p38 MAPK SIGNAL PATHWAY INVOLVED IN ANTI-INFLAMMATORY EFFECT OF CHAIHU-SHUGAN-SAN AND SHEN-LING-BAI-ZHU-SAN ON HEPATOCYTE IN NON-ALCOHOLIC STEATOHEPATITIS RATS|
Yang, QinHe; Xu, YongJian; Feng, GaoFei; Hu, ChaoFeng; Zhang, YuPei; Cheng, ShaoBing; Wang, YanPing & Gong, XiangWen
Background: Traditional Chinese Medicine (TCM), has over thousands-of-years history of use. Chaihu-Shugan-San (CSS), and
Shen-ling-bai-zhu-San (SLBZS), are famous traditional Chinese herbal medicine formulas, which have been used in China, for the treatment of
many chronic diseases.
Materials and Methods:This study investigated the anti-inflammatory effects of CSS and SLBZS on signaling molecules involved in p38
mitogen-activated protein kinase (p38 MAPK), pathway on hepatocytes of non-alcoholic steatohepatitis (NASH), rats induced by high fat diet.
SD male rats were randomly divided into 8 groups: negative control group, model control group, high (9.6g/kg/day)/low (3.2g/kg/day)-dose CSS
group, high (30g/kg/day)/low (10g/kg/day)-dose SLBZS group, high (39.6g/kg/day)/low (13.2g/kg/day)-dose integrated group. The rats of NASH
model were induced by feeding a high-fat diet. After 16, wks, Hepatocytes were isolated from 6, rats in each group by collagenase perfusion. The
liver histopathological changes and serum inflammatory cytokines TNF-α, IL-6 were determined. The proteins of TLR4, phosphor-p38 MAPK
and p38 MAPK involved in p38 MAPK signal pathway were assayed.
Results: The statistical data indicated the NASH model rats reproduced typical histopathological features of NASH in human. CSS and SLBZS
ameliorated lipid metabolic disturbance, attenuated NASH progression, decreased the levels of TNF-α and IL-6 in serum, as well as inhibited
TLR4 protein expression, p38 MAPK phosphorylation, and activation of p38 MAPK. In conclusion, CSS and SLBZS might work as a significant
anti-inflammatory effect on hepatocyte of NASH by inhibiting the activation of TLR4, p-p38 MAPK and p38 MAPK involved in p38 MAPK
Conclusion: To some extent, CSS and SLBZS may be a potential alternative and complementary medicine to protect against liver injury, alleviate
the inflammation reaction, moderate NASH progression.
p38 mitogen-activated protein kinase; Toll like receptor 4; Hepatocytes; Non-alcoholic Steatohepatitis; Traditional Chinese medicine