Abstract
To observe the therapeutic effect of berberine (BBR) on non-alcoholic steatohepatitis (NASH) in rats and the underlying mechanism. A rat model of NASH was established by a high-fat diet, and BBR was used as treatment. Haematoxylin-eosin staining and Oil Red O staining were used to observe the pathological changes in the liver tissue. Western blotting and real-time PCR were used to measure the mRNA and protein levels in the liver. Flow cytometry was performed to detect the number of intrahepatic lymphocyte subtypes. The expression of pro-inflammatory cytokines in the peripheral blood was measured by ELISA. An automatic biochemical method was used to examine the level of blood lipids in the blood. Compared with the rats in the model group, the rats in the BBR group showed significantly improved liver histopathology and serum pro-inflammatory cytokines and free fatty acid (FFA) levels. Moreover, the protein and mRNA expression of chemerin, CMKLR1 and CCR2 in the liver were obviously reduced by BBR treatment. In addition, the high-fat diet remarkably reduced the intrahepatic Treg/Th17 ratio, which could be recovered by BBR treatment. Berberine can ameliorate non-alcoholic steatohepatitis, and its mechanism may be related to restoring the Treg/Th17 ratio, regulating the chemerin/CMKLR1 signalling pathway to reduce liver inflammation and reducing lipid deposition.
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Funding
The study was supported by the Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2018KY322), the Scientific Research Foundation of State Administration of Traditional Chinese Medicine of Zhejiang Province (2016ZB004, 2019ZA024, 2020ZB056) and the Program of Zhejiang Province Natural Science Foundation (LQ20H290002).
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Liyan Wu designed the experiment and revised the manuscript. Zengsheng Lu and Fengbin Lu drafted the article and analysed the data. Zhiyun Chen revised it critically for important intellectual content. Liyan Wu, Fengbin Lu, Beihui He and Maoxiang Yan performed the experiment. All authors promise all data are generated in-house, and did not use a paper mill. All authors read and approved the final manuscript.
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The experimental protocols were established according to the Declaration of Helsinki. All animals used in this study complied with the ARRIVE guidelines and the protocols were approved by the institutional animal committee of Zhejiang Academy of Traditional Chinese Medicine.
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Zengsheng Lu and Fengbin Lu share first authorship.
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Lu, Z., Lu, F., Wu, L. et al. Berberine attenuates non-alcoholic steatohepatitis by regulating chemerin/CMKLR1 signalling pathway and Treg/Th17 ratio. Naunyn-Schmiedeberg's Arch Pharmacol 394, 383–390 (2021). https://doi.org/10.1007/s00210-020-01914-1
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DOI: https://doi.org/10.1007/s00210-020-01914-1