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Oroxylin A Regulates the Turnover of Lipid Droplet via Downregulating Adipose Triglyceride Lipase (ATGL) in Hepatic Stellate Cells

Oroxylin A Regulates the Turnover of Lipid Droplet via Downregulating Adipose Triglyceride Lipase (ATGL) in Hepatic Stellate Cells

Zili Zhang, Mei Guo, Min Shen, Yujia Li, Shanzhong Tan, Jiangjuan Shao, Feng Zhang, Anping Chen, Shijun Wang, Shizhong Zheng

Life Sci. 2019 Dec 1;238:116934.

PMID: 31610205

Abstract:

Proliferation and differentiation of hepatic stellate cells (HSCs) are the most noticeable events in hepatic fibrosis, in which the loss of lipid droplets (LDs) is the most important feature. However, the complex mechanisms of LD disappearance have not been fully elucidated. In the current study, we investigated whether oroxylin A has the pharmacological activity of reversing LDs in activated HSCs, and further examined its potential molecular mechanisms. Using genetic, pharmacological, and molecular biological measure, we found that LD content significantly decreased during HSC activation, whereas oroxylin A markedly reversed LD content in activated HSCs. Interestingly, oroxylin A treatment observably decreased the expression of adipose triglyceride lipase (ATGL) without large differences in classical LD synthesis pathway, LD-related transcription factors, and autophagy pathway. ATGL overexpression could completely impair the effect of oroxylin A on reversing LD content. Importantly, reactive oxygen species (ROS) signaling pathway mediated oroxylin A-induced ATGL downregulation and LD revision in activated HSCs. ROS specific stimulant buthionine sulfoximine (BSO) could dramatically diminish the antioxidant effect of oroxylin A, and in turn, abolish reversal effect of oroxylin A on LD content. Conversely, ROS specific scavenger N-acetyl cystenine (NAC) can significantly enhance the pharmacological effect of oroxylin A on LD revision. Taken together, our study reveals the important molecular mechanism of anti-fibrosis effect of oroxylin A, and also suggests that ROS-ATGL pathway is a potential target for reversing LDs.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP480115	Oroxylin A		480-11-5	Price

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