Home
Resources
Publications
Blockade of Glycolysis-Dependent Contraction by Oroxylin a via Inhibition of Lactate Dehydrogenase-A in Hepatic Stellate Cells

Blockade of Glycolysis-Dependent Contraction by Oroxylin a via Inhibition of Lactate Dehydrogenase-A in Hepatic Stellate Cells

Feixia Wang, Yan Jia, Mengmeng Li, Ling Wang, Jiangjuan Shao, Qinglong Guo, Shanzhong Tan, Hai Ding, Anping Chen, Feng Zhang, Shizhong Zheng

Cell Commun Signal. 2019 Feb 11;17(1):11.

PMID: 30744642

Abstract:

Background:
Contraction of hepatic stellate cells (HSCs) plays an important role in the pathogenesis of liver fibrosis by regulating sinusoidal blood flow and extracellular matrix remodeling. Here, we investigated how HSC contraction was affected by the natural compound oroxylin A, and elucidated the underlying mechanism.
Methods:
Cell contraction and glycolysis were examined in cultured human HSCs and mouse liver fibrosis model upon oroxylin A intervention using diversified cellular and molecular assays, as well as genetic approaches.
Results:
Oroxylin A limited HSC contraction associated with inhibiting myosin light chain 2 phosphorylation. Oroxylin A blocked aerobic glycolysis in HSCs evidenced by reduction in glucose uptake and consumption and lactate production. Oroxylin A also decreased extracellular acidification rate and inhibited the expression and activity of glycolysis rate-limiting enzymes (hexose kinase 2, phosphofructokinase 1 and pyruvate kinas type M2) in HSCs. Then, we identified that oroxylin A blockade of aerobic glycolysis contributed to inhibition of HSC contraction. Furthermore, oroxylin A inhibited the expression and activity of lactate dehydrogenase-A (LDH-A) in HSCs, which was required for oroxylin A blockade of glycolysis and suppression of contraction. Oral administration of oroxylin A at 40 mg/kg reduced liver injury and fibrosis, and inhibited HSC glycolysis and contraction in mice with carbon tetrachloride-induced hepatic fibrosis. However, adenovirus-mediated overexpression of LDH-A significantly counteracted the oroxylin A's effects in fibrotic mice.
Conclusions:
Blockade of aerobic glycolysis by oroxylin A via inhibition of LDH-A reduced HSC contraction and attenuated liver fibrosis, suggesting LDH-A as a promising target for intervention of hepatic fibrosis.

Chemicals Related in the Paper:

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

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: