Polydatin

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.

Polydatin是从传统中药Polygonum cuspidatum中提取的一种天然二苯乙烯类葡萄糖苷，是白藜芦醇的糖苷形式^[1]。Polydatin具有多种生物活性，广泛用于代谢性疾病、心血管疾病和神经退行性疾病的研究^[2]。Polydatin的作用机制涉及SIRT1、NF-κB、MAPK和Nrf2/HO-1等多个信号通路^[3]，研究表明，Polydatin可减轻缺血再灌注损伤、抑制氧化应激和炎症反应^[4]。

在体外，Polydatin（10–40μM）处理BRL-3A和HepG2细胞，显著抑制了果糖诱导的氧化应激、炎症反应和脂质沉积。Polydatin通过上调miR-200a表达，靶向抑制Keap1，激活Nrf2抗氧化通路，降低活性氧（ROS）水平，减少硫氧还蛋白互作蛋白（TXNIP）和NLRP3炎症小体相关蛋白（NLRP3、ASC、Caspase-1、IL-1β）的表达，恢复脂质代谢相关蛋白（PPAR-α、CPT-1）的表达，并抑制SREBP-1和SCD-1的表达，从而减少甘油三酯（TG）和总胆固醇（TC）的积累^[5]。Polydatin（0-120μM）处理人肺上皮细胞系BEAS-2B和肺癌细胞系A549，Polydatin显著抑制了细胞的增殖能力，且呈浓度和时间依赖性。Polydatin的预处理降低了A549细胞在放射线照射（8Gy）中的存活率^[6]。

在体内，Polydatin（50mg/kg）通过腹腔注射给药，用于治疗携带H460非小细胞肺癌（NSCLC）异种移植瘤的BALB/c裸鼠模型，给药频率为每两天一次，持续两周。Polydatin单独使用显著抑制了肿瘤生长，与顺铂（2mg/kg，每三天一次）联合使用时，协同增强了抗肿瘤效果，显著降低了肿瘤体积和重量。此外，Polydatin通过促进NADPH氧化酶5（NOX5）的表达，增加活性氧（ROS）生成，激活内质网应激（ER stress）及c-Jun氨基末端激酶（JNK）和p38丝裂原活化蛋白激酶（MAPK）信号通路^[7]。Polydatin（5mg/kg）通过腹腔注射给药，用于治疗由甲硫氨酸-胆碱缺乏（MCD）饮食诱导的非酒精性脂肪性肝炎（NASH）和肝纤维化的雄性C57BL/6小鼠模型，给药时间为整个4周的饮食诱导期间。Polydatin在该剂量下显著减轻了小鼠的肝脏脂肪变性、肝细胞损伤和炎症反应，降低了血清ALT和AST水平，减少了肝细胞凋亡和氧化应激，并抑制了肝纤维化的发展。此外，Polydatin还抑制了TLR4/NF-κB炎症信号通路，减少了促炎细胞因子（如TNF-α、IL-1β和IL-6）的表达^[8]。