Abstract
Xiaochaihutang (XCHT) is one of classic prescriptions in Treatise on Febrile Diseases in China which was reported to have the effect of anti-hepatic fibrosis in vivo. Activation of hepatic stellate cells (HSCs) is now well established as a central driver of fibrosis in liver injury. Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important element for anti-oxidative damage which is one of the key factors responsible for occurrence. This study was to investigate the effect of XCHT compound serum on HSCs activation and focus on the Nrf2 pathway. Rats in treatment groups were given the appropriate doses of XCHT granules (5 g/kg) and Silybin (50 mg/kg) for 6 days, and the serum were obtained. The compound serum was used to intervene HSCs. The results found that XCHT compound serum significantly inhibited the proliferation of HSCT6 cells. The number of α-SMA positive stained cells in HSCT6 cells and the content of Collagen type I (collagen-I) in supernatant were significantly decreased indicating suppression of activated HSCs. Compared with the control group, the nuclear transcription of Nrf2 and the expressions of Nqo1, GCLC, and GCLM were significantly increased in XCHT group. However, the effects of XCHT were inhibited in Nrf2-siRNA transfected HSCT6 cells. These studies demonstrated that XCHT could inhibit HSCT6 cell proliferation and activation. The mechanism might be related to up-regulation of the Nrf2 pathway against oxidative stress.
Highlights
Liver fibrosis is the rate-limiting step in patients with liver disease on pathological transformation and mortality (Gandhi, 2017)
In order to investigate the effect of XCHT compound serum in Hepatic stellate cell line T6 (HSCT6) cells proliferation, cell viability was assessed with CCK8
Considering hepatic stellate cells (HSCs) proliferation and activation are the critical factor during liver fibrosis (Rockey, 2000; Fagone et al, 2015; Romanelli and Stasi, 2016), hepatic stellate cell line T6 cells were used in this study
Summary
Liver fibrosis is the rate-limiting step in patients with liver disease on pathological transformation and mortality (Gandhi, 2017). The excessive activation and proliferation of hepatic stellate cells (HSCs) give rise to extracellular matrix proteins during the pathogenesis of hepatic fibrosis, initiating matrix deposition in the liver (Campana and Iredale, 2015). More and more reports suggested that the pathogenesis of liver fibrosis was related to oxidative stress, which was marked by the intracellular accumulation of excessive reactive oxygen species (ROS), and the compelling evidence shows the involvement of ROS in the development of liver fibrosis inducing HSCs activation and fibrogenic potential (Novo and Parola, 2008; Xiaochaihutang Inhibits the Activation of HSCs. Novo et al, 2011; Puche et al, 2013). It was found that Nrf regulated the activity of the antioxidant enzymes and the expression of down-stream genes to protect against CCl4induced liver fibrosis (Li et al, 2017)
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