Tithonia Diversifolia and AMPK-Related Metabolic Regulation: Exploring Its Potential Relevance to Aripiprazole-Associated Metabolic Dysregulation

Aripiprazole is often regarded as having a comparatively favorable metabolic profile among second-generation antipsychotics; however, clinically relevant changes in body weight, glucose regulation, and lipid metabolism may still occur in some patients. AMP-activated protein kinase (AMPK) is a central regulator of cellular energy homeostasis, glucose uptake, lipid oxidation, and mitochondrial function, but its effects are tissue- and context-dependent. Tithonia diversifolia (Mexican sunflower) is a medicinal plant with emerging preclinical evidence relevant to metabolic regulation, including reported changes in AMPK phosphorylation in human mesenchymal stem cells, insulin sensitivity and mitochondrial DNA copy number in diabetic rodents, and glucose uptake-related effects of isolated constituents. This review will critically evaluate the evidence linking aripiprazole-associated metabolic dysregulation, tissue-specific AMPK signaling, and the phytochemical and pharmacological properties of T. diversifolia. A structured, multilingual literature search will identify clinical, animal, and cellular studies addressing aripiprazole metabolic outcomes, AMPK signaling, T. diversifolia phytochemistry, metabolic endpoints, toxicity, and potential drug interactions. The central translational question is whether standardized T. diversifolia preparations or isolated constituents warrant further investigation as metabolic modulators in the setting of aripiprazole exposure. At present, the evidence is preclinical and does not establish efficacy, safety, or benefit from co-administration in patients. Direct combination studies, mechanistic validation, pharmacokinetic assessment, and toxicological evaluation are required before clinical consideration.