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Hwang S, Jo M, Hong JE, Kim WS, Kang DH, Yoo SH, Kang K, Rhee KJ. Caffeic Acid Phenethyl Ester Administration Reduces Enterotoxigenic Bacteroides fragilis-Induced Colitis and Tumorigenesis. Toxins (Basel) 2024; 16:403. [PMID: 39330861 PMCID: PMC11435740 DOI: 10.3390/toxins16090403] [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: 08/05/2024] [Revised: 09/08/2024] [Accepted: 09/13/2024] [Indexed: 09/28/2024] Open
Abstract
The human colonic commensal enterotoxigenic Bacteroides fragilis (ETBF) is associated with chronic colitis and colon cancer. ETBF colonization induces colitis via the Bacteroides fragilis toxin (BFT). BFT secreted by ETBF cause colon inflammation via E-cadherin cleavage/NF-κB signaling. ETBF promotes colon tumorigenesis via interleukin 17A (IL-17A)/CXCL-dependent inflammation, but its bioactive therapeutics in ETBF-promoted tumorigenesis remain unexplored. In the current study, we investigated the caffeic acid phenethyl ester (CAPE) in the murine model of ETBF colitis and tumorigenesis. In this study, we observed that CAPE treatment mitigated inflammation induced by ETBF in mice. Additionally, our findings indicate that CAPE treatment offers protective effects against ETBF-enhanced colon tumorigenesis in a mouse model of colitis-associated colon cancer induced by azoxymethane (AOM) and dextran sulfate sodium. Notably, the decrease in colon tumorigenesis following CAPE administration correlates with a reduction in the expression of IL-17A and CXCL1 in the gastrointestinal tract. The molecular mechanism for CAPE-induced protection against ETBF-mediated tumorigenesis is mediated by IL-17A/CXCL1, and by NF-κB activity in intestinal epithelial cells. Our findings indicate that CAPE may serve as a preventive agent against the development of ETBF-induced colitis and colorectal cancer (CRC).
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Affiliation(s)
- Soonjae Hwang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, College of Medicine, Gachon University, 155 Gaetbeol-ro, Yeonsu-gu, Inchon 21999, Republic of Korea
| | - Minjeong Jo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon 16419, Republic of Korea
| | - Ju-Eun Hong
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Woo-Seung Kim
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Da-Hye Kang
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
- Department of Obstetrics, Gynecology and Women’s Health, University of Missouri, Columbia, MO 65211, USA
| | - Sang-Hyeon Yoo
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
| | - Kyungsu Kang
- Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea;
| | - Ki-Jong Rhee
- Department of Biomedical Laboratory Science, College of Software and Digital Healthcare Convergence, Yonsei University MIRAE Campus, Wonju 26493, Republic of Korea; (S.H.); (M.J.); (J.-E.H.); (W.-S.K.); (D.-H.K.); (S.-H.Y.)
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Rivera-Yañez N, Ruiz-Hurtado PA, Rivera-Yañez CR, Arciniega-Martínez IM, Yepez-Ortega M, Mendoza-Arroyo B, Rebollar-Ruíz XA, Méndez-Cruz AR, Reséndiz-Albor AA, Nieto-Yañez O. The Role of Propolis as a Natural Product with Potential Gastric Cancer Treatment Properties: A Systematic Review. Foods 2023; 12:foods12020415. [PMID: 36673507 PMCID: PMC9858610 DOI: 10.3390/foods12020415] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Revised: 01/10/2023] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Gastric cancer is one of the most common, aggressive, and invasive types of malignant neoplasia. It ranks fifth for incidence and fourth for prevalence worldwide. Products of natural origin, such as propolis, have been assessed for use as new complementary therapies to combat cancer. Propolis is a bee product with antiproliferative and anticancer properties. The concentrations and types of secondary metabolites contained in propolis mainly vary according to the geographical region, the season of the year, and the species of bees that make it. The present study is a systematic review of the main articles related to the effects of propolis against gastric cancer published between 2011 and 2021 in the PubMed and Science Direct databases. Of 1305 articles published, only eight studies were selected; among their principal characteristics was the use of in vitro analysis with cell lines from gastric adenocarcinoma and in vivo murine models of the application of propolis treatments. These studies suggest that propolis arrests the cell cycle and inhibits proliferation, prevents the release of oxidizing agents, and promotes apoptosis. In vivo assays showed that propolis decreased the number of tumors by regulating the cell cycle and the expression of proteins related to apoptosis.
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Affiliation(s)
- Nelly Rivera-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
- División de Investigación y Posgrado, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
| | - Porfirio Alonso Ruiz-Hurtado
- Laboratorio de Toxicología de Productos Naturales, Departamento de Farmacia, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Av. Wilfrido Massieu, Esq. Manuel L. Stampa s/n, Gustavo A. Madero, Ciudad de México 07738, Mexico
- Laboratorio de Toxicología Molecular y Celular, Departamento de Farmacia, Instituto Politécnico Nacional, Escuela Nacional de Ciencias Biológicas, Av. Wilfrido Massieu, Esq. Manuel L. Stampa s/n, Gustavo A. Madero, Ciudad de México 07738, Mexico
| | - Claudia Rebeca Rivera-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
| | - Ivonne Maciel Arciniega-Martínez
- Laboratorio de Inmunonutrición, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis esq. Salvador Díaz Mirón s/n, Ciudad de México 11340, Mexico
| | - Mariazell Yepez-Ortega
- Laboratorio de Inmunonutrición, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis esq. Salvador Díaz Mirón s/n, Ciudad de México 11340, Mexico
| | - Belén Mendoza-Arroyo
- Laboratorio de Inmunidad de Mucosas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis esq. Salvador Díaz Mirón s/n, Ciudad de México 11340, Mexico
| | - Xóchitl Abril Rebollar-Ruíz
- Laboratorio de Inmunonutrición, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis esq. Salvador Díaz Mirón s/n, Ciudad de México 11340, Mexico
| | - Adolfo René Méndez-Cruz
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
- Laboratorio de Inmunología, Unidad de Morfofisiología y Función, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
| | - Aldo Arturo Reséndiz-Albor
- Laboratorio de Inmunidad de Mucosas, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, Plan de San Luis esq. Salvador Díaz Mirón s/n, Ciudad de México 11340, Mexico
- Correspondence: (A.A.R.-A.); (O.N.-Y.); Tel.: +52-5521-327-136 (O.N.-Y.)
| | - Oscar Nieto-Yañez
- Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Tlalnepantla 54090, Mexico
- Correspondence: (A.A.R.-A.); (O.N.-Y.); Tel.: +52-5521-327-136 (O.N.-Y.)
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Koistinen VM, Hedberg M, Shi L, Johansson A, Savolainen O, Lehtonen M, Aura A, Hanhineva K, Landberg R. Metabolite Pattern Derived from Lactiplantibacillus plantarum-Fermented Rye Foods and In Vitro Gut Fermentation Synergistically Inhibits Bacterial Growth. Mol Nutr Food Res 2022; 66:e2101096. [PMID: 35960594 PMCID: PMC9787878 DOI: 10.1002/mnfr.202101096] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2021] [Revised: 06/30/2022] [Indexed: 12/30/2022]
Abstract
SCOPE Fermentation improves many food characteristics using microbes, such as lactic acid bacteria (LAB). Recent studies suggest fermentation may also enhance the health properties, but mechanistic evidence is lacking. The study aims to identify a metabolite pattern reproducibly produced during sourdough and in vitro colonic fermentation of various whole-grain rye products and how it affects the growth of bacterial species of potential importance to health and disease. METHODS AND RESULTS The study uses Lactiplantibacillus plantarum DSMZ 13890 strain, previously shown to favor rye as its substrate. Using LC-MS metabolomics, the study finds seven microbial metabolites commonly produced during the fermentations, including dihydroferulic acid, dihydrocaffeic acid, and five amino acid metabolites, and stronger inhibition is achieved when exposing the bacteria to a mixture of the metabolites in vitro compared to individual compound exposures. CONCLUSION The study suggests that metabolites produced by LAB may synergistically modulate the local microbial ecology, such as in the gut. This could provide new hypotheses on how fermented foods influence human health via diet-microbiota interactions.
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Affiliation(s)
- Ville M. Koistinen
- Institute of Public Health and Clinical NutritionUniversity of Eastern FinlandKuopio70211Finland,Food Chemistry and Food Development Unit, Department of BiochemistryUniversity of TurkuTurkuTurku20014Finland,Afekta Technologies Ltd.Kuopio70210Finland
| | - Maria Hedberg
- Department of Odontology/Oral MicrobiologyUmeå UniversityUmeå90187Sweden
| | - Lin Shi
- Division of Food and Nutrition Science, Department of Biology and Biological EngineeringChalmers University of TechnologyGothenburg41296Sweden,College of Food Engineering and Nutritional ScienceShaanxi Normal UniversityXi'an710119China
| | - Anders Johansson
- Department of Odontology/Oral MicrobiologyUmeå UniversityUmeå90187Sweden
| | - Otto Savolainen
- Institute of Public Health and Clinical NutritionUniversity of Eastern FinlandKuopio70211Finland,Division of Food and Nutrition Science, Department of Biology and Biological EngineeringChalmers University of TechnologyGothenburg41296Sweden
| | - Marko Lehtonen
- School of PharmacyUniversity of Eastern FinlandKuopio70211Finland
| | - Anna‐Marja Aura
- VTT Technical Research Centre of Finland Ltd.Espoo02044Finland
| | - Kati Hanhineva
- Institute of Public Health and Clinical NutritionUniversity of Eastern FinlandKuopio70211Finland,Food Chemistry and Food Development Unit, Department of BiochemistryUniversity of TurkuTurkuTurku20014Finland,Division of Food and Nutrition Science, Department of Biology and Biological EngineeringChalmers University of TechnologyGothenburg41296Sweden
| | - Rikard Landberg
- Division of Food and Nutrition Science, Department of Biology and Biological EngineeringChalmers University of TechnologyGothenburg41296Sweden
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Zhao X, Liu Z, Liu H, Guo J, Long S. Hybrid molecules based on caffeic acid as potential therapeutics: A focused review. Eur J Med Chem 2022; 243:114745. [PMID: 36152388 DOI: 10.1016/j.ejmech.2022.114745] [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] [Received: 01/06/2022] [Revised: 09/03/2022] [Accepted: 09/03/2022] [Indexed: 01/29/2023]
Abstract
Caffeic acid-based compounds possess a high degree of structural diversity and show a variety of pharmacological properties, providing a useful framework for the discovery of new therapeutic agents. They are well-known analogues of antioxidants found in many natural products and synthetic compounds. The present review surveys the recent developments in structure-activity relationships (SAR) and mechanism of action (MOA) of various caffeic acid-containing compounds that play important roles in the design and synthesis of new bioactive molecules with antioxidant, antidiabetic, antiviral, antibacterial, anticancer, anti-inflammatory, and other properties. This review should provide inspiration to scientists in the research fields of organic synthesis and medicinal chemistry related to the development of new antioxidants with versatile therapeutic potential.
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Affiliation(s)
- Xue Zhao
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 Optics Valley 1st Rd, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Ziwei Liu
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 Optics Valley 1st Rd, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Hao Liu
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 Optics Valley 1st Rd, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Ju Guo
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 Optics Valley 1st Rd, East Lake New Technology Development District, Wuhan, Hubei, 430205, China
| | - Sihui Long
- Key Laboratory for Green Chemical Process of Ministry of Education, Hubei Key Laboratory of Novel Reactor and Green Chemical Technology, School of Chemical Engineering and Pharmacy, Wuhan Institute of Technology, 206 Optics Valley 1st Rd, East Lake New Technology Development District, Wuhan, Hubei, 430205, China.
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5
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Caffeic acid phenethyl ester loaded in a targeted delivery system based on a solid-in-oil-in-water multilayer emulsion: characterization, stability, and fate of the emulsion during in vivo digestion. Food Res Int 2022; 161:111756. [DOI: 10.1016/j.foodres.2022.111756] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2022] [Revised: 07/02/2022] [Accepted: 07/27/2022] [Indexed: 11/20/2022]
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Sokolova O, Naumann M. Matrix Metalloproteinases in Helicobacter pylori-Associated Gastritis and Gastric Cancer. Int J Mol Sci 2022; 23:1883. [PMID: 35163805 PMCID: PMC8836485 DOI: 10.3390/ijms23031883] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 02/02/2022] [Accepted: 02/04/2022] [Indexed: 02/05/2023] Open
Abstract
Gastric cancer is one of the leading causes of the cancer-related mortality worldwide. The etiology of this disease is complex and involves genetic predisposition and environmental factors, including Helicobacter pylori. Infection of the stomach with H. pylori leads to gastritis and gastric atrophy, which can progress stepwise to gastric cancer. Matrix metalloproteinases (MMPs) actively participate in the pathology development. The further progression of gastric cancer seems to be less dependent on bacteria but of intra-tumor cell dynamics. Bioinformatics data confirmed an important role of the extracellular matrix constituents and specific MMPs in stomach carcinoma invasion and metastasis, and revised their potential as predictors of the disease outcome. In this review, we describe, in detail, the impact of MMPs in H. pylori-associated gastritis and gastric cancer.
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Affiliation(s)
- Olga Sokolova
- Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
| | - Michael Naumann
- Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany
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7
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Al-Hariri M, Alsunni A, Shaikh MH, Gamal Eldin T, Al Ghamdi K, Alharbi AF, Alhawaj H, Chathoth S. Caffeic Acid Phenethyl Ester reduces Pro Inflammatory Cytokines in Moderate Swimming Test in Growing Rats Model. J Inflamm Res 2021; 14:5653-5657. [PMID: 34754212 PMCID: PMC8570724 DOI: 10.2147/jir.s338973] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 10/22/2021] [Indexed: 01/13/2023] Open
Abstract
Background Caffeic acid phenethyl ester (CAPE) is a naturally occurring polyphenolic concentrated in propolis of honeybee hives. CAPE has been shown various physiological and pharmacologic properties. The aim of the present study was to investigate the effects of CAPE on proinflammatory markers in growing rats by performing the moderate swimming test. Methods A total number of 21 male Wistar albino rats were separated into three groups (n = 7): sedentary: negative control group; exercise: positive control group received vehicle orally and exercise + CAPE: CAPE treated group: treated with CAPE (20 mg/kg) orally 30 min before exercise, for 5 days. The animals were left free to swim in the tank, 20 minutes/day for 5 days. At 24 hours after finishing the experiment, rats were euthanised and blood was collected to analyze the level of serum interleukin IL-6 and tumor necrosis factor-α (TNF-α). Results Growing rats subjected to the moderate swimming test and in those treated with CAPE showed a lower level of TNF-α compared to the negative control. More interestingly, the one-way ANOVA data demonstrated a decreased level of proinflammatory IL-6 in the CAPE-treated group compared to the negative control. Conclusion Results of this study indicate that short-term administration of CAPE may modulate proinflammatory cytokine profiles during moderate exercise and may serve to boost the anti-inflammatory effects of exercise. Further studies are needed to evaluate the efficacy and safety of long-term administration of CAPE as an adjective anti-inflammatory agent.
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Affiliation(s)
- Mohammed Al-Hariri
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Ahmed Alsunni
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Mohammad Habeeb Shaikh
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Tharwat Gamal Eldin
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Kholoud Al Ghamdi
- Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Abdulelah Fawzi Alharbi
- Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
| | - Hussain Alhawaj
- Department of Environmental Health, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabi
| | - Shahanas Chathoth
- Department of Biochemistry, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
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Song X, He Y, Liu M, Yang Y, Yuan Y, Yan J, Zhang M, Huang J, Zhang S, Mo F. Mechanism underlying Polygonum capitatum effect on Helicobacter pylori-associated gastritis based on network pharmacology. Bioorg Chem 2021; 114:105044. [PMID: 34157554 DOI: 10.1016/j.bioorg.2021.105044] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 05/24/2021] [Accepted: 05/28/2021] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori (H. pylori) infection is a common disease that can cause H. pylori-associated gastritis (HAG), peptic ulcers, and gastric cancer. As a traditional Chinese medicine, Polygonum capitatum (PC) manifests its unique advantages in the prevention and treatment of complex diseases and chronic diseases, due to its ability to clear heat, detoxify and relieve pain, promote blood circulation, and remove blood stasis. In order to explore the molecular mechanism of PC for HAG, the study collected the predicted targets of active compounds, conducted functional analysis by the STRING database, collected HAG differential expression genes, and conducted KEGG enrichment analysis on the intersection of predicted targets and differential expression genes of gastritis by Cluego. The results show that PC works mainly by affecting phosphorylation of IκBα, NF-κB p65, p38MAPK, and ERK1/2 and nuclear transposition of NF-κB p65 and p-p38MAPK, which has been proved by in vivo and in vitro experiments. These results suggest that PC may act on HAG with multiple targets and pathways, and play a key role in the process of HAG treatment.
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Affiliation(s)
- Xiaohan Song
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Yun He
- Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang 550004, China
| | - Min Liu
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Ye Yang
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Yan Yuan
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Jiaoyan Yan
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Mengwei Zhang
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China
| | - Jian Huang
- Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang 550004, China
| | - Shu Zhang
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China; Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang 550004, China.
| | - Fei Mo
- Department of Basic Clinical Laboratory Medicine, School of Clinical Laboratory Science, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang 550004, China; Department of Clinical Laboratory, Affiliated Hospital of Guizhou Medical University, No. 28 Guiyi Street, Yunyan District, Guiyang 550004, China.
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Olgierd B, Kamila Ż, Anna B, Emilia M. The Pluripotent Activities of Caffeic Acid Phenethyl Ester. Molecules 2021; 26:molecules26051335. [PMID: 33801469 PMCID: PMC7958844 DOI: 10.3390/molecules26051335] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 02/24/2021] [Accepted: 02/26/2021] [Indexed: 12/14/2022] Open
Abstract
Caffeic acid phenethyl ester (CAPE) is a strong antioxidant extracted from honey bee-hive propolis. The mentioned compound, a well-known NF-κB inhibitor, has been used in traditional medicine as a potent anti-inflammatory agent. CAPE has a broad spectrum of biological properties including anti-viral, anti-bacterial, anti-cancer, immunomodulatory, and wound-healing activities. This review characterizes published data about CAPE biological properties and potential therapeutic applications, that can be used in various diseases.
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Affiliation(s)
- Batoryna Olgierd
- Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
- Correspondence: or ; Tel.: +48-602-689-347
| | - Żyła Kamila
- Department of Community Pharmacy, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Banyś Anna
- Department of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia in Katowice, 40-055 Katowice, Poland;
| | - Morawiec Emilia
- Department of Microbiology, Faculty of Medicine in Zabrze, University of Technology in Katowice, 40-555 Katowice, Poland;
- GynCentrum, Laboratory of Molecular Biology and Virology, 40-851 Katowice, Poland
- Department of Histology, Cytophysiology and Embryology in Zabrze, Faculty of Medicine in Zabrze, University of Technology in Katowice, 40-555 Katowice, Poland
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Potential Effects of Nutraceuticals in Retinopathy of Prematurity. Life (Basel) 2021; 11:life11020079. [PMID: 33499180 PMCID: PMC7912639 DOI: 10.3390/life11020079] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 01/15/2021] [Accepted: 01/16/2021] [Indexed: 02/07/2023] Open
Abstract
Retinopathy of prematurity (ROP), the most common cause of childhood blindness, is a hypoxia-induced eye disease characterized by retinal neovascularization. In the normal retina, a well-organized vascular network provides oxygen and nutrients as energy sources to maintain a normal visual function; however, it is disrupted when pathological angiogenesis is induced in ROP patients. Under hypoxia, inadequate oxygen and energy supply lead to oxidative stress and stimulate neovasculature formation as well as affecting the function of photoreceptors. In order to meet the metabolic needs in the developing retina, protection against abnormal vascular formation is one way to manage ROP. Although current treatments provide beneficial effects in reducing the severity of ROP, these invasive therapies may also induce life-long consequences such as systemic structural and functional complications as well as neurodevelopment disruption in the developing infants. Nutritional supplements for the newborns are a novel concept for restoring energy supply by protecting the retinal vasculature and may lead to better ROP management. Nutraceuticals are provided in a non-invasive manner without the developmental side effects associated with current treatments. These nutraceuticals have been investigated through various in vitro and in vivo methods and are indicated to protect retinal vasculature. Here, we reviewed and discussed how the use of these nutraceuticals may be beneficial in ROP prevention and management.
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Anğın AD, Gün I, Sakin Ö, Çıkman MS, Şimşek EE, Karakuş R, Başak K, Kaptanağası AO. Investigation of the preventive effects of dehydroepiandrosterone (DHEA) and Caffeic acid phenethyl ester (CAPE) on cisplatin-induced ovarian damage in rats. Ultrastruct Pathol 2020; 44:71-80. [PMID: 31909696 DOI: 10.1080/01913123.2019.1711479] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
To investigate whether Dehydroepiandrosterone (DHEA) and Caffeic acid phenethyl ester (CAPE) had any preventive effect against the ovarian damage caused by cisplatin (CP) (cis-diamminedichloroplatinum) in rats. On the first day ovaries were removed, Anti-Müllerian hormone (AMH) was measured (Group1, n:6), in the other groups 7.5 mg/kg cisplatin was administered intraperitoneally. In Group 2 (n = 6), 0.1 ml saline, in Group 3 (n = 5), 20 umol/kg CAPE, in Group 4 (n = 7), DHEA 6 mg/kg were administered every day. On the 10th day, ovaries were removed, AMH was measured. Ovary reserve (primordial/primary/secondary/tertiary/atretic follicles, AMH), ovarian damage scores (follicular degeneration, congestion, hemorrhage, edema, inflammation) were compared. The number of tertiary follicles were statistically high in the CAPE group (p = .015), the inflammation score in the DHEA group (p = .012), AMH level (p = .009) in the control group. The lowest number of atretic follicles (AF) was in the control group, while the highest number of AF was in the DHEA group (p = .002). Significant decreases in AF were the case in the cisplatin and DHEA groups compared to the control group (p < .008). The AMH values had the highest positive correlation with the number of primordial follicles and the highest negative correlation with the number of AF. The cut off point for AMH was 1.57 ng/ml as an indicator of low ovarian reserve. Cisplatin causes total damage and increased numbers of AF on the ovary. Depending on this, AMH levels fall. These negative effects of cisplatin are not obstructed by CAPE or DHEA, and may even be increased by DHEA.
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Affiliation(s)
- Ali Doğukan Anğın
- Department of Obstetrics and Gynecology, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
| | - Ismet Gün
- Department of Obstetrics and Gynecology, University of Health Sciences, Sultan Abdülhamid Han Training and Research Hospital, İstanbul, Turkey
| | - Önder Sakin
- Department of Obstetrics and Gynecology, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
| | - Muzaffer Seyhan Çıkman
- Department of Obstetrics and Gynecology, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
| | - Engin Ersin Şimşek
- Department of Family Medicine, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
| | - Resul Karakuş
- Department of Obstetrics and Gynecology, University of Health Sciences, Zeynep Kamil Women's and Children's Disease Training and Research Hospital, İstanbul, Turkey
| | - Kayhan Başak
- Department of Pathology, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
| | - Asuman Orçun Kaptanağası
- Department of Biochemistry, University of Health Sciences, Dr Lütfi Kırdar Kartal Training and Research Hospital, İstanbul, Turkey
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12
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Imai M, Yokoe H, Tsubuki M, Takahashi N. Growth Inhibition of Human Breast and Prostate Cancer Cells by Cinnamic Acid Derivatives and Their Mechanism of Action. Biol Pharm Bull 2019; 42:1134-1139. [DOI: 10.1248/bpb.b18-01002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Affiliation(s)
- Masahiko Imai
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University
| | - Hiromasa Yokoe
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University
| | - Masayoshi Tsubuki
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University
| | - Noriko Takahashi
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University
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13
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Cheng CC, Chi PL, Shen MC, Shu CW, Wann SR, Liu CP, Tseng CJ, Huang WC. Caffeic Acid Phenethyl Ester Rescues Pulmonary Arterial Hypertension through the Inhibition of AKT/ERK-Dependent PDGF/HIF-1α In Vitro and In Vivo. Int J Mol Sci 2019; 20:ijms20061468. [PMID: 30909527 PMCID: PMC6470604 DOI: 10.3390/ijms20061468] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2018] [Revised: 03/19/2019] [Accepted: 03/20/2019] [Indexed: 01/23/2023] Open
Abstract
Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial proliferation and remodeling, resulting in a specific increase in right ventricle systolic pressure (RVSP) and, ultimately right ventricular failure. Recent studies have demonstrated that caffeic acid phenethyl ester (CAPE) exerts a protective role in NF-κB-mediated inflammatory diseases. However, the effect of CAPE on PAH remains to be elucidated. In this study, monocrotaline (MCT) was used to establish PAH in rats. Two weeks after the induction of PAH by MCT, CAPE was administrated by intraperitoneal injection once a day for two weeks. Pulmonary hemodynamic measurements and pulmonary artery morphological assessments were examined. Our results showed that administration of CAPE significantly suppressed MCT-induced vascular remodeling by decreasing the HIF-1α expression and PDGF-BB production, and improved in vivo RV systolic performance in rats. Furthermore, CAPE inhibits hypoxia- and PDGF-BB-induced HIF-1α expression by decreasing the activation of the AKT/ERK pathway, which results in the inhibition of human pulmonary artery smooth muscle cells (hPASMCs) proliferation and prevention of cells resistant to apoptosis. Overall, our data suggest that HIF-1α is regarded as an alternative target for CAPE in addition to NF-κB, and may represent a promising therapeutic agent for the treatment of PAH diseases.
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MESH Headings
- Animals
- Apoptosis/drug effects
- Caffeic Acids/pharmacology
- Cell Line
- Cell Proliferation/drug effects
- Disease Models, Animal
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Gene Expression
- Hemodynamics/drug effects
- Humans
- Hypertension, Pulmonary/diagnosis
- Hypertension, Pulmonary/drug therapy
- Hypertension, Pulmonary/etiology
- Hypertension, Pulmonary/metabolism
- Hypertrophy, Right Ventricular/drug therapy
- Hypertrophy, Right Ventricular/etiology
- Hypertrophy, Right Ventricular/metabolism
- Hypertrophy, Right Ventricular/physiopathology
- Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
- Immunohistochemistry
- Phenylethyl Alcohol/analogs & derivatives
- Phenylethyl Alcohol/pharmacology
- Platelet-Derived Growth Factor/genetics
- Platelet-Derived Growth Factor/metabolism
- Proto-Oncogene Proteins c-akt/metabolism
- Pulmonary Artery/drug effects
- Pulmonary Artery/metabolism
- Pulmonary Artery/physiopathology
- Rats
- Signal Transduction/drug effects
- Vascular Remodeling/drug effects
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Affiliation(s)
- Chin-Chang Cheng
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Department of Physical Therapy, Fooyin University, Kaohsiung 83102, Taiwan.
| | - Pei-Ling Chi
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- Department of Pathology and Laboratory, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
| | - Min-Ci Shen
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Chih-Wen Shu
- School of Medicine for International Students, I-Shou University, Kaohsiung 82445, Taiwan.
| | - Shue-Ren Wann
- Graduate Institute of Clinical Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Kaohsiung Veterans General Hospital, Pingtung Branch, Pintung 91245, Taiwan.
| | - Chun-Peng Liu
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
| | - Ching-Jiunn Tseng
- Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan.
- Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan.
| | - Wei-Chun Huang
- Department of Critical Care Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 81362, Taiwan.
- School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
- Department of Physical Therapy, Fooyin University, Kaohsiung 83102, Taiwan.
- School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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14
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Okabe A, Kiriyama Y, Suzuki S, Sakurai K, Teramoto A, Kato H, Naiki-Ito A, Tahara S, Takahashi S, Kuroda M, Sugioka A, Tsukamoto T. Short-term detection of gastric genotoxicity using the DNA double-strand break marker γ-H2AX. J Toxicol Pathol 2019; 32:91-99. [PMID: 31092975 PMCID: PMC6511543 DOI: 10.1293/tox.2019-0007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Accepted: 02/13/2019] [Indexed: 01/25/2023] Open
Abstract
DNA damage caused by Helicobacter pylori infection and chronic inflammation or exposure to genotoxic agents is considered an important risk factor of gastric carcinogenesis. In this study, we have evaluated a short-term technique to detect DNA damage response to various chemical carcinogens; it involves visualization of Ser 139-phosphorylated histone H2AX (γ-H2AX) foci by immunohistochemistry and expression analysis of other genes by quantitative RT-PCR. Six-week-old male rats were intragastrically administered N-methyl-N-nitrosourea (MNU), 3,2'-dimethyl-4-aminobiphenyl (DMAB), dimethylnitrosamine (DMN), and 1,2- dimethylhydrazine (DMH) for 5 days/week for 4 weeks, using corn oil as a vehicle. Animals were sacrificed at day 28, and their stomachs were excised. γ-H2AX foci formation, indicating DNA double-strand breaks, was observed in the proliferative zone of both fundic and pyloric glands. The number of positive cells per gland was significantly high in pyloric glands in the MNU group and in fundic glands in the MNU and DMAB groups. A significant increase in p21waf1 mRNA level was observed in the DMN group compared with the control, which was in contrast to the decreasing tendency of the h2afx mRNA level in the MNU and DMN groups. Apoptotic cells positive for γ-H2AX pan or peripheral nuclear staining were observed on the surface layer of the fundic mucosa in the MNU group. The fundic pepsinogen a5 (pga5) mRNA level showed a significant decrease, indicating gland damage. The pyloric pepsinogen c mRNA level showed no change. In conclusion, γ-H2AX in combination with other gene expression analyses could be a useful biomarker in a short-term experiment on gastric chemical genotoxicity.
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Affiliation(s)
- Asako Okabe
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Yuka Kiriyama
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.,Department of Diagnostic Pathology, Narita Memorial Hospital, 134 Haneihonmachi, Toyohashi, Aichi 441-8029, Japan
| | - Shugo Suzuki
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Kouhei Sakurai
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Atsushi Teramoto
- Faculty of Radiological Technology, Fujita Health University Graduate School of Health Sciences, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Hiroyuki Kato
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Aya Naiki-Ito
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Sayumi Tahara
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Satoru Takahashi
- Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
| | - Makoto Kuroda
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Atsushi Sugioka
- Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
| | - Tetsuya Tsukamoto
- Department of Diagnostic Pathology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan
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15
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Abstract
The present study evaluates the antibacterial effects of a set of 16 synthesized caffeic acid ester derivatives against strains of Staphylococcus aureus and Escherichia coli, as well as discusses their structure-activity relationship (SAR). The antibacterial assays were performed using microdilution techniques in 96-well microplates to determine minimal inhibitory concentration (MIC). The results revealed that five of the compounds present strong to optimum antibacterial effect. Of the sixteen ester derivatives evaluated, the products with alkyl side chains, as propyl caffeate (3), butyl caffeate (6), and pentyl caffeate (7), presented the best antibacterial activity with MIC values of around 0.20 μM against Escherichia coli and only butyl caffeate (6) showing the same MIC against Staphylococcus aureus. For products with aryl substituents, the best MIC results against the tested strain of Escherichia coli were 0.23 µM for (di-(4-chlorobenzyl)) caffeate (13) and 0.29 µM for diphenylmethyl caffeate (10) and all were less active against the Staphylococcus aureus strain. Preliminary quantitative structure-activity relationship (QSAR) analyses confirmed that certain structural characteristics, such as a median linear carbon chain and the presence of electron withdrawal substituents at the para position of the aromatic ring, help potentiate antibacterial activity.
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16
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Caffeic acid phenethyl ester exerts apoptotic and oxidative stress on human multiple myeloma cells. Invest New Drugs 2018; 37:837-848. [DOI: 10.1007/s10637-018-0701-y] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2018] [Accepted: 11/14/2018] [Indexed: 01/02/2023]
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17
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Zhou ZB, Yang B, Li X, Liu H, Lei G. Lysophosphatidic Acid Promotes Expression and Activation of Matrix Metalloproteinase 9 (MMP9) in THP-1 Cells via Toll-Like Receptor 4/Nuclear Factor-κB (TLR4/NF-κB) Signaling Pathway. Med Sci Monit 2018; 24:4861-4868. [PMID: 30005060 PMCID: PMC6069468 DOI: 10.12659/msm.906450] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023] Open
Abstract
BACKGROUND Lysophosphatidic acid (LPA) is an active compound of oxidized low-density lipoprotein that serves as an endogenous TLR4 ligand. Ligand activation of TLR4 activates nuclear factor-kappaB (NF-κB) and the transcription of NF-κB-regulated inflammatory cytokines, which are involved in the development of atherosclerosis. MMP9 is a member of the MMP family and can affect plaque stability. However, the mechanism responsible for the effect of LPA on the expression and activation of MMP9 has not been fully elucidated. In the present study we examined the effect of LPA on MMP9 expression and activity in THP-1 cells and the involvement of Toll-like receptor 4/nuclear factor-κB (TLR4/NF-κB) signaling pathway in this effect. MATERIAL AND METHODS Human THP-1 cells were treated with 0-10 μM LPA for 4 h, or treated with 1 μM LPA for 0-8 h, and were then transfected with TLR4-specific siRNA or treated with 20 μg/ml cafestol acid phenethyl ester (CAPE, an NF-κB inhibitor). MMP9 mRNA and protein levels were measured by quantitative RT-PCR and Western blot analysis, respectively, and MMP9 activity was measured by zymography. RESULTS LPA upregulated MMP9 mRNA and protein levels and MMP9 activity in THP-1 cells in both concentration- and time-dependent manners. Transfection of cells with TLR4-siRNA-2 or treatment with CAPE significantly inhibited the upregulated MMP9 expression and activation. This inhibition was further enhanced by combining the TLR4-siRNA-2 transfection and CAPE pretreatment. CONCLUSIONS LPA can promote MMP9 expression and enhance MMP9 activity in THP-1 cells, in part via the TLR4/NF-kB signaling pathway.
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Affiliation(s)
- Zhi-Bin Zhou
- Department of Neurology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Bo Yang
- Department of Cardiology, The Third People's Hospital of Hubei, Wuhan, Hubei, China (mainland)
| | - Xiaohao Li
- Department of Internal Medicine, Wuhan Institute of Technology Hospital, Wuhan, Hubei, China (mainland)
| | - Hao Liu
- Department of Neurology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
| | - Gang Lei
- Department of Neurology, Tianyou Hospital Affiliated to Wuhan University of Science and Technology, Wuhan, Hubei, China (mainland)
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18
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Takakura K, Takatou S, Tomiyama R, Le TM, Nguyen DT, Nakamura Y, Konishi T, Matsugo S, Hori O. Inhibition of nuclear factor-κB p65 phosphorylation by 3,4-dihydroxybenzalacetone and caffeic acid phenethyl ester. J Pharmacol Sci 2018; 137:248-255. [PMID: 30037569 DOI: 10.1016/j.jphs.2018.07.003] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2018] [Revised: 06/05/2018] [Accepted: 06/23/2018] [Indexed: 01/14/2023] Open
Abstract
3,4-Dihydroxybenzalacetone (DBL) and caffeic acid phenethyl ester (CAPE) are both catechol-containing phenylpropanoid derivatives with various bioactivities. In the present study, we compared the effects of these compounds and other phenylpropanoid derivatives on the activation of nuclear factor-κB (NF-κB) signaling, a major pathway in the inflammatory response, using RAW 264.7 cells. Lipopolysaccharide (LPS)- and interferon γ-induced production of nitrite was strongly suppressed by CAPE and, to a lesser extent, by DBL and caffeic acid ethyl ester. Consistent with these results, induction of NF-κB downstream genes, such as Nitric oxide synthase, interleukin 1 beta, and interleukin 6, and translocation of NF-κB p65 to the nucleus were reduced after LPS stimulation, to a greater extent with CAPE than with DBL. Interestingly, the phosphorylation of p65 was reduced by both compounds, especially by CAPE, even when the level of IκB was not altered. Furthermore, the thiol groups of p65 were modified by CAPE, and the inhibitory effects of CAPE and DBL on the p65 phosphorylation and nitrite production were reversed by pretreatment with thiol-containing reagents. These results suggest that CAPE has strong inhibitory effects on the NF-κB activation that are associated with the modification of thiol groups and phosphorylation of p65.
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Affiliation(s)
- Ken Takakura
- Graduate School of Natural Science and Technology, Division of Natural System, Kanazawa University, Kanazawa, Ishikawa, Japan; Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Shouhei Takatou
- Graduate School of Natural Science and Technology, Division of Natural System, Kanazawa University, Kanazawa, Ishikawa, Japan; Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Ryoichi Tomiyama
- Graduate School of Natural Science and Technology, Division of Natural System, Kanazawa University, Kanazawa, Ishikawa, Japan; Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Thuong Manh Le
- Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Dinh Thi Nguyen
- Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Yutaka Nakamura
- Faculty of Applied Life Sciences, Niigata University of Pharmacy & Applied Life Sciences (NUPALS), Niigata, Niigata, Japan
| | - Tetsuya Konishi
- Niigata University of Pharmacy & Applied Life Sciences (NUPALS), LIAISON R/D Center, Niigata, Niigata, Japan
| | - Seiichi Matsugo
- Graduate School of Natural Science and Technology, Division of Natural System, Kanazawa University, Kanazawa, Ishikawa, Japan
| | - Osamu Hori
- Graduate School of Medical Sciences, Department of Neuroanatomy, Kanazawa University, Kanazawa, Ishikawa, Japan.
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19
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Hao Y, Wu B, Chen Y, Sun X, Sun Y, Liu J, Wang X. Study on Dual Inhibitors of HIV-1 IN/CCR5 Caffeoyl Derivatives as Neuroprotective Agents. ChemistrySelect 2018. [DOI: 10.1002/slct.201801313] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Affiliation(s)
- Yameng Hao
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
| | - Bolin Wu
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
| | - Ying Chen
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
| | - Xuefeng Sun
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
| | - Yixing Sun
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
| | - Junyi Liu
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
- State Key Laboratory of Natural and Biomimetic Drugs; Peking University; Beijing 100191 China
| | - Xiaowei Wang
- Department of Chemical Biology; School of Pharmaceutical Sciences; Peking University; Beijing 100191 China
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20
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Romana-Souza B, Dos Santos JS, Monte-Alto-Costa A. Caffeic acid phenethyl ester promotes wound healing of mice pressure ulcers affecting NF-κB, NOS2 and NRF2 expression. Life Sci 2018; 207:158-165. [PMID: 29864436 DOI: 10.1016/j.lfs.2018.05.057] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/12/2018] [Accepted: 05/31/2018] [Indexed: 02/07/2023]
Abstract
AIMS In pressure ulcers, the synthesis of reactive oxygen species induced by ischemia and reperfusion leads to chronic inflammation and tissue damage, which impair the closure of these lesions. Caffeic acid phenethyl ester (CAPE), found in propolis, promotes cutaneous wound healing of acute lesions and severe burns. However, the effects of CAPE on wound healing of pressure ulcers have not been investigated. This study investigated the effects of CAPE administration in a murine model of pressure ulcers. MAIN METHODS To induce pressure ulcers, two cycles of ischemia and reperfusion by external application of two magnetic plates were performed in the skin dorsum of mice. After the last cycle, animals were treated daily with CAPE or vehicle until they were euthanized. KEY FINDINGS The nitric oxide synthesis, lipid peroxidation, macrophage migration, protein nuclear factor kappa B and nitric-oxide synthase-2 expression were increased 3 days after ulceration but decreased 7 days later, in pressure ulcers of the CAPE group compared to that of the control group. CAPE reduced the protein expression of nuclear factor-erythroid2-related factor 2 in pressure ulcers 3 days after ulceration, but increased 7 days later. Myofibroblast density was increased in the CAPE group 7 days after ulceration, but reduced 12 days later when compared to control group. In addition, CAPE promoted collagen deposition, re-epithelialization and wound closure of mice pressure ulcers 12 days after ulceration. SIGNIFICANCE CAPE brings forward inflammatory response and oxidative damage involved in injury by ischemia and reperfusion, promoting dermal reconstruction and closure of pressure ulcers.
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Affiliation(s)
- Bruna Romana-Souza
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
| | - Jeanine Salles Dos Santos
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
| | - Andréa Monte-Alto-Costa
- Laboratory of Tissue Repair, Department of Histology and Embryology, State University of Rio de Janeiro, Rio de Janeiro, Brazil
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21
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Rajapriya G, Morya VK, Mai NL, Koo YM. Aspergillus niger whole-cell catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids. Enzyme Microb Technol 2018; 111:67-73. [DOI: 10.1016/j.enzmictec.2017.10.005] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Revised: 08/30/2017] [Accepted: 10/14/2017] [Indexed: 01/17/2023]
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22
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Anti- Helicobacter pylori effect of various extracts of ixeris chinensis on inflammatory markers in human gastric epithelial AGS cells. J Herb Med 2018. [DOI: 10.1016/j.hermed.2017.08.002] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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23
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Noto JM, Romero-Gallo J, Piazuelo MB, Peek RM. The Mongolian Gerbil: A Robust Model of Helicobacter pylori-Induced Gastric Inflammation and Cancer. Methods Mol Biol 2017; 1422:263-80. [PMID: 27246040 DOI: 10.1007/978-1-4939-3603-8_24] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The Mongolian gerbil is an efficient, robust, and cost-effective rodent model that recapitulates many features of H. pylori-induced gastric inflammation and carcinogenesis in humans, allowing for targeted investigation of the bacterial determinants and environmental factors and, to a lesser degree, host constituents that govern H. pylori-mediated disease. This chapter discusses means through which the Mongolian gerbil model has been used to define mechanisms of H. pylori-inflammation and cancer as well as the current materials and methods for utilizing this model of microbially induced disease.
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Affiliation(s)
- Jennifer M Noto
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue MRB IV 1030C, Nashville, TN, 37232-0252, USA
| | - Judith Romero-Gallo
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue MRB IV 1030C, Nashville, TN, 37232-0252, USA
| | - M Blanca Piazuelo
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue MRB IV 1030C, Nashville, TN, 37232-0252, USA
| | - Richard M Peek
- Division of Gastroenterology, Department of Medicine, Vanderbilt University Medical Center, 2215 Garland Avenue MRB IV 1030C, Nashville, TN, 37232-0252, USA.
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Yu HJ, Shin JA, Yang IH, Won DH, Ahn CH, Kwon HJ, Lee JS, Cho NP, Kim EC, Yoon HJ, Lee JI, Hong SD, Cho SD. Apoptosis induced by caffeic acid phenethyl ester in human oral cancer cell lines: Involvement of Puma and Bax activation. Arch Oral Biol 2017; 84:94-99. [DOI: 10.1016/j.archoralbio.2017.09.024] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 08/24/2017] [Accepted: 09/24/2017] [Indexed: 02/06/2023]
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Wolf VG, Bonacorsi C, Raddi MSG, da Fonseca LM, Ximenes VF. Octyl gallate, a food additive with potential beneficial properties to treat Helicobacter pylori infection. Food Funct 2017. [PMID: 28640317 DOI: 10.1039/c7fo00707h] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Helicobacter pylori infection is marked by intense production of reactive oxygen species (ROS) through the activation of neutrophils that are constantly attracted to the infected gastric mucosa. Here, gallic acid and its alkyl esters were evaluated as compounds able to act as antimicrobial agents and inhibitors of ROS released by H. pylori-activated neutrophils simultaneously. We found that the higher hydrophobicity caused by esterification of gallic acid led to a significant increase in its ability as a cytotoxic agent against H. pylori, a scavenger of ROS and an inhibitor of NADPH oxidase in neutrophils. Octyl gallate, a widely used food additive, showed the highest antimicrobial activity against H. pylori, with a minimum inhibitory concentration (MIC) value of 125 μg mL-1, whereas gallic acid had a MIC value higher than 1000 μg mL-1. The production of superoxide anion radicals was almost 100% abolished by the addition of 10 μM (2.82 μg mL-1) octyl gallate, whereas gallic acid inhibited around 20%. A similar tendency was also found when measuring the production of hypochlorous acid. The protective effect of the esters was cytochemically confirmed. In conclusion, this study showed that hydrophobicity is a crucial factor to obtain a significant anti-ROS and anti-H. pylori activity. Finally, it highlights octyl gallate, a food additive widely used in the food industry, as a promising molecule in the treatment of H. pylori infection.
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Affiliation(s)
- Vanessa Gonçalves Wolf
- Department of Clinical Analysis, Faculty of Pharmaceutical Sciences, UNESP - São Paulo State University, 14800-903, Araraquara, São Paulo, Brazil.
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Molecular Mechanisms of Natural Honey Against H. pylori Infection Via Suppression of NF-κB and AP-1 Activation in Gastric Epithelial Cells. Arch Med Res 2017; 47:340-348. [PMID: 27751367 DOI: 10.1016/j.arcmed.2016.09.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2016] [Accepted: 09/02/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIMS Natural honey has been used as a medicine since ancient times. Honey is widely known for its antibacterial properties against H. pylori; however, the mechanisms of its antibacterial activity are not fully known. The present study was performed to examine the molecular mechanisms by which natural honey can inhibit H. pylori infection in gastric epithelial cells. METHODS Electrophoretic mobility shift assay was used to measure NF-κB- and AP-1-DNA binding activity. Western blotting was used to detect IκB-α and COX-2 expression. RESULTS H. pylori induced NF-κB and AP-1 DNA-binding activity in gastric epithelial cells. Manuka honey inhibited H. pylori-induced NF-κB and AP-1 in a time- and dose-dependent manner. Maximum inhibition of H. pylori-induced NF-κB and AP-1 by manuka honey was observed at concentrations of 20% at 1-2 h. Pre-treatment of AGS cells with other commercial natural honeys also inhibited H. pylori-induced NF-κB and AP-1 DNA-binding activity. Honey prevented H. pylori-induced degradation of IκB-α protein and downregulated COX-2 protein levels. CONCLUSIONS Our findings suggest that natural honey exerts its inhibitory effects against H. pylori by inhibiting NF-κB and AP-1 activation and downregulation of COX-2 expression. These results provide new mechanistic insights into honey effects in the suppression of H. pylori infection.
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Gülmez Mİ, Okuyucu Ş, Dokuyucu R, Gökçe H. The effect of caffeic acid phenethyl ester and thymoquinone on otitis media with effusion in rats. Int J Pediatr Otorhinolaryngol 2017; 96:94-99. [PMID: 28390622 DOI: 10.1016/j.ijporl.2017.03.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2016] [Revised: 01/12/2017] [Accepted: 03/04/2017] [Indexed: 02/05/2023]
Abstract
OBJECTIVE In this study, we aimed to investigate the effect of CAPE and thymoquinone in experimental rat otitis media with effusion (OME) model. METHODS Intraoral approach of eustachian tube orifice cauterization were administered to 36 of 40 rats participating the study. After application of exclusion criterias, 22 rats with appropriate conditions were determined. Totally 26 rats (44 otitis model ears and 8 normal ears) were randomly divided into 5 groups. While group I was consisted of healthy rats, the other groups were consisted of rats with otitis model. Group I (saline + control group; n = 8 normal ears) and group II (saline + otitis model; n = 10 otitis model ears) received intraperitoneally saline solution. CAPE was given intraperitoneally to group III (CAPE + otitis model; n = 12 otitis model ears) at a concentration of 10 mg/kg for treatment of otitis media. Group IV (thymoquinone + otitis model; n = 12 otitis model ears) was treated orally with 10 mg/kg of thymoquinone. Group V (methylprednisolone + otitis model; n = 10 otitis model ears) was treated intraperitoneally with 1 mg/kg of methylprednisolone. Tympanic bulla samples were excised after 10th day of treatment and examined under light microscopy. RESULTS Submucosal neutrophil leukocyte count of group I was significantly lower than other groups (II, IV, V) (respectively p < 0,0001, p < 0,001, p < 0,0001, Tukey test), while it was not significantly different from group III (p = 0,056, Tukey test). Submucosal neutrophil leukocyte count of group III was significantly lower than group II and group V (p = 0.029 ve p = 0.03, Tukey test). There was no significant difference between group IV and group V (p = 0,28, Tukey test). CONCLUSION Based on these findings, it could be suggested that CAPE, anti inflammatory properties proven in the literature, plays an important role in OME treatment.
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Affiliation(s)
- Mehmet İhsan Gülmez
- Department of ENT and Head and Neck Surgery, Mustafa Kemal University, Medical Collage, 31030, Hatay, Turkey.
| | - Şemsettin Okuyucu
- Department of ENT and Head and Neck Surgery, Mustafa Kemal University, Medical Collage, 31030, Hatay, Turkey.
| | - Recep Dokuyucu
- Department of Physiology, Mustafa Kemal University, Medical Collage, 31030, Hatay, Turkey.
| | - Hasan Gökçe
- Department of Pathology, Mustafa Kemal University, Medical Collage, 31030, Hatay, Turkey.
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Tolba MF, Omar HA, Azab SS, Khalifa AE, Abdel-Naim AB, Abdel-Rahman SZ. Caffeic Acid Phenethyl Ester: A Review of Its Antioxidant Activity, Protective Effects against Ischemia-reperfusion Injury and Drug Adverse Reactions. Crit Rev Food Sci Nutr 2017; 56:2183-90. [PMID: 25365228 DOI: 10.1080/10408398.2013.821967] [Citation(s) in RCA: 70] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Propolis, a honey bee product, has been used in folk medicine for centuries for the treatment of abscesses, canker sores and for wound healing. Caffeic acid phenethyl ester (CAPE) is one of the most extensively investigated active components of propolis which possess many biological activities, including antibacterial, antiviral, antioxidant, anti-inflammatory, and anti-cancer effects. CAPE is a polyphenolic compound characterized by potent antioxidant and cytoprotective activities and protective effects against ischemia-reperfusion (I/R)-induced injury in multiple tissues such as brain, retina, heart, skeletal muscles, testis, ovaries, intestine, colon, and liver. Furthermore, several studies indicated the protective effects of CAPE against chemotherapy-induced adverse drug reactions (ADRs) including several antibiotics (streptomycin, vancomycin, isoniazid, ethambutol) and chemotherapeutic agents (mitomycin, doxorubicin, cisplatin, methotrexate). Due to the broad spectrum of pharmacological activities of CAPE, this review makes a special focus on the recently published data about CAPE antioxidant activity as well as its protective effects against I/R-induced injury and many adverse drug reactions.
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Affiliation(s)
- Mai F Tolba
- a Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University , Cairo , Egypt.,b Department of Obstetrics and Gynecology , The University of Texas Medical Branch , Galveston , Texas , USA
| | - Hany A Omar
- c Faculty of Pharmacy, Department of Pharmacology, Beni-Suef University , Egypt
| | - Samar S Azab
- a Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University , Cairo , Egypt
| | - Amani E Khalifa
- a Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University , Cairo , Egypt
| | - Ashraf B Abdel-Naim
- a Faculty of Pharmacy, Department of Pharmacology and Toxicology, Ain Shams University , Cairo , Egypt
| | - Sherif Z Abdel-Rahman
- b Department of Obstetrics and Gynecology , The University of Texas Medical Branch , Galveston , Texas , USA
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Li L, Sun W, Wu T, Lu R, Shi B. Caffeic acid phenethyl ester attenuates lipopolysaccharide-stimulated proinflammatory responses in human gingival fibroblasts via NF-κB and PI3K/Akt signaling pathway. Eur J Pharmacol 2016; 794:61-68. [PMID: 27832944 DOI: 10.1016/j.ejphar.2016.11.003] [Citation(s) in RCA: 57] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2016] [Revised: 11/03/2016] [Accepted: 11/04/2016] [Indexed: 10/20/2022]
Abstract
Periodontal diseases often begin with chronic gingival inflammation, which causes the destruction of periodontal tissues. Inflammatory immune responses from host cells to bacteria, such as Porphyromonas gingivalis (P. gingivalis), cause periodontal degradation. Human gingival fibroblasts (HGFs) are the major cells in periodontal soft tissues. When stimulated by lipopolysaccharide (LPS), HGFs could secrete several pro-inflammatory cytokines and chemokines, such as interleukins (ILs) IL-6, IL-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX-2). Caffeic acid phenethyl ester (CAPE) is the main active component of propolis, which is collected by honeybees from different plants and known for its anti-inflammatory effects. The anti-inflammatory effects of CAPE on the LPS-induced HGFs were demonstrated in this study. HGFs were pretreated with CAPE (10, 20, and 30µm) for 1h, followed by LPS stimulation (1μg/ml) for 24h. Enzyme-linked immunosorbent assay, Western blot analysis, and immunofluorescence staining were used to evaluate the production of IL-6, IL-8, iNOS, and COX-2, as well as the activation of TLR4-mediated NF-κB, PI3K/AKT, and MAPK signaling pathways. The results indicated that CAPE inhibits LPS-induced IL-6, IL-8, iNOS, and COX-2 production in a dose-dependent manner. Moreover, CAPE suppresses LPS-induced TLR4/MyD88 and nuclear factor kappa B (NF-κB) activation. In addition, phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT) phosphorylation was inhibited by CAPE. These results demonstrated that CAPE could be effective for treating of periodontal diseases.
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Affiliation(s)
- Lei Li
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Wei Sun
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Tao Wu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Rui Lu
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China
| | - Bin Shi
- The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedical Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People's Republic of China.
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30
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Li H, Wu F, Tan J, Wang K, Zhang C, Zheng H, Hu F. Caffeic acid phenethyl ester exhibiting distinctive binding interaction with human serum albumin implies the pharmacokinetic basis of propolis bioactive components. J Pharm Biomed Anal 2016; 122:21-8. [DOI: 10.1016/j.jpba.2016.01.040] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Revised: 01/14/2016] [Accepted: 01/16/2016] [Indexed: 11/25/2022]
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Toyoda T, Shi L, Takasu S, Cho YM, Kiriyama Y, Nishikawa A, Ogawa K, Tatematsu M, Tsukamoto T. Anti-Inflammatory Effects of Capsaicin and Piperine on Helicobacter pylori-Induced Chronic Gastritis in Mongolian Gerbils. Helicobacter 2016; 21:131-42. [PMID: 26140520 DOI: 10.1111/hel.12243] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
BACKGROUND Spices have been used for thousands of years, and recent studies suggest that certain spices confer beneficial effects on gastric disorders. The purpose of this study was to evaluate possible chemopreventive effects of spice-derived compounds on Helicobacter pylori (H. pylori)-induced gastritis. METHODS We examined the inhibitory effects of curcumin, capsaicin, and piperine on H. pylori in vitro by determining the colony-forming units and real-time RT-PCR in H. pylori stimulated AGS gastric cancer cells. For in vivo analysis, 6-week-old SPF male Mongolian gerbils were infected with H. pylori, fed diets containing 5000 ppm curcumin, 100 ppm capsaicin, or 100 ppm piperine, and sacrificed after 13 weeks. RESULTS All three compounds inhibited in vitro proliferation of H. pylori, with curcumin being the most effective. Infiltration of neutrophils and mononuclear cells was suppressed by piperine both in the antrum and corpus of H. pylori-infected gerbils. Capsaicin also decreased neutrophils in the antrum and corpus and mononuclear cell infiltration and heterotopic proliferative glands in the corpus. mRNA expression of Tnf-α and formation of phospho-IκB-α in the antrum were reduced by both capsaicin and piperine. In addition, piperine suppressed expression of Il-1β, Ifn-γ, Il-6, and iNos, while H. pylori UreA and other virulence factors were not significantly attenuated by any compounds. CONCLUSION These results suggest that capsaicin and piperine have anti-inflammatory effects on H. pylori-induced gastritis in gerbils independent of direct antibacterial effects and may thus have potential for use in the chemoprevention of H. pylori-associated gastric carcinogenesis.
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Affiliation(s)
- Takeshi Toyoda
- Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.,Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Liang Shi
- Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.,Chemicals Safety Department, Mitsui Chemicals Inc., Mobara, Japan
| | - Shinji Takasu
- Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.,Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan
| | - Young-Man Cho
- Division of Pathology, National Institute of Health Sciences, Tokyo, Japan
| | - Yuka Kiriyama
- Department of Diagnostic Pathology I, Fujita Health University School of Medicine, Toyoake, Japan
| | - Akiyoshi Nishikawa
- Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan
| | - Kumiko Ogawa
- Division of Pathology, National Institute of Health Sciences, Tokyo, Japan
| | - Masae Tatematsu
- Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.,Japan Bioassay Research Center, Hadano, Japan
| | - Tetsuya Tsukamoto
- Division of Oncological Pathology, Aichi Cancer Center Research Institute, Nagoya, Japan.,Department of Diagnostic Pathology I, Fujita Health University School of Medicine, Toyoake, Japan
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32
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Kim A, Lim JW, Kim H, Kim H. Supplementation with Angelica keiskei inhibits expression of inflammatory mediators in the gastric mucosa of Helicobacter pylori-infected mice. Nutr Res 2016; 36:488-97. [PMID: 27101766 DOI: 10.1016/j.nutres.2015.12.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2015] [Revised: 12/31/2015] [Accepted: 12/31/2015] [Indexed: 12/23/2022]
Abstract
Oxidative stress is involved in the pathogenesis of Helicobacter pylori-associated gastric ulceration and carcinogenesis. The oxidant-sensitive transcription factor, nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB), regulates expression of inflammatory mediators such as interferon γ (IFN-γ), cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). These inflammatory mediators increased in gastric mucosal tissues from patients infected with H pylori. Angelica keiskei (AK), a green leafy vegetable, is rich in carotenoids and flavonoids and shows antioxidant and anti-inflammatory activities. Therefore, we hypothesized that AK may protect the gastric mucosa of H pylori-infected mice against inflammation. We determined lipid peroxide abundance, myeloperoxidase activity, expression levels of inflammatory mediators (IFN-γ, COX-2, and iNOS), NF-κB-DNA binding activity, and histologic changes in gastric mucosal tissues. The antioxidant N-acetylcysteine served as the positive control treatment. Supplementation with AK suppressed increases in lipid peroxide abundance, myeloperoxidase activity, induction of inflammatory mediators (IFN-γ, COX-2, and iNOS), activation of NF-κB, and degradation of nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor α in gastric mucosal tissue from H pylori-infected mice. Inhibition of H pylori-induced alterations by AK was similar to that by N-acetylcysteine. Taken together, these results suggest that supplementation with AK may prevent H pylori-induced gastric inflammation by inhibiting NF-κB-mediated induction of inflammatory mediators in the gastric mucosa of patients infected with H pylori.
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Affiliation(s)
- Aryoung Kim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
| | - Joo Weon Lim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
| | - Hoguen Kim
- Department of Pathology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brian Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea.
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Zhang X, Jiang A, Qi B, Ma Z, Xiong Y, Dou J, Wang J. Resveratrol Protects against Helicobacter pylori-Associated Gastritis by Combating Oxidative Stress. Int J Mol Sci 2015; 16:27757-69. [PMID: 26610474 PMCID: PMC4661919 DOI: 10.3390/ijms161126061] [Citation(s) in RCA: 54] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2015] [Revised: 11/09/2015] [Accepted: 11/16/2015] [Indexed: 12/12/2022] Open
Abstract
Helicobacter pylori (H. pylori)-induced oxidative stress has been shown to play a very important role in the inflammation of the gastric mucosa and increases the risk of developing gastric cancer. Resveratrol has many biological functions and activities, including antioxidant and anti-inflammatory effect. The purpose of this study was to probe whether resveratrol inhibits H. pylori-induced gastric inflammation and to elucidate the underlying mechanisms of any effect in mice. A mouse model of H. pylori infection was established via oral inoculation with H. pylori. After one week, mice were administered resveratrol (100 mg/kg body weight/day) orally for six weeks. The mRNA and protein levels of iNOS and IL-8 were assessed using RT-PCR, Western blot and ELISA. The expression levels of IκBα and phosphorylated IκBα (which embodies the level and activation of NF-κB), Heme Oxygenase-1 (HO-1; a potent antioxidant enzyme) and nuclear factor-erythroid 2 related factor 2 (Nrf2) were determined using Western blot, and lipid peroxide (LPO) level and myeloperoxidase (MPO) activity were examined using an MPO colorimetric activity assay, thiobarbituric acid reaction, and histological-grade using HE staining of the gastric mucosa. The results showed that resveratrol improved the histological infiltration score and decreased LPO level and MPO activity in the gastric mucosa. Resveratrol down-regulated the H. pylori-induced mRNA transcription and protein expression levels of IL-8 and iNOS, suppressed H. pylori-induced phosphorylation of IκBα, and increased the levels of HO-1 and Nrf2. In conclusion, resveratrol treatment exerted significant effects against oxidative stress and inflammation in H. pylori-infected mucosa through the suppression of IL-8, iNOS, and NF-κB, and moreover through the activation of the Nrf2/HO-1 pathway.
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Affiliation(s)
- Xiaolin Zhang
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Anmin Jiang
- The School of Life Science, University of Science and Technology of China, Hefei 230032, China.
| | - Banghua Qi
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Zhongyou Ma
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Youyi Xiong
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Jinfeng Dou
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
| | - Jianfei Wang
- College of Food and Drug, University of Anhui Science and Technology, Bengbu 233100, China.
- The Ministry of Agriculture Key Laboratory of Microbial Organic Fertilizer, Bengbu 233030, China.
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Lin WC, Wen CC, Chen YH, Hsiao PW, Liao JW, Peng CI, Yang NS. Integrative approach to analyze biodiversity and anti-inflammatory bioactivity of Wedelia medicinal plants. PLoS One 2015; 10:e0129067. [PMID: 26042672 PMCID: PMC4456162 DOI: 10.1371/journal.pone.0129067] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2014] [Accepted: 05/04/2015] [Indexed: 12/12/2022] Open
Abstract
For the development of "medical foods" and/or botanical drugs as defined USA FDA, clear and systemic characterizations of the taxonomy, index phytochemical components, and the functional or medicinal bioactivities of the reputed or candidate medicinal plant are needed. In this study, we used an integrative approach, including macroscopic and microscopic examination, marker gene analysis, and chemical fingerprinting, to authenticate and validate various species/varieties of Wedelia, a reputed medicinal plant that grows naturally and commonly used in Asian countries. The anti-inflammatory bioactivities of Wedelia extracts were then evaluated in a DSS-induced murine colitis model. Different species/varieties of Wedelia exhibited distinguishable morphology and histological structures. Analysis of the ribosomal DNA internal transcribed spacer (ITS) region revealed significant differences among these plants. Chemical profiling of test Wedelia species demonstrated candidate index compounds and distinguishable secondary metabolites, such as caffeic acid derivatives, which may serve as phytochemical markers or index for quality control and identification of specific Wedelia species. In assessing their effect on treating DSS induced-murine colitis, we observed that only the phytoextract from W. chinensis species exhibited significant anti-inflammatory bioactivity on DSS-induced murine colitis among the various Wedelia species commonly found in Taiwan. Our results provide a translational research approach that may serve as a useful reference platform for biotechnological applications of traditional phytomedicines. Our findings indicate that specific Wedelia species warrant further investigation for potential treatment of human inflammatory bowel disease.
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Affiliation(s)
- Wen-Ching Lin
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
- Institute of Plant Biology, National Taiwan University, Taipei, Taiwan
| | - Chih-Chun Wen
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
| | - Yung-Hsiang Chen
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
| | - Pei-Wen Hsiao
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
| | - Jiunn-Wang Liao
- Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan
| | - Ching-I Peng
- Biodiversity Research Center, Academia Sinica, Taipei, Taiwan
| | - Ning-Sun Yang
- Agricultural Biotechnology Research Center, Academia Sinica, Taipei, Taiwan
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Imai M, Kumaoka T, Hosaka M, Sato Y, Li C, Sudoh M, Tamada Y, Yokoe H, Saito S, Tsubuki M, Takahashi N. Inhibitory effects of hydroxylated cinnamoyl esters on lipid absorption and accumulation. Bioorg Med Chem 2015; 23:3788-95. [PMID: 25910587 DOI: 10.1016/j.bmc.2015.03.086] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2015] [Revised: 03/28/2015] [Accepted: 03/30/2015] [Indexed: 10/23/2022]
Abstract
Obesity is a risk factor associated with several lifestyle-related diseases, for example, diabetes, high blood pressure, hyperlipidemia and cancer. Caffeic acid 2-phenylethyl ester (CAPE, 1), a naturally-occurring compound found in various plants and propolis, which exhibits anti-inflammatory, immunomodulatory and cytotoxic activities and inhibits 3T3-L1 differentiation to adipocytes. As part of our efforts to moderate lifestyle-related diseases, we synthesized analogs of 1 and studied their effects on pancreatic lipase activities, lipid absorption, and 3T3-L1 differentiation. We found that catechols 1-4 show inhibitory activities against pancreatic lipase in a dose-dependent manner in vitro. Compounds 1-3 proved to be more potent inhibitors of pancreatic lipase than 5, 6, 8, and 9, which have one hydroxyl group, respectively. Compound 7 has three aromatic hydroxyl groups and restrains greater lipase inhibitory activity than the other compounds. In addition, 7 and 3 significantly suppress a rise in blood triglyceride (TG) levels in mice given corn oil orally. Furthermore, 2 and 3 are more potent at preventing 3T3-L1 differentiation (lipid accumulation) than 1, while 7 is more potent than 3, 8, and 9 in these assays. Compounds 2, 3, and 7 inhibit lipid absorption and accumulation, with new compound 7 being the most potent. These results indicate that 7 may have potential benefits as a health agent with anti-obesity properties.
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Affiliation(s)
- Masahiko Imai
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Takaya Kumaoka
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Makiko Hosaka
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Yui Sato
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Chuan Li
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Masashi Sudoh
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Yoshiko Tamada
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Hiromasa Yokoe
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Setsu Saito
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Masayoshi Tsubuki
- Laboratory of Bioorganic Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan
| | - Noriko Takahashi
- Laboratory of Physiological Chemistry, Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
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Effects of novel hybrids of caffeic acid phenethyl ester and NSAIDs on experimental ocular inflammation. Eur J Pharmacol 2015; 752:78-83. [DOI: 10.1016/j.ejphar.2015.02.012] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2014] [Revised: 02/09/2015] [Accepted: 02/11/2015] [Indexed: 12/14/2022]
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Armutcu F, Akyol S, Ustunsoy S, Turan FF. Therapeutic potential of caffeic acid phenethyl ester and its anti-inflammatory and immunomodulatory effects (Review). Exp Ther Med 2015; 9:1582-1588. [PMID: 26136862 DOI: 10.3892/etm.2015.2346] [Citation(s) in RCA: 113] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2014] [Accepted: 03/03/2015] [Indexed: 12/15/2022] Open
Abstract
Caffeic acid phenethyl ester (CAPE), a naturally occurring compound isolated from propolis extract, has been reported to have a number of biological and pharmacological properties, exerting antioxidant, anti-inflammatory, anticarcinogenic, antibacterial and immunomodulatory effects. Recent in vivo and in vitro study findings have provided novel insights into the molecular mechanisms involved in the anti-inflammatory and immunomodulatory activities of this natural compound. CAPE has been reported to have anti-inflammatory properties involving the inhibition of certain enzyme activities, such as xanthine oxidase, cyclooxygenase and nuclear factor-κB (NF-κB) activation. Since inflammation and immune mechanisms play a crucial role in the onset of several inflammatory diseases, the inhibition of NF-κB represents a rationale for the development of novel and safe anti-inflammatory agents. The primary goal of the present review is to highlight the anti-inflammatory and immunomodulatory activities of CAPE, and critically evaluate its potential therapeutic effects.
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Affiliation(s)
- Ferah Armutcu
- Department of Biochemistry, Cerrahpasa Medical Faculty, Istanbul University, Istanbul 34098, Turkey
| | - Sumeyya Akyol
- Department of Medical Biology, Medical Faculty, Turgut Ozal University, Ankara 06010, Turkey
| | - Seyfettin Ustunsoy
- Department of Biochemistry, Medical Faculty, Fatih University, Istanbul 34500, Turkey
| | - Fatime Filiz Turan
- Department of Biochemistry, Medical Faculty, Fatih University, Istanbul 34500, Turkey
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Abdel-Latif MMM. Chemoprevention of gastrointestinal cancers by natural honey. World J Pharmacol 2015; 4:160-167. [DOI: 10.5497/wjp.v4.i1.160] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2014] [Revised: 01/03/2015] [Accepted: 01/20/2015] [Indexed: 02/06/2023] Open
Abstract
Gastrointestinal cancers are the most common human cancers in both men and women worldwide. Several epidemiological and experimental studies suggest a relationship between gastrointestinal cancers risk and dietary factors. Natural honey has been widely used in traditional medicine for many centuries to treat a wide range of ailments and complaints. Honey contains various components that exhibit wide activities including antibacterial, anti-inflammatory, antioxidant and anticancer properties. The anticancer effects of honey are mediated via diverse mechanisms, including inhibition of proliferation, induction of apoptosis, suppression of free radicals and modulation of inflammatory signalling pathways. The present review assesses the chemopreventive effects of natural honey and its components in the modulation of gastrointestinal cancers and its modes of action in the prevention of the development of gastrointestinal tumors. Honey can be an approach as a cancer-preventive strategy which merits further experimental and clinical research in the near future.
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Gu S, Wang J, Wei X, Cui H, Wu X, Wu F. Enhancement of Lipase-catalyzed Synthesis of Caffeic Acid Phenethyl Ester in Ionic Liquid with DMSO Co-solvent. Chin J Chem Eng 2014. [DOI: 10.1016/j.cjche.2014.09.024] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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Xie D, Yang F, Xie J, Zhang M, Liu W, Fu L. A Rapid and Practical Catalytic Esterification for the Preparation of Caffeic Acid Esters. JOURNAL OF CHEMICAL RESEARCH 2014. [DOI: 10.3184/174751914x14146000527920] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
A convenient and practical catalytic method for the preparation of caffeic acid esters is reported. This esterification was carried out with high efficiency in the presence of ytterbium triflate in nitromethane without any other auxiliary reagents. The wide scope of application and especially the higher reactivity and more convenient procedure than previous methods make it a valuable application for the synthesis of caffeic acid esters and other cinnamic acid esters.
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Affiliation(s)
- Dongsheng Xie
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
| | - Fengzhi Yang
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
| | - Jin Xie
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
| | - Man Zhang
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
| | - Wenlu Liu
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
| | - Lei Fu
- School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, P.R. China
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41
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Wang YC. Medicinal plant activity on Helicobacter pylori related diseases. World J Gastroenterol 2014; 20:10368-10382. [PMID: 25132753 PMCID: PMC4130844 DOI: 10.3748/wjg.v20.i30.10368] [Citation(s) in RCA: 103] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2013] [Revised: 01/17/2014] [Accepted: 04/03/2014] [Indexed: 02/06/2023] Open
Abstract
More than 50% of the world population is infected with Helicobacter pylori (H. pylori). The bacterium highly links to peptic ulcer diseases and duodenal ulcer, which was classified as a group I carcinogen in 1994 by the WHO. The pathogenesis of H. pylori is contributed by its virulence factors including urease, flagella, vacuolating cytotoxin A (VacA), cytotoxin-associated gene antigen (Cag A), and others. Of those virulence factors, VacA and CagA play the key roles. Infection with H. pylori vacA-positive strains can lead to vacuolation and apoptosis, whereas infection with cagA-positive strains might result in severe gastric inflammation and gastric cancer. Numerous medicinal plants have been reported for their anti-H. pylori activity, and the relevant active compounds including polyphenols, flavonoids, quinones, coumarins, terpenoids, and alkaloids have been studied. The anti-H. pylori action mechanisms, including inhibition of enzymatic (urease, DNA gyrase, dihydrofolate reductase, N-acetyltransferase, and myeloperoxidase) and adhesive activities, high redox potential, and hydrophilic/hydrophobic natures of compounds, have also been discussed in detail. H. pylori-induced gastric inflammation may progress to superficial gastritis, atrophic gastritis, and finally gastric cancer. Many natural products have anti-H. pylori-induced inflammation activity and the relevant mechanisms include suppression of nuclear factor-κB and mitogen-activated protein kinase pathway activation and inhibition of oxidative stress. Anti-H. pylori induced gastric inflammatory effects of plant products, including quercetin, apigenin, carotenoids-rich algae, tea product, garlic extract, apple peel polyphenol, and finger-root extract, have been documented. In conclusion, many medicinal plant products possess anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect. Those plant products have showed great potential as pharmaceutical candidates for H. pylori eradication and H. pylori induced related gastric disease prevention.
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Molecular Mechanism of Gastric Carcinogenesis in Helicobacter pylori-Infected Rodent Models. Diseases 2014. [DOI: 10.3390/diseases2020168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
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Ho YJ, Lee AS, Chen WP, Chang WL, Tsai YK, Chiu HL, Kuo YH, Su MJ. Caffeic acid phenethyl amide ameliorates ischemia/reperfusion injury and cardiac dysfunction in streptozotocin-induced diabetic rats. Cardiovasc Diabetol 2014; 13:98. [PMID: 24923878 PMCID: PMC4065079 DOI: 10.1186/1475-2840-13-98] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2014] [Accepted: 05/26/2014] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Caffeic acid phenethyl ester (CAPE) has been shown to protect the heart against ischemia/reperfusion (I/R) injury by various mechanisms including its antioxidant effect. In this study, we evaluated the protective effects of a CAPE analog with more structural stability in plasma, caffeic acid phenethyl amide (CAPA), on I/R injury in streptozotocin (STZ)-induced type 1 diabetic rats. METHODS Type 1 diabetes mellitus was induced in Sprague-Dawley rats by a single intravenous injection of 60 mg/kg STZ. To produce the I/R injury, the left anterior descending coronary artery was occluded for 45 minutes, followed by 2 hours of reperfusion. CAPA was pretreated intraperitoneally 30 minutes before reperfusion. An analog devoid of the antioxidant property of CAPA, dimethoxyl CAPA (dmCAPA), and a nitric oxide synthase (NOS) inhibitor (Nω-nitro-l-arginine methyl ester [l-NAME]) were used to evaluate the mechanism involved in the reduction of the infarct size following CAPA-treatment. Finally, the cardioprotective effect of chronic treatment of CAPA was analyzed in diabetic rats. RESULTS Compared to the control group, CAPA administration (3 and 15 mg/kg) significantly reduced the myocardial infarct size after I/R, while dmCAPA (15 mg/kg) had no cardioprotective effect. Interestingly, pretreatment with a NOS inhibitor, (L-NAME, 3 mg/kg) eliminated the effect of CAPA on myocardial infarction. Additionally, a 4-week CAPA treatment (1 mg/kg, orally, once daily) started 4 weeks after STZ-induction could effectively decrease the infarct size and ameliorate the cardiac dysfunction by pressure-volume loop analysis in STZ-induced diabetic animals. CONCLUSIONS CAPA, which is structurally similar to CAPE, exerts cardioprotective activity in I/R injury through its antioxidant property and by preserving nitric oxide levels. On the other hand, chronic CAPA treatment could also ameliorate cardiac dysfunction in diabetic animals.
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Affiliation(s)
| | | | | | | | | | | | | | - Ming-Jai Su
- Department of Pharmacology, College of Medicine, National Taiwan University, 11F, No, 1, Sec, 1, Jen-Ai Road, Taipei 10051, Taiwan.
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Shi H, Xie D, Yang R, Cheng Y. Synthesis of caffeic acid phenethyl ester derivatives, and their cytoprotective and neuritogenic activities in PC12 cells. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2014; 62:5046-5053. [PMID: 24840770 DOI: 10.1021/jf500464k] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
Twenty-one caffeic acid phenethyl ester (CAPE) derivatives were synthesized, and characterized by IR, HR-MS, (1)H and (13)C NMR analyses. All compounds were evaluated for their cytoprotective effects against H2O2-induced cytotoxicity and neuritogenic activities in the neurite outgrowth in PC12 cells. Compounds 1 and 20 exhibited stronger cytoprotective activities than their parent compound CAPE at 4 nM. Compounds 1, 4, 12 and 13 showed potential neuritogenic activities at 0.5 nM, while compounds 19 and 20 induced neurite outgrowth at 10 nM. The results from this study suggested that CAPE and its derivatives may be potential functional food ingredients for the prevention of neurodegenerative diseases.
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Affiliation(s)
- Haiming Shi
- Institute of Food and Nutraceutical Science, SJTU-Rich Research Institute of Nutrition and Skin Science, School of Agriculture and Biology, Shanghai Jiao Tong University , Shanghai 200240, China
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45
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Yamada T, Wei M, Toyoda T, Yamano S, Wanibuchi H. Inhibitory effect of Raphanobrassica on Helicobacter pylori-induced gastritis in Mongolian gerbils. Food Chem Toxicol 2014; 70:107-13. [PMID: 24835035 DOI: 10.1016/j.fct.2014.04.037] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2013] [Revised: 03/28/2014] [Accepted: 04/24/2014] [Indexed: 01/28/2023]
Abstract
Helicobacter pylori (H. pylori) infection is well known to be associated with chronic gastritis and also development of gastric cancer. Raphanobrassica (RB) is an intergeneric hybrid of the genera Raphanus (radish) and Brassica (cabbages) containing appreciable amounts of glucoraphanin (GR) and glucoraphenin (GRe), which are actively hydrolyzed by the enzyme myrosinase to sulforaphane and sulforaphene, respectively. Both of these metabolites exert antimicrobial and anti-inflammatory activity. The purpose of the present study was to investigate the effect of two freeze-dried products of RB (RB1 and RB2) on H. pylori-induced gastritis in Mongolian gerbils. Six-week-old male Mongolian gerbils were inoculated orally with H. pylori (ATCC 43504), and 2weeks later were fed diets containing no additives or diets supplemented with 2% RB1 (containing both GR and GRe) or 2% RB2 (containing GR only) for 10weeks. In the RB1, but not the RB2 group, mononuclear cell infiltration, mRNA expression of IL-6, and cell proliferation in the gastric mucosa were significantly suppressed. These results indicate that RB1 containing both GR and GRe exerted significant inhibitory effects on H. pylori-induced gastritis in Mongolian gerbils apparently mediated via suppression of IL-6 expression and chronic inflammation.
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Affiliation(s)
- Takanori Yamada
- Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Min Wei
- Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Takeshi Toyoda
- Division of Pathology, National Institute of Health Sciences, Tokyo 158-8501, Japan
| | - Shoutaro Yamano
- Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan
| | - Hideki Wanibuchi
- Department of Pathology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan.
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Ning X, Guo Y, Wang X, Ma X, Tian C, Shi X, Zhu R, Cheng C, Du Y, Ma Z, Zhang Z, Liu J. Design, Synthesis, and Biological Evaluation of (E)-3,4-Dihydroxystyryl Aralkyl Sulfones and Sulfoxides as Novel Multifunctional Neuroprotective Agents. J Med Chem 2014; 57:4302-12. [DOI: 10.1021/jm500258v] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
| | | | | | | | | | | | | | - Can Cheng
- Department
of Pharmaceutical Chemistry, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China
| | - Yansheng Du
- Department
of Neurology, Indiana University School of Medicine, Indianapolis, Indiana 46202, United States
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Kuo CH, Weng BC, Wu CC, Yang SF, Wu DC, Wang YC. Apigenin has anti-atrophic gastritis and anti-gastric cancer progression effects in Helicobacter pylori-infected Mongolian gerbils. JOURNAL OF ETHNOPHARMACOLOGY 2014; 151:1031-1039. [PMID: 24374236 DOI: 10.1016/j.jep.2013.11.040] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/06/2013] [Revised: 11/19/2013] [Accepted: 11/20/2013] [Indexed: 06/03/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Apigenin, one of the most common flavonoids, is abundant in celery, parsley, chamomile, passionflower, and other vegetables and fruits. Celery is recognized as a medicinal vegetable in Oriental countries to traditionally treat inflammation, swelling, blood pressure, serum lipid, and toothache. In this study, we investigated apigenin treatment effects on Helicobacter pylori-induced atrophic gastritis and gastric cancer progression in Mongolian gerbils. MATERIALS AND METHODS Five to eight-week-old Mongolian gerbils were inoculated with Helicobacter pylori for four weeks without (atrophic gastritis group) or with N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (gastric cancer group) in drinking water, and were then rested for two weeks. During the 7th-32th (atrophic gastritis group) or the 7th-52th (gastric cancer group) weeks, they were given various doses (0-60 mg/kgbw/day) of apigenin. At the end of the 32th (atrophic gastritis group) or the 52th (atrophic gastritis group) week, all Mongolian gerbils were sacrificed using the CO2 asphyxia method. The histological changes of Helicobacter pylori colonization, neutrophil and monocyte infiltrations, and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils were examined using immunohistochemistry stain and Sydney System scoring. RESULTS Apigenin treatments (30-60 mg/kgbw/day) effectively decreased atrophic gastritis (atrophic gastritis group) and dysplasia/gastric cancer (gastric cancer group) rates in Mongolian gerbils. Apigenin treatment (60 mg/kgbw/day) significantly decreased Helicobacter pylori colonization and Helicobacter pylori-induced histological changes of neutrophil and monocyte infiltrations and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils. CONCLUSIONS Apigenin has the remarkable ability to inhibit Helicobacter pylori-induced atrophic gastritis and gastric cancer progression as well as possessing potent anti-gastric cancer activity.
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Affiliation(s)
- Chao-Hung Kuo
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC
| | - Bi-Chuang Weng
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC
| | - Chun-Chieh Wu
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC
| | - Sheau-Fang Yang
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Pathology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan, ROC
| | - Deng-Chang Wu
- Division of Gastroenterology, Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, ROC; Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC; Division of Internal Medicine, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
| | - Yuan-Chuen Wang
- Department of Food Science and Biotechnology, National Chung Hsing University, Taichung, Taiwan, ROC.
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Zhao WX, Wang L, Yang JL, Li LZ, Xu WM, Li T. Caffeic acid phenethyl ester attenuates pro-inflammatory and fibrogenic phenotypes of LPS-stimulated hepatic stellate cells through the inhibition of NF-κB signaling. Int J Mol Med 2013; 33:687-94. [PMID: 24378685 DOI: 10.3892/ijmm.2013.1613] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2013] [Accepted: 12/05/2013] [Indexed: 11/06/2022] Open
Abstract
Hepatic stellate cells (HSCs) are the major cell type involved in liver fibrosis. Lipopolysaccharide (LPS)-mediated signaling through Τoll-like receptor 4 (TLR4) in HSCs has been identified as a key event in liver fibrosis, and as the molecular link between inflammation and liver fibrosis. In this study, we investigated the effects of caffeic acid phenethyl ester (CAPE), one of the main medicinal components of propolis, on the pro-inflammatory and fibrogenic phenotypes of LPS-stimulated HSCs. HSCs from rats were isolated and cultured in Dulbecco's modified Eagle's medium (DMEM). Following treatment with LPS, HSCs showed a strong pro-inflammatory phenotype with an upregulation of pro-inflammatory mediators, and a fibrogenic phenotype with enhanced collagen synthesis, mediated by transforming growth factor-β1 (TGF-β1). CAPE significantly and dose-dependently reduced LPS-induced nitrite production, as well as the transcription and protein synthesis of monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6) and inducible nitric oxide synthase (iNOS), as determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting and enzyme-linked immunosorbent assays (ELISA). CAPE further reduced the TGF-β1-induced transcription and translation (protein synthesis) of the gene coding for collagen type I α1 (col1A1), in LPS-stimulated HSCs. Following LPS stimulation, the phosphorylation of the nuclear factor-κB (NF-κB) inhibitor IκBα and consequently, the nuclear translocation of NF-κB, were markedly increased in the HSCs, and these changes were reversed by pre-treatment with CAPE. In conclusion, CAPE attenuates the pro-inflammatory phenotype of LPS-stimulated HSCs, as well as the LPS-induced sensitization of HSCs to fibrogenic cytokines by inhibiting NF-κB signaling. Our results provide new insight into the treatment of hepatic fibrosis through regulation of the TLR4 signaling pathway.
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Affiliation(s)
- Wen-Xing Zhao
- Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China
| | - Li Wang
- Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China
| | - Ju-Lun Yang
- Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China
| | - Lian-Zhen Li
- School of Life Sciences of Yunnan University, Kunming, Yunnan 650091, P.R. China
| | - Wen-Mang Xu
- Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China
| | - Tao Li
- Department of Pathology, Kunming General Hospital of PLA, Kunming, Yunnan 650032, P.R. China
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Inhibitory effects of caffeic acid phenethyl ester derivatives on replication of hepatitis C virus. PLoS One 2013; 8:e82299. [PMID: 24358168 PMCID: PMC3866116 DOI: 10.1371/journal.pone.0082299] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2013] [Accepted: 10/31/2013] [Indexed: 02/08/2023] Open
Abstract
Caffeic acid phenethyl ester (CAPE) has been reported as a multifunctional compound. In this report, we tested the effect of CAPE and its derivatives on hepatitis C virus (HCV) replication in order to develop an effective anti-HCV compound. CAPE and CAPE derivatives exhibited anti-HCV activity against an HCV replicon cell line of genotype 1b with EC50 values in a range from 1.0 to 109.6 µM. Analyses of chemical structure and antiviral activity suggested that the length of the n-alkyl side chain and catechol moiety are responsible for the anti-HCV activity of these compounds. Caffeic acid n-octyl ester exhibited the highest anti-HCV activity among the tested derivatives with an EC50 value of 1.0 µM and an SI value of 63.1 by using the replicon cell line derived from genotype 1b strain Con1. Treatment with caffeic acid n-octyl ester inhibited HCV replication of genotype 2a at a similar level to that of genotype 1b irrespectively of interferon signaling. Caffeic acid n-octyl ester could synergistically enhance the anti-HCV activities of interferon-alpha 2b, daclatasvir, and VX-222, but neither telaprevir nor danoprevir. These results suggest that caffeic acid n-octyl ester is a potential candidate for novel anti-HCV chemotherapy drugs.
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Bae M, Jang S, Lim JW, Kang J, Bak EJ, Cha JH, Kim H. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils. J Ginseng Res 2013; 38:8-15. [PMID: 24558304 PMCID: PMC3915327 DOI: 10.1016/j.jgr.2013.11.005] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2013] [Revised: 08/01/2013] [Accepted: 09/04/2013] [Indexed: 01/27/2023] Open
Abstract
Helicobacter pylori-induced gastric inflammation includes induction of inflammatory mediators interleukin (IL)-8 and inducible nitric oxide synthase (iNOS), which are mediated by oxidant-sensitive transcription factor NF-κB. High levels of lipid peroxide (LPO) and increased activity of myeloperoxidase (MPO), a biomarker of neutrophil infiltration, are observed in H. pylori-infected gastric mucosa. Panax ginseng Meyer, a Korean herb medicine, is widely used in Asian countries for its biological activities including anti-inflammatory efficacy. The present study aims to investigate whether Korean Red Ginseng extract (RGE) inhibits H. pylori-induced gastric inflammation in Mongolian gerbils. One wk after intragastric inoculation with H. pylori, Mongolian gerbils were fed with either the control diet or the diet containing RGE (200 mg RGE/gerbil) for 6 wk. The following were determined in gastric mucosa: the number of viable H. pylori in stomach; MPO activity; LPO level; mRNA and protein levels of keratinocyte chemoattractant factor (KC, a rodent IL-8 homolog), IL-1β, and iNOS; protein level of phospho-IκBα (which reflects the activation of NF-κB); and histology. As a result, RGE suppressed H. pylori-induced mRNA and protein levels of KC, IL-1β, and iNOS in gastric mucosa. RGE also inhibited H. pylori-induced phosphorylation of IκBα and increases in LPO level and MPO activity of gastric mucosa. RGE did not affect viable H. pylori colonization in the stomach, but improved the histological grade of infiltration of polymorphonuclear neutrophils, intestinal metaplasia, and hyperplasia. In conclusion, RGE inhibits H. pylori-induced gastric inflammation by suppressing induction of inflammatory mediators (KC, IL-1β, iNOS), MPO activity, and LPO level in H. pylori-infected gastric mucosa.
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Affiliation(s)
- Minkyung Bae
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Sungil Jang
- Department of Oral Biology, Oral Cancer Research Institute, Brain Korea 21 Project, Yonsei University, College of Dentistry, Seoul, Korea
| | - Joo Weon Lim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
| | - Jieun Kang
- Department of Oral Biology, Oral Cancer Research Institute, Brain Korea 21 Project, Yonsei University, College of Dentistry, Seoul, Korea
| | - Eun Jung Bak
- Department of Oral Biology, Oral Cancer Research Institute, Brain Korea 21 Project, Yonsei University, College of Dentistry, Seoul, Korea
| | - Jeong-Heon Cha
- Department of Oral Biology, Oral Cancer Research Institute, Brain Korea 21 Project, Yonsei University, College of Dentistry, Seoul, Korea
| | - Hyeyoung Kim
- Department of Food and Nutrition, Brain Korea 21 PLUS Project, College of Human Ecology, Yonsei University, Seoul, Korea
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