1. Academic Validation
  2. Qushi Huayu decoction attenuated hepatic lipid accumulation via JAK2/STAT3/CPT-1A-related fatty acid β-oxidation in mice with non-alcoholic steatohepatitis

Qushi Huayu decoction attenuated hepatic lipid accumulation via JAK2/STAT3/CPT-1A-related fatty acid β-oxidation in mice with non-alcoholic steatohepatitis

  • Pharm Biol. 2022 Dec;60(1):2124-2133. doi: 10.1080/13880209.2022.2134898.
QinMei Sun 1 Xin Wang 1 Xin Xin 1 ZiMing An 1 YiYang Hu 1 2 3 Qin Feng 1 2 3
Affiliations

Affiliations

  • 1 Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • 2 Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China.
  • 3 Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai, China.
Abstract

Context: Qushi Huayu decoction (QHD) has been clinically used for treating non-alcoholic steatohepatits (NASH). However, little is known about the effect of QHD on fatty acid β-oxidation (FAO)-dependent lipid consumption.

Objective: To investigate the mechanism of QHD on FAO-related hepatic lipid accumulation.

Materials and methods: Male C57BL/6J mice were randomly divided into 5 groups (n = 8): normal diet and drinking water (CON), high-fat and high-carbohydrate diet (HFHC), QHD-L (2.875 g/kg), QHD-H (11.5 g/kg) and obeticholic acid (OCA) (10 mg/kg/day) groups. All mice freely consumed an appropriate diet for 18 weeks, and QHD was orally administered in the last 6 weeks. Measurements of general condition, hepatic histopathology, and JAK2/STAT3 signalling pathway were taken.

Results: QHD significantly improved NASH in mice, as reflected by improving serum glucolipid metabolism, decreasing Enzymes activities, reducing hepatic triglyceride (HFHC: 70.07 ± 2.81 mg/g; QHD-H: 34.06 ± 5.74 mg/g) and ameliorating hepatic steatosis, inflammation in pathology. Further, both the mRNA and protein level of hepatic CPT-1A (p < 0.05), a rate-limiting Enzyme of FAO, increased drastically following QHD treatment. Meanwhile, the content of hepatic ATP (p < 0.05) increased significantly after treatment with QHD. Further mechanistic results revealed that both the total protein and nuclear p-STAT3 in the liver were significantly down-regulated after QHD treatment. The protein level of hepatic p-JAK2 was significantly inhibited by QHD (p < 0.05 or p < 0.01).

Conclusions: QHD could attenuate lipid accumulation by increasing JAK2/STAT3/CPT-1A-related FAO, which provides a scientific basis for the clinical application of QHD in treating NASH.

Keywords

NASH; hepatic steatohepatitis; lipid metabolism; traditional Chinese medicine.

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