Hesperidin, a flavonoid predominantly found in citrus fruits, has gained attention as a potential nutraceutical for managing various components of metabolic syndrome, including obesity, hypertension, dyslipidemia, and insulin resistance. This review aims to provide a comprehensive overview of the pharmacological properties of hesperidin, emphasizing its therapeutic potential in combating metabolic syndrome through both in vivo and in silico investigations. Preclinical studies have demonstrated that hesperidin exerts anti-inflammatory, antioxidant, and lipid-lowering effects, contributing to the improvement of metabolic parameters. Mechanistically, hesperidin is known to modulate key signaling pathways, including the peroxisome proliferator-activated receptor gamma (PPAR-γ), AMP-activated protein kinase (AMPK), and nuclear factor-kappa B (NF-κB), to restore metabolic homeostasis. Moreover, recent in-silico studies have identified potential protein targets of hesperidin, shedding light on its molecular mechanisms and enabling the prospect for the design of more effective therapeutic strategies. Consistently, this current report integrates findings from experimental models and computational approaches to narratively outline the promise of hesperidin as a multi-target agent for managing metabolic syndrome. Therefore, this report has elucidated the need for clinical trials to validate these preclinical outcomes and establish hesperidin as a viable therapeutic option for patients with metabolic syndrome.
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