中医药通过SIRT1/AMPK信号通路防治代谢性疾病的研究进展OA

Metabolic diseases,characterized by systemic dysregulation of glucose,lipid,protein,and energy homeostasis,encompass a cluster of multisystem disorders and have emerged as a critical global public health challenge.The silent information regulator 1(SIRT1)/adenosine monophosphate-activated protein kinase(AMPK)signaling pathway serves as a central hub for cellular energy sensing and stress response.By synergistically promoting downstream effectors such as peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),this signaling axis orchestrates mitochondrial biogenesis,enhances fatty acid β-oxidation,restrains nuclear factor kappa B(NF-κB)-driven chronic low-grade inflammation,and induces indispensable autophagy to maintain intracellular homeostasis.Emerging evidence indicates that the widespread functional impairment of the SIRT1/AMPK pathway acts as a shared microscopic mechanism prevailing across a broad spectrum of metabolic disorders,including obesity,hyperlipidemia,non-alcoholic fatty liver disease(NAFLD),type 2 diabetes mellitus(T2DM),atherosclerosis(AS),polycystic ovary syndrome(PCOS),hyperuricemia(HUA)and gout,and osteoporosis(OP).Remarkably,there thrives a profound biological convergence between the down-regulation of the SIRT1/AMPK circuitry and the pathogenesis cascade delineating the"dysfunction of Sanjiao Qi transformation and intermingling of phlegm and blood stasis"in traditional Chinese medicine(TCM)theories.Various TCM herbs(such as Atractylodes lancea and Poria cocos),active botanical monomers(e.g.,resveratrol,berberine,quercetin),and compound formulations possessing the efficacy of fortifying the spleen,replenishing Qi,resolving phlegm,and removing blood stasis can elegantly mimic"caloric restriction"physiological effects to uniformly and sustainably activate this pathway.This targeted reactivation fundamentally actualizes the classical wisdom of"treating different diseases with the same method"(homotherapy for heteropathy).This review systematically delineates the molecular regulatory network of the SIRT1/AMPK pathway,explores its pathological interplay with disparate metabolic diseases and the corresponding TCM microscopic pathogenesis,and summarizes the latest pharmacological intervention strategies of TCM.Furthermore,it critically evaluates the pre-clinical dilemmas such as"concentration gap"in pharmacokinetics and the imperative need for translational TCM symptom-target mapping,thereby providing robust theoretical paradigms and evidentiary references for clinical precision treatment and innovative drug development.