绞股蓝黄酮对氧化受损LLC-PK1细胞的保护作用
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摘要
利用色谱法从绞股蓝中分离得到4个黄酮类化合物,通过MS及NMR分别被鉴定为槲皮素-3-O-(2″,6″-α-L-二鼠李糖基)-β-D-吡喃半乳糖苷(1)、槲皮素-3-O-(2″,6″-α-L-二鼠李糖基)-β-D-吡喃葡萄糖苷(2)、槲皮素-3-O-(2″-α-L-鼠李糖基)-β-D-吡喃半乳糖苷(3)和槲皮素-3-O-(2″-α-L-鼠李糖基)-β-D-吡喃葡萄糖苷(4)。其中化合物1～3为首次从葫芦科中分离得到。这4个黄酮化合物体外对DPPH,·OH和■自由基均有较强的清除作用,尤其是对DPPH自由基的清除能力,IC_(50)分别为71.4,29.5,48.3,79.2μmol·L~(-1)。此外,这4个黄酮化合物对AAPH诱导氧化受损的猪肾小管上皮LLC-PK1细胞具有保护作用,抑制细胞丙二醛(MDA)的升高及超氧化物歧化酶(SOD)和谷胱甘肽(GSH)的减少。尽管还需要进一步的研究来证明其在体内和临床试验中的有效性,但这项研究为在绞股蓝中寻找潜在的抗氧化剂提供了可能。
Four flavonoids were isolated from Gynostemma pentaphyllum by chromatography methods and their structures were identified by MS and NMR spectra data as quercetin-3-O-( 2″,6″-di-α-L-rhamnosyl)-β-D-galactopyranoside( 1),quercetin-3-O-( 2″,6″-di-α-L-rhamnosyl)-β-D-glucopyranoside( 2),quercetin-3-O-( 2″-α-L-rhamnosyl)-β-D-galactopyranoside( 3),and quercetin-3-O-( 2″-α-L-rhamnosyl)-β-D-glucopyranoside( 4). Among them,compounds 1-3 were obtained from the Cucurbitaceae family for the first time.The four flavonoids showed potent antioxidant effects against the DPPH,·OH and ■radicals in vitro,especially for DPPH radical scavenging activity with the IC50 values of 71. 4,29. 5,48. 3 and 79. 2 μmol·L~(-1),respectively. Moreover,the four flavonoids displayed strong cytoprotection against AAPH-induced oxidative damage in LLC-PK1 cells by suppressing the increase of malondialdehyde( MDA) and the decrease of the superoxide dismutase( SOD) and glutathione( GSH). Since further research is needed to prove its efficacy in vivo and clinical trial,the study may provide four potential antioxidants from G. pentaphyllum.
Four flavonoids were isolated from Gynostemma pentaphyllum by chromatography methods and their structures were identified by MS and NMR spectra data as quercetin-3-O-( 2″,6″-di-α-L-rhamnosyl)-β-D-galactopyranoside( 1),quercetin-3-O-( 2″,6″-di-α-L-rhamnosyl)-β-D-glucopyranoside( 2),quercetin-3-O-( 2″-α-L-rhamnosyl)-β-D-galactopyranoside( 3),and quercetin-3-O-( 2″-α-L-rhamnosyl)-β-D-glucopyranoside( 4). Among them,compounds 1-3 were obtained from the Cucurbitaceae family for the first time.The four flavonoids showed potent antioxidant effects against the DPPH,·OH and ■radicals in vitro,especially for DPPH radical scavenging activity with the IC50 values of 71. 4,29. 5,48. 3 and 79. 2 μmol·L~(-1),respectively. Moreover,the four flavonoids displayed strong cytoprotection against AAPH-induced oxidative damage in LLC-PK1 cells by suppressing the increase of malondialdehyde( MDA) and the decrease of the superoxide dismutase( SOD) and glutathione( GSH). Since further research is needed to prove its efficacy in vivo and clinical trial,the study may provide four potential antioxidants from G. pentaphyllum.
引文
[1]Nookabkaew S,Rangkadilok N,Prachoom N,et al.Concentrations of trace elements in organic fertilizers and animal manures and feeds and cadmium contamination in herbal tea(Gynostemma pentaphyllum Makino)[J].J Agri Food Chem,2016,64(16):3119.
[2]Huang T H,Tran V H,Roufogalis B D,et al.Gypenoside XLIX,a naturally occurring PPAR-alpha activator,inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells[J].Eur J Pharmacol,2007,565(1/3):158.
[3]王玉荣,杨康,崔伟业,等.绞股蓝黄酮对过氧化氢损伤A549细胞的作用[J].中国中药杂志,2018,43(5):1014.
[4]王梁,吴伟,陈龙,等.绞股蓝总皂苷对口腔鳞状癌细胞增殖和凋亡的影响[J].中华全科医学,2018,16(9):1441.
[5]Xie Z,Huang H,Zhao Y,et al.Chemical composition and antiproliferative and anti-inflammatory effects of the leaf and wholeplant samples of diploid and tetraploid Gynostemma pentaphyllum(Thunb.)Makino[J].Food Chem,2012,132(1):125.
[6]孙立峰,郭华,孟剑锋,等.绞股蓝总黄酮通过抑制氧化应激反应抗心肌缺血保护作用的研究[J].中华中医药学刊,2018,36(10):2513.
[7]Sheweita S A,Mashaly S,Newairy A A,et al.Changes in oxidative stress and antioxidant enzyme activities in streptozotocin-induced diabetes mellitus in rats:role of Alhagi maurorum extracts[J].Oxid Med Cell Long,2016,2016:5264064.
[8]Al-Dosari D I,Ahmed M M,Al-Rejaie S S,et al.Flavonoid naringenin attenuates oxidative stress,apoptosis and improves neurotrophic effects in the diabetic rat retina[J].Nutrients,2017,9(10):1.
[9]Karam B S,Chavez-Moreno A,Koh W,et al.Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes[J].Cardiovas Diabetol,2017,16(1):120.
[10]Viswanatha G L,Shylaja H,Moolemath Y.The beneficial role of naringin--a citrus bioflavonoid,against oxidative stress-induced neurobehavioral disorders and cognitive dysfunction in rodents:a systematic review and Meta-analysis[J].Biomed Pharmacother,2017,94:909.
[11]Wilmanski T,Zhou X,Zheng W,et al.Inhibition of pyruvate carboxylase by 1alpha,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression[J].Cancer Lett,2017,411:171.
[12]Hatano T,Edamatsu R,Hiramatsu M,et al.Effects of the interaction of tannins with co-existing substances.VI.:effects of tannins and related polyphenols on superoxide anion radical,and on1,1-diphenyl-2-picrylhydrazyl radical[J].Chem Pharm Bull,1989,37:2016.
[13]Yasukawa K,Sekine H,Takido M.Two flavonol glycosides from Lysimachia fortunei[J].Phytochemistry,1989,28(8):2215.
[14]Zhou X,Peng J,Fan G,et al.Isolation and purification of flavonoid glycosides from Trollius ledebouri using high-speed counter-current chromatography by stepwise increasing the flowrate of the mobile phase[J].J Chromatogr,2005,1092(2):216.
[15]王盈盈,梁鑫,钟惠民.云贵腺药珍珠菜化学成分研究[J].中草药,2012,43(7):1280.
[16]赵玉静,李建宽,张鑫,等.番石榴叶黄酮类化学成分及其抗氧化活性研究[J].中国中药杂志,2018,43(4):760.
[17]张四杰,钱正,刘京晶,等.铁皮石斛花中花色成分抗氧化性和稳定性研究[J].中国中药杂志,2018,43(10):2025.
[18]Zhang H,Zhang S,Wang J,et al.Wheat bran feruloyl oligosaccharides protect against AAPH-induced oxidative injury via p38MAPK/PI3K-Nrf2/Keap1-MafK pathway[J].J Funct Foods,2017,29:53.
[19]Qi Z,Cai C K,Li J,et al.Baicalin and rutin are major constituents in Shuanghuanglian injection involving anaphylactoid reaction[J].J Trad Chin Med,2017,37(3):412.
[20]Musa K H,Abdullah A,Al-Haiqi A.Determination of DPPHfree radical scavenging activity:application of artificial neural networks[J].Food Chem,2016,194:705.
[21]Song J L,Choi J H,Seo J H,et al.Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells[J].Nutr Res Prac,2014,8(2):138.
[22]Hu Y,Ma H,Zou Z,et al.Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress[J].Biomed Pharmacother,2017,85:313.
[23]So M J,Cho E J.Phloroglucinol attenuates free radical-induced oxidative stress[J].Prev Nutr Food Sci,2014,19(3):129.
[24]Li X,Xu L,Zhou W,et al.Chronic exposure to microcystin-LRaffected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice[J].Environ Pollut,2016,210:48.
[25]Yuan-jing F,Wei W,Jian-ping L,et al.Genistein promotes the metabolic transformation of acetaminophen to glucuronic acid in human L-O2,HepG2 and Hep3b cells via the Nrf2/Keap1 pathway[J].Food Funct,2016,7(11):4683.
[26]Park M,Han J.Protective effects of the fermented Laminaria japonica extract on oxidative damage in LLC-PK1 cells[J].Prev Nutr Food Sci,2013,18(4):227.
[27]邱海鹏,张晓璇,申兴斌,等.补肾益智方联合丁苯酞对阿尔茨海默病患者Aβ,GSH-Px,SOD及MDA水平的影响[J].中国实验方剂学杂志,2016,22(14):187.
[2]Huang T H,Tran V H,Roufogalis B D,et al.Gypenoside XLIX,a naturally occurring PPAR-alpha activator,inhibits cytokine-induced vascular cell adhesion molecule-1 expression and activity in human endothelial cells[J].Eur J Pharmacol,2007,565(1/3):158.
[3]王玉荣,杨康,崔伟业,等.绞股蓝黄酮对过氧化氢损伤A549细胞的作用[J].中国中药杂志,2018,43(5):1014.
[4]王梁,吴伟,陈龙,等.绞股蓝总皂苷对口腔鳞状癌细胞增殖和凋亡的影响[J].中华全科医学,2018,16(9):1441.
[5]Xie Z,Huang H,Zhao Y,et al.Chemical composition and antiproliferative and anti-inflammatory effects of the leaf and wholeplant samples of diploid and tetraploid Gynostemma pentaphyllum(Thunb.)Makino[J].Food Chem,2012,132(1):125.
[6]孙立峰,郭华,孟剑锋,等.绞股蓝总黄酮通过抑制氧化应激反应抗心肌缺血保护作用的研究[J].中华中医药学刊,2018,36(10):2513.
[7]Sheweita S A,Mashaly S,Newairy A A,et al.Changes in oxidative stress and antioxidant enzyme activities in streptozotocin-induced diabetes mellitus in rats:role of Alhagi maurorum extracts[J].Oxid Med Cell Long,2016,2016:5264064.
[8]Al-Dosari D I,Ahmed M M,Al-Rejaie S S,et al.Flavonoid naringenin attenuates oxidative stress,apoptosis and improves neurotrophic effects in the diabetic rat retina[J].Nutrients,2017,9(10):1.
[9]Karam B S,Chavez-Moreno A,Koh W,et al.Oxidative stress and inflammation as central mediators of atrial fibrillation in obesity and diabetes[J].Cardiovas Diabetol,2017,16(1):120.
[10]Viswanatha G L,Shylaja H,Moolemath Y.The beneficial role of naringin--a citrus bioflavonoid,against oxidative stress-induced neurobehavioral disorders and cognitive dysfunction in rodents:a systematic review and Meta-analysis[J].Biomed Pharmacother,2017,94:909.
[11]Wilmanski T,Zhou X,Zheng W,et al.Inhibition of pyruvate carboxylase by 1alpha,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression[J].Cancer Lett,2017,411:171.
[12]Hatano T,Edamatsu R,Hiramatsu M,et al.Effects of the interaction of tannins with co-existing substances.VI.:effects of tannins and related polyphenols on superoxide anion radical,and on1,1-diphenyl-2-picrylhydrazyl radical[J].Chem Pharm Bull,1989,37:2016.
[13]Yasukawa K,Sekine H,Takido M.Two flavonol glycosides from Lysimachia fortunei[J].Phytochemistry,1989,28(8):2215.
[14]Zhou X,Peng J,Fan G,et al.Isolation and purification of flavonoid glycosides from Trollius ledebouri using high-speed counter-current chromatography by stepwise increasing the flowrate of the mobile phase[J].J Chromatogr,2005,1092(2):216.
[15]王盈盈,梁鑫,钟惠民.云贵腺药珍珠菜化学成分研究[J].中草药,2012,43(7):1280.
[16]赵玉静,李建宽,张鑫,等.番石榴叶黄酮类化学成分及其抗氧化活性研究[J].中国中药杂志,2018,43(4):760.
[17]张四杰,钱正,刘京晶,等.铁皮石斛花中花色成分抗氧化性和稳定性研究[J].中国中药杂志,2018,43(10):2025.
[18]Zhang H,Zhang S,Wang J,et al.Wheat bran feruloyl oligosaccharides protect against AAPH-induced oxidative injury via p38MAPK/PI3K-Nrf2/Keap1-MafK pathway[J].J Funct Foods,2017,29:53.
[19]Qi Z,Cai C K,Li J,et al.Baicalin and rutin are major constituents in Shuanghuanglian injection involving anaphylactoid reaction[J].J Trad Chin Med,2017,37(3):412.
[20]Musa K H,Abdullah A,Al-Haiqi A.Determination of DPPHfree radical scavenging activity:application of artificial neural networks[J].Food Chem,2016,194:705.
[21]Song J L,Choi J H,Seo J H,et al.Antioxidative effects of fermented sesame sauce against hydrogen peroxide-induced oxidative damage in LLC-PK1 porcine renal tubule cells[J].Nutr Res Prac,2014,8(2):138.
[22]Hu Y,Ma H,Zou Z,et al.Activation of Akt and JNK/Nrf2/NQO1 pathway contributes to the protective effect of coptisine against AAPH-induced oxidative stress[J].Biomed Pharmacother,2017,85:313.
[23]So M J,Cho E J.Phloroglucinol attenuates free radical-induced oxidative stress[J].Prev Nutr Food Sci,2014,19(3):129.
[24]Li X,Xu L,Zhou W,et al.Chronic exposure to microcystin-LRaffected mitochondrial DNA maintenance and caused pathological changes of lung tissue in mice[J].Environ Pollut,2016,210:48.
[25]Yuan-jing F,Wei W,Jian-ping L,et al.Genistein promotes the metabolic transformation of acetaminophen to glucuronic acid in human L-O2,HepG2 and Hep3b cells via the Nrf2/Keap1 pathway[J].Food Funct,2016,7(11):4683.
[26]Park M,Han J.Protective effects of the fermented Laminaria japonica extract on oxidative damage in LLC-PK1 cells[J].Prev Nutr Food Sci,2013,18(4):227.
[27]邱海鹏,张晓璇,申兴斌,等.补肾益智方联合丁苯酞对阿尔茨海默病患者Aβ,GSH-Px,SOD及MDA水平的影响[J].中国实验方剂学杂志,2016,22(14):187.