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Kanlayavattanakul M, Mersni D, Lourith N. Plant-derived saponins and their prospective for cosmetic and personal care products. BOTANICAL STUDIES 2024; 65:32. [PMID: 39514141 PMCID: PMC11549071 DOI: 10.1186/s40529-024-00438-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Accepted: 10/17/2024] [Indexed: 11/16/2024]
Abstract
Plants are industrially cultivated and processed serving for specified sectors for human consumptions including cosmetic and personal care products. Where, the consumers' awareness towards sustainability are increasing year by year. Among which, those of the materials derived from the plants produced with good agricultural and manufacturing practices abided with bio-circular-green economy theme, are of eminence. This perspective is in line with the researchers' bioprospective onto natural products. Special attention sheds on saponins, the biosurfactants that will not cause detrimental effects on the environment. Which, plants are regarded as the sustainable sources of these cosmetic substances. However, among tremendous plants that have been continuously explored upon their potential applications. Most of the studies focus on preparation of the saponins and biological activities. Surprisingly, those that are abided with the list published in the European Commission (CosIng) that are of crucially for cosmetic regulation are insufficiently demonstrated, which burden their applications in the sector. This context summarizes the industrial crops that are registered as plant saponin in the CosIng database. Those that are insufficiently exploited on the information required for cosmetic formulations are therefore encouraged to be examined. In addition, multidirectional cosmetic beneficials of the filled plants saponin would be encouraged to be explored. These plants will be properly knowledge managed for their sustainable utilizations as the bio-based materials promising for cosmetic and personal care industrial perspectives.
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Affiliation(s)
- Mayuree Kanlayavattanakul
- School of Cosmetic Science, Mae Fah Luang University, Chiang Rai, 57100, Thailand
- Phytocosmetics and Cosmeceuticals Research Group, Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Donia Mersni
- School of Cosmetic Science, Mae Fah Luang University, Chiang Rai, 57100, Thailand
- Phytocosmetics and Cosmeceuticals Research Group, Mae Fah Luang University, Chiang Rai, 57100, Thailand
- Nantes-Atlantic National College of Veterinary Medicine, Food Science and Engineering, Rue de la Geraudiere, CS 82225, Nantes, 44322, France
| | - Nattaya Lourith
- School of Cosmetic Science, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
- Phytocosmetics and Cosmeceuticals Research Group, Mae Fah Luang University, Chiang Rai, 57100, Thailand.
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Battaglia E, Bertolusso L, Del Prete M, Monzani M, Astegiano M. Overlapping approach Proton Pump Inhibitors/Nux vomica-Heel as new intervention for gastro-esophageal reflux management: Delphi consensus study. World J Gastroenterol 2024; 30:2467-2478. [PMID: 38764766 PMCID: PMC11099396 DOI: 10.3748/wjg.v30.i18.2467] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2024] [Revised: 02/28/2024] [Accepted: 04/16/2024] [Indexed: 05/11/2024] Open
Abstract
BACKGROUND Gastro-esophageal reflux disease (GERD) may affect the upper digestive tract; up to 20% of population in Western nations are affected by GERD. Antacids, histamine H2-receptor antagonists, and Proton Pump Inhibitors (PPIs) are considered the referring medications for GERD. Nevertheless, PPIs must be managed carefully because their use, especially chronic, could be linked with some adverse effects. An effective and safe alternative pharmacological tool for GERD is needed. After the identification of potentially new medications to flank PPIs, it is mandatory to revise and improve good clinical practices even through a consensus process. AIM To optimize diagnosis and treatment guidelines for GERD through a consensus based on Delphi method. METHODS The availability of clinical studies describing the action of the multicomponent/multitarget medication Nux vomica-Heel, subject of the consensus, is the basic prerequisite for the consensus itself. A modified Delphi process was used to reach a consensus among a panel of Italian GERD specialists on the overlapping approach PPIs/Nux vomica-Heel as a new intervention model for the management of GERD. The Voting Consensus group was composed of 49 Italian Medical Doctors with different specializations: Gastroenterology, otolaryngology, geriatrics, and general medicine. A scientific committee analyzed the literature, determined areas that required investigation (in agreement with the multiple-choice questionnaire results), and identified two topics of interest: (1) GERD disease; and (2) GERD treatment. Statements for each of these topics were then formulated and validated. The Delphi process involved two rounds of questioning submitted to the panel experts using an online platform. RESULTS According to their routinary GERD practice and current clinical evidence, the panel members provided feedback to each questionnaire statement. The experts evaluated 15 statements and reached consensus on all 15. The statements regarding the GERD disease showed high levels of agreement, with consensus ranging from 70% to 92%. The statements regarding the GERD treatment also showed very high levels of agreement, with consensus ranging from 90% to 100%. This Delphi process was able to reach consensus among physicians in relevant aspects of GERD management, such as the adoption of a new approach to treat patients with GERD based on the overlapping between PPIs and Nux vomica-Heel. The consensus was unanimous among the physicians with different specializations, underlying the uniqueness of the agreement reached to identify in the overlapping approach between PPIs and Nux vomica-Heel a new intervention model for GERD management. The results support that an effective approach to deprescribe PPIs through a progressive decalage timetable (reducing PPIs administration to as-needed use), should be considered. CONCLUSION Nux vomica-Heel appears to be a valid opportunity for GERD treatment to favor the deprescription of PPIs and to maintain low disease activity together with the symptomatology remission.
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Affiliation(s)
- Edda Battaglia
- Gastroenterology Unit, ASLTO4, Ivrea 10015, Turin, Italy
| | | | - Marco Del Prete
- Specialist in Nephrology International Academy of Physiological Regulating Medicine, Milan 20100, Italy
| | - Marco Monzani
- Specialist in Endocrinology, Territorial Social and Health Authority of Brianza, Monza 20900, Italy
| | - Marco Astegiano
- Gastroenterology Specialist, Retired from Gastroenterology and Hepatology Unit, AOU Città della Salute e della Scienza, Turin 10123, Italy
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Jie Y, Yang X, Chen W. Pulsatilla Decoction Combined with 5-Fluorouracil Triggers Immunogenic Cell Death in Colorectal Cancer Cells. Cancer Biother Radiopharm 2022; 37:945-954. [PMID: 34042519 DOI: 10.1089/cbr.2020.4369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Background: Our research is designed to explore the role of 5-FU and Pulsatilla decoction (PD) through modulation of Immunogenic cell death (ICD) for the co-treatment of Colorectal cancer (CRC). Materials and Methods: Cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazol-3-ium bromide (MTT) assays. Cell apoptosis was assessed using flow cytometry. Phosphorylation of STAT3 and expression of Mcl-1 and Bcl-xl were measured by Western blot assays. The levels of ATP and HMGB1 in the supernatants of the culture medium were analyzed by ATP assays and the HMGB1 enzyme linked immunosorbent assay kit. The cell surface levels of CRT were measured by immunofluorescence assays. The tumor growth was analyzed in mice. Results: PD increased 5-FU-induced ICD in CRC cells, as demonstrated by the extracellular levels of adenosine triphosphate (ATP) and high-mobility group box 1 (HMGB1), and the surface levels of calreticulin (CRT). Our mechanism study showed that PD promoted 5-FU-induced ICD by inactivating signal transducer and activator of transcription 3 (STAT3). Furthermore, the co-treatment of 5-FU and PD further promoted 5-FU-induced CRT expression and T cell infiltration in vivo. Tumorigenicity analysis revealed that 5-FU combined with PD notably reduced tumor growth. Conclusion: This study indicated that PD enhances 5-FU-induced ICD and anti-tumor effect in CRC by inactivating STAT3. The combined application of 5-FU with PD may improve the anti-tumor activity of 5-FU in CRC.
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Affiliation(s)
- Yanghua Jie
- Radiotherapy Center, Affiliated Hospital of Traditional Chinese Medicine, Xinjiang Medical University, Urumqi, China
| | - Xiaobei Yang
- Department of Anorectal, Urumqi City Hospital of Traditional Chinese Medicine, Urumqi, China
| | - Weidong Chen
- Department of Anorectal, Hospital (T.C.M) Affiliated to Southwest Medical University, Luzhou, China
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Han Q, Deng LR, Zou M, Tang HZ, Huang CY, Chen FJ, Tomlinson B, Li YH. Anemoside B4 protects against chronic relapsing colitis in mice by modulating inflammatory response, colonic transcriptome and the gut microbiota. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2022; 106:154416. [PMID: 36037770 DOI: 10.1016/j.phymed.2022.154416] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2022] [Revised: 08/10/2022] [Accepted: 08/21/2022] [Indexed: 06/15/2023]
Abstract
BACKGROUND Anemoside B4 (AB4) is reported to prevent acute colitis when given via intraperitoneal injection by two recent studies. However, whether oral AB4 protects against chronic colitis which resembles the clinical phenotype of ulcerative colitis (UC) and its mechanism of action are largely unknown. PURPOSE To systemically investigate the effects of oral AB4 against chronic colitis and illustrate the underlying mechanism of action. METHODS The preventive, therapeutic, and dose-dependent effects of AB4 against UC were examined in mice with acute or chronic relapsing colitis induced by dextran sulfate sodium (DSS). The inflammatory responses, colonic transcriptome, and 16S rDNA sequencing of the intestinal content of mice were analyzed. RESULTS Oral administration of AB4 alleviated disease severity and colon shortening in mice with chronic relapsing colitis in a dose-dependent manner. The effects of AB4 were comparable to those of two positive-control compounds: tofacitinib and berberine. Unlike tofacitinib, AB4 did not have a deleterious effect on DSS-induced splenic swelling and anemia. Furthermore, AB4 inhibited the inflammatory responses of colitis, as evidenced by in-vivo, ex-vivo, and in-vitro studies. Transcriptomics revealed that AB4 treatment reversed the DSS-mediated decrease in the expression of colonic Pelo, B3gat2 and Mir8010. In addition, AB4 reversed DSS-induced alterations in the intestinal microbiome in mice. Through fecal microbiota transplantation, we proved that AB4 partially exerted its anti-colitis effects by modulating the gut microbiota. CONCLUSIONS We demonstrated for the first time that AB4 has dose-dependent therapeutic effects against chronic relapsing colitis by modulating the inflammatory response, colonic gene expression, and intestinal microbiota.
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Affiliation(s)
- Qian Han
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Li-Rong Deng
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Min Zou
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Hua-Zheng Tang
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Chang-Yin Huang
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Fang-Jun Chen
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China
| | - Brian Tomlinson
- Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau, China
| | - Yan-Hong Li
- The Second Affiliated Hospital, School of Medicine, South China University of Technology, Guangzhou, China.
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Lin MK, Yang YT, Lin LJ, Yu WH, Chen HY. Pulsatilla decoction suppresses matrix metalloproteinase-7-mediated leukocyte recruitment in dextran sulfate sodium-induced colitis mouse model. BMC Complement Med Ther 2022; 22:211. [PMID: 35933374 PMCID: PMC9356479 DOI: 10.1186/s12906-022-03696-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 07/05/2022] [Indexed: 11/18/2022] Open
Abstract
Background Intestinal inflammation is considered to be an important characteristic of ulcerative colitis (UC) and the current medical treatments for UC are usually proposed to suppress abnormal intestinal immune responses. Pulsatilla decoction (PD), a traditional Chinese medicine, is frequently used in UC treatments in Asian countries; however, the mechanism of the action of PD remains unclear. In the present study, the mechanism of the action of PD was elucidated in the dextran sulfate sodium (DSS)-induced colitis mouse model, a model to mimic UC. Methods Murine colitis was evaluated by comparing the disease activity index score. The intestinal inflammation was examined by histology analyses. The leukocyte infiltration in the colonic tissues was examined by immunohistochemistry analyses. The cytokines level in colonic tissues was examined by Multi-Plex immunoassay. The epithelial proliferation was evaluated by histological analyses. Immunofluorescence double staining was used to examine the expression of MMP-7 in the immune cells. Results In the DSS-induced colitis mouse model, administration of PD attenuated the intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells. Immunohistochemical analyses further showed that matrix metalloproteinase-7 (MMP-7) expressed by the infiltrating leukocytes, including neutrophils and macrophages was inhibited by PD treatment. PD increases the cytokine level of IL-6 in colonic tissues. Conclusion PD suppresses intestinal inflammation, with a marked decrease in colonic infiltration of innate immune cells, through decreasing MMP-7 expression. Supplementary Information The online version contains supplementary material available at 10.1186/s12906-022-03696-w.
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Zhong J, Tan L, Chen M, He C. Pharmacological activities and molecular mechanisms of Pulsatilla saponins. Chin Med 2022; 17:59. [PMID: 35606807 PMCID: PMC9125917 DOI: 10.1186/s13020-022-00613-8] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2022] [Accepted: 04/22/2022] [Indexed: 11/10/2022] Open
Abstract
Saponins are found in a variety of higher plants and display a wide range of pharmacological activities, including expectorant, anti-inflammatory, vasoprotective and antimicrobial properties. Pulsatilla chinensis (P. chinensis, Bai Tou Weng, ) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria, and it is rich in triterpenoid saponins. In recent decades, anemoside B4 (Pulchinenoside C) is well studied since it has been used as a quality control marker for P. chinensis. At the same time, more and more other active compounds were found in the genus of Pulsatilla. In this review, we summarize the pharmacological activities of Pulsatilla saponins (PS) and discuss the cellular or molecular mechanisms that mediate their multiple activities, such as inducing cancer cell apoptosis, inhibiting tumor angiogenesis, and protecting organs via anti-inflammatory and antioxidant measures. We aim to provide comprehensive analysis and summary of research progress and future prospects in this field to facilitate further study and drug discovery of PS.
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Affiliation(s)
- Jinmiao Zhong
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao SAR, China.,Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao SAR, China.,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Taipa, 999078, Macao SAR, China
| | - Lihua Tan
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao SAR, China.,Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao SAR, China.,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Taipa, 999078, Macao SAR, China
| | - Meiwan Chen
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao SAR, China.,Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao SAR, China
| | - Chengwei He
- State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa, 999078, Macao SAR, China. .,Department of Pharmaceutical Science, Faculty of Health Sciences, University of Macau, Taipa, 999078, Macao SAR, China. .,Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, University of Macau, Taipa, 999078, Macao SAR, China.
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Qiu D, Zhang W, Song Z, Xue M, Zhang Y, Yang Y, Tong C, Cai D. Berberine suppresses cecal ligation and puncture induced intestinal injury by enhancing Treg cell function. Int Immunopharmacol 2022; 106:108564. [DOI: 10.1016/j.intimp.2022.108564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 12/24/2021] [Accepted: 01/20/2022] [Indexed: 11/17/2022]
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Anemoside B4 inhibits enterovirus 71 propagation in mice through upregulating 14-3-3 expression and type I interferon responses. Acta Pharmacol Sin 2022; 43:977-991. [PMID: 34321612 DOI: 10.1038/s41401-021-00733-1] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 06/29/2021] [Indexed: 01/03/2023]
Abstract
Enterovirus 71 (EV71) is the major pathogens of human hand, foot, and mouth disease (HFMD). EV71 efficiently escapes innate immunity responses of the host to cause infection. At present, no effective antiviral drugs for EV71 are available. Anemoside B4 (B4) is a natural saponin isolated from the roots of Pulsatilla chinensis (Bunge) Regel. P. chinensis extracts that shows a wide variety of biological activities. In this study, we investigated the antiviral activities of B4 against EV71 both in cell culture and in suckling mice. We showed that B4 (12.5-200 μM) dose dependently increased the viability of EV71-infected RD cells with an IC50 value of 24.95 ± 0.05 μM against EV71. The antiviral activity of B4 was associated with enhanced interferon (IFN)-β response, since knockdown of IFN-β abolished its antiviral activity. We also confirmed that the enhanced IFN response was mediated via activation of retinoic acid-inducible gene I (RIG-I) like receptors (RLRs) pathway, and it was executed by upregulation of 14-3-3 protein, which disrupted the interaction between yes-associated protein (YAP) and interferon regulatory factor 3 (IRF3). By using amino acids in cell culture (SILAC)-based proteomics profiling, we identified the Hippo pathway as the top-ranking functional cluster in B4-treated EV71-infected cells. In vivo experiments were conducted in suckling mice (2-day-old) infected with EV71 and subsequently B4 (200 mg · kg-1 · d-1, i.p.) was administered for 16 days. We showed that B4 administration effectively suppressed EV71 replication and improved muscle inflammation and limb activity. Meanwhile, B4 administration regulated the expressions of HFMD biomarkers IL-10 and IFN-γ, attenuating complications of EV71 infection. Collectively, our results suggest that B4 could enhance the antiviral effect of IFN-β by orchestrating Hippo and RLRs pathway, and B4 would be a potential lead compound for developing an anti-EV71 drug.
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Hua YL, Jia YQ, Zhang XS, Yuan ZW, Ji P, Hu JJ, Wei YM. Baitouweng Tang ameliorates DSS-induced ulcerative colitis through the regulation of the gut microbiota and bile acids via pathways involving FXR and TGR5. Biomed Pharmacother 2021; 137:111320. [PMID: 33578232 DOI: 10.1016/j.biopha.2021.111320] [Citation(s) in RCA: 46] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 01/16/2021] [Accepted: 01/21/2021] [Indexed: 02/07/2023] Open
Abstract
In China, Baitouweng Tang (BTWT) is a commonly prescribed remedy for the treatment of ulcerative colitis (UC). Herein, the present study aims to assess the anti-colitis activity of BTWT and its underlying mechanisms in UC BALB/c mice. Induction of UC in BALB/c mice was carried out by adding 3.5% DSS in the drinking water of underlined mice. After UC induction, the mice were administrated with BTWT for 7 days. Clinical symptoms were assessed, followed by analyzing the bile acids (BAs) in serum, liver, colon, bile, and feces of UC mice through UPLC-MS/MS. The modified 16S rDNA high-throughput sequencing was carried out to examine the gut microbiota of feces. BTWT significantly improved the clinical symptoms such as and histological injury and colon shortening in UC induced mice. Furthermore, BTWT remarkably ameliorated colonic inflammatory response. After BTWT treatment, the increased concentrations of UDCA, HDCA, αMCA, βMCA, CA, and GLCA in UC were decreased, and the levels of some BAs, especially CA, αMCA, and βMCA were normalized. Moreover, the relative species abundance and gut microbiota diversity in the BTWT-exposed groups were found to be considerably elevated than those in the DSS-treated group. BTWT increased the relative abundance of Firmicutes, Proteobacteria, Actinobacteria, Tenericutes, and TM7, which were statistically lower in the fecal microbiota of UC mice. The relative abundance of Bacteroidetes was found to be elevated in the DSS group and normalized after BTWT treatment. BTWT increased the expression of FXR and TGR5 in the liver. BTWT administration improved DSS-induced mice signs by increasing the TGR5 and FXR expression levels. This result was achieved by the regulation of the BAs and gut microbiota.
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Affiliation(s)
- Yong-Li Hua
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Ya-Qian Jia
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Xiao-Song Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Zi-Wen Yuan
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Peng Ji
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Jun-Jie Hu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
| | - Yan-Ming Wei
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, Gansu Province, 730070, People's Republic of China.
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Zhang Y, Zha Z, Shen W, Li D, Kang N, Chen Z, Liu Y, Xu G, Xu Q. Anemoside B4 ameliorates TNBS-induced colitis through S100A9/MAPK/NF-κB signaling pathway. Chin Med 2021; 16:11. [PMID: 33461587 PMCID: PMC7814617 DOI: 10.1186/s13020-020-00410-1] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2020] [Revised: 11/10/2020] [Accepted: 12/10/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Despite the increased morbidity of ulcerative colitis (UC) in the developing countries, available treatments remain unsatisfactory. Therefore, it is urgent to discover more effective therapeutic strategies. Pulsatilla chinensis was widely used for the treatment of inflamed intestinal diseases including UC for thousands of years in China. Anemoside B4, the most abundant triterpenoid saponin isolated from P. chinensis, exerts anti-inflammatory and antioxidant effects and may be the most active compounds, which is responsible for the therapeutic effects. However, the mechanism how anemoside B4 executes its biological functions is still elusive. METHODS Here, we used the 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis rat model to evaluate the therapeutic effect of anemoside B4. Blood samples of colitis rats were collected for hematology analysis. The inflammation-associated factors were investigated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis was determined with EdU cell proliferation assay and TUNEL assay. The proteins regulated by anemoside B4 were identified by label-free quantitative proteomics. The significantly down-regulated proteins were verified by Western blotting analysis. mRNA expression was analyzed by quantitative real-time RT-PCR. RESULTS The results showed that anemoside B4 ameliorated TNBS-induced colitis symptoms, including tissue damage, inflammatory cell infiltration, and pro-inflammatory cytokine production, apoptosis and slowed proliferation in colon. Quantitative proteomic analyses discovered that 56 proteins were significantly altered by anemoside B4 in the TNBS-induced rats. These proteins mainly clustered in tricarboxylic acid (TCA) cycle and respiratory electron transport chain. Among the altered proteins, S100A9 is one of the most significantly down-regulated proteins and associated with NF-κB and MAPK signaling pathways in the pathogenesis of UC. Further experiments revealed that anemoside B4 suppressed the expression of S100A9 and its downstream genes including TLR4 and NF-κB in colon. In vitro, anemoside B4 could inhibit the NF-κB signaling pathway induced by recombinant S100A9 protein in human intestinal epithelial Caco-2 cells. Moreover, anemoside B4 inhibits neutrophils recruitment and activation in colon induced by TNBS. CONCLUSIONS Our results demonstrate that anemoside B4 prevents TNBS-induced colitis by inhibiting the NF-κB signaling pathway through deactivating S100A9, suggesting that anemoside B4 is a promising therapeutic candidate for colitis.
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Affiliation(s)
- Yong Zhang
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Zhengxia Zha
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Wenhua Shen
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Dan Li
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China.,Jiangsu Key Laboratory of Neuropsychiatric Diseases and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Naixin Kang
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Zhong Chen
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Yanli Liu
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China
| | - Guoqiang Xu
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China. .,Jiangsu Key Laboratory of Neuropsychiatric Diseases and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Soochow University, Suzhou, 215123, Jiangsu, China.
| | - Qiongming Xu
- College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China.
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Anemoside B4 Protects against Acute Lung Injury by Attenuating Inflammation through Blocking NLRP3 Inflammasome Activation and TLR4 Dimerization. J Immunol Res 2020; 2020:7502301. [PMID: 33344657 PMCID: PMC7732379 DOI: 10.1155/2020/7502301] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 11/17/2020] [Accepted: 11/18/2020] [Indexed: 12/25/2022] Open
Abstract
Acute lung injury (ALI) is an acute inflammatory process in the lung parenchyma. Anemoside B4 (B4) was isolated from Pulsatilla, a plant-based drug against inflammation and commonly applied in traditional Chinese medicine. However, the anti-inflammatory effect and the mechanisms of B4 are not clear. In this study, we explored the potential mechanisms and anti-inflammatory activity of B4 both in vitro and in vivo. The results indicated that B4 suppressed the expression of iNOS, COX-2, NLRP3, caspase-1, and IL-1β. The ELISA assay results showed that B4 significantly restrained the release of inflammatory cytokines like TNF-α, IL-6, and IL-1β in macrophage cells. In addition, B4 rescued mitochondrial membrane potential (MMP) loss in (lipopolysaccharide) LPS plus ATP stimulated macrophage cells. Co-IP and molecular docking results illustrated that B4 disrupted the dimerization of TLR4. For in vivo results, B4 exhibited a protective effect on LPS and bleomycin- (BLM-) induced ALI in mice through suppressing the lesions of lung tissues, the release of inflammatory cytokines, and the levels of white blood cells, neutrophils, and lymphoid cells in the blood. Collectively, B4 has a protective effect on ALI via blocking TLR4 dimerization and NLRP3 inflammasome activation, suggesting that B4 is a potential agent for the treatment of ALI.
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Li YH, Zou M, Han Q, Deng LR, Weinshilboum RM. Therapeutic potential of triterpenoid saponin anemoside B4 from Pulsatilla chinensis. Pharmacol Res 2020; 160:105079. [PMID: 32679180 DOI: 10.1016/j.phrs.2020.105079] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/11/2020] [Revised: 07/02/2020] [Accepted: 07/10/2020] [Indexed: 11/30/2022]
Abstract
Pulsatilla Decoction (Bai-Tou-Weng-Tang) has been used medically in China for thousands of years for the treatment of diseases caused by bacteria. In recent decades, Pulsatilla Decoction is becoming a well-known formula prescription used for the treatment of ulcerative colitis in traditional Chinese medicine. Pulsatilla chinensis is the chief herbal source of Pulsatilla Decoction, and it is rich in triterpenoid saponins, such as anemoside B4, anemoside A3, and 23-hydroxybetulinic acid. Anemoside B4 is the most abundant of that group and has been used as a quality control marker for Pulsatilla chinensis. As the major active component of Pulsatilla chinensis, anemoside B4 has also received attention as a pure compound for its therapeutic potential. In this review, we systematically analyze the findings on triterpenoid saponins, especially anemoside B4, anemoside A3 and 23-hydroxybetulinic acid, included in Pulsatilla chinensis and Pulsatilla Decoction. We discuss the pharmacokinetics and tissue distribution of these triterpenoid saponins as well as their biological activities. We also summarize the pharmacological effects of anemoside B4 and its two possible metabolites, anemoside A3 and 23-hydroxybetulinic acid, as pure compounds. In summary, this review sketches a profile of the state of existing knowledge with regard to the pharmacological effects of anemoside B4, especially its anti-inflammatory and immunomodulatory effects. These findings point to the possibility that anemoside B4 has potential to be studied further as a natural compound-originated immunomodulatory agent for the treatment of inflammatory diseases such as ulcerative colitis and thus, may represent one of the most important active components of Pulsatilla Decoction responsible for its anti-ulcerative colitis efficacy.
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Affiliation(s)
- Yan-Hong Li
- School of Medicine, South China University of Technology, Guangzhou, China; Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
| | - Min Zou
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Qian Han
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Li-Rong Deng
- School of Medicine, South China University of Technology, Guangzhou, China
| | - Richard M Weinshilboum
- Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
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13
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He J, Yuan R, Cui X, Cui Y, Han S, Wang QQ, Chen Y, Huang L, Yang S, Xu Q, Zhao Y, Gao H. Anemoside B4 protects against Klebsiella pneumoniae- and influenza virus FM1-induced pneumonia via the TLR4/Myd88 signaling pathway in mice. Chin Med 2020; 15:68. [PMID: 32625244 PMCID: PMC7330533 DOI: 10.1186/s13020-020-00350-w] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 06/26/2020] [Indexed: 02/07/2023] Open
Abstract
Background Pneumonia refers to the inflammation of the terminal airway, alveoli and pulmonary interstitium, which can be caused by pathogenic microorganisms, physical and chemical factors, immune damage, and drugs. Anemoside B4, the major ingredient of Pulsatilla chinensis (Bunge) Regel, exhibited anti-inflammatory activity. However, the therapeutic effect of anemoside B4 on pneumonia has not been unraveled. This study aims to investigate that anemoside B4 attenuates the inflammatory responses in Klebsiella pneumonia (KP)- and influenza virus FM1 (FM1)-induced pneumonia mice model. Methods The network pharmacology and molecular docking assays were employed to predict the targets of anemoside B4’s treatment of pneumonia. Two models (bacterial KP-infected mice and virus FM1-infected mice) were employed in our study. BALB/c mice were divided into six groups: control, model group (KP-induced pneumonia or FM1-induced pneumonia), anemoside B4 (B4)-treated group (2.5, 5, 10 mg/kg), and positive drug group (ribavirin or ceftriaxone sodium injection). Blood samples were collected for hematology analysis. The effects of B4 on inflammation-associated mediators were investigated by Enzyme-linked immunosorbent assay (ELISA) and hematoxylin and eosin staining (HE) staining. Proteins expression was quantified by western blotting. Results The network results indicated that many pro-inflammatory cytokines such as tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) participated in anemoside B4’s anti-inflammatory activity. The counts of neutrophil (NEU) and white blood cell (WBC), the level of myeloperoxidase (MPO), and the release of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 increased by KP or FM1 infection, which were reversed by anemoside B4. In addition, anemoside B4 significantly suppressed the FM1-induced expression of toll-like receptor 4 (TLR4), myeloid differential protein-88 (MyD88), and myeloid differentiation protein-2 (MD-2), which were further validated by molecular docking data that anemoside B4 bound to bioactive sites of TLR4. Therefore, anemoside B4 exhibited a significant therapeutic effect on pneumonia via the TLR4/MyD88 pathway. Conclusion Our findings demonstrated that anemoside B4 attenuates pneumonia via the TLR4/Myd88 signaling pathway, suggesting that anemoside B4 is a promising therapeutic candidate for bacterial-infected or viral-infected pneumonia.
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Affiliation(s)
- Jia He
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Renyikun Yuan
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004 China
| | - Xiaolan Cui
- Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700 China
| | - Yushun Cui
- Jiangxi University of Traditional Chinese Medicine, Nanchang, 330004 China
| | - Shan Han
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Qin-Qin Wang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Yangling Chen
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Liting Huang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Shilin Yang
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
| | - Qiongming Xu
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,College of Pharmaceutical Science, Soochow University, Suzhou, 215123 China
| | - Yonghui Zhao
- Qingdao Central Hospital, The Second Affiliated Hospital of Qingdao University, Qingdao, 266109 China
| | - Hongwei Gao
- College of Pharmacy, Guangxi University of Chinese Medicine, Nanning, 530000 China.,Guangxi Engineering Technology Research Center of Advantage Chinese Patent Drug and Ethnic Drug Development, Nanning, 530020 China
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14
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Liu X, He S, Li Q, Mu X, Hu G, Dong H. Comparison of the Gut Microbiota Between Pulsatilla Decoction and Levofloxacin Hydrochloride Therapy on Escherichia coli Infection. Front Cell Infect Microbiol 2020; 10:319. [PMID: 32714880 PMCID: PMC7344306 DOI: 10.3389/fcimb.2020.00319] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2020] [Accepted: 05/26/2020] [Indexed: 12/26/2022] Open
Abstract
Gut microbiota serves as a critical indicator for gut health during treatment of pathogenic bacterial infection. Both Pulsatilla Decoction (abbreviated to PD, a traditional Chinese medicine compound) and Levofloxacin Hydrochloride (LVX) were known to have therapeutic effects to intestinal infectious disease. However, the changes of gut microbiota after PD or LVX treatment remain unclear. Herein, this work aimed to investigate the changes of intestinal flora after PD or LVX therapy of Escherichia coli infection in rats. Results revealed that PD exhibited a valid therapeutic approach for E. coli infection via the intestinal protection, as well as the inhibited release of IL-8 and ICAM-1. Besides, PD was beneficial to rebuild the gut microbiota via restoring Bacteroidetes spp in the composition of the gut microbiota. Comparatively, LVX treatment promoted the infection and ravaged gut microbiota by significantly decreasing Bacteroidetes and increasing Firmicutes. These findings not only highlight the mechanism of Chinese herbal formula, but extend the application of PD as veterinary medicine, feed additive and pre-mixing agent for improving the production of animal derived foods.
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Affiliation(s)
- Xiaoye Liu
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China.,Department of Mechanics and Engineering Science, College of Engineering, Academy for Advanced Interdisciplinary Studies, and Beijing Advanced Innovation Center for Engineering Science and Emerging Technology, College of Engineering, Peking University, Beijing, China.,Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing, China
| | - Shangwen He
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Qiuyue Li
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Xiang Mu
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Ge Hu
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
| | - Hong Dong
- Beijing Traditional Chinese Veterinary Engineering Center and Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing, China
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15
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Huangfu S, Dou R, Zhong S, Guo M, Gu C, Jurczyszyn A, Yang Y, Jiang B. Modified Pulsatillae decoction inhibits DSS-induced ulcerative colitis in vitro and in vivo via IL-6/STAT3 pathway. BMC Complement Med Ther 2020; 20:179. [PMID: 32517784 PMCID: PMC7285600 DOI: 10.1186/s12906-020-02974-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2020] [Accepted: 05/26/2020] [Indexed: 02/07/2023] Open
Abstract
Background Ulcerative colitis (UC) is a chronic inflammatory disorder of the colon and rectum, which is positively correlated with the occurrence of IBD-related colorectal cancer (IBD-CRC). Conventional therapies based on drugs such as corticosteroids, mesalamine, and immunosuppression have serious side effects. Pulsatillae decoction (PD) served as a classical prescription for the treatment of colitis in China, has been shown to exert prominent curative effects and good safety. Based on clinical experience and our amelioration, we added an extra herb into this classical prescription, but its therapeutic effect on UC and the underlying mechanism are still unclear. Results We first found the curative effect of modified PD on dextran sodium sulfate (DSS)-incubated NCM460 cells. Then C57BL/6 mice were administered DSS to induce UC to evaluate the therapeutic of modified PD. The results showed that modified PD alleviated the inflammatory injury, manifested in body weight, colon length, and disease activity index, with histological analysis of colon injury. Transcriptomic sequencing indicated that modified PD treatment downregulated the IL-6/STAT3 signaling pathway, and reduced the levels of p-NF-κB, IL-1β and NLRP3, which were confirmed by western blot. Conclusions Collectively, our results indict that modified PD could efficiently relieve clinical signs and inflammatory mediators of UC, providing evidence of the anti-colitis effect of modified PD, which might provide novel strategies for therapeutic intervention in UC, which may be applied to the prevention of IBD-CRC.
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Affiliation(s)
- Shaohua Huangfu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Renjie Dou
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Sixia Zhong
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Mengjie Guo
- School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Chunyan Gu
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.,School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Artur Jurczyszyn
- Department of Hematology, Jagiellonian University Medical College, 30-051, Cracow, Poland
| | - Ye Yang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China. .,Laboratory for Combination of Acupuncture and Chinese Materia Medica of Chinese Ministry of Education, Nanjing University of Chinese Medicine, Nanjing, China.
| | - Bin Jiang
- Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.
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16
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Hua YL, Ma Q, Zhang XS, Jia YQ, Peng XT, Yao WL, Ji P, Hu JJ, Wei YM. Pulsatilla Decoction Can Treat the Dampness-Heat Diarrhea Rat Model by Regulating Glycerinphospholipid Metabolism Based Lipidomics Approach. Front Pharmacol 2020; 11:197. [PMID: 32194420 PMCID: PMC7064006 DOI: 10.3389/fphar.2020.00197] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Accepted: 02/13/2020] [Indexed: 12/17/2022] Open
Abstract
Ethnopharmacological Relevance Diarrhea is a major medical problem in clinical practice. According to the theory of traditional Chinese medicine (TCM), different types of diarrhea should be treated with different TCM formulations based on the targeted medical condition. Dampness-heat diarrhea (DHD) is a serious diarrheal disease and Pulsatilla decoction (PD), a TCM, has been found effective against DHD. Objective The aim of this study was to clarify the mechanism of action of PD in DHD using an untargeted lipidomics strategy. Materials and Methods Wistar rats were randomized to four groups, including the control group, model group, PD groups and self-healing group. The PD groups were given a daily intragastric gavage of PD at doses of 3.76 g/kg. The rat model of DHD established by such complex factors as high-sugar and high-fat diet, improper diet, high temperature and humidity environment, drinking and intraperitoneal injection of Escherichia coli., which imitated the inducing conditions of DHD. Then the clinical symptoms and signs, blood routine, serum inflammatory cytokines levels and the histopathological changes of main organs were detected and observed to evaluate DHD model and therapeutic effect of PD. Lipid biomarkers of DHD were selected by comparing the control and model groups with the colon lipidomics technology and an ultra-high performance liquid chromatography (UHPLC) coupled with Q Exactive plus mass analyzer. Multivariate statistical analysis and pattern recognition were employed to examine different lipids within the colon of PD-treated rats. Results The clinical symptoms and signs of the model rats were consistent with the diagnostic criteria of DHD. After treatment with PD, the clinical symptoms and signs of the rats with DHD were improved; the indexes of blood routine and inflammatory cytokines levels tended to be normal. The lipidomics profile of the model group were evidently disordered when compared to the control group. A total of 42 significantly altered lipids between the model-control groups were identified by multivariate statistical analysis. DHD may result from such lipid disorders which are related to glycerophospholipid metabolism, arachidonic acid (AA) metabolism, and sphingolipid metabolism. After PD treatment, the lipidomic profiles of the disorders tended to recover when compared to the model group. Twenty lipid molecules were identified and some glycerophospholipids and AA levels returned close to the normal level. Conclusion Glycerophospholipid metabolism may play an important role in the treatment of dampness-heat induced diarrhea using PD.
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Affiliation(s)
- Yong-Li Hua
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Qi Ma
- Institute of Animal Science, Southwestern University, Chongqing, China
| | - Xiao-Song Zhang
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Ya-Qian Jia
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Xiao-Ting Peng
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Wan-Ling Yao
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Peng Ji
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Jun-Jie Hu
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
| | - Yan-Ming Wei
- College of Veterinary Medicine, Gansu Agricultural University, Lanzhou, China
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17
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Tarabasz D, Kukula-Koch W. Palmatine: A review of pharmacological properties and pharmacokinetics. Phytother Res 2019; 34:33-50. [PMID: 31496018 DOI: 10.1002/ptr.6504] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/18/2019] [Accepted: 08/19/2019] [Indexed: 12/11/2022]
Abstract
The aim of this review is to collect together the results of the numerous studies over the last two decades on the pharmacological properties of palmatine published in scientific databases like Scopus and PubMed, which are scattered across different publications. Palmatine, an isoquinoline alkaloid from the class of protoberberines, is a yellow compound present in the extracts from different representatives of Berberidaceae, Papaveraceae, Ranunculaceae, and Menispermaceae. It has been extensively used in traditional medicine of Asia in the treatment of jaundice, liver-related diseases, hypertension, inflammation, and dysentery. New findings describe its possible applications in the treatment of civilization diseases like central nervous system-related problems. This review intends to let this alkaloid come out from the shade of a more frequently described alkaloid: berberine. The toxicity, pharmacokinetics, and biological activities of this protoberberine alkaloid will be developed in this work.
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Affiliation(s)
| | - Wirginia Kukula-Koch
- Chair and Department of Pharmacognosy with Medicinal Plants Unit, Medical University of Lublin, Lublin, Poland
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18
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Liu YC, Hsiao YY, Ku KL, Liao HF, Chao WC. Mahonia oiwakensis Extract and Its Bioactive Compounds Exert Anti-Inflammatory Activities and VEGF Production Through M2-Macrophagic Polarization and STAT6 Activation. J Med Food 2018; 21:654-664. [PMID: 29652553 DOI: 10.1089/jmf.2017.4084] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Macrophages play an indispensable role in the host immune defense. Macrophages can undergo polarization into classically (M1) and alternatively (M2) activated macrophages. M1 macrophages activate immune and inflammatory response, while M2 macrophages are involved in tissue remodeling. Mahonia oiwakensis (Mo) is a herbal medicine in Asia used for its anti-inflammatory and analgesic properties; however, the mechanism is unclear. This study analyzed the effect of Mo extracts and its effects on the polarization of both macrophage RAW264.7 cells and mouse splenic macrophages. Water (Mo-W) and EtOH extracts (Mo-E) did not change the viability of RAW264.7 cells, whereas Mo-E inhibited nitric oxide (NO) production. The major compounds, berberine and palmatine, decreased the viability and NO levels of cells. The secretion of inflammatory cytokines CXCL16, IL-6, L-selectin, MCP1, RANTES, and sTNF-R1 was downregulated, whereas the production of vascular endothelial growth factor (VEGF) was upregulated by Mo-E, berberine, and palmatine treatments. Mo-E, berberine, and palmatine stimulated the expression of macrophage CD68 and M2-type CD204 markers, decreased M1-mediated p-STAT1 and NF-κB, and increased M2-mediated p-STAT6 expression. Similar effects on M2 polarization were also observed in splenic macrophages from mice. In conclusion, Mo-E, berberine, and palmatine modulated macrophages through the suppression of M1-mediated inflammation and the recruitment of M2-mediated VEGF secretion and STAT6 expression.
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Affiliation(s)
- Yea-Chen Liu
- 1 Department of Biological Resources, National Chiayi University , Chiayi, Taiwan
| | - Yu-Ying Hsiao
- 2 Department of Biochemical Science and Technology, National Chiayi University , Chiayi, Taiwan
| | - Kuo-Lung Ku
- 3 Department of Applied Chemistry, National Chiayi University , Chiayi, Taiwan
| | - Hui-Fen Liao
- 2 Department of Biochemical Science and Technology, National Chiayi University , Chiayi, Taiwan
| | - Wei-Chun Chao
- 4 Department of Forestry and Natural Resources, National Chiayi University , Chiayi, Taiwan
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19
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Zhang YZ, Zhang JW, Wang CZ, Zhou LD, Zhang QH, Yuan CS. Polydopamine-Coated Magnetic Molecularly Imprinted Polymers with Fragment Template for Identification of Pulsatilla Saponin Metabolites in Rat Feces with UPLC-Q-TOF-MS. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2018; 66:653-660. [PMID: 29260546 DOI: 10.1021/acs.jafc.7b05747] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/07/2023]
Abstract
In this work, a modified pretreatment method using magnetic molecularly imprinted polymers (MMIPs) was successfully applied to study the metabolites of an important botanical with ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The MMIPs for glucoside-specific adsorption was used to identify metabolites of Pulsatilla chinensis in rat feces. Polymers were prepared by using Fe3O4 nanoparticles as the supporting matrix, d-glucose as fragment template, and dopamine as the functional monomer and cross-linker. Results showed that MMIPs exhibited excellent extraction performance, large adsorption capacity (5.65 mg/g), fast kinetics (60 min), and magnetic separation. Furthermore, the MMIPs coupled with UPLC-Q-TOF-MS were successfully utilized for the identification of 17 compounds including 15 metabolites from the Pulsatilla saponin metabolic pool. This study provides a reliable protocol for the separation and identification of saponin metabolites in a complex biological sample, including those from herbal medicines.
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Affiliation(s)
- Yu-Zhen Zhang
- School of Chemistry and Chemical Engineering, Chongqing University , Chongqing 400044, China
| | - Jia-Wei Zhang
- School of Chemistry and Chemical Engineering, Chongqing University , Chongqing 400044, China
| | - Chong-Zhi Wang
- Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago , Chicago, Illinois 60637, United States
| | - Lian-Di Zhou
- Basic Medical College, Chongqing Medical University , Chongqing 400016, China
| | - Qi-Hui Zhang
- School of Chemistry and Chemical Engineering, Chongqing University , Chongqing 400044, China
- Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago , Chicago, Illinois 60637, United States
| | - Chun-Su Yuan
- Tang Center for Herbal Medicine Research and Department of Anesthesia & Critical Care, University of Chicago , Chicago, Illinois 60637, United States
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20
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Guo X, Xie Y, Lian S, Li Z, Gao Y, Xu Z, Hu P, Chen M, Sun Z, Tian X, Huang C. A sensitive HPLC-MS/MS method for the simultaneous determination of anemoside B4, anemoside A3 and 23-hydroxybetulinic acid: Application to the pharmacokinetics and liver distribution of Pulsatilla chinensis saponins. Biomed Chromatogr 2017; 32. [PMID: 29078255 DOI: 10.1002/bmc.4124] [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: 08/03/2017] [Revised: 10/05/2017] [Accepted: 10/17/2017] [Indexed: 11/07/2022]
Abstract
Pulsatilla chinensis saponins, the major active components in the herb, have drawn great attention as potential hepatitis B virus infection and hepatoma treatments. Here, a sensitive and accurate HPLC-MS/MS method was established for simultaneous determination of three saponins - anemoside B4, anemoside A3 and 23-hydroxybetulinic acid - in rat plasma and liver, and fully validated. The method was successfully applied to a pharmacokinetics and liver distribution study of P. chinensis saponins. Consequently, 23-hydroxybetulinic acid, with an extremely low content in the P. chinensis saponins, exhibited the highest exposure in the liver and in sites before and after hepatic disposition, namely, in the portal vein plasma and systemic plasma, followed by anemoside B4, which showed the highest content in the herb, whereas anemoside A3 displayed quite limited exposure. The hepatic first-pass effects were 71% for 23-hydroxybetulinic acid, 27% for anemoside B4 and 37% for anemoside A3, corresponding to their different extents of liver distribution. To our knowledge, this is the first investigation on the liver first-pass effect and distribution of P. chinensis saponins to date. These results also provide valuable information for the understanding of the pharmacological effect of P. chinensis saponins on liver diseases.
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Affiliation(s)
- Xiaozhen Guo
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Yang Xie
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,Harbin University of Commerce, Harbin, China
| | - Shan Lian
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,Harbin University of Commerce, Harbin, China
| | - Zhixiong Li
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Yu Gao
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Zhou Xu
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Pei Hu
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Mingcang Chen
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Zhaolin Sun
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Xiaoting Tian
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
| | - Chenggang Huang
- Shanghai Institute of Material Medica, Chinese Academy of Science, Shanghai, China.,University of Chinese Academy of Science, Beijing, China
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21
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Cheng J, Chen T, Li P, Wen J, Pang N, Zhang L, Wang L. Sodium tanshinone IIA sulfonate prevents lipopolysaccharide-induced inflammation via suppressing nuclear factor-κB signaling pathway in human umbilical vein endothelial cells. Can J Physiol Pharmacol 2017; 96:26-31. [PMID: 28658584 DOI: 10.1139/cjpp-2017-0023] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
Sodium tanshinone IIA sulfonate (STS), a water-soluble derivative of tanshinone IIA, has been demonstrated to have potent anti-inflammatory properties. However, the protective effects of STS on lipopolysaccharide (LPS)-induced inflammation in endothelial cells remain to be elucidated. In the present study, human umbilical vein endothelial cells (HUVECs) were used to explore the effects of STS on LPS-induced inflammation and the molecular mechanism involved. HUVECs were pretreated with STS for 2 h, followed by stimulation with LPS. Then expression and secretion of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, and the activation of nuclear factor-κB (NF-κB) were assessed. The results demonstrated that STS significantly decreased LPS-induced TNF-α and IL-1β protein expression in HUVECs. Similarly, the increased levels of TNF-α and IL-1β in cell supernatants stimulated by LPS were also significantly inhibited by STS. Furthermore, STS inhibited LPS-induced NF-κB p65 phosphorylation and nuclear translocation. All the results suggest that STS prevents LPS-induced inflammation through suppressing NF-κB signaling pathway in endothelial cells, indicating the potential utility of STS for the treatment of inflammatory diseases.
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Affiliation(s)
- Jun Cheng
- a Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Tangting Chen
- a Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Pengyun Li
- a Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Jing Wen
- a Key Laboratory of Medical Electrophysiology of Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Ningbo Pang
- b Drug Discovery Research Center, Southwest Medical University, Luzhou 646000, Sichuan, China.,c Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Liping Zhang
- b Drug Discovery Research Center, Southwest Medical University, Luzhou 646000, Sichuan, China.,c Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China
| | - Liqun Wang
- b Drug Discovery Research Center, Southwest Medical University, Luzhou 646000, Sichuan, China.,c Laboratory for Cardiovascular Pharmacology of Department of Pharmacology, The School of Pharmacy, Southwest Medical University, Luzhou 646000, Sichuan, China
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Olivieri MF, Marzari F, Kesel AJ, Bonalume L, Saettini F. Pharmacology and psychiatry at the origins of Greek medicine: The myth of Melampus and the madness of the Proetides. JOURNAL OF THE HISTORY OF THE NEUROSCIENCES 2017; 26:193-215. [PMID: 27625080 DOI: 10.1080/0964704x.2016.1211901] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/06/2023]
Abstract
Melampus is a seer-healer of Greek myth attributed with having healed the young princesses of Argos of madness. Analysis of this legend and its sources sheds light on the early stages of the "medicalizing" shift in the history of ancient Greek medicine. Retrospective psychological diagnosis suggests that the descriptions of the youths' madness rose from actual observation of behavioral and mental disorders. Melampus is credited with having healed them by administering hellebore. Pharmacological analysis of botanical specimens proves that Helleborus niger features actual neurological properties effective in the treatment of mental disorders. The discussion aims at examining the rational aspects of the treatment of mental conditions in Greco-Roman antiquity.
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Affiliation(s)
- Matteo F Olivieri
- a Department of Historical Studies , University of Milan , Milan , Italy
| | - Francesca Marzari
- b Centro Antropologia e Mondo Antico , University of Siena , Siena , Italy
| | | | - Laura Bonalume
- d Department of Psychology , University of Milano-Bicocca , Milan , Italy
| | - Francesco Saettini
- e San Gerardo Hospital, Department of Pediatrics , University of Milano-Bicocca , Milan , Italy
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Zhang L, Gong AGW, Riaz K, Deng JY, Ho CM, Lin HQ, Dong TTX, Lee YK, Tsim KWK. A novel combination of four flavonoids derived from Astragali Radix relieves the symptoms of cyclophosphamide-induced anemic rats. FEBS Open Bio 2017; 7:318-323. [PMID: 28286727 PMCID: PMC5337903 DOI: 10.1002/2211-5463.12146] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2016] [Revised: 09/27/2016] [Accepted: 09/29/2016] [Indexed: 11/23/2022] Open
Abstract
By using a feedback system control scheme, the best combination of formononetin, ononin, calycosin, and calycosin‐7‐O‐β‐d‐glucoside derived from Astragali Radix was shown to activate a hypoxia response element, a regulator for erythropoietin (EPO) transcription, in kidney fibroblast. In cyclophosphamide‐induced anemic rats, the treatment of combined flavonoids, or EPO, improved the levels of red blood cells, white blood cells, hemoglobin, and hematocrit. In addition, the altered levels of antioxidant capacity, super oxidase dismutase, and malondialdehyde, triggered in anemic rats, were restored to control levels by the treatment of flavonoids. Here, we proposed a possible therapy by using the common flavonoids in treating anemia.
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Affiliation(s)
- Li Zhang
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China; School of Pharmacy Shanghai University of Traditional Chinese Medicine China
| | - Amy G W Gong
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China
| | - Kashif Riaz
- Department of Mechanical and Aerospace Engineering The Hong Kong University of Science and Technology China
| | - Jun Y Deng
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China
| | - Chih M Ho
- Department of Mechanical and Aerospace Engineering University of California Los Angeles CA USA
| | - Huang Q Lin
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China; HKUST Shenzhen Research Institute Nanshan Shenzhen Guangdong Province China
| | - Tina T X Dong
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China; HKUST Shenzhen Research Institute Nanshan Shenzhen Guangdong Province China
| | - Yi-Kuen Lee
- Department of Mechanical and Aerospace Engineering The Hong Kong University of Science and Technology China
| | - Karl W K Tsim
- Division of Life Science and Center for Chinese Medicine The Hong Kong University of Science and Technology China; HKUST Shenzhen Research Institute Nanshan Shenzhen Guangdong Province China
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Wan JY, Zhang YZ, Yuan JB, Yang FQ, Chen Y, Zhou LD, Zhang QH. Biotransformation and metabolic profile of anemoside B4 with rat small and large intestine microflora by ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry. Biomed Chromatogr 2016; 31. [PMID: 27761923 DOI: 10.1002/bmc.3873] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2016] [Revised: 09/19/2016] [Accepted: 10/18/2016] [Indexed: 12/23/2022]
Abstract
Pulsatilla chinensis (Bunge) Regel is commonly used in Asia, and anemoside B4 (AB4) is its major saponin, with diverse pharmaceutical effects. Previous studies showed that intestinal flora plays an important role in the metabolism of herbs administered orally. In this study, the metabolic profile of AB4 with microflora in rat small and large intestines in vitro was investigated. Gut microflora was collected from different intestinal segments and anaerobically incubated with AB4 at 37°C for 24, 48, 72 and 96 h, respectively. A total of 10 metabolites were detected and identified by ultra- performance liquid chromatography/quadrupole time-of-flight mass spectrometry, involving the products of oxygenation and deglycosylation reactions. Gut microflora in the large intestine generated more comprehensive metabolic pathways, which appears to be attributable to the wider range of bacterial types and numbers of bacteria. Human cancer cell lines SMMC-7721, Hela and MCF-7 were treated with metabolite pools by MTT assay, together with M6 as the greatest deglycosylation product. As a result, M6 exhibited a reduction in cell viability of SMMC-7721 with an IC50 value of 22.28 ± 1.26 μg/mL. The present study provided scientific evidence for AB4 metabolism in small and large intestines, which is helpful to reveal the active forms of AB4 in vivo.
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Affiliation(s)
- Jin-Yi Wan
- College of Pharmacy, Chongqing University, Chongqing, China.,School of Pharmacy, Jiangsu University, Zhenjiang, China
| | - Yu-Zhen Zhang
- College of Pharmacy, Chongqing University, Chongqing, China.,Basic Medical College, Chongqing Medical University, Chongqing, China
| | - Jin-Bin Yuan
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Feng-Qing Yang
- College of Pharmacy, Chongqing University, Chongqing, China
| | - Yan Chen
- Key Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Lian-Di Zhou
- Basic Medical College, Chongqing Medical University, Chongqing, China
| | - Qi-Hui Zhang
- College of Pharmacy, Chongqing University, Chongqing, China
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Wang X, Fan F, Cao Q. Modified Pulsatilla decoction attenuates oxazolone-induced colitis in mice through suppression of inflammation and epithelial barrier disruption. Mol Med Rep 2016; 14:1173-9. [PMID: 27278299 PMCID: PMC4940073 DOI: 10.3892/mmr.2016.5358] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2015] [Accepted: 05/05/2016] [Indexed: 01/01/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are chronic inflammatory gastrointestinal disorders caused by a dysregulated mucosal immune response and epithelial barrier disruption. Conventional treatment of IBD is currently limited to overcoming patient symptoms and is often associated with severe adverse effects from the drugs used. Modified Pulsatilla decoction has been used previously to treat ulcerative colitis (UC) in clinical practice in China, however, the underlying mechanism in the treatment of UC remains to be elucidated. In the present study, the efficiency and mechanisms of modified Pulsatilla decoction in the treatment of oxazolone-induced colitis were investigated. Assessment of clinical colitis and histological examination found that the administration of modified Pulsatilla decoction attenuated the severity of oxazolone-induced colitis in mice. Measurement of cytokine concentration, western blotting and reverse transcription-quantitative polymerase chain reaction demonstrated modified Pulsatilla decoction treatment significantly reduced the secretion of pro-inflammatory cytokines and restored alterations in tight junction proteins in the colon tissues. In addition, modified Pulsatilla decoction suppressed the activation of the nuclear factor-κB signaling pathway. Thus, the findings of the present study demonstrated that modified Pulsatilla decoction offers an effective therapeutic approach for the treatment of IBD and revealed the underlying mechanisms of action offered by modified Pulsatilla decoction.
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Affiliation(s)
- Xuewei Wang
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Fugang Fan
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
| | - Qin Cao
- Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, P.R. China
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Xiao K, Cao ST, Jiao LF, Lin FH, Wang L, Hu CH. Anemonin improves intestinal barrier restoration and influences TGF-β1 and EGFR signaling pathways in LPS-challenged piglets. Innate Immun 2016; 22:344-52. [PMID: 27189428 DOI: 10.1177/1753425916648223] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2016] [Accepted: 04/14/2016] [Indexed: 01/30/2023] Open
Abstract
The present study was aimed at investigating whether dietary anemonin could alleviate LPS-induced intestinal injury and improve intestinal barrier restoration in a piglet model. Eighteen 35-d-old pigs were randomly assigned to three treatment groups (control, LPS and LPS+anemonin). The control and LPS groups were fed a basal diet, and the LPS + anemonin group received the basal diet + 100 mg anemonin/kg diet. After 21 d of feeding, the LPS- and anemonin-treated piglets received i.p. administration of LPS; the control group received saline. At 4 h post-injection, jejunum samples were collected. The results showed that supplemental anemonin increased villus height and transepithelial electrical resistance, and decreased crypt depth and paracellular flux of dextran (4 kDa) compared with the LPS group. Moreover, anemonin increased tight junction claudin-1, occludin and ZO-1 expression in the jejunal mucosa, compared with LPS group. Anemonin also decreased TNF-α, IL-6, IL-8 and IL-1β mRNA expression. Supplementation with anemonin also increased TGF-β1 mRNA and protein expression, Smad4 and Smad7 mRNA expressions, and epidermal growth factor and epidermal growth factor receptor (EGFR) mRNA expression in the jejunal mucosa. These findings suggest that dietary anemonin attenuates LPS-induced intestinal injury by improving mucosa restoration, alleviating intestinal inflammation and influencing TGF-β1 canonical Smads and EGFR signaling pathways.
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Affiliation(s)
- Kan Xiao
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
| | - Shu Ting Cao
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
| | - Le Fei Jiao
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
| | - Fang Hui Lin
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
| | - Li Wang
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
| | - Cai Hong Hu
- Animal Science College, Zhejiang University, The Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou, 310058, China
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Zhou X, Lin X, Xiong Y, Jiang L, Li W, Li J, Wu L. Chondroprotective effects of palmatine on osteoarthritis in vivo and in vitro: A possible mechanism of inhibiting the Wnt/β-catenin and Hedgehog signaling pathways. Int Immunopharmacol 2016; 34:129-138. [DOI: 10.1016/j.intimp.2016.02.029] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 02/20/2016] [Accepted: 02/23/2016] [Indexed: 10/22/2022]
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Zhao F, Guochun L, Yang Y, Shi L, Xu L, Yin L. A network pharmacology approach to determine active ingredients and rationality of herb combinations of Modified-Simiaowan for treatment of gout. JOURNAL OF ETHNOPHARMACOLOGY 2015; 168:1-16. [PMID: 25824593 DOI: 10.1016/j.jep.2015.03.035] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2014] [Revised: 01/25/2015] [Accepted: 03/10/2015] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Modified Simiaowan (MSW) is a traditional Chinese medicine (TCM) formula and is widely used as a clinically medication formula for its efficiency in treating gouty diseases.To predict the active ingredients in MSW and uncover the rationality of herb combinations of MSW. MATERIALS AND METHODS Three drug-target networks including the "candidate ingredient-target network" (cI-cT) that links the candidate ingredients and targets, the "core ingredient-target-pathway network" connecting core potential ingredients and targets through related pathways, and the "rationality of herb combinations of MSW network", which was derived from the cI-cT network, were developed to dissect the active ingredients in MSW and relationship between ingredients in herb combinations and their targets for gouty diseases. On the other hand, herbal ingredients comparisons were also conducted based on six physicochemical properties to investigate whether the herbs in MSW are similar in chemicals. Moreover, HUVEC viability and expression levels of ICAM-1 induced by monosodium urate (MSU) crystals were assessed to determine the activities of potential ingredients in MSW. RESULTS Predicted by the core ingredient-target-pathway network, we collected 30 core ingredients in MSW and 25 inflammatory cytokines and uric acid synthetase or transporters, which are effective for gouty treatment through some related pathways. Experimental results also confirmed that those core ingredients could significantly increase HUVEC viability and attenuate the expression of ICAM-1, which supported the effectiveness of MSW in treating gouty diseases. Moreover, heat-clearing and dampness-eliminating herbs in MSW have similar physicochemical properties, which stimulate all the inflammatory and uric acid-lowing targets respectively, while the core drug and basic prescription in MSW stimulate the major and almost all the core targets, respectively. CONCLUSION Our work successfully predicts the active ingredients in MSW and explains the cooperation between these ingredients and corresponding targets through related pathways for gouty diseases, and provides basis for an alternative approach to investigate the rationality of herb combinations of MSW on the network pharmacology level, which might be beneficial to drug development and applications.
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Affiliation(s)
- Fangli Zhao
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Li Guochun
- College of Preclinical Medical, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Yanhua Yang
- Changzhou Seventh People's Hospital, Changzhou 213011, Jiangsu, China
| | - Le Shi
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Li Xu
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China
| | - Lian Yin
- College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China.
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Liu Y, Bao L, Xuan L, Song B, Lin L, Han H. Chebulagic acid inhibits the LPS-induced expression of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation. Exp Ther Med 2015; 10:263-268. [PMID: 26170946 DOI: 10.3892/etm.2015.2447] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2014] [Accepted: 04/13/2015] [Indexed: 01/17/2023] Open
Abstract
Inflammatory response in the vasculature, including the overexpression of tumor necrosis factor (TNF)-α and interleukin (IL)-1β, has been demonstrated to increase the risk of thrombosis development. Chebulagic acid (CA) is a key chemical component in the traditional Mongolian anti-thrombotic drug Garidi-13, and has been suggested to exert anti-inflammatory and anti-infective effects. The present study aimed to evaluate the regulatory impact of CA on a number of biological processes, including lipopolysaccharide (LPS)-induced inflammation, LPS-promoted mitogen-activated protein kinase (MAPK) activation and the expression of toll-like receptor (TLR)4 in EA.hy926 human endothelial cells. The results indicated that CA significantly inhibited the LPS-induced upregulation of TNF-α and IL-1β in a dose- and time-dependent manner. Furthermore, LPS-activated MAPK signaling was inhibited by CA treatment in the EA.hy926 cells. However, TLR4, which serves a key function in LPS-induced inflammation as the receptor of LPS, was not regulated by the CA treatment. In summary, the results of the present study indicate that CA inhibits the LPS-induced promotion of TNF-α and IL-1β in endothelial cells by suppressing MAPK activation, which may contribute to the anti-thrombotic effect of Garidi-13.
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Affiliation(s)
- Yueying Liu
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
| | - Luer Bao
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
| | - Liying Xuan
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
| | - Baohua Song
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
| | - Lin Lin
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
| | - Hao Han
- Teaching and Research Section of Physiology and Pathophysiology, Medical College, Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia 028041, P.R. China
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Hu Y, He K, Wang X. Role of Chinese herbal medicinal ingredients in secretion of cytokines by PCV2-induced endothelial cells. J Immunotoxicol 2015; 13:141-7. [PMID: 25721049 DOI: 10.3109/1547691x.2015.1017624] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
While T-lymphocytes are the major cell type responsible for host responses to a virus (including induction of inflammatory responses to aid in ultimate removal of virus), other cells, including macrophages, epithelial and dendritic cells also have key roles. Endothelial cells also play important roles in physiologic/pathologic processes, like inflammation, during viral infections. As endothelial cells can be activated to release various endogenous compounds, including some cytokines, ex vivo measures of cytokine formation by the cells can be used to indirectly assess any potential endothelial dysfunction in situ. The research presented here sought to investigate potential immunolomodulatory effects of five saponins on endothelial cells: Saikosaponins A (SSA) and D (SSD), Panax Notoginseng Saponin (PNS) and Notoginsenoside R1 (SR1) and Anemoside B4 (AB4). For this, cells (porcine iliac artery endothelial line) were challenged with a virus isolate PCV2-AH for 24 h and then treated with the test saponin (at 1, 5 or 10 μg/ml) for an additional 24 h at 37 °C. The culture supernatants were then collected and analyzed for interleukin (IL)-2, -4 and -10, as well as interferon (IFN)-γ by ELISA. The results revealed that PNS and SR1 inhibited the production of IL-4; PNS, SR1 and AB4 inhibited the secretion of IL-10; SSA, SSD and PNS up-regulated IL-2 expression; SSA and SSD increased the level of IFNγ. All these changes were significant. Taken together, the data suggested these saponins might potentially have a capacity to regulate immune responses in vivo via changes in production of these select cytokines by infected endothelial cells. Nevertheless, the impact of these agents on other key cell types involved in anti-viral responses, including T-lymphocytes, remains to be determined.
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Affiliation(s)
- Yiyi Hu
- a Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing, PR China, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses , Yangzhou , PR China
| | - Kongwang He
- a Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing, PR China, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses , Yangzhou , PR China
| | - Xiaomin Wang
- a Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology of Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Nanjing, PR China, and Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses , Yangzhou , PR China
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Abstract
AbstractHelleborus (family Ranunculaceae) are well-known as ornamental plants, but less known for their therapeutic benefits. Over the past few years, Helleborus sp. has become a subject of interest for phytochemistry, pharmacology and other medical research areas. On the basis of their usefulness in traditional medicine, it was assumed that their biochemical profile could be a source of metabolites with the potential to overcome critical medical issues. There are studies involving natural extracts from these species which demonstrate that Helleborus plants are a valuable source of chemical compounds with great medical potential. Some phytochemicals produced by these species have been separated and identified a few decades ago: hellebrin, deglucohellebrin, 20-hydroxyecdysone and protoanemonin. Lately, many other active compounds have been reported and considered as promising remedies for severe diseases such as cancer, ulcer, diabetes and also for common medical problems such as toothache, eczema, low immunity and arthritis. This paper is an overview of the Helleborus genus focusing on some recentlydiscovered compounds and their potential for finding new drugs and useful biochemicals derived from these species.
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Choi HJ, Chung TW, Kim JE, Jeong HS, Joo M, Cha J, Kim CH, Ha KT. Aesculin inhibits matrix metalloproteinase-9 expression via p38 mitogen activated protein kinase and activator protein 1 in lipopolysachride-induced RAW264.7 cells. Int Immunopharmacol 2012; 14:267-74. [DOI: 10.1016/j.intimp.2012.07.013] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Revised: 06/24/2012] [Accepted: 07/20/2012] [Indexed: 11/16/2022]
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Ma BL, Ma YM, Gao CL, Wu JS, Qiu FR, Wang CH, Wang XH. Lipopolysaccharide increased the acute toxicity of the Rhizoma coptidis extract in mice by increasing the systemic exposure to Rhizoma coptidis alkaloids. JOURNAL OF ETHNOPHARMACOLOGY 2011; 138:169-174. [PMID: 21924335 DOI: 10.1016/j.jep.2011.08.074] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Revised: 08/23/2011] [Accepted: 08/30/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Rhizoma coptidis is used as an antidysenteric in clinics in China. However, patients suffering from dysentery are susceptible to the acute toxicity of Rhizoma coptidis. The current study investigates the effects of lipopolysaccharide (LPS), which are a key pathogenic factor in dysentery, on the acute toxicity of a Rhizoma coptidis extract in mice; possible mechanisms are proposed. MATERIALS AND METHODS Acute toxicity and pharmacokinetic experiments in mice were conducted. The plasma concentration of Rhizoma coptidis alkaloids in mice was determined using liquid chromatography/tandem mass spectrometry. The activity of acetylcholinesterase (AChE) in the tissue homogenate was determined using an AChE determination kit. RESULTS Pretreatment with LPS for 16 h increased the acute toxicity of the oral Rhizoma coptidis extract. Systemic exposure to Rhizoma coptidis alkaloids was also increased by LPS pretreatment. Neostigmine significantly increased whereas pyraloxime methylchloride reduced the acute toxicity of the Rhizoma coptidis extract. LPS pretreatment alone showed no significant effect on the activity of thoracoabdominal diaphragm AChE. However, it enhanced the inhibitory effect of the Rhizoma coptidis extract. LPS pretreatment did not affect the acute toxicity of various dosages of tail vein-injected berberine. CONCLUSIONS LPS increased the acute toxicity of the oral Rhizoma coptidis extract in mice by increasing the systemic exposure to the Rhizoma coptidis alkaloids.
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Affiliation(s)
- Bing-Liang Ma
- Laboratory of Pharmacokinetics, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
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Hu PF, Chen WP, Tang JL, Bao JP, Wu LD. Protective effects of berberine in an experimental rat osteoarthritis model. Phytother Res 2010; 25:878-85. [PMID: 21108488 DOI: 10.1002/ptr.3359] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2010] [Revised: 10/15/2010] [Accepted: 10/18/2010] [Indexed: 01/06/2023]
Abstract
Berberine shows anticancer, antibacterial, antiinflammatory and antioxidant effects and may be useful in many clinical applications. The effects of berberine on articular cartilage metabolism remain unknown, so this study was performed to evaluate these effects in vitro and in vivo. For the in vitro work, rat articular chondrocytes were cultured in a monolayer and matrix metalloproteinase-1 (MMP-1), -3, -13 and tissue inhibitor of metalloproteinase (TIMP-1) expression was evaluated by real-time quantitative PCR. Nitric oxide (NO) levels were determined using the Griess reaction, and glycosaminoglycan (GAG) release was measured using the dimethylmethylene blue method. For the in vivo work, berberine was administered by intraarticular injection, and the effects on MMPs and TIMP-1 were examined at the gene and protein levels. Berberine was found to inhibit the expression of MMP-1, -3 and -13, and increased the level of TIMP-1 at the mRNA level in a dose-dependent manner. In IL-1β-induced rat articular chondrocytes, berberine decreased IL-1β-induced GAG release and NO production. Meanwhile, high-dose berberine exhibited an anticatabolic effect in an IL-1β-induced rat osteoarthritis (OA) model. These findings suggest that berberine may play a protective role in the development of OA and may be useful in the treatment of OA.
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Affiliation(s)
- Peng-fei Hu
- Department of Orthopaedic Surgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, PR China
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