Abstract
The study aims to screen potential anti-inflammatory phytochemicals and explore its mechanism from Tetrastigma hemsleyanum Diels et Gilg based on their molecular docking with Keap1 protein and low-grade inflammatory model of vascular endothelial cells, and further analyzes the effects of active ingredients on the gene and protein expression of pro-inflammatory factors. Results showed that kaempferol-3-O-rutinoside, isoquercitrin, and rutin in root and 5-caffeoylquinic acid, vitexin, and orientin in leaf had significant interactions with Keap1 protein, all of which occurred in the binding cavity of Keap1 with Nrf2 protein, possibly leading to the dissociation of Nrf2 and activation. All of these six phytochemicals could alleviate vascular low-grade inflammation, and among which vitexin had the strongest protective effect. It was further found that vitexin could significantly up-regulate Nrf2 gene and protein expression in cells, while down-regulate Keap1 protein expression, indicating that Nrf2 was activated. In addition, vitexin was highly stable in cell culture medium and buffer salt solution, and it could be absorbed by vascular endothelial cells in a prototype form. Furthermore, vitexin significantly inhibited the gene and protein expression of IL-6, IL-1β, and ICAM, as well as the phosphorylation level of NF-κB p65 in a dose-dependent manner. Therefore, vitexin may have a strong anti-inflammatory function by directly binding with Keap1 to potentially activate Nrf2 and affecting the activity of NF-κB pathway.
Publication Date
5-28-2020
First Page
46
Last Page
53,110
DOI
10.13652/j.issn.1003-5788.2020.05.009
Recommended Citation
Qian, XING; Liu-feng, ZHENG; Ting, GAN; Ting, XIAO; Ze-yuan, DENG; and Xiao-ru, LIU
(2020)
"nti-inflammatory effect and mechanism of major components in Tetrastigma hemsleyanum Diels et Gilg,"
Food and Machinery: Vol. 36:
Iss.
5, Article 9.
DOI: 10.13652/j.issn.1003-5788.2020.05.009
Available at:
https://www.ifoodmm.cn/journal/vol36/iss5/9
References
[1] SOWERS J R.Obesity and cardiovascular disease[J].Clinical Chemistry,2020,44(8):8-10.
[2] 胡盛寿.《中国心血管病报告2018》概要[J].中国循环杂志,2019,34(3):209-220.
[3] LUIGI F,ELISA F.Inflammageing:Chronic inflammation in ageing,cardiovascular disease,and frailty[J].Nature Reviews Cardiology,2018,15(1):505-522.
[4] GRIVENNIKOV S,GRETEN F,KARIN M.Immunity,inflammation,and cancer[J].Cell,2010,140(6):883-899.
[5] TAUBE A,SCHLICH R,SELL H,et al.Inflammation and metabolic dysfunction:links to cardiovascular diseases[J].Am J Physiol Heart Circ Physiol,2012,302(11):2 148-2 155.
[6] LI J J,LI Y S,FANG C H,et al.Effects of simvastatin within two weeks on anti-inflammatory cytokine interleukin 10 in patients with unstable angina[J].Heart,2006,92(4):529-530.
[7] FERRIE J,KIVIM K,SHIPLEY M,et al.Job insecurity and incident coronary heart disease:The whitehall II prospective cohort study[J].Atherosclerosis,2013,227(1):178-181.
[8] SUN Shao-mei,WU Hong-mei,ZHANG Qing,et al.Subnormal peripheral blood leukocyte counts are related to the lowest prevalence and incidence of metabolic syndrome:Tianjin chronic low-grade systemic inflammation and health cohort study[J].Mediators of Inflammation,2015,2 014(1):1-12.
[9] 刘文静,刘东波,张志旭,等.药食兼用植物抑菌和抗炎作用研究进展[J].中草药,2016,47(19):3 535-3 542.
[10] 李瑛琦,陆文超,于治国.三叶青的化学成分研究[J].中草药,2003,34(11):982-983.
[11] 陈红,廖淑彬,陈丹,等.闽产三叶青地上部分抗炎提取物的急性毒性研究[J].福建医科大学学报,2017,51(5):287-290.
[12] 刘培刚,魏克民.三叶青生物学、药理学及临床应用相关研究进展[J].中国中医药科技,2018,25(6):927-933.
[13] 徐硕,金鹏飞,徐文峰,等.民间中药三叶青的研究进展[J].中南药学,2016,14(12):1 336-1 341.
[14] 程权,傅华洲.三叶青药理作用及临床应用研究进展[J].辽宁中医药大学学报,2016,18(4):235-238.
[15] PENG Xin,ZHANG Yuan-yuan,WANG Jin,et al.Ethylacetate extract from Tetrastigma hemsleyanum induces apoptosis via the mitochondrial caspase-dependent intrinsic pathway in HepG2 cells[J].Tumor Biology,2015,37(1):865-876.
[16] LIU Dan-dan,CAO Gang,HAN Li-kai,et al.Flavonoids from Radix Tetrastigmae inhibit TLR4/MD-2 mediated JNK and NF-κB pathway with anti-inflammatory properti-es[J].Cytokine,2016,84:29-36.
[17] 孙永.三叶青化学成分及其抗氧化和抗癌活性的研究[D].南昌:南昌大学,2018:25-48.
[18] KASHIHARA N,SATOH M,KANWAR Y.Reactive oxygen species in the pathogenesis of chronic kidney disease:lessons derived from diabetic nephropathy[J].Systems Biology of Free Radicals & Antioxidants,2016,118:2 675-2 703.
[19] REULAND D,MCCORD J,HAMILTON K.The role of Nrf2 in the attenuation of cardiovascular disease[J].Exercise & Sport Sciences Reviews,2013,41(3):162-168.
[20] MILLS E,RYAN D,PRAG H,et al.Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1[J].Nature,2018,556:113-117.
[21] LU Meng-chen,JI Jian-ai,JIANG Zheng-yu,et al.The Keap1-Nrf2-ARE pathway as a potential preventive and therapeutic target:An update[J].Medicinal Research Reviews,2016,36(5):924-963.
[22] SUN Hao-peng,ZHU Jie,LIN Hong-zhi,et al.Recent progress in the development of small molecule Nrf2 modulators:A patent review(2012—2016)[J].Expert Opinion on Therapeutic Patents,2017,7(27):763-785.
[23] 董丽莎,李妍妍,张红燕,等.黑线鳕鱼皮胶原蛋白胰蛋白酶酶解多肽对UVB诱导HaCaT光损伤的抑制作用[J].食品科学,2018,39(10):185-192.
[24] ZHENG Liu-feng,WEI Hong-kui,YU Hui-chao,et al.Fish skin gelatin hydrolysate produced by ginger powder induces glutathione synthesis to prevent hydrogen peroxide-induced intestinal oxidative stress via Pept1-p62-Nrf2 cascade[J].Journal of Agricultural and Food Chemistry,2018,66(44):11 601-11 611.
[25] 彭瀚.黑豆不同形态多酚的组成、消化特性及其抗氧化活性的研究[D].南昌:南昌大学,2017:77-78.
[26] LU Ying,YU Ting,LIU Jing-yao,et al.Vitexin attenuates lipopolysaccharide-induced acute lung injury by controlling the Nrf2 pathway[J].PLOS One,2018,13(4):1-12.
[27] XIAO Jian-bo,GGER P.Stability of dietary polyphenols under the cell culture conditions:avoiding erroneous conclusions[J].Journal of Agricultural & Food Chemistry,2015,63(5):1 547-1 557.
[28] TANG Fen,XIE Yi-xi,CAO Hui,et al.Fetal bovine serum influences the stability and bioactivity of resveratrol analogues:A polyphenol-protein interaction approach[J].Food Chemistry,2017,219:321-328.
[29] BHARDWAJ M,CHO H,PAUL S,et al.Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells[J].Oncotarget,2017,9(3):3 278-3 291.