α-Mangostin Alleviated HIF-1α-Mediated Angiogenesis in Rats With Adjuvant-Induced Arthritis by Suppressing Aerobic Glycolysis

• DOI: 10.3389/fphar.2021.785586
• Publication Date: 2021-12-20T11:33:35Z
• Authors: Tian-Tian Jiang; Chao-Fan Ji; Xiu-Ping Cheng; Shao-Fei Gu; Rui Wang; Yan Li; Jian Zuo; Jun Han
• Keywords: Matrigel; Lactate dehydrogenase A

A previously validated anti-rheumatic compound α-mangostin (MAN) shows significant metabolism regulatory effects. The current study aimed to clarify whether this property contributed its inhibition on synovial angiogenesis. Male wistar rats with adjuvant-induced arthritis (AIA) were orally treated by MAN for 32 days. Afterwards, biochemical parameters and cytokines in plasma determined corresponding kits, glycometabolism-related metabolites further accurately quantified LC-MS method. Anti-angiogenic effects of preliminarily assessed joints based-immunohistochemical examination matrigel plug assay. Obtained results then experiments vitro . AIA-caused increase circulating transforming growth factor beta, interleukin 6, hypoxia inducible factor-1 alpha (HIF-1α) vascular endothelial (VEGF) blood local HIF-1α/VEGF expression was abrogated treatment, pannus formation within plugs implanted AIA inhibited too. Scratch transwell assays revealed the inhibitory human umbilical vein cells (HUVECs) migration. Furthermore, tubule capability HUVECs potential rat arterial ring-derived Meanwhile, eased oxidative stress, altered glucose vivo Glycolysis-related including 6-phosphate, fructose 3-phosphoglyceric acid phosphoenolpyruvic decreased MAN, while impaired pyruvate-synthesizing lactate dehydrogenase (LDH) recovered. Consistently, restored lipopolysaccharide-elicited changes levels LDH culture system, exerted similar inhibitor stiripentol glycometabolism VEGF production as well HUVECs. These evidences show that treatment aerobic glycolysis rats, which consequently inflammation-related hypoxia, hampered pathological neovascularization.