Finger citron fruit ameliorates ovariectomy-induced postmenopausal metabolic syndrome through regulation of lipogenesis and ferroptosis-related alterations

ETHNOPHARMACOLOGICAL RELEVANCE: In Traditional Chinese Medicine (TCM), "Jianpi Liqi Huatan" (strengthening the spleen, regulating qi, and resolving phlegm) represents a traditional therapeutic strategy for managing obesity-associated metabolic disorders. According to TCM theory, postmenopausal MS is primarily associated with spleen deficiency, qi stagnation, and phlegm-dampness accumulation. Finger Citron Fruit (FCF), a representative Lingnan medicinal and edible herb and a core herb for Jianpi Liqi Huatan, The correspondence between the traditional properties of FCF and this TCM pathological framework provides an ethnopharmacological rationale for investigating its effects on postmenopausal metabolic dysfunction. AIM OF THE STUDY: To explore the metabolic effects and mechanisms of FCF in postmenopausal MS. MATERIALS AND METHODS: An ovariectomy (OVX)-induced mouse model, OA&PA-induced primary hepatocytes, and untargeted serum metabolomics were employed to evaluate the therapeutic effects and molecular mechanisms of FCF against postmenopausal MS. RESULTS: FCF significantly improved metabolic homeostasis by reducing body weight gain, dyslipidemia, hepatic steatosis, adipose tissue accumulation, and systemic inflammation, while increasing whole-body energy expenditure. Untargeted metabolomics revealed that FCF restored a candidate metabolite putatively annotated as indole-3-acetylglutamic acid. FCF improved hepatic steatosis in association with downregulation of SREBP-1c/ChREBP-related lipogenic signaling and restoration of GPX4 and SLC40A1 expression, thereby alleviating oxidative stress and lipid peroxidation. CONCLUSIONS: FCF ameliorated postmenopausal MS by suppressing hepatic lipogenesis and attenuating ferroptosis-related alterations. These findings provide metabolomic and molecular evidence supporting its traditional "Jianpi Liqi Huatan" functions and highlight its therapeutic potential for postmenopausal MS.

ChREBP · Citrus medica var. sarcodactylis · Dyslipidemia · ferroptosis · GPX4 · hepatic steatosis · Lipid peroxidation · Lipogenesis · ovariectomy · Oxidative stress · serum metabolomics · SLC40A1 · spleen deficiency · SREBP-1c · Traditional Chinese medicine · Diet, Metabolism, and Disease · Natural Antidiabetic Agents Studies · Traditional Chinese Medicine Analysis

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