CHEN Mengxia, WANG Ni, MENG Fanqiang, et al. Isolation of Gingerols and Its Preventive Effect on Insulin Resistance of HepG2 Cells[J]. Science and Technology of Food Industry, 2022, 43(22): 387−395. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022030039.
Citation: CHEN Mengxia, WANG Ni, MENG Fanqiang, et al. Isolation of Gingerols and Its Preventive Effect on Insulin Resistance of HepG2 Cells[J]. Science and Technology of Food Industry, 2022, 43(22): 387−395. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2022030039.

Isolation of Gingerols and Its Preventive Effect on Insulin Resistance of HepG2 Cells

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  • Received Date: March 03, 2022
  • Available Online: September 12, 2022
  • Objective: To investigate the prevention effect of gingerols on insulin resistance of HepG2 cells, extraction and isolation of ginger gingerols were carried out. Methods: The crude extract of gingerols were extracted by using ethanol and water bath oscillation. The crude extract of gingerols were separated and purified by ethyl acetate extraction and petroleum ether. The antioxidant activity of gingerols were determined using 1,1-diphenyl-2-picrhydrazyl (DPPH) and 2,2'-biazo-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS). Insulin resistance model of HepG2 cells were constructed, and the effects of gingerols on glucose consumption, superoxide dismutase (SOD), catalase (CAT) activity and PI3K/AKT pathway related gene expression were determined. Results: The optimum extraction conditions determined by orthogonal experiment were as follows: Solid-liquid ratio of 1:50 g/mL, extraction time of 80 min, ethanol volume fraction of 60%, extraction temperature of 50 ℃. Under these conditions, the yield of gingerols was 1.885%±0.071%. After extraction with ethyl acetate and petroleum ether, gingerols content was more than 34.55%. Antioxidant analysis showed that the semi-scavenging concentrations (EC50) of gingerols on DPPH and ABTS+ were 0.501 and 0.111 mg·mL−1, respectively. After treating with 25 μg·mL−1 insulin for 48 h, cells exhibited reduced glucose consumption (P<0.05). Gingerols treatment significantly increased glucose consumption, SOD and CAT activities in a dose-dependent manner (P<0.05). In addition, the expressions of PI3K, IRS-2 and AKT genes were significantly up-regulated in gingerols treatment group (P<0.05), and the expressions of GSK-3β, FoxOI and PEPCK were significantly down-regulated in gingerols treatment group. Conclusion: Gingerols had desirable antioxidant activity, and also prevented insulin resistance through PI3K/AKT pathway.
  • [1]
    WANG H, LIU S, CUI Y, et al. Hepatoprotective effects of flavonoids from common buckwheat hulls in type 2 diabetic rats and HepG2 cells[J]. Food Science & Nutrition,2021,9(9):4793−4802.
    [2]
    ZHAO Y, XING H. A different perspective for management of diabetes mellitus: Controlling viral liver diseases[J]. J Diabetes Res,2017(2017):5625371.
    [3]
    BEDI O, AGGARWAL S, TREHANPATI N, et al. Molecular and pathological events involved in the pathogenesis of diabetes-associated nonalcoholic fatty liver disease[J]. J Clin Exp Hepatol,2019,9(5):607−618. doi: 10.1016/j.jceh.2018.10.004
    [4]
    DOU Z, LIU C, FENG X, et al. Camel whey protein (CWP) ameliorates liver injury in type 2 diabetes mellitus rats and insulin resistance (IR) in HepG2 cells via activation of the PI3K/Akt signaling pathway[J]. Food & Function,2021,13(1):255−269.
    [5]
    WANG C, BATEY R, YAMAHARA J, et al. Multiple molecular targets in the liver, adipose tissue and skeletal muscle in ginger-elicited amelioration of nonalcoholic fatty liver disease[J]. Journal of Functional Foods,2017,36:43−51. doi: 10.1016/j.jff.2017.06.040
    [6]
    KIM H J, KIM B, MUN E G, et al. The antioxidant activity of steamed ginger and its protective effects on obesity induced by high-fat diet in C57BL/6J mice[J]. Nutr Res Pract,2018,12(6):503−511. doi: 10.4162/nrp.2018.12.6.503
    [7]
    SHUKLA A, NAIK S N, GOUD V V, et al. Supercritical CO2 extraction and online fractionation of dry ginger for production of high-quality volatile oil and gingerols enriched oleoresin[J]. Industrial Crops and Products,2019,130:352−362. doi: 10.1016/j.indcrop.2019.01.005
    [8]
    SEMWAL R B, SEMWAL D K, COMBRINCK S, et al. Gingerols and shogaols: Important nutraceutical principles from ginger[J]. Phytochemistry,2015,117:554−568. doi: 10.1016/j.phytochem.2015.07.012
    [9]
    WEI Q Y, MA J P, CAI Y J, et al. Cytotoxic and apoptotic activities of diarylheptanoids and gingerol-related compounds from the rhizome of Chinese ginger[J]. J Ethnopharmacol,2005,102(2):177−184. doi: 10.1016/j.jep.2005.05.043
    [10]
    VARAKUMAR S, UMESH K V, SINGHAL R S. Enhanced extraction of oleoresin from ginger (Zingiber officinale) rhizome powder using enzyme-assisted three phase partitioning[J]. Food Chem,2017,216:27−36. doi: 10.1016/j.foodchem.2016.07.180
    [11]
    FAJRIN F A, NUGROHO A E, NURROCHMAD A, et al. Ginger extract and its compound, 6-shogaol, attenuates painful diabetic neuropathy in mice via reducing TRPV1 and NMDAR2B expressions in the spinal cord[J]. J Ethnopharmacol,2020,249:112396. doi: 10.1016/j.jep.2019.112396
    [12]
    CHAKRABORTY D, MUKHERJEE A, SIKDAR S, et al. [6]-Gingerol isolated from ginger attenuates sodium arsenite induced oxidative stress and plays a corrective role in improving insulin signaling in mice[J]. Toxicol Lett,2012,210(1):34−43. doi: 10.1016/j.toxlet.2012.01.002
    [13]
    XU Y, BAI L, CHEN X, et al. 6-Shogaol ameliorates diabetic nephropathy through anti-inflammatory, hyperlipidemic, anti-oxidative activity in db/db mice[J]. Biomed Pharmacother,2018,97:633−641. doi: 10.1016/j.biopha.2017.10.084
    [14]
    张明昶, 李健, 蒙继昭. 紫外分光光度法测定姜中姜辣素类化合物的含量[J]. 贵州医药,2003,27:283−284. [ZHANG M C, LI J, MENG J Z. Determination of gingerol compounds in ginger by UV spectrophotometry[J]. Guizhou Medicine,2003,27:283−284. doi: 10.3969/j.issn.1000-744X.2003.03.054
    [15]
    李冰. 生姜挥发油成分分析及其主要活性成分6-姜酚的抗炎机制初步探究[D]. 沈阳: 中国医科大学, 2019

    LI B. Analysis of volatile oil and preliminary study on anti-inflammatory mechanism of 6-gingerol, the main active component of ginger[D]. Shenyang: China Medical University, 2019.
    [16]
    梅丽娟, 岳邵. 一种从生姜中提取纯化6-姜酚的方法: 中国, 201210553119.2[P]. 2014-12-03

    MEI L J, YUE S. A method of extracting and purifying 6-gingerol from ginger: China, 201210553119.2[P]. 2014-12-03.
    [17]
    潘勤, 吴孙. 一种高纯度总姜酚、其制备方法及用途: 中国, 201610771664.7[P]. 2018-03-09

    PAN Q, WU S. Preparation method and use of high purity total gingerol: China, 201610771664.7[P]. 2018-03-09.
    [18]
    AN K, WEI L, FU M, et al. Effect of carbonic maceration (CM) on the vacuum microwave drying of Chinese ginger (Zingiber officinale Roscoe) slices: Drying characteristic, moisture migration, antioxidant activity, and microstructure[J]. Food and Bioprocess Technology,2020,13(9):1661−1674. doi: 10.1007/s11947-020-02504-y
    [19]
    AN K, ZHAO D, WANG Z. Comparison of different drying methods on Chinese ginger (Zingiber officinale Roscoe): Changes in volatiles, chemical profile, antioxidant properties, and microstructure[J]. Food Chemistry,2016,197:1292−1300. doi: 10.1016/j.foodchem.2015.11.033
    [20]
    肖徐阳. 基于肠道菌群和胰岛素通路研究黄芪甲苷降糖作用和机制[D]. 西安: 陕西科技大学, 2020

    XIAO X Y. Study on the hypoglycemic effect and mechanism of astragaloside IV based on intestinal flora and insulin pathway[D]. Xi'an: Shaanxi University of Science and Technology, 2020.
    [21]
    JIANG H W, MA Y J, YAN J Q, et al. Geniposide promotes autophagy to inhibit insulin resistance in HepG2 cells via P62/NF-κB/GLUT-4[J]. Molecular Medicine Reports,2017,16:7237−7244. doi: 10.3892/mmr.2017.7503
    [22]
    MANDAL S K, BISWAS R, BHATTACHARYYA S S, et al. Lycopodine from Lycopodium clavatum extract inhibits proliferation of Hela cells through induction of apoptosis via caspase-3 activation[J]. Eur J Pharmacol,2010,626(2-3):115−122. doi: 10.1016/j.ejphar.2009.09.033
    [23]
    项敏. 生姜中姜辣素的提取与分离工艺研究[D]. 武汉: 武汉工程大学, 2015

    XIANG M. Extraction and separation of gingerol from ginger[D]. Wuhan: Wuhan Institute of Technology, 2015.
    [24]
    BHATTARAI S, TRAN V H, DUKE C C. The stability of gingerol and shogaol in aqueous solutions[J]. Journal of Pharmaceutical Sciences,2001,90(10):1658−1664. doi: 10.1002/jps.1116
    [25]
    张鲁明, 王龙厚, 周峥嵘, 等. 乙醇提取姜辣素的工艺条件研究[J]. 中国农学通报,2010,26(19):58−61. [ZHANG L M, WANG L H, ZHOU Z R, et al. Study on the technological conditions of ethanol extraction of gingerol[J]. Chinese Agricultural Science Bulletin,2010,26(19):58−61.
    [26]
    李田叶, 刘卫华, 梁娜, 等. 评估生姜及其不同炮制品中姜辣素和其抗氧化活性[J]. 食品工业,2016,37(12):180−183. [LI T Y, LIU W H, LIANG N, et al. Evaluation of gingerol and its antioxidant activity in ginger and its processed products[J]. Food Industry,2016,37(12):180−183.
    [27]
    SHUKLA A, GOUD V V, DAS C. Antioxidant potential and nutritional compositions of selected ginger varieties found in Northeast India[J]. Industrial Crops and Products,2019,128:167−176. doi: 10.1016/j.indcrop.2018.10.086
    [28]
    刘步云, 王永丽, 张健, 等. 不同品种生姜的抗氧化及抗炎症活性[J]. 食品与发酵工业,2015,41(11):81−86. [LIU B Y, WANG Y L, ZHANG J, et al. Antioxidant and anti-inflammatory activities of different ginger cultivars[J]. Food and Fermentation Industries,2015,41(11):81−86.
    [29]
    TOHMA H, GÜLÇIN İ, BURSAL E, et al. Antioxidant activity and phenolic compounds of ginger (Zingiber officinale Rosc.) determined by HPLC-MS/MS[J]. Journal of Food Measurement and Characterization,2016,11(2):556−566.
    [30]
    BARTLETT P J, GASPERS L D, PIEROBON N, et al. Calcium-dependent regulation of glucose homeostasis in the liver[J]. Cell Calcium,2014,55(6):306−316. doi: 10.1016/j.ceca.2014.02.007
    [31]
    LIU Y, LIANG X, ZHANG G, et al. Galangin and pinocembrin from propolis ameliorate insulin resistance in HepG2 Cells via regulating Akt/mTOR signaling[J]. Evid Based Complement Alternat Med,2018,2018:1−10.
    [32]
    姜保平. 两色金鸡菊茶饮巧2型糖尿病膜岛素抵抗的预防作用及机制研究[D]. 北京: 北京协和医学院, 2015

    JIANG B P. Study on the preventive effect and mechanism of membrane insulin resistance of type 2 diabetes mellitus by two-color golden chrysanthemum tea[D]. Beijing: Peking Union Medical College, 2015.
    [33]
    王芳, 符晨星, 陈家顺, 等. 过氧化氢酶的生物学功能及在动物中的应用[J]. 饲料研究,2021,5:126−129. [WANG F, FU C X, CHEN J S, et al. Biological function and application of catalase in animals[J]. Feed Research,2021,5:126−129.
    [34]
    SHANMUGAM K R, MALLIKARJUNA K, NISHANTH K, et al. Protective effect of dietary ginger on antioxidant enzymes and oxidative damage in experimental diabetic rat tissues[J]. Food Chemistry,2011,124(4):1436−1442. doi: 10.1016/j.foodchem.2010.07.104
    [35]
    CULLEN M, TANIGUCHI B E A C R K. Critical nodes in signalling pathways: Insights into insulin action[J]. Nat Rev Mol Cell Biol,2006,7:85−96.
    [36]
    DOMINIC SANTOLERI P M T. Resolving the paradox of hepatic insulin resistance[J]. Cellular and Molecular Gastroenterology and Hepatology,2019,7(2):447−456. doi: 10.1016/j.jcmgh.2018.10.016
    [37]
    ZHANG J, CHEN Y, LIU C, et al. N(1)-methylnicotinamide improves hepatic insulin sensitivity via activation of SIRT1 and inhibition of FOXO1 acetylation[J]. J Diabetes Res,2020:1−11.
    [38]
    CHEN B, ABAYDULA Y, LI D, et al. Taurine ameliorates oxidative stress by regulating PI3K/Akt/GLUT4 pathway in HepG2 cells and diabetic rats[J]. Journal of Functional Foods,2021,85:1−10.
    [39]
    MAZIBUKO-MBEJE S E, DLUDLA P V, ROUX C, et al. Aspalathin-enriched green rooibos extract reduces hepatic insulin resistance by modulating PI3K/AKT and AMPK pathways[J]. Int J Mol Sci,2019,20(3):1−16.
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