The mechanism of Qingre Quzhuo capsule in the treatment of nonalcoholic steatohepatitis by inhibiting ferroptosis

LI Hua-jun, LV Shu-quan, WANG Li-xin, LIU Ai-ru, WANG Ya-nan, SU Xiu-hai, WANG Yuan-song

CangZhou Hospital of Integrated Traditional Chinese and Western Medicine, Cangzhou 314000, China

ARTICLE INFO

Article history:

Received 14 May 2023

Received in revised form 13 August 2023

Accepted 8 Oct 2023

Available online 14 Nov 2023

Keywords:

Non-alcoholic steatohepatitis

Qingre Quzhuo Capsule

Ferroptosis

GPX4

Antioxidation

ABSTRACT

Objective:To explore the effect of Qingre Quzhuo Capsule (QRQZ)in the treatment of nonalcoholic steato-hepatitis (NASH)and to explore its mechanism from the perspective of inhibiting ferroptosis.Methods: 60 C57BL/6J mice were randomly divided into 6 groups:Control, model, ferroptosis inhibitor (Fer-1, 10 mg/kg, gavage), low-dose QRQZ (QRQZL,482 mg/kg, gavage), medium-dose QRQZ(QRQZM, 964 mg/kg, gavage), and high-dose QRQZ(QRQZH, 1 929 mg/kg, gavage).The control group was given normal diet, and the other experimental groups were given MCD diet.The whole administration process lasted for 6 weeks.The body weight of mice was counted every week.After 6 weeks, the blood of mice was collected, and the serum was separated to determine ALT and AST.The liver of mice was weighed and fixed.The same part was stained with HE and Oil Red O to observe the pathological changes of liver tissue.The levels of TC, TG, total iron, GSH and GSSG in liver tissue were measured by kit.The expression of Gpx4 mRNA was detected by RT-qPCR, and the expression of FTH1, FTL and GPX4 protein was detected by Western blotting.Results:Compared with the model group, after treatment with Fer-1 and QRQZ, the body weight and liver index of NASH mice increased, the liver tissue lesions were alleviated, TC, TG, ALT and AST were improved, the liver tissue iron level decreased significantly, the relative levels of FTH1 and FTL proteins in-creased significantly, GSH/GSSG increased significantly, and the expression of Gpx4 mRNA and GPX4 protein increased significantly.Conclusion: QRQZ alleviates liver injury in NASH mice by promoting the expression of GSH/GPX4 antioxidant system and inhibiting ferroptosis.