Gastrodin as a Multitarget Anticancer Agent: Mechanisms, Pharmacokinetics, Toxicology, and Clinical Evidence
Akayed Hasan, Imam Hossen Rakib, Uzma Asif, Abul Bashar Ripon Khalipha, Mohammad Y. Alshahrani, Samy Selim, Md Asaduzzaman Jony, Emon Mia, Noshin Tasnim Yana, Rakib Hossan, Rituparna Biswas Suma, Md. Sakib Al HasanABSTRACT
Gastrodin (GAS), a natural polyphenolic compound derived primarily from Gastrodia elata , exhibited a wide spectrum of pharmacological activities, with growing evidence supporting its anticancer potential. This review summarized preclinical findings on the anticancer effects of GAS across multiple cancer types, including brain, breast, colorectal, liver, oral, and skin cancers. The literature was systematically collected from major databases such as PubMed, Scopus, Web of Science, and Google Scholar, focusing on studies published from 2013 onward. Evidence indicates that GAS exerted anticancer effects via multiple cellular and molecular mechanisms, including apoptosis, ferroptosis, cell cycle arrest, inhibition of glycolysis, suppression of oncogenic signaling pathways (e.g., NF‐κB, PI3K/Akt), immune modulation, and attenuation of inflammation and oxidative stress. Preclinical in vitro and in vivo studies demonstrated significant tumor growth suppression and the ability of GAS to overcome drug resistance. Pharmacokinetic studies revealed favorable drug‐like properties, while toxicological evaluations highlighted its high safety margin with minimal adverse effects. Despite promising findings, the lack of clinical trials and standardized protocols remained a major limitation. Collectively, GAS represents a promising natural product candidate with potential as an adjunct or alternative anticancer therapy, warranting further translational and clinical investigation.