Protective Effect of Danshen Zexie Decoction Against Non-Alcoholic Fatty Liver Disease Through Inhibition of ROS/NLRP3/IL-1β Pathway by Nrf2 Signaling Activation

Abstract

Lipid metabolism disorders are a prominent characteristic in the pathological development of non-alcoholic fatty liver disease (NAFLD). Danshen zexie decoction (DZD) is a Chinese herbal medicine that is based on zexie decoction and has an effect of regulating lipid mechanism. However, the anti-NAFLD effect and mechanism of DZD remain unclear. In this study, we observed the therapeutic effect of DZD on NAFLD rats and investigated its possible mechanisms. Sixty Sprague Dawley rats were randomly assigned to six groups: control group, model group, Yishanfu (polyene phosphatidylcholine) group, and low, medium and high-dose DZD groups. High-fat diet (HFD) was fed to the rats to establish an NAFLD model, and each treatment group was given corresponding drugs at the same time for eight consecutive weeks. The results revealed that the obvious lipid metabolism disorder and liver injury induced by HFD were alleviated by treatment with DZD, which was verified by decreased serum TC, TG, ALT, AST, liver TC, TG, and FFA, as well as the alleviation of hepatic steatosis. The production of ROS in rats was reduced after treatment with DZD. The SOD activity and GSH content were increased with DZD treatment, while the MDA level was decreased. The administration of DZD could decrease serum IL-1β and IL-18 contents. Moreover, DZD upregulated the expressions of Nrf2, HO-1, GCLC, and GCLM, while it suppressed the expressions of NLRP3, caspase-1, GSDMD, and GSDMD-N. In conclusion, the data showed that DZD can reduce lipid accumulation, alleviate oxidative stress and inflammation, and inhibit pyroptosis in NAFLD rats, which might be ascribed to suppression of the ROS/NLRP3/IL-1β signaling pathway by activation of Nrf2. Overall, these results indicated that DZD is expected to be a therapeutic drug for NAFLD.

A Flavonoid Glycoside Compound from Siraitia grosvenorii with Anti-Inflammatory and Hepatoprotective Effects In Vitro

“…Under controlled conditions, Nrf2 binds to related proteins and exists in an inactive state in the cytoplasm. However, when activated by a stimulus, Nrf2 detaches and translocates to the nucleus, binds to the ARE, and then activates the transcription of downstream antioxidant genes, which could assist in reducing ROS levels and inhibiting oxidative stress [36,37]. HO-1 attenuates oxidative damage and serves as a downstream gene for Nrf2 [38].…”

Integrated traditional Chinese and Western medicine in the prevention and treatment of non-alcoholic fatty liver disease: future directions and strategies

“…Zexie Baizhu Decoction impedes lipogenesis and promotes fatty acid oxidation to alleviate lipid disorders and protect the liver in NAFLD [ 151 ]. Danshen Zexie Decoction suppresses the ROS/NLRP3/IL-1β signaling pathway by activating Nrf2 to reduce lipid accumulation and alleviate oxidative stress, inflammation and pyroptosis in NAFLD rats [ 152 ]. Qige Decoction inhibits hepatic steatosis by reducing hepatic insulin resistance and triglyceride biosynthesis via the PPP1R3C/SIK1 signaling axis [ 153 ].…”

Recent advances in pyroptosis, liver disease, and traditional Chinese medicine: A review

“…The activation of these genes leads to increased superoxide dismutase activity and elevated glutathione (GSH) levels, both of which can scavenge ROS. In turn, reduced ROS levels can inhibit NLRP3 and prevent caspase‐1‐mediated pyroptosis (Biao et al, 2022). Several studies have demonstrated that the Danshen Zexie Decoction (Biao et al, 2022), baicalin (Shi, Qiao, et al, 2022), and 6‐gingerol (Hong et al, 2020) block pyroptosis through the activation of the Nrf2 pathway, offering the potential to treat NAFLD, NASH, and sepsis‐induced LI.…”