethanol and acetic acid, respectively, and to identify the mechanism of action of this essential oil in male Wistar rats. MATERIALS AND METHODS The plant material used to obtain EOBT was collected in the southern region of Brazil and was analyzed by chromatography-mass spectrometry (GCMS) demonstrate its characteristic chemical composition, with carquejyl acetate as its main component. Different doses of EOBT (50, 100, and 200 mg/kg) were administered orally in male Wistar rats as an acute treatment against absolute ethanol-induced gastric lesions. The gastric healing effect of EOBT (100 mg/kg) was evaluated once a day after 7, 10, and 14 days of treatment. After treatment, the stomachs of rats from all groups were collected to measure the lesion area (mm2), the activity of myeloperoxidase (MPO), and the relative expression of caspases -3, -8, -9, cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF). The zymography method was used to elucidate the activity of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) in the healing action of EOBT. We also analyzed toxicological parameters (body weight evolution and biochemical parameters) that could result after treatment with this essential oil for 14 days. RESULTS Pretreatment with EOBT (100 and 200 mg/kg) significantly decreased the severity of gastric damage induced by absolute ethanol and decreased MPO activity in gastric tissue. After 10 and 14 days of treatment with EOBT (100 mg/kg) once a day, the lesion area was significantly reduced by 61% and 65.5%, respectively, compared to the negative control group. The gastric healing effect of EOBT was followed by a decrease in the expression of COX-1 compared to that in the negative control group. Notably, treatment with EOBT for 14 days increased the expression of VEGF compared to that using an anti-ulcer drug (lansoprazole). Additionally, analyses of MMP-2 and MMP-9 activities in the gastric mucosa confirmed the accelerated gastric healing effect of EOBT, with a significant decrease in the activity of pro-MMP-2. No sign of toxicity was observed after treatment with EOBT for 14 consecutive days. CONCLUSION These findings indicated that EOBT was effective in preventing and accelerating ulcer healing by decreasing MPO activity, increasing VEGF expression, and decreasing MMP-2 activity. These actions collectively contribute to the rapid recovery of gastric mucosa following treatment with EOBT, without any observed toxicity.
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Affiliation(s)
- Gabriela Bueno
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Stefanni Liliane Chavez Rico
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Larissa Lucena Périco
- Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Alberta, Canada
| | - Rie Ohara
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Vinicius Peixoto Rodrigues
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Maycon Tavares Emílio-Silva
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Renata Assunção
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Lucia Regina Machado da Rocha
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Domingos Sávio Nunes
- Department of Chemistry, UEPG-Ponta Grossa State University, CEP, 84030-900, Ponta Grossa, Paraná, Brazil
| | | | - Gustavo Heiden
- Herbário ECT - Embrapa Clima Temperado, Rodovia BR 392, Km 78, CEP, 96010-971, Pelotas, RS, Brazil
| | - Ana Carolina Lima Camargo
- Department of Structural and Functional Biology (Morphology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Luis Antonio Justulin
- Department of Structural and Functional Biology (Morphology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Structural and Functional Biology (Physiology), Biosciences Institute, UNESP-São Paulo State University, CEP, 18618-689, Botucatu, São Paulo, Brazil.
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Spósito L, Fortunato GC, de Camargo BAF, Ramos MADS, Souza MPCD, Meneguin AB, Bauab TM, Chorilli M. Exploiting drug delivery systems for oral route in the peptic ulcer disease treatment. J Drug Target 2021; 29:1029-1047. [PMID: 33729081 DOI: 10.1080/1061186x.2021.1904249] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.
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Affiliation(s)
- Larissa Spósito
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Giovanna Capaldi Fortunato
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Bruna Almeida Furquim de Camargo
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | | | | | - Andréia Bagliotti Meneguin
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Taís Maria Bauab
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Marlus Chorilli
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
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Dantas FGDS, Castilho PFD, Almeida-Apolonio AAD, Araújo RPD, Oliveira KMPD. Mutagenic potential of medicinal plants evaluated by the Ames Salmonella/microsome assay: A systematic review. MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH 2020; 786:108338. [PMID: 33339578 DOI: 10.1016/j.mrrev.2020.108338] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Revised: 10/02/2020] [Accepted: 10/06/2020] [Indexed: 01/21/2023]
Abstract
The Ames test has become one of the most commonly used tests to assess the mutagenic potential of medicinal plants since they have several biological activities and thus have been used in traditional medicine and in the pharmaceutical industry as a source of raw materials. Accordingly, this review aims to report previous use of the Ames test to evaluate the mutagenic potential of medicinal plants. A database was constructed by curating literature identified by a search on the electronic databases Medline (via Pubmed), Science Direct, Scopus, and Web of Science from 1975 to April 2020, using the following terms: "genotoxicity tests" OR "mutagenicity tests" OR "Ames test" AND "medicinal plants." From the research, 239 articles were selected, including studies of 478 species distributed across 111 botanical families, with Fabaceae, Asteraceae and Lamiaceae being the most frequent. It was identified that 388 species were non-mutagenic. Of these, 21% (83/388) showed antimutagenic potential, most notable in the Lamiaceae family. The results also indicate that 18% (90/478) of the species were mutagenic, of which 54% were mutagenic in the presence and absence of S9. Strains TA98 and TA100 showed a sensitivity of 93% in detecting plant extracts with mutagenic potential. However, the reliability of many reviewed studies regarding the botanical extracts may be questioned due to technical issues, such as testing being performed only in the presence or absence of S9, use of maximum doses below 5 mg/plate and lack of information on the cytotoxicity of tested doses. These methodological aspects additionally demonstrated that a discussion about the doses used in research on mixtures, such as the ones assessed with botanical extracts and the most sensitive strains employed to detect the mutagenic potential, should be included in a possible update of the guidelines designed by the regulatory agencies.
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Affiliation(s)
- Fabiana Gomes da Silva Dantas
- Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil; Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil
| | | | | | - Renata Pires de Araújo
- Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil; Faculty of Exact Sciences and Technology, Federal University of Grande Dourados, Dourados, MS, Brazil
| | - Kelly Mari Pires de Oliveira
- Faculty of Health Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil; Faculty of Biological and Environmental Sciences, Federal University of Grande Dourados, Dourados, MS, Brazil.
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Gastroprotective Effects of Inulae Flos on HCl/Ethanol-Induced Gastric Ulcers in Rats. Molecules 2020; 25:molecules25235623. [PMID: 33260419 PMCID: PMC7730672 DOI: 10.3390/molecules25235623] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Revised: 11/24/2020] [Accepted: 11/28/2020] [Indexed: 12/20/2022] Open
Abstract
Inulae Flos, the flower of Inula britannica L., is used as a dietary supplement, beverage, and medicine in East Asia. In this study, we evaluated the gastroprotective effects of Inulae Flos extract (IFE) against gastric mucosal lesions induced by hydrochloric acid (HCl)/ethanol in rats and explored its potential mechanisms by measuring antioxidant enzyme activity, mucus secretion, and prostaglandin E2 (PGE2) levels. Pretreatment with IFE at doses of 100 and 300 mg/kg significantly inhibited gastric lesions in HCl/ethanol-treated rats. IFE increased the activities of superoxide dismutase and catalase and the levels of glutathione and PGE2 in gastric tissues. The administration of IFE also significantly increased the gastric wall mucus contents in HCl/ethanol-induced gastric lesions. These findings suggest that IFE has gastroprotective effects against HCl/ethanol-induced gastric lesions and exerts these effects through increased antioxidant levels and gastric mucus secretion. Inulae Flos may be a promising agent for the prevention and treatment of gastritis and gastric ulcers.
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Longo B, Sommerfeld EP, Dos Santos AC, da Silva RDCMVDAF, Somensi LB, Mariano LNB, Boeing T, Faloni de Andrade S, de Souza P, da Silva LM. Dual role of eugenol on chronic gastric ulcer in rats: Low-dose healing efficacy and the worsening gastric lesion in high doses. Chem Biol Interact 2020; 333:109335. [PMID: 33245926 DOI: 10.1016/j.cbi.2020.109335] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 11/08/2020] [Accepted: 11/20/2020] [Indexed: 12/11/2022]
Abstract
This study evaluated the gastric healing activity of eugenol, the main bioactive compound from clove (Syzygium aromaticun) essential oil. Five groups of female Wistar rats were submitted to acetic acid-induced ulcer model and treated with Vehicle (1 mL/kg, p.o.), eugenol (1, 10 or 100 mg/kg, p.o) or omeprazole (20 mg/kg, p.o), twice a day, by seven or fourteen days. Macroscopic, microscopic and biochemical analyses were performed in the ulcerated site. Eugenol (1 mg/kg, p.o) administered by 7 or 14 days accelerated the gastric healing process by 33% and 52%, respectively. The healing actions of eugenol were accompanied by the rescue on the histological architecture and the normalization of the superoxide dismutase and catalase activity. Moreover, eugenol (1 mg/kg, p.o) reduced the gastric mucosal myeloperoxidase activity and increased the mucin secretion. In contrast, eugenol at a dose of 100 mg/kg administered by 7 days enhanced 49% the ulcerated area, but at 10 mg/kg did not change the ulcer area after 7 or 14 days of treatment. Thus, despite the undesirable results due to the worsening of the gastric lesion with the use of eugenol in high doses, the antiulcer potential of this compound is evident and manageable in an adequate dose.
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Affiliation(s)
- Bruna Longo
- Curso de Nutrição, Escola de Ciências da Saúde (ECS), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Ellen Perfoll Sommerfeld
- Curso de Nutrição, Escola de Ciências da Saúde (ECS), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Ana Caroline Dos Santos
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | | | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Luísa Nathalia Bolda Mariano
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Priscila de Souza
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil
| | - Luísa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, 88302-901, Santa Catarina, SC, Brazil.
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Kim YS, Nam Y, Song J, Kim H. Gastroprotective and Healing Effects of Polygonum cuspidatum Root on Experimentally Induced Gastric Ulcers in Rats. Nutrients 2020; 12:nu12082241. [PMID: 32727104 PMCID: PMC7468921 DOI: 10.3390/nu12082241] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/20/2020] [Accepted: 07/23/2020] [Indexed: 12/22/2022] Open
Abstract
Polygonum cuspidatum is widely used as food and medicine in Korea, China, and Japan. Its major bioactive components, resveratrol and emodin, reportedly protect against gastric lesions. We therefore aimed to investigate: (1) the gastroprotective effects of P. cuspidatum roots in hydrochloric acid/ethanol (HCl/EtOH)- and indomethacin-induced acute gastric ulcer rat models; (2) the healing effects in an acetic acid-induced ulcer model; and (3) potential mechanisms by measuring gastric acid secretion-related parameters in a pyloric ligation-induced ulcer model, and by measuring antioxidant enzyme and prostaglandin E2 levels in the gastric tissue of HCl/EtOH-treated rats. Oral administration of P. cuspidatum extract (PCE) at doses of 100 and 300 mg/kg significantly decreased HCl/EtOH- and indomethacin-induced gastric lesions. PCE at 300 mg/kg significantly reduced gastric lesions in acetic acid-induced ulcers. PCE increased superoxide dismutase (SOD)activity and glutathione(GSH) and prostaglandin E2 levels in gastric tissue, whereas it did not alter gastric acid secretion-related parameters. Our findings indicate that PCE has gastroprotective effects against HCl/EtOH and non-steroidal anti-inflammatory drugs(NSAIDs) and promotes healing of acetic acid-induced ulcers. These gastric mucosal protection and ulcer healing effects are associated with antioxidant effects and the augmentation of prostaglandin E2 and suggest that P. cuspidatum might be a promising preventive and therapeutic agent for treating gastric ulcers.
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Affiliation(s)
| | | | - Jungbin Song
- Correspondence: (J.S.); (H.K.); Tel.: +82-2-961-9394 (J.S.); +82-2-961-0419 (H.K.)
| | - Hocheol Kim
- Correspondence: (J.S.); (H.K.); Tel.: +82-2-961-9394 (J.S.); +82-2-961-0419 (H.K.)
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Ohara R, Périco LL, Rodrigues VP, Bueno G, Zanatta AC, Campaner Dos Santos L, Vilegas W, Constatino FB, Justulin LA, Hiruma-Lima CA. Terminalia catappa L. infusion accelerates the healing process of gastric ischemia-reperfusion injury in rats. JOURNAL OF ETHNOPHARMACOLOGY 2020; 256:112793. [PMID: 32240780 DOI: 10.1016/j.jep.2020.112793] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Revised: 03/18/2020] [Accepted: 03/22/2020] [Indexed: 06/11/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Terminalia catappa L. (Combretaceae), known as "amendoeira da praia" in Brazil, has been recognized as a medicinal plant in folk medicine for the treatment of gastrointestinal disorders and other inflammatory conditions. The present study aimed to investigate the preventive and healing effects of the infusion of leaves of T. catappa (ILTC) against gastric lesions caused by ischemia and reperfusion (I/R) injury and characterize its mechanism of action in the gastric mucosa of rats. MATERIALS AND METHODS Different doses (30, 100, and 300 mg/kg) of ILTC were orally administered as acute and subacute treatments against I/R-induced gastric lesion in rats. After treatment, the stomach of rats was collected to measure the lesion area, redox parameters malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) and inflammatory parameters myeloperoxidase activity (MPO), interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α). The activities of matrix metalloproteinases 2 and 9 (MMPs 2 and 9) were assessed by zymography method to clarify the mechanisms of the healing acceleration promoted by ILTC. RESULTS Pretreatment with ILTC (100 mg/kg) was effective in preventing the aggravation of lesions in the acute model by reducing MPO activity by 38% relative to control group, despite the lack of clarity of this action at the macroscopical level at the lesion area (p < 0.05). After three days of treatment with ILTC (30 and 100 mg/kg), this infusion significantly reduced the lesion area by 95% and 89%, respectively, compared the control (p < 0.05). The gastric healing effect of all doses of ILTC was followed by a reduction in MPO activity (decrease by 70-78%). Compared to the negative control, an improvement in gastric healing owing to treatment with ILTC was observed and this was followed by an increase in MMP-2 (20-47%) (p < 0.05). CONCLUSION Three days of treatment with ILTC could accelerate the healing process in I/R-induced lesions in rats. By decreasing MPO levels, ILTC enabled the action of MMP-2, which led to tissue recovery in the gastric mucosa.
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Affiliation(s)
- Rie Ohara
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil
| | - Larissa Lucena Périco
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil; Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Alberta, Canada
| | - Vinicius Peixoto Rodrigues
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil
| | - Gabriela Bueno
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil
| | - Ana Caroline Zanatta
- Biosciences Institute, UNESP-São Paulo State University, CEP 11330-900, São Vicente, São Paulo, Brazil; Institute of Chemistry, UNESP-São Paulo State University, CEP 14800-900, Araraquara, São Paulo, Brazil
| | | | - Wagner Vilegas
- Biosciences Institute, UNESP-São Paulo State University, CEP 11330-900, São Vicente, São Paulo, Brazil
| | - Flavia Bessi Constatino
- Laboratory of Extracellular Matrix, UNESP- São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil
| | - Luis Antonio Justulin
- Laboratory of Extracellular Matrix, UNESP- São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689, Botucatu, São Paulo, Brazil.
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Chrysin Modulates Genes Related to Inflammation, Tissue Remodeling, and Cell Proliferation in the Gastric Ulcer Healing. Int J Mol Sci 2020; 21:ijms21030760. [PMID: 31979417 PMCID: PMC7038074 DOI: 10.3390/ijms21030760] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2019] [Revised: 12/15/2019] [Accepted: 12/16/2019] [Indexed: 12/24/2022] Open
Abstract
Chrysin exhibits anti-inflammatory and antioxidant activities. Here, the gastroprotective effect of chrysin was investigated in mouse models of gastric ulcer induced by absolute ethanol, acetic acid, and ischemia-reperfusion injury. The gastric-healing effect was evaluated at 7 and 14 days after treatment; the mechanism of action was verified using the expression of metalloproteinase 2 (MMP-2) and 9 (MMP-9), caspase-3, cyclooxygenase 1 (COX-1) and 2 (COX-2), epidermal growth factor (EGF), and interleukin-10. Chrysin (10 mg/kg) inhibited macroscopic lesions and increased catalase activity in the mouse model established using absolute ethanol. It ameliorated the gastric ulcer caused by acetic acid by improving the expression of inflammatory genes such as COX-2, inhibiting negative remodeling promoted by MMP-9, increasing cell proliferation effect via EGF, and reducing cellular apoptosis by modulating caspase-3. A faster healing effect was evident in the first 7 days of treatment compared to 14 days of treatment, indicating the pharmacological potential of chrysin. Overall, these results demonstrate the potent effect of chrysin in the gastrointestinal tract and elucidate the genes involved in the healing of gastric ulcers. Moreover, an increase in the levels of gastric mucosa defensive factors is involved in the activity of chrysin in the gastric mucosa.
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Nascimento RA, Possomato-Vieira JS, Bonacio GF, Rizzi E, Dias-Junior CA. Reductions of Circulating Nitric Oxide are Followed by Hypertension during Pregnancy and Increased Activity of Matrix Metalloproteinases-2 and -9 in Rats. Cells 2019; 8:cells8111402. [PMID: 31703340 PMCID: PMC6912623 DOI: 10.3390/cells8111402] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 09/03/2019] [Indexed: 12/14/2022] Open
Abstract
Hypertensive pregnancy has been associated with reduced nitric oxide (NO), bioavailability, and increased activity of matrix metalloproteinases (MMPs). However, it is unclear if MMPs activation is regulated by NO during pregnancy. To this end, we examined activity of MMP-2 and MMP-9 in plasma, placenta, uterus and aorta, NO bioavailability, oxidative stress, systolic blood pressure (SBP), and fetal-placental development at the early, middle, and late pregnancy stages in normotensive and Nω-Nitro-L-arginine methyl-ester (L-NAME)-induced hypertensive pregnancy in rats. Reduced MMP-2 activity in uterus, placenta, and aorta and reduced MMP-9 activity in plasma and placenta with concomitant increased NO levels were found in normotensive pregnant rats. By contrast, increased MMP-2 activity in uterus, placenta, and aorta, and increased MMP-9 activity in plasma and placenta with concomitant reduced NO levels were observed in hypertensive pregnant rats. Also, elevated oxidative stress was displayed by hypertensive pregnant rats at the middle and late stages. These findings in the L-NAME-treated pregnant rats were also followed by increases in SBP and associated with fetal growth restrictions at the middle and late pregnancy stages. We concluded that NO bioavailability may regulate MMPs activation during normal and hypertensive pregnancy.
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Affiliation(s)
- Regina A. Nascimento
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University – UNESP, Botucatu, Sao Paulo 18.618-689, Brazil; (R.A.N.); (J.S.P.-V.)
| | - Jose S. Possomato-Vieira
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University – UNESP, Botucatu, Sao Paulo 18.618-689, Brazil; (R.A.N.); (J.S.P.-V.)
| | - Giselle F. Bonacio
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo 14096-900, Brazil; (G.F.B.); (E.R.)
| | - Elen Rizzi
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo 14096-900, Brazil; (G.F.B.); (E.R.)
| | - Carlos A. Dias-Junior
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University – UNESP, Botucatu, Sao Paulo 18.618-689, Brazil; (R.A.N.); (J.S.P.-V.)
- Correspondence: ; Tel.: +55 14 3880-0214
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do Carmo Ota E, Honorato CA, Heredia-Vieira SC, Flores-Quintana CI, de Castro Silva TS, Inoue LAKA, Cardoso CAL. Hepatic and gastroprotective activity of Serjania marginata leaf aqueous extract in Nile tilapia (Oreochromis niloticus). FISH PHYSIOLOGY AND BIOCHEMISTRY 2019; 45:1051-1065. [PMID: 31089991 DOI: 10.1007/s10695-019-00622-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/27/2018] [Accepted: 02/14/2019] [Indexed: 06/09/2023]
Abstract
The aim of this study was to assess the leaf aqueous extract composition of Serjania marginata and the effects of its inclusion on the diet of Nile tilapia (Oreochromis niloticus), with respect to the activity of digestive enzymes and enzymes associated with the metabolism of the liver and intestine and liver histopathology. Fish (initial mean weight, 54.36 ± 17.04 g) were divided into groups: fasting (without feeding), control (commercial feed), and treatment (commercial feed with leaf aqueous extract of Serjania marginata), and in each aquarium, there were five individuals and the fish fed ad libitum for 15 days. Treatment fish had ingested on average 224.3 mg of extract/kg of fish/day. In the extract analysis by mass spectrometry, quercitrin, isoquercitrin, A-type proanthocyanidin trimer, and quinic acid were identified. In the enzymatic activity, fish from the treatment group showed higher level of alkaline phosphatase, while the hepatotoxic markers (AST and ALT) and levels of lipase, amylase, and nonspecific protease did not differ (p > 0.05). In liver histopathological analysis, it was observed that fish from the treatment showed normal structure, while abnormalities were associated with control (fibrosis, loss of cordonal architecture, vacuolated hepatocytes with nucleus displaced to the periphery) and fasting (reduction in hepatocyte size and sinusoidal space). The intestine histopathology evidenced that the extract favored the development of goblet cells and intestinal fold height. The results indicated that the leaf aqueous extract of S. marginata assists in the structural maintenance of the liver and intestine and stimulates intestinal alkaline phosphatase production in Nile tilapia, suggesting that the identified compounds act on the liver and intestine, showing hepatoprotective effects and stimulating intestinal digestion.
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Affiliation(s)
- Erika do Carmo Ota
- Center of Studies on Natural Resources, Mato Grosso do Sul State University (UEMS), Cidade Universitária de Dourados, Rod. Dourados-Itahúm, Km 12, C.P. 351, Dourados, Mato Grosso do Sul, 79804-970, Brazil.
| | | | | | | | | | | | - Claudia Andrea Lima Cardoso
- Center of Studies on Natural Resources, Mato Grosso do Sul State University (UEMS), Cidade Universitária de Dourados, Rod. Dourados-Itahúm, Km 12, C.P. 351, Dourados, Mato Grosso do Sul, 79804-970, Brazil
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Périco LL, Rodrigues VP, Ohara R, Nunes VVA, da Rocha LRM, Vilegas W, Dos Santos C, Hiruma-Lima CA. Can the gastric healing effect of Eugenia punicifolia be the same in male and female rats? JOURNAL OF ETHNOPHARMACOLOGY 2019; 235:268-278. [PMID: 30763697 DOI: 10.1016/j.jep.2019.02.012] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 01/20/2019] [Accepted: 02/06/2019] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Eugenia punicifolia (Kunth) DC. (Myrtaceae), an Amazonian medicinal plant known as "pedra-ume-caá," is popularly used as a natural remedy for inflammation, wounds, infections, diabetes, fever, and flu. Its anti-inflammatory, antinociceptive, and gastroprotective effects have already been characterized. We evaluated the gastric healing effect of the hydroalcoholic extract of the leaves of E. punicifolia (HEEP) in male and female Wistar rats against nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol. MATERIALS AND METHODS The healing effect of HEEP on the gastric mucosa of adult male and female Wistar rats was measured after the chronic application of aggressive factors such as NSAIDs or 80% ethanol. Male, and intact and ovariectomized (OVZ) female rats were treated with HEEP for two days (NSAIDs) or one, two, four, and six days (80% ethanol). The stomachs were analyzed macroscopically for ulcerative lesions (mm2), and the healing process was measured using biochemical analysis with anti-inflammatory and antioxidant parameters. RESULTS Macroscopic evaluation of the gastric mucosa showed that gastric lesions induced by NSAIDs were significantly healed (66%) and pro-inflammatory interleukin 5 cytokine level was decreased after two-day oral treatment with HEEP compared with those in the negative control group (p < 0.05). However, the gastric lesions induced by NSAIDs did not heal in HEEP-treated female rats (p > 0.05). In addition, four-day treatment with HEEP significantly healed the gastric lesions induced by ethanol in male and female rats (63% and 78%, respectively) compared to those of the negative control group (p < 0.05). However, the OVZ group required six days of HEEP treatment to heal gastric ulcers (67% compared to the control group). HEEP exerts the healing effect against ethanol by significantly reducing neutrophil infiltration into the gastric mucosa by decreasing myeloperoxidase activity in male and OVZ rats after four and six days of treatment, respectively (p < 0.05). Four-day treatment with HEEP also increased the level of a non-enzymatic antioxidant, reduced glutathione in intact females compared to that of the negative control group (p < 0.05). CONCLUSION These findings indicated that HEEP was effective in promoting the healing of gastric ulcers induced by NSAIDs or ethanol. The gastric healing effects of this extract could be affected by female sex hormone interference; in future, comprehensive studies should be performed by considering sex differences.
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Affiliation(s)
- Larissa Lucena Périco
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil
| | - Vinícius Peixoto Rodrigues
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil
| | - Rie Ohara
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil
| | - Vânia Vasti Alfieri Nunes
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil
| | - Lúcia Regina Machado da Rocha
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil
| | - Wagner Vilegas
- Biosciences Institute, UNESP-São Paulo State University, CEP 11330-900 São Vicente, São Paulo, Brazil
| | - Catarina Dos Santos
- Department of Biological Science, Faculty of Sciences and Languages, UNESP-São Paulo State University, CEP 19806-900 Assis, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Physiology, Biosciences Institute, UNESP-São Paulo State University, CEP 18618-689 Botucatu, São Paulo, Brazil.
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Costa P, Boeing T, Somensi LB, Cury BJ, Espíndola VL, França TCS, de Almeida MO, Arruda C, Bastos JK, da Silva LM, de Andrade SF. Hydroalcoholic extract from Baccharis dracunculifolia recovers the gastric ulcerated tissue, and p-coumaric acid is a pivotal bioactive compound to this action. Biofactors 2019; 45:479-489. [PMID: 30974027 DOI: 10.1002/biof.1503] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Accepted: 02/26/2019] [Indexed: 12/28/2022]
Abstract
Baccharis dracunculifolia is a medicinal plant native to southeastern Brazil and is the main botanical source used by bees (Apis mellifera) in the manufacture of green propolis and display similar gastroprotective action and chemical profile. This article reports the healing gastric ulcer activity of the hydroethanolic extract of B. dracunculifolia (HEBD) in an acetic acid-induced ulcer model. In addition to the extract, the isolated compounds ferulic acid, p-coumaric acid, caffeic acid, baccharin, and aromadendrin-4'-O-methyl ether were also assayed. HEBD at a dose of 300 mg/kg reduced the ulcerated area by 49.4% after treatment for 7 days, twice a day. Histological analyses revealed that the margins and base of the ulcer obtained significant regeneration, and periodic acid Schiff base staining showed a 78.2% increase in the mucin levels. The action on the enzymatic antioxidant system demonstrated an increased activity of superoxide dismutase and glutathione-S-transferase, in addition to raising glutathione reduced levels and myeloperoxidase activity. HEBD did not show cytotoxicity in the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylterazole bromine test. In vitro, HEBD inhibited the H+ /K+ -ATPase enzyme and showed antioxidant activity in the 2,2 diphenyl-1-picryllydrazyl test. Regarding the isolated compounds, oral administration of p-coumaric acid (15 mg/kg) reduced the ulcerated area by 66.2%. The results suggest that HEBD recovers the gastric ulcerated tissue, raising mucus and antioxidant enzyme levels, and reducing the H+ /K+ -ATPase activity. In addition, the findings confirm that p-coumaric acid is a pivotal bioactive compound on the gastric healing effects elicited by HEBD. © 2019 BioFactors, 45(3):479-489, 2019.
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Affiliation(s)
- Philipe Costa
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Vanessa Lopes Espíndola
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Tauani Caroline Santos França
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Marília Oliveira de Almeida
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Caroline Arruda
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Jairo Kenupp Bastos
- School of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
| | - Luisa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas, Universidade do Vale do Itajaí, Itajaí, South Carolina, Brazil
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Spósito L, Oda FB, Vieira JH, Carvalho FA, Dos Santos Ramos MA, de Castro RC, Crevelin EJ, Crotti AEM, Santos AG, da Silva PB, Chorilli M, Bauab TM. In vitro and in vivo anti-Helicobacter pylori activity of Casearia sylvestris leaf derivatives. JOURNAL OF ETHNOPHARMACOLOGY 2019; 233:1-12. [PMID: 30594606 DOI: 10.1016/j.jep.2018.12.032] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/04/2018] [Revised: 12/14/2018] [Accepted: 12/16/2018] [Indexed: 05/27/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The number of bacterial strains that are resistant to multiple conventional antimicrobial agents is increasing. In this context, natural products have been widely used as a strategy to treat diseases caused by bacteria. Infections by Helicobacter pylori have attracted attention because they are directly related to severe gastric medical conditions. Casearia sylvestris Swartz, popularly known as guaçatonga, is largely employed to treat gastric disorders in Brazilian folk medicine. This plant species has aroused much interest mainly because it displays anti-inflammatory activity and can act as an antiulcer agent. AIM OF THE STUDY To evaluate the in vitro and in vivo anti-H. pylori action of C. sylvestris leaf derivatives incorporated or not in a nanostructured drug delivery system. MATERIALS AND METHODS The essential oil (obtained by hydrodistillation) and ethanolic extract (obtained by maceration) were obtained from C. sylvestris leaves. The ethanolic extract was submitted to fractionation through solid phase extraction and column chromatography, to yield the ethanolic fractions. Hydrolyzed casearin J was achieved by submitting isolated casearin J to acid hydrolysis. The derivatives were chemically characterized by nuclear magnetic resonance (NMR), gas chromatography (GC), and gas chromatography-mass spectrometry (GC-MS) analyses. A nanostructured lipid system was used as drug delivery system. To assess the in vitro antibacterial activity of C. sylvestris leaf essential oil, ethanolic extract, and derivatives, microdilution, biofilm, and time-kill assays were performed against H. pylori ATCC 43504. Finally, the in vivo action was investigated by employing male Wistar rats experimentally infected with H. pylori. RESULTS Many C. sylvestris leaf derivatives presented significant in vitro activity against H. pylori. Among the derivatives, fraction 2 (F2) was the most effective. In vivo tests showed that both the ethanolic extract and F2 decreased the ulcerative lesion size, but only the ethanolic extract eradicated H. pylori from the gastric lesions. Incorporation of plant derivatives in nanostructured lipid system blunted the in vitro action, as demonstrated by the microdilution assay. However, this incorporation improved the ethanolic extract activity against biofilms. CONCLUSION C. sylvestris leaf derivatives are effective against H. pylori both in vitro and in vivo. According to phytochemical analyses, these derivatives are rich in terpenoids, which could be related to the anti-H. pylori action. Synergism could also underlie C. sylvestris efficacy judging from the fact that the sub-fractions and isolated compounds had lower activity than the extract. Incorporation in a nanostructured lipid system did not improve the activity of the compounds in our in vivo protocol.
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Affiliation(s)
- Larissa Spósito
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Fernando Bombarda Oda
- Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Júlia Hunger Vieira
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Flávio Alexandre Carvalho
- Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | | | - Rogério Cardoso de Castro
- Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Eduardo José Crevelin
- Department of Chemistry, Faculty of Philosophy, Sciences and Letters, USP, Ribeirão Preto, SP, Brazil
| | | | - André Gonzaga Santos
- Department of Natural Active Principles and Toxicology, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Patrícia Bento da Silva
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Marlus Chorilli
- Department of Drugs and Medicines, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil
| | - Taís Maria Bauab
- Department of Biological Sciences, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
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da Silva Moreira S, Tamashiro LK, Jorge BC, da Silva Balin P, Heredia-Vieira SC, de Almeida GL, Cardoso CAL, Kassuya CAL, Arena AC. Toxicological safety evaluation in acute and 28-day studies of aqueous extract from Serjania marginata Casar. (Sapindaceae) leaves in rats. JOURNAL OF ETHNOPHARMACOLOGY 2019; 231:197-204. [PMID: 30453050 DOI: 10.1016/j.jep.2018.11.024] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Revised: 09/26/2018] [Accepted: 11/14/2018] [Indexed: 06/09/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Serjania marginata Casar. (Sapindaceae) is a species traditionally known to be used for the treatment of gastric pain and inflammatory symptoms. AIM OF THIS STUDY Due to the therapeutic importance of this species, this study investigated the toxicological effects of S. marginata leaves (AESM), after a single and a repeated exposure in rats. MATERIALS AND METHODS For the acute toxicity test, 2000 mg/kg of AESM was administered to male and female rats by gavage, whereas for subacute toxicity test, 30, 150, or 750 mg/kg of AESM were used. RESULTS No evidence of toxicity was observed in the animals acutely exposed to the extract, indicating that the LD50 is higher than 2000 mg/kg. After the repeated administration of AESM the hematological and biochemical parameters were unaltered, except the erythrocytes number and albumin levels in the exposed animals. Moreover, daily administration of this extract caused alteration on kidney histology. AESM also induced an increase of abnormal sperm, however the other reproductive parameters analyzed, in both sexes, were not altered by the treatment. CONCLUSION Although AESM was not toxic after a single exposure, its use after prolonged periods affected some analyzed parameters, indicating that precautions should be taken when it is given over longer periods.
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Affiliation(s)
- Suyane da Silva Moreira
- Department of Morphology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista - Botucatu, São Paulo State, Brazil.
| | - Leticia Kaory Tamashiro
- Department of Morphology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista - Botucatu, São Paulo State, Brazil.
| | - Bárbara Campos Jorge
- Department of Morphology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista - Botucatu, São Paulo State, Brazil.
| | - Paola da Silva Balin
- Department of Morphology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista - Botucatu, São Paulo State, Brazil.
| | | | - Gabriela Lessa de Almeida
- Center for Natural Resource Studies, Mato Grosso do Sul State University, UEMS - Dourados, Mato Grosso do Sul State, Brazil.
| | - Claudia Andrea Lima Cardoso
- Center for Natural Resource Studies, Mato Grosso do Sul State University, UEMS - Dourados, Mato Grosso do Sul State, Brazil.
| | | | - Arielle Cristina Arena
- Department of Morphology, Institute of Biosciences of Botucatu, UNESP - Univ. Estadual Paulista - Botucatu, São Paulo State, Brazil.
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Byrsonima intermedia A. Juss partitions promote gastroprotection against peptic ulcers and improve healing through antioxidant and anti-inflammatory activities. Biomed Pharmacother 2019; 111:1112-1123. [DOI: 10.1016/j.biopha.2018.12.132] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2018] [Revised: 12/21/2018] [Accepted: 12/30/2018] [Indexed: 12/16/2022] Open
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Chimini JS, Possomato-Vieira JS, da Silva MLS, Dias-Junior CA. Placental nitric oxide formation and endothelium-dependent vasodilation underlie pravastatin effects against angiogenic imbalance, hypertension in pregnancy and intrauterine growth restriction. Basic Clin Pharmacol Toxicol 2018; 124:385-393. [PMID: 30318719 DOI: 10.1111/bcpt.13149] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2018] [Accepted: 10/08/2018] [Indexed: 12/17/2022]
Abstract
Pre-eclampsia and hypertensive disorders of pregnancy are frequently associated with foeto-placental growth restriction, and that may be triggered by angiogenic imbalance and endothelial dysfunction. Impaired nitric oxide (NO) bioavailability seems to be involved in these pathophysiological changes observed in hypertensive pregnancy. Pravastatin has shown efficacy and to be safe during hypertension in pregnancy. However, NO involvement in pravastatin effects during maternal hypertension and foeto-placental development is unclear. Therefore, we aimed to examine pravastatin effects on placental NO formation, endothelium-dependent vasodilation, systolic blood pressure and foeto-placental development in hypertensive pregnant rats. Biochemical determinants of angiogenesis and oxidative stress were also assessed. Pregnant rats were distributed into four groups: normal pregnancy (Norm-Preg), pregnancy+pravastatin (Preg-Prava), hypertensive pregnancy (HTN-Preg) and hypertensive pregnancy+pravastatin (HTN-Preg+Prava). Our results showed that pravastatin treatment blunts hypertension and foeto-placental growth restriction. Also, increases in placental NO levels were found in the HTN-Preg+Prava group. Pravastatin prevents impaired endothelium-dependent acetylcholine-induced vasodilation, exacerbated contractile response to phenylephrine and increases in oxidative stress in the HTN-Preg+Prava group. Increased soluble fms-like tyrosine kinase-1-to-placental growth factor (sFlt-1/PlGF) ratio is reversed by pravastatin treatment in the HTN-Preg+Prava group. We conclude that NO formation and endothelium-dependent vasodilation underlie pleiotropic effects associated with pravastatin treatment against hypertension in pregnancy, intrauterine growth restriction, vascular dysfunction and angiogenic imbalance.
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Affiliation(s)
- Jessica Sabbatine Chimini
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Brazil
| | - Jose Sergio Possomato-Vieira
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Brazil
| | - Maria Luiza Santos da Silva
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Brazil
| | - Carlos A Dias-Junior
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Brazil
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Nascimento RA, Possomato-Vieira JS, Gonçalves-Rizzi VH, Bonacio GF, Rizzi E, Dias-Junior CA. Hypertension, augmented activity of matrix metalloproteinases-2 and -9 and angiogenic imbalance in hypertensive pregnancy are attenuated by doxycycline. Eur J Pharmacol 2018; 840:60-69. [PMID: 30336141 DOI: 10.1016/j.ejphar.2018.10.017] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Revised: 10/10/2018] [Accepted: 10/12/2018] [Indexed: 02/07/2023]
Abstract
Preeclampsia is manifested as maternal hypertension and fetal growth restriction. Matrix metalloproteinases (MMPs) are involved in hypertension and doxycycline reduces blood pressure by inhibition of MMPs. Moreover, excessive levels of MMPs and reduced nitric oxide (NO) bioavailability have been related to preeclampsia. We investigated the involvement of MMPs in hypertension in pregnancy induced by Nω-Nitro-L-arginine methyl ester (L-NAME) in rats. To this end, zimography was performed to evaluate the activity of MMPs -2 and -9 in placenta, uterus and thoracic aorta, and systolic blood pressure, feto-placental development and metabolites of NO were evaluated. Also, plasma antioxidant capacity, plasma levels of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PLGF) were examined. Doxycycline prevented hypertensive pregnancy and significant reductions in number of pups induced by L-NAME. Low NO bioavailability was found in hypertensive pregnant rats treated (or not) with doxycycline. Increased activity of placental MMP-2 and MMP-9 and uterine MMP-2 were attenuated by doxycycline. MMP-2 activity of thoracic aorta showed no change after hypertension. Increases in PLGF with concomitant decreases in sFlt-1 levels were found with doxycycline treatment. Also, plasma antioxidant capacity was improved with doxycycline. Also, elevations of plasma antioxidant capacity were observed in hypertensive rats treated with doxycycline. Therefore, we suggest that L-NAME reduced NO and this triggered the increases in MMP-2 and -9 activities during hypertensive pregnancy. Importantly, increases in MMPs activation and angiogenic imbalance were attenuated by doxycycline and these effects were associated with decreases in systolic blood pressure.
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Affiliation(s)
- Regina A Nascimento
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - José S Possomato-Vieira
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - Victor H Gonçalves-Rizzi
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - Gisele F Bonacio
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo, Brazil
| | - Elen Rizzi
- Unit of Biotechnology, University of Ribeirao Preto, UNAERP, Ribeirao Preto, Sao Paulo, Brazil
| | - Carlos A Dias-Junior
- Department of Pharmacology, Biosciences Institute of Botucatu, Sao Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil.
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Périco LL, Rodrigues VP, Ohara R, Bueno G, Nunes VVA, dos Santos RC, Camargo ACL, Júnior LAJ, de Andrade SF, Steimbach VMB, da Silva LM, da Rocha LRM, Vilegas W, dos Santos C, Hiruma-Lima CA. Sex-specific effects of Eugenia punicifolia extract on gastric ulcer healing in rats. World J Gastroenterol 2018; 24:4369-4383. [PMID: 30344421 PMCID: PMC6189849 DOI: 10.3748/wjg.v24.i38.4369] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2018] [Revised: 07/11/2018] [Accepted: 08/01/2018] [Indexed: 02/06/2023] Open
Abstract
AIM To evaluate the sex-specific effects of a hydroalcoholic extract from Eugenia punicifolia (HEEP) leaves on gastric ulcer healing.
METHODS In this rat study involving males, intact (cycling) females, and ovariectomized females, gastric ulcers were induced using acetic acid. A vehicle, lansoprazole, or HEEP was administered for 14 d after ulcer induction. Body weight was monitored throughout the treatment period. At the end of treatment, the rats were euthanized and the following in vivo and in vitro investigations were performed: macroscopic examination of the lesion area and organ weights, biochemical analysis, zymography, and evaluation of protein expression levels. Additionally, the concentration-dependent effect of HEEP was evaluated in terms of subacute toxicity and cytotoxicity.
RESULTS Compared to the vehicle, HEEP demonstrated a great healing capacity by substantially reducing the ulcerative lesion area in males (52.44%), intact females (85.22%), and ovariectomized females (65.47%), confirming that HEEP accelerates the healing of acetic acid-induced gastric lesions and suggesting that this effect is modulated by female sex hormones. The antiulcer effect of HEEP was mediated by prostaglandin E2 only in male rats. Overall, the beneficial effect of HEEP was the highest in intact females. Notably, HEEP promoted the expression of vascular endothelial growth factor (intact vs ovariectomized females) and decreased the expression of Caspase-8 and Bcl-2 (intact female vs male or ovariectomized female). Additionally, HEEP enhanced fibroblast proliferation and migration into a wounded area in vitro, confirming its healing effect. Finally, no sign of subacute toxicity or cytotoxicity of HEEP was observed.
CONCLUSION In gastric ulcers, HEEP-induced healing (modulated by female sex hormones; in males, mediated by prostaglandin) involves extracellular matrix remodeling, with gastric mucosa cell proliferation and migration.
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Affiliation(s)
- Larissa Lucena Périco
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Vinícius Peixoto Rodrigues
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Rie Ohara
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Gabriela Bueno
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Vânia Vasti Alfieri Nunes
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Raquel Cássia dos Santos
- Laboratory of Bioactive Compounds, São Francisco University, Bragança Paulista 12916-900, São Paulo, Brazil
| | - Ana Carolina Lima Camargo
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Luis Antônio Justulin Júnior
- Department of Morphology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Viviane Miranda Bispo Steimbach
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Luísa Mota da Silva
- Programa de Pós-graduação em Ciências Farmacêuticas, Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí - UNIVALI, Itajaí 88302-901, Santa Catarina, Brazil
| | - Lúcia Regina Machado da Rocha
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
| | - Wagner Vilegas
- Coastal Campus of São Vicente, São Paulo State University (UNESP), São Vicente 11330-900, São Paulo, Brazil
| | - Catarina dos Santos
- Department of Biological Science, Faculty of Sciences and Languages, São Paulo State University (UNESP), Assis 19806-900, São Paulo, Brazil
| | - Clélia Akiko Hiruma-Lima
- Department of Physiology, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-970, São Paulo, Brazil
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Possomato-Vieira JS, Chimini JS, da Silva MLS, Dias-Junior CA. Increases in placental nitric oxide, but not nitric oxide-mediated relaxation, underlie the improvement in placental efficiency and antihypertensive effects of hydrogen sulphide donor in hypertensive pregnancy. Clin Exp Pharmacol Physiol 2018; 45:1118-1127. [PMID: 29927503 DOI: 10.1111/1440-1681.13000] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 06/07/2018] [Accepted: 06/20/2018] [Indexed: 12/17/2022]
Abstract
Dysregulation of hydrogen sulphide (H2 S) producing enzymes has been related to hypertensive pregnancy, and H2 S donor, sodium hydrosulphide (NaHS) exerts antihypertensive effects, modulates angiogenic factors production and acts as an antioxidant. Moreover, reduction in nitric oxide (NO) bioavailability is related to hypertensive pregnancy and H2 S may interact with NO, modulating its production. We aimed to investigate the NaHS effects in hypertension-in-pregnancy and also in feto-placental parameters. Female Wistar rats (200-250 g) were mated and desoxycorticosterone acetate injections followed by replacement of water by 0.9% saline solution were used to induce hypertensive pregnancy. Rats were divided into four groups: normal pregnant (Norm-Preg), pregnant + NaHS (Preg+NaHS), hypertensive pregnant (HTN-Preg) and HTN-Preg+NaHS. Systolic blood pressure was increased in HTN-Preg and this increase was blunted in HTN-Preg+NaHS. Fetal and placental weights were decreased in HTN-Preg animals, while fetal growth restriction was improved in HTN-Preg+NaHS. Placental weight was lower in HTN-Preg+NaHS than in HTN-Preg; however, placental efficiency was re-established in HTN-Preg+NaHS rats. We observed that a partial contribution of placental NO, but not changes in anti-angiogenic factors may mediate the increases in placental efficiency in HTN-Preg+NaHS. HTN-Preg presented thoracic aorta hyperreactivity to phenylephrine while NaHS treatment blunted this hyperreactivity, which seems not to be related to NO-mediated relaxation induced by acetylcholine. Therefore, changes in vascular responsiveness promoted by NaHS treatment may underlie the beneficial effects in systolic blood pressure and feto-placental parameters in our study.
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Affiliation(s)
- Jose S Possomato-Vieira
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - Jessica S Chimini
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - Maria L S da Silva
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
| | - Carlos A Dias-Junior
- Department of Pharmacology, Biosciences Institute of Botucatu, São Paulo State University - UNESP, Botucatu, Sao Paulo, Brazil
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Sharifi-Rad M, Fokou PVT, Sharopov F, Martorell M, Ademiluyi AO, Rajkovic J, Salehi B, Martins N, Iriti M, Sharifi-Rad J. Antiulcer Agents: From Plant Extracts to Phytochemicals in Healing Promotion. Molecules 2018; 23:E1751. [PMID: 30018251 PMCID: PMC6100067 DOI: 10.3390/molecules23071751] [Citation(s) in RCA: 112] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2018] [Revised: 07/12/2018] [Accepted: 07/14/2018] [Indexed: 12/12/2022] Open
Abstract
In this narrative review, we have comprehensively reviewed the plant sources used as antiulcer agents. From traditional uses as herbal remedies, we have moved on to preclinical evidence, critically discussing the in vitro and in vivo studies focusing on plant extracts and even isolated phytochemicals with antiulcerogenic potential. A particular emphasis was also paid to Helicobacter pylori activity, with emphasis on involved mechanisms of action. Lastly, the issue of safety profile of these plant products has also been addressed.
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Affiliation(s)
- Mehdi Sharifi-Rad
- Department of Medical Parasitology, Zabol University of Medical Sciences, Zabol 61663335, Iran.
| | | | - Farukh Sharopov
- Department of Pharmaceutical Technology, Avicenna Tajik State Medical University, Rudaki 139, Dushanbe 734003, Tajikistan.
| | - Miquel Martorell
- Nutrition and Dietetics Department, School of Pharmacy, University of Concepción, Concepción 4070386, VIII⁻Bio Bio Region, Chile.
| | - Adedayo Oluwaseun Ademiluyi
- Functional Foods, Nutraceuticals and Phytomedicine Unit, Department of Biochemistry, Federal University of Technology, Akure 340001, Nigeria.
| | - Jovana Rajkovic
- Institute of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, Belgrade 11129, Serbia.
| | - Bahare Salehi
- Medical Ethics and Law Research Center, Shahid Beheshti University of Medical Sciences, Tehran 88777539, Iran.
- Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran 22439789, Iran.
| | - Natália Martins
- Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, Porto 4200-319, Portugal.
- Institute for Research and Innovation in Health (i3S), University of Porto⁻Portugal, Porto 4200-135, Portugal.
| | - Marcello Iriti
- Department of Agricultural and Environmental Sciences, Milan State University, via G. Celoria 2, Milan 20133, Italy.
| | - Javad Sharifi-Rad
- Phytochemistry Research Center, Shahid Beheshti University of Medical Sciences, Tehran 11369, Iran.
- Department of Chemistry, Richardson College for the Environmental Science Complex, The University of Winnipeg, Winnipeg, MB R3B 2G3, Canada.
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de Barros NR, Heredia-Vieira SC, Borges FA, Benites NM, dos Reis CE, Miranda MCR, Cardoso CAL, Herculano RD. Natural rubber latex biodevice as controlled release system for chronic wounds healing. Biomed Phys Eng Express 2018. [DOI: 10.1088/2057-1976/aab33a] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
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Clinical and Experimental Evidences of Hydrogen Sulfide Involvement in Lead-Induced Hypertension. BIOMED RESEARCH INTERNATIONAL 2018; 2018:4627391. [PMID: 29789795 PMCID: PMC5896357 DOI: 10.1155/2018/4627391] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/06/2017] [Revised: 02/09/2018] [Accepted: 02/20/2018] [Indexed: 12/15/2022]
Abstract
Lead- (Pb-) induced hypertension has been shown in humans and experimental animals and cardiovascular effects of hydrogen sulfide (H2S) have been reported previously. However, no studies examined involvement of H2S in Pb-induced hypertension. We found increases in diastolic blood pressure and mean blood pressure in Pb-intoxicated humans followed by diminished H2S plasmatic levels. In order to expand our findings, male Wistar rats were divided into four groups: Saline, Pb, NaHS, and Pb + NaHS. Pb-intoxicated animals received intraperitoneally (i.p.) 1st dose of 8 μg/100 g of Pb acetate and subsequent doses of 0.1 μg/100 g for seven days and sodium hydrosulfide- (NaHS-) treated animals received i.p. NaHS injections (50 μmol/kg/twice daily) for seven days. NaHS treatment blunted increases in systolic blood pressure, increased H2S plasmatic levels, and diminished whole-blood lead levels. Treatment with NaHS in Pb-induced hypertension seems to induce a protective role in rat aorta which is dependent on endothelium and seems to promote non-NO-mediated relaxation. Pb-intoxication increased oxidative stress in rats, while treatment with NaHS blunted increases in plasmatic MDA levels and increased antioxidant status of plasma. Therefore, H2S pathway may be involved in Pb-induced hypertension and treatment with NaHS exerts antihypertensive effect, promotes non-NO-mediated relaxation, and decreases oxidative stress in rats with Pb-induced hypertension.
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Propolis and Its Potential to Treat Gastrointestinal Disorders. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:2035820. [PMID: 29736177 PMCID: PMC5875067 DOI: 10.1155/2018/2035820] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Accepted: 11/21/2017] [Indexed: 12/17/2022]
Abstract
There are a number of disorders that affect the gastrointestinal tract. Such disorders have become a global emerging disease with a high incidence and prevalence rates worldwide. Inflammatory and ulcerative processes of the stomach or intestines, such as gastritis, ulcers, colitis, and mucositis, afflict a significant proportion of people throughout the world. The role of herbal-derived medicines has been extensively explored in order to develop new effective and safe strategies to improve the available gastrointestinal therapies that are currently used in the clinical practice. Studies on the efficacy of propolis (a unique resinous aromatic substance produced by honeybees from different types of species of plants) are promising and propolis has been effective in the treatment of several pathological conditions. This review, therefore, summarizes and critiques the contents of some relevant published scientific papers (including those related to clinical trials) in order to demonstrate the therapeutic value of propolis and its active compounds in the treatment and prevention of gastrointestinal diseases.
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Gonçalves-Rizzi VH, Possomato-Vieira JS, Nascimento RA, Caldeira-Dias M, Dias-Junior CA. Maternal hypertension and feto-placental growth restriction is reversed by sildenafil: Evidence of independent effects of circulating nitric oxide levels. Eur J Pharmacol 2018; 822:119-127. [PMID: 29355552 DOI: 10.1016/j.ejphar.2018.01.010] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2017] [Revised: 01/04/2018] [Accepted: 01/15/2018] [Indexed: 12/17/2022]
Abstract
Sildenafil has shown nitric oxide (NO)-independent pleiotropic effects, however the mechanisms involved are unclear. We investigated the protective effects of sildenafil against hypertension in pregnancy and feto-placental growth restriction induced by NO inhibition, and if sodium nitrite-derived NO formation influences sildenafil effects. We evaluated the plasmatic levels of NO metabolites, cyclic guanosine monophosphate (cGMP), oxidative stress and myeloperoxidase, which are involved in endothelial dysfunction during hypertension in pregnancy. Also, we performed in vitro experiments to examine cell viability and NO synthesis in human umbilical vein endothelial cells (HUVECs) cultures incubated with plasma from healthy or hypertensive pregnant rats treated (or not) with both drugs, either alone or in association. Sildenafil blunted hypertension in pregnancy and protected against feto-placental growth restriction induced by NO inhibition and these effects of sildenafil alone were similar to those presented by its association with sodium nitrite. Protective effects of sildenafil were observed even with low plasmatic NO levels and were not followed by increases in cGMP levels. Also, sildenafil, but not sodium nitrite, blunted the increases in myeloperoxidase activity. Both drugs (isolated or in association) presented antioxidant effects. Plasma from hypertensive pregnant rats treated with sildenafil, but not sodium nitrite alone, increased the viability of HUVECs. NO synthesis in HUVECs cultures was increased with plasma from rats treated with both drugs. We conclude that sildenafil effects are not dependent of circulating NO levels in hypertension and feto-placental growth restriction. These findings may reflect a protection against myeloperoxidase and pro-oxidant activation in hypertension in pregnancy.
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Affiliation(s)
- Victor Hugo Gonçalves-Rizzi
- Department of Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - José Sérgio Possomato-Vieira
- Department of Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Regina Aparecida Nascimento
- Department of Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Mayara Caldeira-Dias
- Department of Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil
| | - Carlos Alan Dias-Junior
- Department of Pharmacology, Institute of Biosciences of Botucatu, São Paulo State University (UNESP), Botucatu, Sao Paulo, Brazil.
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Essential oil of Cymbopogon citratus (lemongrass) and geraniol, but not citral, promote gastric healing activity in mice. Biomed Pharmacother 2017; 98:118-124. [PMID: 29248831 DOI: 10.1016/j.biopha.2017.12.020] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Revised: 11/16/2017] [Accepted: 12/04/2017] [Indexed: 02/06/2023] Open
Abstract
Cymbopogon citratus, popularly known as lemongrass, is used for the treatment of gastric, nervous and hypertensive disorders, in addition to its use in the food and pharmaceutical industries. This study evaluated the gastroprotective and gastric healing effect of essential oil of C. citratus (EOCC), citral and geraniol at doses of 1-100 mg/kg (p.o) on acute ethanol-induced ulcer and chronic acetic acid-induced ulcer. Histological and histochemical evaluation was also performed, as well as the in vitro evaluation of the effects of these phytochemicals on H+/K+-ATPase activity. In the ethanol-induced gastric ulcer, the minimum effective oral dose of EOCC, citral and geraniol were 10, 100 and 3 mg/kg, reducing the ulcer area by 51.67%, 96.57% and 55.74%, respectively, compared to vehicle group (25.82 ± 3.59 mm2). Moreover, EOCC (10 mg/kg, p.o) and geraniol (3 mg/kg), but not citral (100 mg/kg), accelerated the gastric healing process by 34.52 and 80.57%, compared to acetic-acid ulcerated group treated with vehicle (36.04 ± 1.03 mm2). These healing effects were confirmed histologically by the contraction of the ulcer base and by the enhancement on mucin staining in slices of ulcer site from mice treated with EOCC or geraniol. Interestingly, EOCC and citral at 100 μg/ml inhibited the H+/ K+-ATPase activity by 28.26% and 44.36%, whereas geraniol did not change this parameter. Together, these findings confirm the gastroprotective and healing gastric ulcer effects of essential oil from aerial parts of C. citratus and added the information that geraniol, but not citral, promotes healing effects on installed ulcers.
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Arunachalam K, Balogun SO, Pavan E, de Almeida GVB, de Oliveira RG, Wagner T, Cechinel Filho V, de Oliveira Martins DT. Chemical characterization, toxicology and mechanism of gastric antiulcer action of essential oil from Gallesia integrifolia (Spreng.) Harms in the in vitro and in vivo experimental models. Biomed Pharmacother 2017; 94:292-306. [PMID: 28763752 DOI: 10.1016/j.biopha.2017.07.064] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2017] [Revised: 07/01/2017] [Accepted: 07/14/2017] [Indexed: 12/12/2022] Open
Abstract
Gallesia integrifolia is a Brazilian Amazon tree whose bark decoction is popularly used to treat peptic ulcer. The essential oil from the inner stem bark of G. integrifolia (EOGi) was chemically characterized by GC/MS. The in vitro cytotoxicity and genotoxicity were evaluated in CHO-K1 cells, while the in vivo oral acute toxicity was performed in mice. The gastroprotective effect of EOGi was assessed in acidified ethanol and piroxicam and ulcer healing on acetic acid -induced ulcer models in rodents. Anti-secretory, mucus, K+-ATP channels, prostaglandins (PGs), nitric oxide (NO), TNF-α, IL-1β, IL-10, catalase (CAT) and myeloperoxidase (MPO) activities and in vitro Helicobacter pylori action by EOGi were evaluated. EOGi exhibited cytotoxic effects only at 72h and no acute toxicity. EOGi showed gastroprotective and ulcer healing effects. EOGi gastroprotection was attenuated by indomethacin pre-treatment. Gastric volume and total acidity were reduced, while gastric pH was elevated. EOGi increased mucus and NO productions and CAT activity, and inhibited MPO activity, TNF-α and IL-1β concentrations and augmented IL-10. EOGi was not active against H. pylori. These results indicated that EOGi is safe and exerts preventive and curative gastric ulcer effects by multitarget actions. Twenty compounds were identified and (-)-alpha-santalene was the main compound.
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Affiliation(s)
- Karuppusamy Arunachalam
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Sikiru Olaitan Balogun
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil; Curso de Farmácia, Faculdade Noroeste do Mato Grosso, Associação Juinense de Ensino Superior (AJES), Juína, Mato Grosso, Brazil
| | - Eduarda Pavan
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Guilherme Vieira Botelho de Almeida
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Ruberlei Godinho de Oliveira
- Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, Brazil
| | - Theodoro Wagner
- Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas e Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí, Itajaí, Santa Catarina, Brazil
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Somensi LB, Boeing T, Cury BJ, Steimbach VMB, Niero R, de Souza LM, da Silva LM, de Andrade SF. Hydroalcoholic extract from bark of Persea major (Meisn.) L.E. Kopp (Lauraceae) exerts antiulcer effects in rodents by the strengthening of the gastric protective factors. JOURNAL OF ETHNOPHARMACOLOGY 2017; 209:294-304. [PMID: 28807848 DOI: 10.1016/j.jep.2017.08.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Revised: 07/28/2017] [Accepted: 08/02/2017] [Indexed: 06/07/2023]
Abstract
ETHOPHARMACOLOGICAL RELEVANCE The Persea major (Meisn.) L.E. Kopp (Lauraceae) (botanical synonym: Persea pyrifolia (D. Don) Spreng, Persea pyrifolia Nees and Mart., Persea cordata var. major (Meisn.) Mez and Persea willdenovii Kosterm) is a medicinal plant native in the south of Brazil, where is popularly known as Pau de Andrade, Maçaranduba or Abacate-do-Mato. Its barks are commonly used to prepare an infusion which is administered orally or topically to treat ulcers and wounds, respectively. Thus, this study has been undertaken to contribute to the validation of the popular use of P. major to treat of ulcerative disorders from gastrointestinal system, using different experimental models in rodents. MATERIAL AND METHODS Firstly, ultra-performance liquid chromatography coupled to a mass spectrophotometer has been performed. Next, the potential gastroprotective of hydroalcoholic extract of P. major barks (HEPM) (30-300mg/kg) has been evaluated in ulcer models acute as: ethanol, ethanol/HCl and indomethacin-induced ulcer. The extract (300mg/kg) has been also tested in acetic acid-induced chronic ulcer model. Histological, toxicological, histochemical, oxidative stress and gastric secretion parameters were analyzed. RESULTS The main compounds found in HEPM were polyphenols as condensed tannins, flavonoids heterosides derivatives from quercetin and kaempferol. HEPM (300mg/kg, p.o) prevented gastric lesions induced by ethanol or indomethacin in rats by 58.98% and 97.48%, respectively, compared to vehicle group (148.00±14.83mm2 and 12.07±1.61mm2, respectively). In acetic acid-induced chronic ulcer model the HEPM (300mg/kg, p.o) reduced the ulcer are by 40.58%, compared to vehicle group (127.90±12.04mm2). The healing effect was confirmed histologically, by an increase in mucin content and by the reduction in oxidative and inflammatory parameters at the ulcer site. Neither significant effect on gastric acid secretion nor toxicological effects and cytotoxicity were provoked by administration of HEPM. CONCLUSIONS The results allows to conclude that HEPM exerts gastroprotective and gastric cicatrizing effects favoring on protective defenses, but not possess antisecretory effect in contrast to the current antiulcer therapy, besides the extract present good tolerability and absence of cytotoxicity. Moreover, the results presented here contribute to the validation to the popular use of the P. major in the treatment of gastric ulcer.
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Affiliation(s)
- Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Viviane Miranda Bispo Steimbach
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Rivaldo Niero
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Lauro Mera de Souza
- Instituto de Pesquisa Pelé Pequeno Príncipe, Faculdades Pequeno Príncipe, 80250-200 Curitiba, Paraná, Brazil
| | - Luisa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Núcleo de Investigacões Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202 Itajaí, SC, Brazil.
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Silva FL, Silva JLD, Silva JM, Marcolin LS, Nouailhetas VL, Yoshida M, Vendramini PH, Eberlin MN, Barbosa-Filho JM, Moreno PR. Antispasmodic activity from Serjania caracasana fractions and their safety. REVISTA BRASILEIRA DE FARMACOGNOSIA-BRAZILIAN JOURNAL OF PHARMACOGNOSY 2017. [DOI: 10.1016/j.bjp.2016.12.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/24/2022]
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Geck MS, Reyes García AJ, Casu L, Leonti M. Acculturation and ethnomedicine: A regional comparison of medicinal plant knowledge among the Zoque of southern Mexico. JOURNAL OF ETHNOPHARMACOLOGY 2016; 187:146-159. [PMID: 27114060 DOI: 10.1016/j.jep.2016.04.036] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/20/2015] [Revised: 04/21/2016] [Accepted: 04/22/2016] [Indexed: 06/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE In rural areas of Mexico the impact of modernization has changed healthcare and health seeking behaviour to varying degrees. This has rarely been accounted for when discussing and comparing medicinal floras. The ethnomedical system of the Zoque has never before been systematically studied. AIM OF THE STUDY The objective of this study was to document medical practices and medicinal plant knowledge of the Zoque of Chiapas and Oaxaca, the latter being more strongly affected by acculturation. The medicinal floras are compared in order to detect similarities and differences and establishing links to the cultural transformation. METHODS Research was carried out in a total of nine Zoque municipalities, attempting to adequately represent the cultural and ecological diversity of the Zoque territory. Standard anthropological and ethnobotanical methods were used for data collection. The recorded medicinal uses were classified into 17 disease categories according to emic medical concepts. In each category, the recorded taxa were rank-ordered based on number of use-reports and the informant consensus factor was calculated. The characteristics of the disease categories and the most salient taxa were compared across the two field sites. RESULTS AND DISCUSSION A total of 6598 use-reports on 544 species have been collected. With the strongly acculturated Zoque of Oaxaca we have documented a considerably less extensive medicinal flora. The ethnopharmacopoeias of the two Zoque groups share 144 species. These species are of over-proportionate salience, accounting for two-thirds of the total use-reports. In both field sites gastrointestinal disorders are of particular importance, followed by women's diseases, respiratory diseases and musculoskeletal ailments. Children's and spiritual illnesses seem to have lost their importance in Oaxaca, as the underlying concepts are often considered backwards and superstitious. CONCLUSION While it is difficult to establish a quantitative causal relation between acculturation and medicinal plant knowledge, in qualitative terms there are clear indicators for the changes acculturation has brought about in the medical system of the Zoque of Oaxaca. The results suggest the development of an increasingly homogenized pan-Mesoamerican medicinal flora.
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Affiliation(s)
- Matthias S Geck
- Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy
| | | | - Laura Casu
- Department of Life and Environmental Sciences, University of Cagliari, 09124 Cagliari, Italy
| | - Marco Leonti
- Department of Biomedical Sciences, University of Cagliari, 09124 Cagliari, Italy.
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de Barros M, Mota da Silva L, Boeing T, Somensi LB, Cury BJ, de Moura Burci L, Santin JR, de Andrade SF, Monache FD, Cechinel-Filho V. Pharmacological reports about gastroprotective effects of methanolic extract from leaves of Solidago chilensis (Brazilian arnica) and its components quercitrin and afzelin in rodents. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:403-17. [PMID: 26758066 DOI: 10.1007/s00210-015-1208-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 12/29/2015] [Indexed: 12/28/2022]
Abstract
Solidago chilensis Meyenmost (Asteraceae), popularly known as "Brazilian arnica" or "arnica-do-campo," is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H(+),K(+)-ATPase activity at a concentration of 1-100 μg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.
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Affiliation(s)
- Mariel de Barros
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Luisa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Ligia de Moura Burci
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade Federal do Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-970, Curitiba, PR, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil.
| | - Franco Delle Monache
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Valdir Cechinel-Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
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da Silva LM, Boeing T, Somensi LB, Cury BJ, Steimbach VMB, Silveria ACDO, Niero R, Cechinel Filho V, Santin JR, de Andrade SF. Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies. JOURNAL OF ETHNOPHARMACOLOGY 2015; 175:75-85. [PMID: 26364940 DOI: 10.1016/j.jep.2015.09.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 08/31/2015] [Accepted: 09/05/2015] [Indexed: 05/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear. AIM OF THE STUDY The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage. MATERIAL AND METHODS To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice. RESULTS Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 ± 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 µg/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 µg/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals. CONCLUSIONS The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer.
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Affiliation(s)
- Luisa Mota da Silva
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil.
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | | | | | - Rivaldo Niero
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
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