Network Pharmacology Insights Into Statin‐Induced Coenzyme <scp>Q10</scp> Deficiency: Lipid Metabolic Crosstalk, <scp>TNF</scp> – <scp>MAPK</scp> Signaling, and Muscle Toxicity

Abstract

ABSTRACT This in silico network‐pharmacology investigation delineates the molecular interplay linking statin‐induced Coenzyme Q10 (CoQ10) deficiency to statin‐associated muscle symptoms (SAMS). GeneCards‐derived targets related to SAMS, CoQ10 deficiency, and statins were integrated, and the intersecting gene set was analyzed through STRING‐based protein–protein interaction mapping, followed by hub‐gene prioritization using CytoHubba. Functional enrichment via ShinyGO revealed that the 145 common genes converge predominantly on inflammatory, metabolic, and mitochondrial pathways. Tumor necrosis factor (TNF) emerged as a principal regulatory node, exerting influence through Mitogen‐Activated Protein Kinase (MAPK)‐mediated apoptotic and stress‐response cascades that plausibly contribute to mitochondrial dysfunction, oxidative stress, impaired energy metabolism, and myocellular injury in the context of CoQ10 depletion. The constructed pathway‐based interaction network illustrates how suppression of the mevalonate pathway by statins disrupts CoQ10 biosynthesis, sensitizing muscle tissue to cytokine‐driven inflammatory signaling and amplifying apoptotic susceptibility. Collectively, the findings highlight the TNF–MAPK axis as a mechanistic core of SAMS pathophysiology and underscore the interconnected roles of immune activation, lipid metabolic imbalance, and mitochondrial impairment. These insights provide a molecular rationale for therapeutic strategies targeting mitochondrial preservation or inflammatory modulation, including CoQ10 supplementation, and reinforce the need for experimental and clinical validation to substantiate computationally derived predictions.

Affiliated Institutions

• Saveetha University IN

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