期刊
PHARMACEUTICAL BIOLOGY
卷 60, 期 1, 页码 2124-2133出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/13880209.2022.2134898
关键词
NASH; traditional Chinese medicine; lipid metabolism; hepatic steatohepatitis
资金
- National Natural Science Foundation of China [82174040, 82174186, 81973456]
- National Science & Technology Major Project Key New Drug Creation and Manufacturing Program, China [2019ZX09201001-001-002]
- Shanghai Science and Technology Development Funds [18401933100]
- Innovative Projects of Shanghai University of Traditional Chinese Medicine [Y2021081]
The study showed that Qushi Huayu decoction could attenuate lipid accumulation by increasing the fatty acid beta-oxidation (FAO) dependent on the JAK2/STAT3/CPT-1A pathway, providing a scientific basis for its clinical application in the treatment of non-alcoholic steatohepatits.
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 beta-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.
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