WANG Min, XU Guohui, ZHAO Yiling, et al. Inhibition Effect and Molecular Mechanism of Hypericin on Xanthine Oxidase[J]. Science and Technology of Food Industry, 2022, 43(12): 92−99. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021090207.
Citation: WANG Min, XU Guohui, ZHAO Yiling, et al. Inhibition Effect and Molecular Mechanism of Hypericin on Xanthine Oxidase[J]. Science and Technology of Food Industry, 2022, 43(12): 92−99. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2021090207.

Inhibition Effect and Molecular Mechanism of Hypericin on Xanthine Oxidase

More Information
  • Received Date: September 15, 2021
  • Available Online: April 11, 2022
  • Dietary flavonoid has been reported to possess a high potential for inhibition xanthine oxidase (XOD). Herein, hypericin was investigated for its inhibition effect and interaction mechanism on XOD by enzyme inhibition kinetics, multi-spectroscopy and molecular docking. Enzyme kinetics analysis indicated that hypericin reversibly inhibited XOD in a mix-competitive manner with IC50 value of (162.059±2.291) μmol/L and inhibition constant (Ki) value of (18.079±0.154) μmol/L. Multi-spectroscopy displayed that hypericin bound to XOD with high affinity, and the interaction was predominately driven by hydrogen bond and van der Waals forces. Circular dichroism (CD) demonstrated that hypericin induced the conformational change of XOD with increased α-helix and Random coil while reduced β-sheet and β-turn. Molecular docking suggested that hypericin interacted with residues located within the active pocket of XOD (e.g. GLN767, GLY797 and PHE798). These results would provide experimental and theoretical basis for hypericin in development of functional food or drug.
  • [1]
    ZHANG C, ZHANG G, PAN J, et al. Galangin competitively inhibits xanthine oxidase by a ping-pong mechanism[J]. Food Research International,2016,89:152−160. doi: 10.1016/j.foodres.2016.07.021
    [2]
    CHEN Y Y, ZHAO Z A, LI Y M, et al. Baicalein alleviates hyperuricemia by promoting uric acid excretion and inhibiting xanthine oxidase[J]. Phytomedicine,2021,80(40):153374.
    [3]
    ZHANG C, ZHANG G W, LIAO Y J, et al. Myricetin inhibits the generation of superoxide anion by reduced form of xanthine oxidase[J]. Food Chemistry,2017,221:1569−1577. doi: 10.1016/j.foodchem.2016.10.136
    [4]
    樊慧杰, 柴智, 周然. 金丝桃苷对神经系统保护作用的研究进展[J]. 中华中医药杂志,2018,33(10):4560−4562. [FAN Huijie, CHAI Zhi, ZHOU Ran. Research progress on neuroprotective effects of hyperoside[J]. Chinese Journal of Traditional Chinese Medicine,2018,33(10):4560−4562.

    FAN Huijie, CHAI Zhi, ZHOU Ran. Research progress on neuroprotective effects of hyperoside[J]. Chinese Journal of Traditional Chinese Medicine, 2018, 33(10): 4560-4562.
    [5]
    董靖雯, 况泽安, 殷明晓, 等. 金丝桃苷通过下调PD-L1表达发挥抗非小细胞肺癌作用研究[J]. 药学学报, 2021, 56(10): 2817−2824.

    DONG Jingwen, KUANG Zean, YIN Mingxiao, et al. Hyperoside exerts its anti-tumor activity by reducing the PD-L1 level in non-small cell lung cancer[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2817−2824.
    [6]
    郑传痴, 杨艳, 韦余, 等. 金丝桃苷对小鼠的抗疲劳作用及机制研究[J]. 食品工业科技,2021,42(23):6. [ZHENG Chuanchi, YANG Yan, WEI Yu, et al. Study on the effects and mechanism of hyperoside on anti-Fatigue in mice[J]. Science and Technology of Food Industry,2021,42(23):6.

    ZHENG Chuanchi, YANG Yan, WEI Yu, et al. Study on the effects and mechanism of hyperoside on anti-Fatigue in mice[J]. Science and Technology of Food Industry, 2021, 42(23): 6.
    [7]
    WANG J, SUN S W, ZHAO K, et al. Insights into the inhibitory mechanism of purpurogallin on xanthine oxidase by multiple spectroscopic techniques and molecular docking[J]. Journal of Molecular Structure,2021,1228:129772. doi: 10.1016/j.molstruc.2020.129772
    [8]
    LI Jiaqi, TIAN Ran, LIANG Guizhao, et al. Interaction mechanism of flavonoids with whey protein isolate: A spectrofluorometric and theoretical investigation[J]. Food Chemistry,2021,355:129617. doi: 10.1016/j.foodchem.2021.129617
    [9]
    LI Q Y, SHI C C, WANG M, et al. Tryptophan residue enhances in vitro walnut protein-derived peptides exerting xanthine oxidase inhibition and antioxidant activities[J]. Journal of Functional Foods Journal,2019,53:276−285. doi: 10.1016/j.jff.2018.11.024
    [10]
    胡鹏. 几种多酚与牛乳蛋白相互作用研究[D]. 南昌: 南昌大学, 2019.

    HU Peng. The study on the interaction between polyphenols and milk protein[D]. Nanchang: Nanchang University, 2019.
    [11]
    LIN Suyun, ZHANG Guowen, LIAO Yijing, et al. Inhibition of chrysin on xanthine oxidase activity and its inhibition mechanism[J]. International Journal of Biological Macromolecules,2015,81:274−282. doi: 10.1016/j.ijbiomac.2015.08.017
    [12]
    ZHAO Jie, HUANG Lin, SUN Chunyong, et al. Studies on the structure-activity relationship and interaction mechanism of flavonoids and xanthine oxidase through enzyme kinetics, spectroscopy methods and molecular simulations[J]. Food Chemistry,2020,323:126807. doi: 10.1016/j.foodchem.2020.126807
    [13]
    HUANG Y M, WU P, YING J, et al. Mechanistic study on inhibition of porcine pancreatic α-amylase using the flavonoids from dandelion[J]. Food Chemistry,2021,344:128610. doi: 10.1016/j.foodchem.2020.128610
    [14]
    NORIYOSHI M, KENICHI N, AYAMI M, et al. Inhibitory effects of cardols and related compounds on superoxide anion generation by xanthine oxidase[J]. Food Chemistry,2015,166:270−274. doi: 10.1016/j.foodchem.2014.06.021
    [15]
    LIU Xiaotian, LIU Tiantian, XU Huilong, et al. Inhibitory kinetics and bioactivities of nuciferine and methyl ganoderate on Mucor miehei lipase and 3T3-L1 preadipocytes[J]. International Journal of Biological Macromolecules,2020,163:1719−1728. doi: 10.1016/j.ijbiomac.2020.09.127
    [16]
    SHARAT S, SOURAV D, ATANU S R. Protective actions of bioactive flavonoids chrysin and luteolin on the glyoxal induced formation of advanced glycation end products and aggregation of human serum albumin: In vitro and molecular docking analysis[J]. International Journal of Biological Macromolecules,2020,165:2275−2285. doi: 10.1016/j.ijbiomac.2020.10.023
    [17]
    LI Xiangrong, WANG Xuezhen, LIU Hongyi, et al. Mechanism evaluation of the interactions between eight flavonoids and γ-globulin based on multi-spectroscopy[J]. Journal of Molecular Structure,2021,1225:129291. doi: 10.1016/j.molstruc.2020.129291
    [18]
    OU Rongrong, LIN Lianzhu, ZHAO Mouming, et al. Action mechanisms and interaction of two key xanthine oxidase inhibitors in galangal: Combination of in vitro and in silico molecular docking studies[J]. International Journal of Biological Macromolecules,2020,162:1526−1535. doi: 10.1016/j.ijbiomac.2020.07.297
    [19]
    YANG Jichen, WANG Xiaoli, ZHANG Chuanying, et al. Comparative study of inhibition mechanisms of structurally different flavonoid compounds on α-glucosidase and synergistic effect with acarbose[J]. Food Chemistry,2021,347:129056. doi: 10.1016/j.foodchem.2021.129056
    [20]
    YU Jie, LI Xiangrong, LIU Hongyi, et al. Interaction behavior between five flavonoids and pepsin: Spectroscopic analysis and molecular docking[J]. Journal of Molecular Structure,2021,1223:128978. doi: 10.1016/j.molstruc.2020.128978
    [21]
    ZHANG Cen, WANG Rui, ZHANG Guowen, et al. Mechanistic insights into the inhibition of quercetin on xanthine oxidase[J]. International Journal of Biological Macromolecules,2018,112:405−412. doi: 10.1016/j.ijbiomac.2018.01.190
    [22]
    SI Yuexiu, WANG Zhijiang, DAEUI Park, et al. Effect of hesperetin on tyrosinase: Inhibition kinetics integrated computational simulation study[J]. International Journal of Biological Macromolecules,2012,50:257−262. doi: 10.1016/j.ijbiomac.2011.11.001
    [23]
    XIE Lianghua, XIE Jiahong, XU Yang, et al. Discovery of anthocyanins from cranberry extract as pancreatic lipase inhibitors using a combined approach of ultrafiltration, molecular simulation and spectroscopy[J]. Food Function,2020,11:8527−8536. doi: 10.1039/D0FO01262A
    [24]
    HE X M, CARTER D C. Atomic structure and chemistry of human serum albumin[J]. Nature,1992,358:209−215. doi: 10.1038/358209a0
    [25]
    PHILIP D, ROSS S SUBRAMANIAN. Thermodynamics of macromolecular association reactions: Analysis of forces contributing to stabilization[J]. Biophysical Journal,1980,32:79−81. doi: 10.1016/S0006-3495(80)84918-6
    [26]
    GE Feng, CHEN Chaoyin, LIU Diqiu, et al. Study on the interaction between theasinesin and human serum albumin by fluorescence spectroscopy[J]. Journal of Luminescence,2010,130:168−173. doi: 10.1016/j.jlumin.2009.08.003
    [27]
    LOREDANA DUMITRAS C, NICOLETA ST˘ANCIUC, IULIANA APRODU. New insights into xanthine oxidase behavior upon heating using spectroscopy and in silico approach[J]. International Journal of Biological Macromolecules,2016,88:306−312. doi: 10.1016/j.ijbiomac.2016.03.072
    [28]
    KANAKIS C, HASNI I, BOURASSA P, et al. Milk β-lactoglobulin complexes with tea polyphenols[J]. Food Chemistry,2011,127:1046−1055. doi: 10.1016/j.foodchem.2011.01.079
  • Cited by

    Periodical cited type(1)

    1. 王英,张会,刘小莉,施亚萍,夏秀东,周剑忠. 不同发酵剂对浅渍发酵豇豆风味成分和滋味的影响. 中国酿造. 2022(11): 89-95 .

    Other cited types(0)

Catalog

    Article Metrics

    Article views (324) PDF downloads (32) Cited by(1)

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return