WANG Mengyuan, LIU Xianjun, MENG Xianglong, et al. Role and Mechanism of 20-Hydroxyecdysone in Oxidative Damage of HepG2 Cells Induced by High Glucose[J]. Science and Technology of Food Industry, 2024, 45(20): 369−377. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023120297.
Citation: WANG Mengyuan, LIU Xianjun, MENG Xianglong, et al. Role and Mechanism of 20-Hydroxyecdysone in Oxidative Damage of HepG2 Cells Induced by High Glucose[J]. Science and Technology of Food Industry, 2024, 45(20): 369−377. (in Chinese with English abstract). doi: 10.13386/j.issn1002-0306.2023120297.

Role and Mechanism of 20-Hydroxyecdysone in Oxidative Damage of HepG2 Cells Induced by High Glucose

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  • Received Date: December 26, 2023
  • Available Online: August 17, 2024
  • Objective: To explore the protective effects of 20-Hydroxyecdysone (20-HE) on high glucose induced HepG2 cells and its related molecular mechanism. Methods: In this study, high glucose (50 mmol/L glucose) was used to establish the oxidative damage model in HepG2 cells. The CCK-8 assay, caspase-3 assay, fluorescent probe method, and colorimetric method were used to assess the levels of cell viability, apoptosis, oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA), respectively. The signaling pathways involved in the regulation of 20-HE were predicted using bioinformatics analysis. The phosphorylation level of Akt protein was detected by Western blot to evaluate the activation level of the PI3K/Akt signaling pathway. The involvement of the PI3K/Akt signaling pathway in the regulatory effects of 20-HE was verified using the inhibitor LY294002. Results: Treatment with 20-HE had no significant toxic effect on HepG2 cells at concentrations lower than 20 μmol/L. In the injured cells, 20-HE could significantly improve the viability (P<0.05), inhibit the apoptosis (P<0.05), down-regulate the level of ROS, improve the levels of SOD and CAT (P<0.05), and down-regulate the level of MDA (P<0.05). PI3K/Akt signaling pathway was the potential downstream mechanism of regulatory effects exerted by 20-HE. 20-HE could significantly up-regulate the level of PI3K/Akt signaling pathway in the injured cells (P<0.05). LY294002 could reverse the protective effects exerted by 20-HE on the injured cells. Conclusion: 20-HE exerted protective effects on high glucose induced oxidative damage in HepG2 cells by activating the PI3K/Akt signaling pathway.
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  • [1]
    LIU J L, LIU M, CHAI Z L, et al. Projected rapid growth in diabetes disease burden and economic burden in China:A spatio-temporal study from 2020 to 2030[J]. The Lancet Regional Health-Western Pacific,2023,33:100700. doi: 10.1016/j.lanwpc.2023.100700
    [2]
    KUMAR S, DUAN Q H, WU R X, et al. Pathophysiological communication between hepatocytes and non-parenchymal cells in liver injury from NAFLD to liver fibrosis[J]. Advanced Drug Delivery Reviews,2021,176:113869. doi: 10.1016/j.addr.2021.113869
    [3]
    EKTA, GUPTA M, KAUR A, et al. Pathobiological and molecular connections involved in the high fructose and high fat diet induced diabetes associated nonalcoholic fatty liver disease[J]. Inflammation Research,2020,69(9):851−867. doi: 10.1007/s00011-020-01373-7
    [4]
    RAHAMAN M M, HOSSAIN R, HERRERA-BRAVO J, et al. Natural antioxidants from some fruits, seeds, foods, natural products, and associated health benefits:An update[J]. Food Science & Nutrition,2023,11(4):1657−1670.
    [5]
    胡一晨, 赵钢, 秦培友, 等. 藜麦活性成分研究进展[J]. 作物学报, 2018, 44(11):1579−1591. [HU Y C, ZHAO G, QIN P Y, et al. Research progress on bioactive components of Quinoa (Chenopodium quinoa Willd.) [J]. Acta Agronomica Sinica, 2018, 44(11):1579−1591.]

    HU Y C, ZHAO G, QIN P Y, et al. Research progress on bioactive components of Quinoa (Chenopodium quinoa Willd.) [J]. Acta Agronomica Sinica, 2018, 44(11): 1579−1591.
    [6]
    KIZELSZTEIN P, GOVORKO D, KOMARNYTSKY S, et al. 20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model[J]. American Journal of Physiology-Endocrinology and Metabolism,2009,296(3):E433−E439. doi: 10.1152/ajpendo.90772.2008
    [7]
    PLOTNIKOV M B, ZIBAREVA L N, VASIL'EV A S, et al. Antihyperglycaemic, haemorheological and antioxidant activities of Lychnis chalcedonica L. extract in a streptozotocin-induced rat model of diabetes mellitus[J]. Journal of Complementary & Integrative Medicine,2019,17(2):jcim−2017-0028.
    [8]
    SHUVALOV O, KIRDEEVA Y, FEFILOVA E, et al. 20-Hydroxyecdysone confers antioxidant and antineoplastic properties in human non-small cell lung cancer cells[J]. Metabolites,2023,13(5):656. doi: 10.3390/metabo13050656
    [9]
    SOUZA L, DA FONSECA S, FERRARI A, et al. β-ecdysone content and antioxidant capacity in different organs of Brazilian ginseng[J]. Ciencia Rural,2021,51(5):e20200618. doi: 10.1590/0103-8478cr20200618
    [10]
    WANG J C, HU K L, CAI X Y, et al. Targeting PI3K/AKT signaling for treatment of idiopathic pulmonary fibrosis[J]. Acta Pharmaceutica Sinica B,2022,12(1):18−32. doi: 10.1016/j.apsb.2021.07.023
    [11]
    LIU S H, JIA Y B, MENG S R, et al. Mechanisms of and potential medications for oxidative stress in ovarian granulosa cells:A review[J]. International Journal of Molecular Sciences,2023,24(11):9205. doi: 10.3390/ijms24119205
    [12]
    RAI S N, DILNASHIN H, BIRLA H, et al. The role of PI3K/Akt and ERK in neurodegenerative disorders[J]. Neurotoxicity Research,2019,35(3):775−795. doi: 10.1007/s12640-019-0003-y
    [13]
    SUBRAMANIYAN S D, NATARAJAN A K. Citral, A monoterpene protect against high gucose induced oxidative injury in HepG2 cell in vitro-an experimental study[J]. Journal of Dlinical and Diagnostic Research:JCDR,2017,11(8):BC10−BC15.
    [14]
    DAINA A, MICHIELIN O, ZOETE V. Swiss target prediction:Updated data and new features for efficient prediction of protein targets of small molecules[J]. Nucleic Acids Research,2019,47(W1):W357−W364. doi: 10.1093/nar/gkz382
    [15]
    STELZER G, ROSEN N, PLASCHKES I, et al. The GeneCards suite:From gene data mining to disease genome sequence analyses[J]. Current Protocols in Bioinformatics, 2016, 54:1−33.
    [16]
    SHERMAN B T, HAO M, QIU J, et al. DAVID:a web server for functional enrichment analysis and functional annotation of gene lists (2021 update)[J]. Nucleic Acids Research,2022,50(W1):W216−W221. doi: 10.1093/nar/gkac194
    [17]
    TANG D D, CHEN M J, HUANG X H, et al. SRplot:A free online platform for data visualization and graphing[J]. PloS one,2023,18(11):e0294236. doi: 10.1371/journal.pone.0294236
    [18]
    KANEHISA M, SATO Y. KEGG Mapper for inferring cellular functions from protein sequences[J]. Protein Science,2020,29(1):28−35. doi: 10.1002/pro.3711
    [19]
    LI S L, YI Z J, DENG M H, et al. TSLP protects against liver I/R injury via activation of the PI3K/Akt pathway[J]. Jci Insight,2019,4(22):e129013. doi: 10.1172/jci.insight.129013
    [20]
    赵悦竹, 金鑫, 张屿楠, 等. 芦荟多糖对D-半乳糖致HepG2细胞氧化损伤的保护作用[J]. 食品工业科技,2023,44(1):405−412. [ZHAO Y Z, JIN X, ZHANG Y N, et al. Protective effect of aloe polysaccharide on oxidative stress injury of HepG2 cells induced by D-galactose[J]. Science and Technology of Food Industry,2023,44(1):405−412.]

    ZHAO Y Z, JIN X, ZHANG Y N, et al. Protective effect of aloe polysaccharide on oxidative stress injury of HepG2 cells induced by D-galactose[J]. Science and Technology of Food Industry, 2023, 44(1): 405−412.
    [21]
    鲁亚君, 刘莹, 王益, 等. 莲壳多酚对T-BHP致HepG2氧化应激损伤的保护作用[J]. 食品工业科技,2023,44(12):397−404. [LU Y J, LIU Y, WANG Y, et al. Protective effects of polyphenol of lotus seed epicarp on oxidative stress damage induced by T-BHP[J]. Science and Technology of Food Industry,2023,44(12):397−404.]

    LU Y J, LIU Y, WANG Y, et al. Protective effects of polyphenol of lotus seed epicarp on oxidative stress damage induced by T-BHP[J]. Science and Technology of Food Industry, 2023, 44(12): 397−404.
    [22]
    DING X Q, JIAN T Y, WU Y X, et al. Ellagic acid ameliorates oxidative stress and insulin resistance in high glucose-treated HepG2 cells via miR-223/keap1-Nrf2 pathway[J]. Biomedicine & Pharmacotherapy,2019,110:85−94.
    [23]
    LI J T, HAN X P, TANG L, et al. 20-Hydroxyecdysone protects wheat seedlings from salt stress[J]. Archives of Biological Sciences,2018,70(2):379−386. doi: 10.2298/ABS170722056L
    [24]
    HU J, LUO C X, CHU W H, et al. 20-Hydroxyecdysone protects against oxidative stress-induced neuronal injury by scavenging free radicals and modulating NF-κB and JNK pathways[J]. PLoS One,2012,7(12):e50764. doi: 10.1371/journal.pone.0050764
    [25]
    NOJIMA Y, BONO H, YOKOYAMA T, et al. Superoxide dismutase down-regulation and the oxidative stress is required to initiate pupation in Bombyx mori[J]. Scientific Reports,2019,9(1):14693. doi: 10.1038/s41598-019-51163-3
    [26]
    HU J N, FENG Y, LI B L, et al. Identification of quality markers for Cyanotis arachnoidea and analysis of its physiological mechanism based on chemical pattern recognition, network pharmacology, and experimental validation[J]. PeerJ,2023,11:e15948. doi: 10.7717/peerj.15948
    [27]
    WANG J, ZHAO Y P. Knockdown of PRUNE2 alleviates hypoxia-induced oxidative stress inhibits cell proliferation in trophoblast cells, and reverses LY294002-induced PI3K/AKT pathway inhibition[J]. Tropical Journal of Pharmaceutical Research,2023,22(2):305−311. doi: 10.4314/tjpr.v22i2.12
    [28]
    WANG H Q, CHEN M, ZHANG T, et al. Recombinant human erythropoietin upregulates PPARγ through the PI3K/Akt pathway to protect neurons in rats subjected to oxidative stress[J]. European Journal of Neuroscience,2022,56(3):4045−4059. doi: 10.1111/ejn.15735
    [29]
    ROMANIUK-DRAPALA A, LISIAK N, TOTON E, et al. Proapoptotic and proautophagic activity of 20-hydroxyecdysone in breast cancer cells in vitro[J]. Chemico-Biological Interactions,2021,342:109479. doi: 10.1016/j.cbi.2021.109479
    [30]
    CAI M J, ZHAO W L, JING Y P, et al. 20-hydroxyecdysone activates Forkhead box O to promote proteolysis during Helicoverpa armigera molting[J]. Development,2016,143(6):1005−1015.
    [31]
    JIAN C X, LIU X F, HU J, et al. 20-hydroxyecdysone-induced bone morphogenetic protein-2-dependent osteogenic differentiation through the ERK pathway in human periodontal ligament stem cells[J]. European Journal of Pharmacology,2013,698(1−3):48−56. doi: 10.1016/j.ejphar.2012.07.044
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