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1.广西中医药大学,南宁 530200
2.广西中医药大学 壮瑶药重点实验室,南宁 530200
Received:20 August 2021,
Published Online:29 September 2021,
Published:20 November 2021
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林思,秦慧真,邓玲玉等.虎杖苷药理作用及机制研究进展[J].中国实验方剂学杂志,2021,27(22):241-250.
LIN Si,QIN Hui-zhen,DENG Ling-yu,et al.Research Progress on Pharmacological Effect and Mechanism of Polydatin[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(22):241-250.
林思,秦慧真,邓玲玉等.虎杖苷药理作用及机制研究进展[J].中国实验方剂学杂志,2021,27(22):241-250. DOI: 10.13422/j.cnki.syfjx.20212236.
LIN Si,QIN Hui-zhen,DENG Ling-yu,et al.Research Progress on Pharmacological Effect and Mechanism of Polydatin[J].Chinese Journal of Experimental Traditional Medical Formulae,2021,27(22):241-250. DOI: 10.13422/j.cnki.syfjx.20212236.
虎杖苷是从传统中药虎杖中分离出的一种多酚类单体化合物,是虎杖的主要有效成分,具有多种药理活性。近年来,有关虎杖苷药理作用及机制的研究日益增多。现代药理学研究表明,虎杖苷对神经系统,心脑血管系统,呼吸系统等均有保护作用,对肝、肾、肺等器官亦作用明显,其调节血糖血脂的作用对抗动脉粥样硬化效果显著;其抗纤维化的作用对肝、肾保护效果明显。虎杖苷对多种肿瘤细胞均有抑制作用,可抑制肿瘤细胞增殖并诱导肿瘤细胞凋亡。虎杖苷还具有抗炎,保护骨髓,促进创面愈合,抗辐射等药理活性。笔者查阅有关虎杖苷的药理作用文献发现其单个药理作用机制往往受多靶点蛋白、多条通路调控,但大多还未明确其作用靶点,有待深入研究。该文就近5年来有关虎杖苷的药理作用及机制研究进展进行归纳总结,并对其研究现状及未来研究方向提出相关建议,以期拓宽科研者的研究思路,加快明确其发挥药效作用的靶点,为虎杖苷的进一步开发利用提供科学的理论依据。
Polydatin, a polyphenolic compound, is the main active component of Chinese medicine Polygoni Cuspidati Rhizoma et Radix and has a variety of pharmacological activities. In recent years, there are more studies on the pharmacological effects and mechanisms of polydatin. Modern pharmacological studies show that polydatin has protective effects on the nervous system, cardio-cerebral vascular system, and respiratory system, and also has significant effects on the liver, kidney, lung, and other organs. Its effect of regulating blood glucose and blood lipid on atherosclerosis is significant, and the anti-fibrosis effect is significant on the liver and kidney. Polydatin can inhibit many types of tumor cells, suppress proliferation and induce apoptosis of tumor cells. Polydatin can also resist inflammation and radiation, protect bone marrow, and promote wound healing. Based on the literature on the pharmacological effects of polydatin, the authors found that the single pharmacological mechanism of polydatin is often regulated by multi-target proteins and multiple pathways, but the most of action targets are unclear, which needs to be further investigated. This study summarized the research progress on the pharmacological action and mechanism of polydatin in the past five years and put forward some suggestions on its present research situation and future research direction to broaden the research ideas of researchers and speed up the identification of the targets of its pharmacological effect. This study is expected to provide a scientific theoretical basis for the further development and utilization of polydatin.
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LAI Y L , ZHOU C Y , HUANG P , et al . Polydatin alleviated alcoholic liver injury in zebrafish larvae through ameliorating lipid metabolism and oxidative stress [J]. J Pharmacol Sci , 2018 , 138 ( 1 ): 46 - 53 .
徐志广 , 张朴花 . 虎杖苷通过调控Nrf2/HO-1信号通路减轻大鼠肝脏缺血再灌注损伤 [J]. 中成药 , 2021 , 43 ( 2 ): 362 - 368 .
CHEN L Y , LAN Z . Polydatin attenuates potassium oxonate-induced hyperuricemia and kidney inflammation by inhibiting NF- κ B/NLRP3 inflammasome activation via the AMPK/SIRT1 pathway [J]. Food Funct , 2017 , 8 ( 5 ): 1785 - 1792 .
HAN B , GONG M J , LI Z , et al . NMR-based metabonomic study reveals intervention effects of polydatin on potassium oxonate-induced hyperuricemia in rats [J]. Oxid Med Cell Longev , 2020 , 2020 : 6943860 .
WANG L J , HUANG L J , LI N , et al . Ameliorative effect of polydatin on hyperglycemia and renal injury in streptozotocin-induced diabetic rats [J]. Cell Mol Biol , 2019 , 65 ( 7 ): 55 - 59 .
张正菊 , 孟凤仙 , 白华 , 等 . 虎杖苷对糖尿病肾病小鼠AMPK α 1/TLR4信号通路的影响 [J]. 中国中西医结合杂志 , 2019 , 39 ( 11 ): 1378 - 1384 .
GU L N , LIU J Y , XU D , et al . Polydatin prevents LPS-induced acute kidney injury through inhibiting inflammatory and oxidative responses [J]. Microb Pathogenesis , 2019 , 137 : 103688 .
高友光 , 林献忠 , 曾振华 , 等 . 虎杖苷对脓毒症急性肾损伤大鼠炎症反应和氧化应激的影响 [J]. 临床麻醉学杂志 , 2017 , 33 ( 6 ): 584 - 587 .
徐小惠 , 郑妮 . 虎杖苷通过TLR4/NF- κ B信号通路调控糖尿病肾病大鼠肾脏炎症作用的研究 [J]. 中国医院药学杂志 , 2018 , 38 ( 16 ): 1677 - 1680 .
闫恩法 , 程康 , 李思勉 , 等 . 虎杖苷对热应激大鼠肾脏损伤的影响 [J]. 中国兽医学报 , 2020 , 40 ( 4 ): 761 - 764 .
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左斌 , 夏晓枫 , 车彪 , 等 . 虎杖苷对小鼠腰椎间盘退变髓核细胞凋亡及SIRT1/mTOR通路的影响 [J]. 中国组织工程研究 , 2021 , 25 ( 35 ): 5619 - 5625 .
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SHEN Y S , CHEN X J , WURI S N , et al . Polydatin improves osteogenic differentiation of human bone mesenchymal stem cells by stimulating TAZ expression via BMP2-Wnt/ β -catenin signaling pathway [J]. Stem Cell Res Ther , 2020 , 11 ( 1 ): 204 .
徐敏敏 , 刘绍凡 , 万锐杰 , 等 . 虎杖苷对去卵巢骨质疏松大鼠 β -catenin及GSK-3 β 蛋白表达的影响 [J]. 中国现代应用药学 , 2018 , 35 ( 1 ): 103 - 106 .
PENG Y , XU J , ZENG Y , et al . Polydatin attenuates atherosclerosis in apolipoprotein E-deficient mice:role of reverse cholesterol transport [J]. Phytomedicine , 2019 , 62 : 152935 .
XIONG Q P , YAN Z , LIANG J . Polydatin alleviates high-fat diet induced atherosclerosis in apolipoprotein E-deficient mice by autophagic restoration [J]. Phytomedicine , 2020 , 2020 : 153301 .
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HUANG Z Y , TIAN G Y , CHENG S B , et al . Polydatin attenuates atherosclerosis in ApoE -/- mice through PBEF mediated reduction of cholesterol deposition [J]. Am J Chin Med , 2018 , 46 ( 8 ): 1841 - 1859 .
毕静 , 白晓雪 , 王超 . 虎杖苷通过激活Nrf2/HO-1信号抑制氧化应激诱导的心肌细胞损伤 [J]. 中国老年学杂志 , 2020 , 40 ( 2 ): 407 - 409 .
DAI J H , MA J B , LIAO Y F , et al . Polydatin protects H9c2 cells from hypoxia-induced injury via up-regulating long non-coding RNA DGCR5 [J]. Braz J Med Biol Res , 2019 , 52 ( 12 ): e8834 .
TAN Y Y , CHEN L X , FANG L , et al . Cardioprotective effects of polydatin against myocardial injury in diabetic rats via inhibition of NADPH oxidase and NF- κ B activities [J]. BMC Complement Med , 2020 , 20 ( 1 ): 378 - 378 .
ZHANG M M , WANG S J , CHENG Z , et al . Polydatin ameliorates diabetic cardiomyopathy via Sirt3 activation [J]. Biochem Bioph Res Co , 2017 , 493 ( 3 ): 1280 - 1287 .
YU L M , LI Z , DONG X , et al . Polydatin protects diabetic heart against ischemia-reperfusion injury via Notch1/Hes1-mediated activation of Pten/Akt signaling [J]. Oxid Med Cell Longev , 2018 , 2018 : 2750695 .
LI L , TAN H P , LIU C Y , et al . Polydatin prevents the induction of secondary brain injury after traumatic brain injury by protecting neuronal mitochondria [J]. Neural Regen Res , 2019 , 14 ( 9 ): 1573 - 1582 .
RUAN W C , LI J W , XU Y Z , et al . MALAT1 up-regulator polydatin protects brain microvascular integrity and ameliorates stroke through C/EBP β /MALAT1/CREB/PGC-1 α /PPAR γ pathway [J]. Cell Mol Neurobiol , 2019 , 39 ( 2 ): 265 - 286 .
LAN T , ZHUANG L H , LI S G , et al . Polydatin attenuates hepatic stellate cell proliferation and liver fibrosis by suppressing sphingosine kinase 1 [J]. Biomed Pharmacother , 2020 , 130 : 110586 .
CHEN Z Q , SUN X H , LI X J , et al . Polydatin attenuates renal fibrosis in diabetic mice through regulating the Cx32-Nox4 signaling pathway [J]. Acta Pharmacol Sin , 2020 , 41 ( 12 ): 1587 - 1596 .
GONG W Y , LI J , CHEN Z Q , et al . Polydatin promotes Nrf2-ARE anti-oxidative pathway through activating CKIP-1 to resist HG-induced up-regulation of FN and ICAM-1 in GMCs and diabetic mice kidneys [J]. Free Radical Bio Med , 2017 , 106 : 393 - 405 .
王松 , 赵晓玉 , 梁艳 , 等 . 虎杖苷对肾纤维化模型大鼠肾组织中MMP-9和TIMP-1蛋白表达的影响 [J]. 中国药房 , 2018 , 29 ( 7 ): 936 - 940 .
李鹏 , 杨荣华 , 彭福生 , 等 . 虎杖苷对单侧输尿管梗阻大鼠肾间质纤维化的治疗作用研究 [J]. 中国临床药理学杂志 , 2020 , 36 ( 10 ): 1274 - 1276 .
TANG J , LI Y G , WANG J Q , et al . Polydatin suppresses the development of lung inflammation and fibrosis by inhibiting activation of the NACHT domain‐,leucine‐rich repeat‐,and pyd‐containing protein 3 inflammasome and the nuclear factor‐ κ B pathway after Mycoplasma pneumoniae infection [J]. J Cell Biochem , 2019 , 120 ( 6 ): 10137 - 10144 .
LIU Y L , CHEN B Y , NIE J , et al . Polydatin prevents bleomycin-induced pulmonary fibrosis by inhibiting the TGF- β /Smad/ERK signaling pathway [J]. Exp Ther Med , 2020 , 20 ( 5 ): 62 .
李卫玲 , 茹琴 , 林款 , 等 . 虎杖苷对四氧嘧啶诱导的大鼠胰岛细胞损伤的保护作用 [J]. 食品工业科技 , 2020 , 41 ( 3 ): 315 - 320 .
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MOSTAFA F , ABDELMONEIM A , ABDULHAMID M , et al . Polydatin and polydatin-loaded chitosan nanoparticles attenuate diabetic cardiomyopathy in rats [J]. J Mol Histol , 2021 , 52 ( 2 ): 135 - 152 .
HAO J , HUANG K P , CHEN C , et al . Polydatin improves glucose and lipid metabolisms in insulin-resistant HepG2 cells through the AMPK pathway [J]. Biol Pharm Bull , 2018 , 41 ( 6 ): 891 - 898 .
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ZHENG L , WU J Y , MO J F , et al . Polydatin inhibits adipose tissue inflammation and ameliorates lipid metabolism in high-fat-fed mice [J]. Biomed Res Int , 2019 , doi: 10.1155/2019/7196535 http://dx.doi.org/10.1155/2019/7196535 .
郑丽 , 鲍轶 , 吴加元 , 等 . 虎杖苷对3T3-L1前脂肪细胞增殖与分化的影响及其作用机制 [J]. 中华中医药学刊 , 2017 , 35 ( 10 ): 2521 - 2525 .
CHEN G X , YANG Z Y , WEN D , et al . Polydatin has anti-inflammatory and antioxidant effects in LPS-induced macrophages and improves DSS-induced mice colitis [J]. Immun Inflamm Dis , 2021 , 9 ( 3 ): 959 - 970 .
LI R , MAIMAI T , YAO H M , et al . Protective effects of polydatin on LPS-induced endometritis in mice [J]. Microb Pathogenesis , 2019 , 137 : 103720 .
刘佳静 , 李秋逸 , 马沛广 , 等 . 基于PKC θ /STAT3信号通路探讨虎杖苷抑制溃疡性结肠炎小鼠Th17细胞的效应 [J]. 中国实验方剂学杂志 , 2021 , 27 ( 17 ): 40 - 45 .
BONGKYUN P , KYUHYUNG J , TAE G L , et al . Polydatin inhibits NLRP3 inflammasome in dry eye disease by attenuating oxidative stress and inhibiting the NF- κ B pathway [J]. Nutrients , 2019 , 11 ( 11 ): 2792 .
SUN S Y , ZOU Y R , HAO S C , et al . Polydatin inhibits LPS-induced inflammatory response in BV2 microglia by disrupting the formation of lipid rafts [J]. Immunopharm Immunot , 2021 , 43 ( 2 ): 138 - 144 .
ZHAO X J , YU H W , YANG Y Z , et al . Polydatin prevents fructose-induced liver inflammation and lipid deposition through increasing miR-200a to regulate Keap1/Nrf2 pathway [J]. Redox Biol , 2018 , 18 : 124 - 137 .
CHEN X T , CHAN H , ZHANG L , et al . The phytochemical polydatin ameliorates non-alcoholic steatohepatitis by restoring lysosomal function and autophagic flux [J]. J Cell Mol Med , 2019 , 23 ( 6 ): 4290 - 4300 .
BAI L C , MA Y K , WANG X , et al . Polydatin inhibits cell viability,migration,and invasion through suppressing the c-Myc expression in human cervical cancer [J]. Front Cell Dev Biol , 2021 , 9 : 587218 .
潘纪红 , 王海滨 , 杜晓飞 , 等 . 虎杖苷通过PI3K/Akt/mTOR信号通路诱导人宫颈癌细胞凋亡的初步研究 [J]. 中国中药杂志 , 2017 , 42 ( 12 ): 2345 - 2349 .
CHEN Y D , NIU J M , LI L L , et al . Polydatin executes anticancer effects against glioblastoma multiforme by inhibiting the EGFR-Akt/ERK1/2/STAT3-SOX2/Snail signaling pathway [J]. Life Sci , 2020 , 258 : 118158 .
JIANG C Q , MA L L , LV Z D , et al . Polydatin induces apoptosis and autophagy via STAT3 signaling in human osteosarcoma MG-63 cells [J]. J Nat Med-Tokyo , 2020 , 74 ( 3 ): 533 - 544 .
JIN Y , ZHAN X B , ZHANG B , et al . Polydatin exerts an antitumor effect through regulating the miR-382/PD-L1 Axis in colorectal cancer [J]. Cancer Biother Radio , 2020 , 35 ( 2 ): 83 - 91 .
CHEN Q , ZENG Y N , ZHANG K , et al . Polydatin increases radiosensitivity by inducing apoptosis of stem cells in colorectal cancer [J]. Int J Biol Sci , 2019 , 15 ( 2 ): 430 - 440 .
JIANG J , CHEN Y D , DONG T X , et al . Polydatin inhibits hepatocellular carcinoma via the Akt/STAT3‑FOXO1 signaling pathway [J]. Oncol Lett , 2019 , 17 ( 5 ): 4505 - 4513 .
JIAO Y , WU Y , DU D . Polydatin inhibits cell proliferation,invasion and migration,and induces cell apoptosis in hepatocellular carcinoma [J]. Braz J Med Biol Res , 2018 , 51 ( 4 ): e6867 .
CHEN S J , TAO J L , ZHONG F Y , et al . Polydatin down-regulates the phosphorylation level of Creb and induces apoptosis in human breast cancer cell [J]. PLoS One , 2017 , 12 ( 5 ): e0176501 .
ZHANG X C . Effects of polydatin on the proliferation,migration,and invasion of ovarian cancer [J]. Biocell , 2019 , 43 ( 4 ): 313 - 319 .
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LI H X , SHI B Y , LI Y Y , et al . Polydatin inhibits cell proliferation and induces apoptosis in laryngeal cancer and HeLa cells via suppression of the PDGF/Akt signaling pathway [J]. J Biochem Mol Toxic , 2017 , 31 ( 7 ): e21900 .
YANG B J , ZHAO S X . Polydatin regulates proliferation,apoptosis and autophagy in multiple myeloma cells through mTOR/p70s6k pathway [J]. Oncotargets Ther , 2017 , 10 : 935 - 944 .
孙蓓 , 叶因涛 . 虎杖苷对肺癌A549细胞增殖和侵袭的抑制作用及机制探讨 [J]. 天津医药 , 2019 , 47 ( 3 ): 255 - 259 .
CHEN L L , CHEN Z X , XU Z Q , et al . Polydatin protects Schwann cells from methylglyoxal induced cytotoxicity and promotes crushed sciatic nerves regeneration of diabetic rats [J]. Phytother Res , 2021 , 35 ( 8 ): 4592 - 4604 .
SHAH F A , KURY L A , LI T , et al . Polydatin attenuates neuronal loss via reducing neuroinflammation and oxidative stress in rat MCAO models [J]. Front Pharmacol , 2019 , 10 : 663 .
ZHAO X M , QIN J X , LI H T , et al . Effect of polydatin on neurological function and the Nrf2 pathway during intracerebral hemorrhage [J]. J Mol Neurosci , 2020 , 70 ( 9 ): 1332 - 1337 .
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ZHANG S Z , WANG S J , SHI X Z , et al . Polydatin alleviates parkinsonism in MPTP-model mice by enhancing glycolysis in dopaminergic neurons [J]. Neurochem Int , 2020 , 139 : 104815 .
周勇 , 余洋 , 程文涛 , 等 . 虎杖苷对慢性阻塞性肺疾病大鼠气道炎症及TLR4/NF- κ B信号通路的影响 [J]. 中药药理与临床 , 2019 , 35 ( 2 ): 35 - 40 .
朴玉华 , 王知广 , 朴艺花 , 等 . 虎杖苷对实验性哮喘小鼠气道炎症的影响及其机制 [J]. 吉林大学学报:医学版 , 2020 , 46 ( 6 ): 1111 - 1116,1345 .
赵雨喆 , 姜京植 , 叶晶 , 等 . 虎杖苷通过p38 MAPK/Nrf2/HO-1通路减轻小鼠哮喘模型气道炎症 [J]. 中国药理学通报 , 2018 , 34 ( 6 ): 851 - 856 .
韩延忠 , 沈娟 , 吴立蓉 , 等 . 虎杖苷对Ⅱ型糖尿病小鼠溃疡创面愈合影响的实验研究 [J]. 中国临床药理学杂志 , 2017 , 33 ( 19 ): 1934 - 1937 .
王曌华 , 张永 , 裴敬仲 . 虎杖苷对严重烧伤小鼠早期肠损伤及SIRT1/NF- κ B通路的影响 [J]. 中国免疫学杂志 , 2020 , 36 ( 5 ): 566 - 570,576 .
GUO J M , LIU T T , MA L , et al . Polydatin attenuates 14.1 MeV neutron-induced injuries via regulating the apoptosis and antioxidative pathways and improving the hematopoiesis of mice [J]. Oxid Med Cell Longev , 2020 , doi: 10.1155/2020/8905860 http://dx.doi.org/10.1155/2020/8905860 .
CAO K , LEI X , LIU H , et al . Polydatin alleviated radiation-induced lung injury through activation of Sirt3 and inhibition of epithelial-mesenchymal transition [J]. J Cell Mol Med , 2017 , 21 ( 12 ): 3264 - 3276 .
BONUCCI M , RAGGI R , VACCA R A . Polydatin and its potential protective effect on COVID-19 [J]. Clin Nutr , 2020 , 39 ( 12 ): 3850 - 3851 .
DOUSTIMOTLAGH A H , EFTEKHARI M . Glucose-6-phosphate dehydrogenase inhibitor for treatment of severe COVID-19:polydatin [J]. Clin Nutr ESPEN , 2021 , 43 : 197 - 199 .
WU Y , XUE L , DU W M , et al . Polydatin restores endothelium-dependent relaxation in rat aorta rings impaired by high glucose:a novel insight into the PPAR β -NO signaling pathway [J]. PLoS One , 2017 , 10 ( 5 ): e0126249 .
HU W H , WANG H Y , KONG X P , et al . Polydatin suppresses VEGF-induced angiogenesis through binding with VEGF and inhibiting its receptor signaling [J]. FASEB J , 2019 , 33 ( 1 ): 532 - 544 .
BAVETTA M , SILVAGGIO D , CAMPIONE E , et al . The effects of association of topical polydatin improves the preemptive systemic treatment on EGFR inhibitors cutaneous adverse reactions [J]. J Clin Med , 2021 , 10 ( 3 ): 466 .
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