Polygonum cuspidatum as a Multi-Target Therapeutic Candidate for Polycystic Ovary Syndrome: From Molecular Mechanisms to Clinical Translation

Introduction : Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder in which hyperandrogenism, chronic low-grade inflammation, and insulin resistance function as interdependent, mutually reinforcing processes rather than isolated clinical features. Nuclear factor kappa B (NF-κB) signaling occupies a convergence point in this network, linking metabolic stress to ovarian dysfunction, while conventional therapies — lifestyle modification, insulin sensitizers, oral contraceptives, and anti-androgens — remain largely symptomatic and do not address these interconnected pathways directly. Polygonum cuspidatum (Hu Zhang), a traditional medicinal plant rich in stilbenes (resveratrol, polydatin), anthraquinones (emodin, physcion), and polyphenols, offers a multi-targeted pharmacological profile aligned with this pathophysiology. Methods : A structured literature search of PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar (January 2005–June 2026) was conducted using combinations of “ Polygonum cuspidatum ,” “Hu Zhang,” “resveratrol,” “polydatin,” “emodin,” and PCOS- and pathway-specific terms. Of 612 records identified across databases, 108 studies spanning in vitro , animal, and clinical investigations met the eligibility criteria and were narratively synthesized, with evidence explicitly stratified by source (isolated constituent versus whole-plant extract) and experimental model (PCOS-specific versus non-ovarian). Results : Preclinical studies of individual constituents, particularly resveratrol, together with limited evidence from P. cuspidatum extracts, suggest potential modulation of inflammatory, steroidogenic, metabolic, and redox pathways relevant to PCOS. Clinical data, though encouraging, are drawn almost exclusively from isolated resveratrol rather than standardized whole-plant extracts, and report reductions in circulating androgens and improvements in insulin sensitivity in small, short-duration trials. Discussion : Pharmacokinetic limitations of resveratrol, alongside the need for phytochemical standardization and quality-controlled formulations, remain key barriers to translation. This review synthesizes the mechanistic case for P. cuspidatum as a multi-target adjunctive candidate in PCOS, while identifying the standardization, safety, and whole-extract clinical evidence still required before mechanism-guided therapeutic use can be recommended.