Potential of Gynostemma Pentaphyllum for Breast Cancer Endocrine Therapy: Prevention and Treatment

Vollständiger Abstract

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Introduction/Objective: Endocrine therapy is the cornerstone of treatment for Hormone Receptor-positive (HR+) breast cancer, but its long-term administration is frequently accompanied by multiple adverse effects. Gynostemma pentaphyllum (GP), a traditional Chinese herbal medicine with a long history of ethnomedical application, has been widely used for "tonifying qi, nourishing yin, clearing heat, and resolving dampness." This narrative review aims to synthesize preclinical evidence evaluating the potential and underlying mechanisms of GP as an adjunctive therapy for breast cancer endocrine therapy, integrating its ethnopharmacological basis with modern mechanistic data. Methods: Preclinical studies investigating GP extracts or their bioactive components were systematically collected from PubMed, Web of Science, Scopus, and CNKI (January 2010– December 2025) and narratively synthesized to summarize their multi-target mechanisms in enhancing efficacy and reducing toxicity during endocrine therapy. As a narrative review, a quantitative meta-analysis and a formal risk-of-bias assessment were not performed; however, study characteristics and quality indicators were tabulated for transparency. Results: Preclinical evidence suggests that GP exhibits pleiotropic pharmacological activities that align with its ethnopharmacological properties. For enhanced efficacy, GP potentiates the effects of endocrine drugs and may help overcome drug resistance by modulating key signaling pathways including ERα, PI3K/AKT/mTOR, and STAT3. For toxicity mitigation, GP has been shown in preclinical models to improve lipid and glucose metabolism via activation of AMPK/PPARα pathways, alleviate anxiety, insomnia, and vasomotor symptoms by regulating GABA/5-HT and neurokinin B signaling, reduce systemic inflammation by inhibiting NF- κB/NLRP3 pathways, and exert antioxidant and immunoprotective effects through Nrf2 pathway activation and potential gut microbiota modulation. These effects collectively address the metabolic, neurological, immune, and organ-related challenges associated with long-term endocrine therapy, though primarily based on in vitro and animal studies. Discussion: Based on its ethnopharmacological background and multi-target network, GP shows preclinical promise as a potential integrative strategy for "enhancing efficacy and reducing toxicity" in breast cancer endocrine therapy. These findings should be interpreted within a broader translational context: the multi-target pharmacology of GP is conceptually consistent with the complex, systemic nature of endocrine therapy-related adverse effects, suggesting that a single botanical agent could simultaneously address metabolic, neurological, immune, and organ-related sequelae. However, current evidence is primarily derived from preclinical studies with substantial variability in extract composition and characterization, limiting direct clinical extrapolation. Conclusion: GP exhibits pleiotropic preclinical activities supporting its potential as an adjunctive agent in breast cancer endocrine therapy. High-quality clinical trials are urgently needed to validate its clinical efficacy, safety, optimal dosage, pharmacokinetic profile, herb-drug interaction potential, and potential combinations with emerging therapies.