Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner

Yulian Chen; Huanguo Jiang; Zhikun Zhan; Jindi Lu; Tanwei Gu; Ping Yu; Weimin Liang; Xi Zhang; Shilong Zhong; Lan Tang

doi:10.1016/j.jpha.2023.08.010

Volume 13 Issue 11

Nov. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(11): 1281-1295

Yulian Chen, Huanguo Jiang, Zhikun Zhan, Jindi Lu, Tanwei Gu, Ping Yu, Weimin Liang, Xi Zhang, Shilong Zhong, Lan Tang. Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1281-1295. doi: 10.1016/j.jpha.2023.08.010

Citation:

Yulian Chen, Huanguo Jiang, Zhikun Zhan, Jindi Lu, Tanwei Gu, Ping Yu, Weimin Liang, Xi Zhang, Shilong Zhong, Lan Tang. Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1281-1295. doi: 10.1016/j.jpha.2023.08.010

Citation:

Yulian Chen, Huanguo Jiang, Zhikun Zhan, Jindi Lu, Tanwei Gu, Ping Yu, Weimin Liang, Xi Zhang, Shilong Zhong, Lan Tang. Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner[J]. Journal of Pharmaceutical Analysis, 2023, 13(11): 1281-1295. doi: 10.1016/j.jpha.2023.08.010

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Oridonin restores hepatic lipid homeostasis in an LXRα-ATGL/EPT1 axis-dependent manner

doi: 10.1016/j.jpha.2023.08.010

a. NMPA Key Laboratory for Research and Evaluation of Drug Metabolism, Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, 510515, China;
b. Department of Pharmacy, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510515, China

Funds:

This work was supported by the National Natural Science Foundation of China (Grant No.: 81973388), Marine Economy Development Project of Guangdong Province (Project No.: GDNRC[2021]52), and the Key Research and Development Program of Guangdong Province (Program No.: 2020B1111030005).

Received Date: Mar. 01, 2023
Accepted Date: Aug. 10, 2023
Rev Recd Date: Aug. 01, 2023
Publish Date: Aug. 21, 2023

Abstract

Abstract

Hepatosteatosis is characterized by abnormal accumulation of triglycerides (TG), leading to prolonged and chronic inflammatory infiltration. To date, there is still a lack of effective and economical therapies for hepatosteatosis. Oridonin (ORI) is a major bioactive component extracted from the traditional Chinese medicinal herb Rabdosia rubescens. In this paper, we showed that ORI exerted significant protective effects against hepatic steatosis, inflammation and fibrosis, which was dependent on LXRα signaling. It is reported that LXRα regulated lipid homeostasis between triglyceride (TG) and phosphatidylethanolamine (PE) by promoting ATGL and EPT1 expression. Therefore, we implemented the lipidomic strategy and luciferase reporter assay to verify that ORI contributed to the homeostasis of lipids via the regulation of the ATGL gene associated with TG hydrolysis and the EPT1 gene related to PE synthesis in a LXRα-dependent manner, and the results showed the TG reduction and PE elevation. In detail, hepatic TG overload and lipotoxicity were reversed after ORI treatment by modulating the ATGL and EPT1 genes, respectively. Taken together, the data provide mechanistic insights to explain the bioactivity of ORI in attenuating TG accumulation and cytotoxicity and introduce exciting opportunities for developing novel natural activators of the LXRα-ATGL/EPT1 axis for pharmacologically treating hepatosteatosis and metabolic disorders.
- Oridonin,
- Lipid homeostasis,
- TG reduction,
- PE elevation,
- LXRα-ATGL/EPT1 axis

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References(48)

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