Trigonelline regulates glycolysis and energy metabolism during hepatic fibrosis ...

연구 요약

Trigonelline regulates glycolysis and energy metabolism during hepatic fibrosis via Glut-1-HIF-1α axis: Focusing the interaction of macrophages and HSCs.

Phytomedicine : international journal of phytotherapy and phytopharmacology 학술지에 발표된 이 연구는 Gao C, Liu W, Liu SH 외 연구팀이 수행하였습니다.

이 연구는 'Trigonelline regulates glycolysis and energy metabolism during hepatic fibrosis via Glut-1-HIF-1α axis: Focusing the interaction of macrophages and HSCs.'에 대한 과학적 분석을 제공합니다.

핵심 내용

BACKGROUND: Reprogramming of aerobic glycolysis occurs with HSCs activation and is associated with regression of liver fibrosis. Trigonelline (TRG), a plant alkaloid extracted from Trigonella foenum-graecum L seeds, has a variety of pharmacological effect. PURPOSE: The current study investigated the hepatoprotective effect and mechanism of TRG against hepatic fibrosis by regulating glycolysis. METHODS: Anti-hepatic fibrosis effects of TRG were detected in thioacetamide (TAA)-induced hepatic fibrosis mice. HSCs or LX-2 were stimulated with TGF-β or conditioned medium (CM) from LPS-stimulated THP-1, then incubated with TRG, phloretin (PHL), rosiglitazone (RGZ), siRNA Glut-1 or plasmid with Glut-1. RESULTS: TRG significantly reduced serum transaminase levels, liver histopathological changes, excessive collagen deposition, inflammatory response, and neutrophil recruitment in TAA-induced mice. TAA increased hepatic Glut-1, HIF-1α and key enzymes of glycolysis expressions, while TRG completely reversed this effect. TRG also obviously regulated the combination of Glut-1 and HIF-1α to affect glycolysis in activated HSCs. TRG could inhibit α-SMA, IL-6, IL1R1, and HIF-1α expressions accompanying inhibition of Glut-1, function as PHL (Glut-1 inhibitor). Glut-1 silencing weakened α-SMA, IL-6, IL1R1, and HIF-1α expressions and enhanced the effect of TRG in activated LX-2. TRG inhibited LX-2 activation caused by Glut-1 overexpression, even demonstrated in interaction between LX-2 and macrophages. Further, TRG shown that improved fibrogenesis and inflammatory response by inhibiting Glut-1 compared with PHL in vivo. CONCLUSION: TRG could ameliorate hepatic fibrosis through inhibiting ECM excessive deposition and inflammatory response. Inhibiting Glut-1-HIF-1α axis and glycolysis was a potential therapeutic strategy for TRG ameliorating liver microenvironment, further against hepatic fibrosis.

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