Abstract

Cynatratoside A (CyA) is a C21 Steroidal glycoside with pregnane skeleton isolated from the root of Cynanchum atratum Bunge (Asclepiadaceae). This study aimed to investigate the effects of CyA on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) and the underlying mechanism. CyA was orally administered to mice at 10 and 40 mg/kg 8 h before and 1 h after Con A treatment. The effects of CyA on Con A-induced spleen and liver in mice were assessed via histopathological changes, T lymphocyte amounts and the expressions of IL-1β and ICAM-1. Con A-induced L-02 hepatocytes were used to evaluate whether CyA (0.1–10 μM) can directly protect hepatocytes from cytotoxicity and the possible mechanism. The results revealed that CyA treatment could significantly improve the histopathological changes of spleen and liver, reduce the proliferation of splenic T lymphocytes, and decrease the expressions of IL-1β and ICAM-1 in liver. The experiment in vitro showed that CyA inhibited Con A-induced hepatotoxicity in a concentration-dependent manner. CyA (10 μM) significantly increased/decreased the expression of Bcl-2/Bax and reduced the levels of cleaved caspases-9 and -3. Our study demonstrated for the first time that CyA has a significant protective effect on Con A-induced AIH by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis.

Highlights

  • The liver is the largest digestive gland and metabolic organ in the human body

  • Our study demonstrated for the first time that Cynatratoside A (CyA) has a significant protective effect on concanavalin A (Con A)-induced autoimmune hepatitis (AIH) by inhibiting the activation and adhesion of T lymphocytes and blocking hepatocyte apoptosis

  • AIH is closely associated with the center of the body

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Summary

Introduction

The liver is the largest digestive gland and metabolic organ in the human body. It has the functions of detoxification, immunity and hematopoiesis [1,2]. The liver is a vital organ and supports almost every other organ in the body. More and more evidences have shown that the liver plays an important role in immune response, immune regulation and immune tolerance [3,4,5]. The liver is prone to many diseases, the most common of which is hepatitis [6,7]. Viral hepatitis is the most common, non-viral factors such as autoimmunity can cause hepatitis

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