Kinsenoside inhibits the inflammatory mediator release in a type-II collagen induced arthritis mouse model by regulating the T cells responses

Hung-Bo Hsiao,Ho Lin,Wen-Chuan Lin,Jin-Bin Wu,Chang-Chi Hsieh

doi:10.1186/s12906-016-1054-8

Abstract

BackgroundAnoectochilus formosanus has been used as a Chinese folk medicine and is known as the “King of medicine” in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. Kinsenoside is an essential and active compound of A. formosanus (Orchidaceae). However, the anti-arthritic activity of kinsenoside has still not been demonstrated. In the present study, we confirmed that the kinsenoside treatment rheumatoid arthritis induced by collagen-induced arthritis in mice.MethodsMale DBA/1 J mice were immunized by intradermal injection of 100 μg of type II collagen in CFA. Kinsenoside was administered orally at a dose of 100 and 300 mg/kg once a day after 2nd booster injection. Paw swelling, arthritic score and histological change were measured. ELISA was used to measure cytokines including tumor necrosis factor alpha (TNF-α), interleukin-10 (IL-10), interleukin-17 (IL-17) and interferon-γ (IFN-γ) in the splenocyte according to the manufacturer’s instructions.ResultsCompared with model group, kinsenoside significantly inhibited paw edema and decreased the arthritis score and disease incidence. Histopathological examination demonstrated that kinsenoside effectively protected bone and cartilage of knee joint from erosion, lesion and deformation versus those from the CIA group. Kinsenoside also decreased IL-1β, TNF-α, and MMP-9 expression, and increased the expression of IL-10 in inflamed joints. The administration of kinsenoside significantly suppressed levels of TNF-α, IFN-γ, and IL-17, but increased concentrations of IL-10 in the supernatants of each of the splenocytes in CIA mice compared with that in the H2O-treated mice with CIA. Using flow cytometric analysis, we demonstrated that kinsenoside increases the population of CD4+CD25+ regulatory T cells, thereby inhibiting the Th1 cell and B cell populations. Anticollagen IgG1 and IgG2a levels decreased in the serum of kinsenoside-treated mice.ConclusionsThese results suggest that the administration of kinsenoside effectively suppressed inflammatory mediators’ production and bone erosion in mice with collagen-induced arthritis showing the potential as an anti-arthritis agent.

Highlights

Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the “King of medicine” in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis
Effects of kinsenoside on mice with collagen-induced arthritis We used a mouse CIA model to determine whether kinsenoside exerts suppressive effects on Rheumatoid arthritis (RA)
The expression of IL-10 in the joints of mice with CIA was significantly lower than that of healthy mice (Fig. 3), and the administration of 300 mg/kg of kinsenoside increased IL-10 gene expression to levels comparable with those of the H2O-treated group. These results suggested that kinsenoside prevented the destruction of connective tissues by simultaneously augmenting IL-10 production and reducing IL-1β, TNF-α, and matrix metalloproteinases (MMP)-9 production at inflammatory sites in mice with RA

Summary

Introduction

Anoectochilus formosanus has been used as a Chinese folk medicine and is known as the “King of medicine” in Chinese society due to its versatile pharmacological effects such as anti-hypertension, anti-diabetes, anti-heart disease, anti-lung and liver diseases, anti-nephritis and anti-Rheumatoid arthritis. According to the guidelines of the American College of Rheumatology, patients with newly diagnosed RA are strongly recommended to begin dual treatment by using NSAIDs to relieve nociceptive pain and control inflammation, and DMARDs to reduce disease activity, prevent joint deformity, and improve joint function [6]. The administration of these drugs is limited by the severe adverse effects of the drugs, such as gastrointestinal lesions, cardiovascular complications, and reproductive toxicity [7]. This growing interest in alternative medical practices clearly indicates the necessity for more safe and effective anti-RA botanicals used in traditional medicine

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Conclusion