Polydatin is a natural stilbene glucoside extracted from the traditional Chinese medicine Polygonum cuspidatum, and Polydatin is the glycoside form of resveratrol[1]. Polydatin exhibits a wide range of biological activities and is widely used in research on metabolic, cardiovascular, and neurodegenerative diseases[2]. Polydatin mechanisms of action involve multiple signaling pathways, including SIRT1, NF-κB, MAPK, and Nrf2/HO-1[3]. Studies have shown that Polydatin can alleviate ischemia-reperfusion injury, inhibit oxidative stress, and reduce inflammatory responses[4].
In vitro, treatment with Polydatin (10–40μM) in BRL-3A and HepG2 cells significantly inhibited fructose-induced oxidative stress, inflammation, and lipid accumulation. Polydatin upregulated miR-200a expression, which targeted and inhibited Keap1, thereby activating the Nrf2 antioxidant pathway. This led to a reduction in reactive oxygen species (ROS) levels and decreased expression of thioredoxin-interacting protein (TXNIP) and NLRP3 inflammasome-related proteins (NLRP3, ASC, Caspase-1, IL-1β). Additionally, Polydatin restored the expression of lipid metabolism-related proteins (PPAR-α, CPT-1) and inhibited the expression of SREBP-1 and SCD-1, thereby reducing the accumulation of triglycerides (TG) and total cholesterol (TC)[5]. Polydatin (0–120μM) treatment in human lung epithelial cell line BEAS-2B and lung cancer cell line A549 significantly inhibited cell proliferation in a concentration- and time-dependent manner. Pretreatment with Polydatin also reduced the survival rate of A549 cells exposed to radiation (8Gy) [6].
In vivo, Polydatin (50mg/kg) was administered via intraperitoneal injection to BALB/c nude mice bearing H460 non-small cell lung cancer (NSCLC) xenografts. The treatment was given every two days for two weeks. Polydatin alone significantly inhibited tumor growth, and when combined with cisplatin (2mg/kg; i.p.; every 3 days), Polydatin synergistically enhanced the antitumor effect, markedly reducing tumor volume and weight. Furthermore, Polydatin promoted the expression of NADPH oxidase 5 (NOX5), increased ROS production, and activated endoplasmic reticulum (ER) stress and the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) signaling pathways[7]. Polydatin (5mg/kg), administered via intraperitoneal injection, was used to treat male C57BL/6 mice with nonalcoholic steatohepatitis (NASH) and liver fibrosis induced by a methionine-choline-deficient (MCD) diet. The treatment was given throughout the 4-week dietary induction period. At this dose, Polydatin significantly alleviated hepatic steatosis, hepatocyte injury, and inflammation, reduced serum ALT and AST levels, decreased hepatocyte apoptosis and oxidative stress, and inhibited the progression of liver fibrosis. Moreover, Polydatin suppressed the TLR4/NF-κB inflammatory signaling pathway and reduced the expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6[8].
References:
[1] Karami A, Fakhri S, Kooshki L, et al. Therapeutic Targets, Biological Activities, and Health Benefits. Molecules. 2022 Oct 1;27(19):6474.
[2] Luo J, Chen S, Wang L, et al. Pharmacological effects of polydatin in the treatment of metabolic diseases: A review. Phytomedicine. 2022 Jul 20;102:154161.
[3] Tang D, Zhang Q, Duan H, et al. Polydatin: A Critical Promising Natural Agent for Liver Protection via Antioxidative Stress. Oxid Med Cell Longev. 2022 Feb 10;2022:9218738.
[4] Tang KS. Protective Effects of Polydatin Against Dementia-Related Disorders. Curr Neuropharmacol. 2021;19(2):127-135.
[5] Zhao XJ, Yu HW, Yang YZ, et al. Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway. Redox Biol. 2018 Sep;18:124-137.
[6] Guo J, Ding W, Cai S, et al. Polydatin radiosensitizes lung cancer while preventing radiation injuries by modulating tumor-infiltrating B cells. J Cancer Res Clin Oncol. 2023 Sep;149(12):9529-9542.
[7] Wu S, Zhao Q, Liu S, Vanbever R, et al. Polydatin, a potential NOX5 agonist, synergistically enhances antitumor activity of cisplatin by stimulating oxidative stress in non‑small cell lung cancer. Int J Oncol. 2024 Aug;65(2):77.
[8] Li R, Li J, Huang Y, et al. Polydatin attenuates diet-induced nonalcoholic steatohepatitis and fibrosis in mice. Int J Biol Sci. 2018 Jul 30;14(11):1411-1425.