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In preclinical models, apigenin restores insulin sensitivity and ovarian function by inhibiting PI3K/Akt and downstream mTOR activation, thereby reducing excessive follicular growth and anovulation ( 9 Toxicological and safety data Experimental research indicates that apigenin is neither mutagenic nor genotoxic and is widely regarded as safe, given its broad occurrence in dietary sources such as parsley, chamomile, and celery ( 10 Microbiome and gut-ovary axis The pathophysiology of PCOS is now understood to be significantly influenced by the complex interaction between the gut microbiota and the ovaries, known as the gut-ovary axis ( Bifidobacterium species and Akkermansia muciniphila ( 11 Discussion on nano delivery or formulation strategies The therapeutic use of apigenin and ellagic acid is limited by poor oral bioavailability due to low solubility, rapid metabolism, and restricted permeability ( Table 5 outlines the main delivery systems investigated for apigenin and ellagic acid, highlighting their potential benefits and current research status

Scientific interest lies in potential complementarity: activating HGF + BDNF could theoretically produce synergistic synaptogenic effect, an active subject of preclinical research