Ban-xia-xie-xin-tang ameliorates hepatic steatosis by regulating Cidea and Cidec expression in HFD-fed mice

Qing-Song Xia; Yang Gao; Wu Wen-Bin; Fan Wu; Hui Dong; Li-Jun Xu; Ke Fang; Mei-Lin Hu; Fen Yuan; Fu-Er Lu; Jing Gong

doi:10.1016/j.phymed.2022.154351

Ban-xia-xie-xin-tang ameliorates hepatic steatosis by regulating Cidea and Cidec expression in HFD-fed mice

Phytomedicine. 2022 Oct:105:154351. doi: 10.1016/j.phymed.2022.154351. Epub 2022 Jul 21.

Authors

Qing-Song Xia¹, Yang Gao², Wu Wen-Bin¹, Fan Wu¹, Hui Dong¹, Li-Jun Xu¹, Ke Fang³, Mei-Lin Hu³, Fen Yuan³, Fu-Er Lu⁴, Jing Gong⁵

Affiliations

¹ Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
² Beijing Tcmages Pharmaceutical Co., Ltd, Beijing 100000, China.
³ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
⁴ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: felutjh88@163.com.
⁵ Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China. Electronic address: jgongtcm@126.com.

PMID: 35908522
DOI: 10.1016/j.phymed.2022.154351

Abstract

Background: Ban-xia-xie-xin-tang (BXXXT) has been applied in treating metabolic diseases, such as nonalcohol fatty liver disease, diabetes mellitus, and obesity. However, the underlying molecular mechanism of BXXXT in treating diabetes mellitus is unknown.

Purpose: To clarify the underlying molecular mechanism of BXXXT in alleviating hepatic steatosis in high-fat diet (HFD)-fed mice.

Methods: After 12 weeks of HFD treatment, mice were administered BXXXT for 4 weeks. The main chemical components of BXXXT were identified by UPLC-TQ-MS/MS. Indicators associated with insulin resistance and lipid metabolism were detected. The effect of improving glucose and lipid metabolism between BXXXT and the different components was compared. Differentially expressed genes (DEGs) were identified by hepatic transcriptomics. Key DEGs and proteins were further detected by real-time quantitative polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence staining. LDs and mitochondria were detected by transmission electron microscopy.

Results: First of all, our data demonstrated that the capacity to improve glucose and lipid metabolism for BXXXT was significantly superior to different components of BXXXT. BXXXT was found to improve HFD-induced insulin resistance. Moreover, BXXXT decreased weight, serum/hepatic triglycerides, total cholesterol, and FFAs to alleviate HFD-induced hepatic steatosis. According to the results of the hepatic transcription, Cidea and Cidec were identified as critical DEGs for promoting LD fusion and reducing FFAs β-oxidation in mitochondria and peroxisome resulting in hepatic steatosis, which was reversed by BXXXT.

Conclusion: BXXXT ameliorates HFD-induced hepatic steatosis and insulin resistance by increasing Cidea and Cidec-mediated mitochondrial and peroxisomal fatty acid oxidation, which may provide a potential strategy for therapy of NAFLD and T2DM.

Keywords: Ban-xia-xie-xin-tang; Cidea; Cidec; Fatty acid oxidation; Hepatic steatosis.

MeSH terms

Animals
Apoptosis Regulatory Proteins
Diet, High-Fat
Fatty Acids, Nonesterified
Glucose
Insulin Resistance*
Liver
Mice
Mice, Inbred C57BL
Non-alcoholic Fatty Liver Disease*
Pinellia*
Tandem Mass Spectrometry

Substances

Apoptosis Regulatory Proteins
Cidea protein, mouse
Fatty Acids, Nonesterified
Glucose