Therapeutic effect of various ginsenosides on rheumatoid arthritis

Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is...

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Main Authors: Meng Zhang, Hongwei Ren, Kun Li, Shengsheng Xie, Ru Zhang, Longlong Zhang, Jiaxuan Xia, Xing Chen, Xilin Li, Jianxin Wang
Format: Article
Language:English
Published: BMC 2021-05-01
Series:BMC Complementary Medicine and Therapies
Subjects:
Online Access:https://doi.org/10.1186/s12906-021-03302-5
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author Meng Zhang
Hongwei Ren
Kun Li
Shengsheng Xie
Ru Zhang
Longlong Zhang
Jiaxuan Xia
Xing Chen
Xilin Li
Jianxin Wang
author_facet Meng Zhang
Hongwei Ren
Kun Li
Shengsheng Xie
Ru Zhang
Longlong Zhang
Jiaxuan Xia
Xing Chen
Xilin Li
Jianxin Wang
author_sort Meng Zhang
collection DOAJ
description Abstract Background Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. Methods The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. Results All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. Conclusion Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.
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spelling doaj.art-f36e1a9ed4424e52a70cfe8fc9a5a2172022-12-21T19:46:45ZengBMCBMC Complementary Medicine and Therapies2662-76712021-05-0121111210.1186/s12906-021-03302-5Therapeutic effect of various ginsenosides on rheumatoid arthritisMeng Zhang0Hongwei Ren1Kun Li2Shengsheng Xie3Ru Zhang4Longlong Zhang5Jiaxuan Xia6Xing Chen7Xilin Li8Jianxin Wang9School of Pharmacy, Shanghai University of Traditional Chinese MedicineDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationScience and Technology Innovation Center, Guangzhou University of Chinese MedicineDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationSchool of Pharmacy, Shanghai University of Traditional Chinese MedicineDepartment of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of EducationAbstract Background Rheumatoid arthritis (RA) is an autoimmune disease which causes disability and threatens the health of humans. Therefore, it is of great significance to seek novel effective drugs for RA. It has been reported that various ginsenoside monomers are able to treat RA. However, it is still unclear which ginsenoside is the most effective and has the potential to be developed into an anti-RA drug. Methods The ginsenosides, including Rg1, Rg3, Rg5, Rb1, Rh2 and CK, were evaluated and compared for their therapeutic effect on RA. In in vitro cell studies, methotrexate (MTX) and 0.05% dimethyl sulfoxide (DMSO) was set as a positive control group and a negative control group, respectively. LPS-induced RAW264.7 cells and TNF-α-induced HUVEC cells were cultured with MTX, DMSO and six ginsenosides, respectively. Cell proliferation was analyzed by MTT assay and cell apoptosis was carried out by flow cytometry. CIA mice model was developed to evaluate the therapeutic efficacy of ginsenosides. The analysis of histology, immunohistochemistry, flow cytometry and cytokine detections of the joint tissues were performed to elucidate the action mechanisms of ginsenosides. Results All six ginsenosides showed good therapeutic effect on acute arthritis compared with the negative control group, Ginsenoside CK provided the most effective treatment ability. It could significantly inhibit the proliferation and promote the apoptosis of RAW 264.7 and HUVEC cells, and substantially reduce the swelling, redness, functional impairment of joints and the pathological changes of CIA mice. Meanwhile, CK could increase CD8 + T cell to down-regulate the immune response, decrease the number of activated CD4 + T cell and proinflammatory M1-macrophages, thus resulting in the inhibition of the secretion of proinflammatory cytokine such as TNF-α and IL-6. Conclusion Ginsenoside CK was proved to be a most potential candidate among the tested ginsenosides for the treatment of RA, with a strong anti-inflammation and immune modulating capabilities.https://doi.org/10.1186/s12906-021-03302-5CIAGinsenoside compound KPanax ginsengRheumatoid arthritisTherapeutic effect
spellingShingle Meng Zhang
Hongwei Ren
Kun Li
Shengsheng Xie
Ru Zhang
Longlong Zhang
Jiaxuan Xia
Xing Chen
Xilin Li
Jianxin Wang
Therapeutic effect of various ginsenosides on rheumatoid arthritis
BMC Complementary Medicine and Therapies
CIA
Ginsenoside compound K
Panax ginseng
Rheumatoid arthritis
Therapeutic effect
title Therapeutic effect of various ginsenosides on rheumatoid arthritis
title_full Therapeutic effect of various ginsenosides on rheumatoid arthritis
title_fullStr Therapeutic effect of various ginsenosides on rheumatoid arthritis
title_full_unstemmed Therapeutic effect of various ginsenosides on rheumatoid arthritis
title_short Therapeutic effect of various ginsenosides on rheumatoid arthritis
title_sort therapeutic effect of various ginsenosides on rheumatoid arthritis
topic CIA
Ginsenoside compound K
Panax ginseng
Rheumatoid arthritis
Therapeutic effect
url https://doi.org/10.1186/s12906-021-03302-5
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