Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

Yuping Zhou; Ze Dai; Kaili Deng; Yubin Wang; Jiamin Ying; Donghui Chu; Jinyue Zhou; Chunlan Tang

doi:10.1016/j.jpha.2023.05.012

Eight Zhes Decoction ameliorates the lipid dysfunction of nonalcoholic fatty liver disease using integrated lipidomics, network pharmacology and pharmacokinetics

J Pharm Anal. 2023 Sep;13(9):1058-1069. doi: 10.1016/j.jpha.2023.05.012. Epub 2023 May 24.

Authors

Yuping Zhou^{1

2

3}, Ze Dai^{1

2}, Kaili Deng^{1

2}, Yubin Wang², Jiamin Ying², Donghui Chu², Jinyue Zhou², Chunlan Tang^{1

2}

Affiliations

¹ The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315020, China.
² School of Public Health, Health Science Center, Ningbo University, Ningbo, Zhejiang, 315211, China.
³ Institute of Digestive Disease of Ningbo University, Ningbo, Zhejiang, 315020, China.

Abstract

Nonalcoholic fatty liver disease (NAFLD) has developed into the most common chronic liver disease and can lead to liver cancer. Our laboratory previously developed a novel prescription for NAFLD, "Eight Zhes Decoction" (EZD), which has shown good curative effects in clinical practice. However, the pharmacodynamic material basis and mechanism have not yet been revealed. A strategy integrating lipidomics, network pharmacology and pharmacokinetics was used to reveal the active components and mechanisms of EZD against NAFLD. The histopathological results showed that EZD attenuated the degrees of collagen deposition and steatosis in the livers of nonalcoholic steatofibrosis model mice. Furthermore, glycerophospholipid metabolism, arachidonic acid metabolism, glycerolipid metabolism and linoleic acid metabolism with phospholipase A2 group IVA (PLA2G4A) and cytochrome P450 as the core targets and 12,13-cis-epoxyoctadecenoic acid, 12(S)-hydroxyeicosatetraenoic acid, leukotriene B4, prostaglandin E2, phosphatidylcholines (PCs) and triacylglycerols (TGs) as the main lipids were found to be involved in the treatment of NAFLD by EZD. Importantly, naringenin, artemetin, canadine, and bicuculline were identified as the active ingredients of EZD against NAFLD; in particular, naringenin reduces PC consumption by inhibiting the expression of PLA2G4A and thus promotes sufficient synthesis of very-low-density lipoprotein to transport excess TGs in the liver. This research provides valuable data and theoretical support for the application of EZD against NAFLD.

Keywords: Eight Zhes Decoction; Lipidomics; Network pharmacology; Nonalcoholic fatty liver disease; Pharmacokinetics.