Basic Research

The analysis of effect of serum containing Gegen Qinlian Decoction on regulating hypoxia-induced glucose metabolism in L02 Cells and related metabolic mechanisms

  • Yan YOU ,
  • Hongjing CUI ,
  • Chengcheng PENG ,
  • Li JIANG ,
  • Qiyun ZHANG ,
  • Bingtao LI ,
  • Guoliang XU
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  • *.Department of Pharmacy,the Fourth Affiliated Hospital of Nanchang University,Nanchang 330003,Jiangxi,China

Received date: 2024-11-27

  Online published: 2025-04-23

Abstract

Objective The study aimedto investigate the effects and metabolic mechanisms of Gegen Qinlian Decoction (GQD) containing serum on hypoxia?induced glucose metabolism in L02 cells. Methods The effects of five hypoxia durations (6, 12, 18, 24, and 48 hours) on glucose consumption and cell viability of L02 cells were examined under hypoxic conditions to determine the optimal hypoxia time. Normal hepatocytes served as the normal control group. L02 cells with hypoxia?induced reduction in glucose consumption were divided into several groups: hypoxia group, metformin 2 mmol/L group, and 25 g/kg GQD groups treated with 5%, 10%, and 15% GQD containing serum. Glucose consumption was used as an indicator of drug efficacy. High?resolution liquid chromatography tandem quadrupole time?of?flight mass spectrometry (UPLC?Q?TOF?MS) was employed to collect metabolite signals from each group. Data were analyzed by using Progenesis QI software, and potential biomarkers were identified through online databases such as HMDB. Finally, metabolic pathways of potential biomarkers were analyzed via the Metabo Analyst 5.0 website. Results An 18 hour hypoxia period was identified as the optimal duration for the replication of the hypoxia?induced L02 cell model. GQD containing serums at 5% and 10% significantly increased glucose consumption in hypoxia?induced L02 cells after 18 hours. 14 biomarkers of hypoxia?induced L02 cells were identified, with the levels of 13 biomarkers significantly increased and 1 biomarker significantly decreased. GQD containing serum notably regulated the levels of 3 biomarkers. Conclusion GQD containing serum might improve hypoxia?induced abnormal glucose metabolism in L02 cells and enhance glucose consumption by modulating glycerophospholipid metabolism, glycosylphosphatidylinositol biosynthesis, and sphingolipid metabolism.

Cite this article

Yan YOU , Hongjing CUI , Chengcheng PENG , Li JIANG , Qiyun ZHANG , Bingtao LI , Guoliang XU . The analysis of effect of serum containing Gegen Qinlian Decoction on regulating hypoxia-induced glucose metabolism in L02 Cells and related metabolic mechanisms[J]. The Journal of Practical Medicine, 2025 , 41(7) : 936 -943 . DOI: 10.3969/j.issn.1006-5725.2025.07.002

References

1 中华医学会糖尿病学分会. 中国2型糖尿病防治指南(2020年版)[J]. 中华糖尿病杂志, 2021,13(4):315-409.
2 徐红双,金立,张伟. 组织缺氧对2型糖尿病患者胰岛素抵抗的影响[J]. 中国现代医学杂志,2 018,28(27):120-123.
3 王慧. 高脂饮食诱导C57/BL6小鼠胰岛素抵抗及其机制的研究[D]. 天津:天津医科大学, 2012:38.
4 陈素峰,夏骏,单志明,等. 男性代谢综合征患者中组织缺氧与胰岛素抵抗的相关性研究[J]. 中华内分泌代谢杂志, 2016,32(8):652-656.
5 曾国威,余日跃,盛译萱,等. 肥胖胰岛素抵抗大鼠血气分析研究[J]. 江西中医药大学学报, 2020,32(2):84-87.
6 WAN X D, YANG W B, XIA Y Z, et al. Disruption of glucose homeostasis and induction of insulin resistance by elevated free fatty acids in human L02hepatocytes[J]. J Endocrinol Inves, 2009,32(5):454-459. doi:10.1007/bf03346485
7 刘子琦,王玥,姜鑫,等. 高稳定性L02细胞胰岛素抵抗模型的建立及其分子机制[J]. 扬州大学学报(农业与生命科学版),2022,43(6):73-79.
8 李佳怡,杨晓琨,高颖,等. 葛根芩连汤防治湿热型2型糖尿病的研究进展[J]. 中医药临床杂志, 2023,35(7):1443-1447.
9 李颖萌,范雪梅,王义明,等. 葛根芩连汤对2型糖尿病大鼠的治疗作用及其机制探讨[J]. 药学学报,2013,48(9):1415-1421.
10 朱晓静,范玲,陆荣欣,等. 葛根芩连汤在糖尿病患者中的治疗效果及对证候积分和胰岛功能的影响研究[J]. 糖尿病新世界,2023,26(12):13-16.
11 PERNICOVA I, KORBONITS M. Metformin--mode of action and clinical implications for diabetes and cancer[J]. Nat Rev Endocrinol, 2014, 10(3):143-156. doi:10.1038/nrendo.2013.256
12 彭程程,许清松,朱娜,等. 葛根芩连汤先煎葛根后下诸药的解表清里功效相关成分分析[J]. 时珍国医国药,2021,32(6):1357-1360.
13 张启云,陈瑶,姜丽,等. 葛根芩连汤含药血清调节胰岛素抵抗脂肪细胞代谢机制研究[J]. 中药药理与临床, 2021,37(6):14-18.
14 DETTMER K, NURNBERGER N, KASPAR H, et al. Metabolite extraction from adherently growing mammalian cells for metabolomics studies: Optimization of harvesting and extraction protocols[J]. Anal Bioanal Chem,2011, 399(3):1127-1139. doi:10.1007/s00216-010-4425-x
15 彭程程. 缺氧对细胞糖代谢的影响及葛根芩连汤含药血清干预机制的研究[D]. 南昌:江西中医药大学,2021:39-42.
16 许清松,彭程程,李冰涛,等. 葛根芩连汤含药血清对缺氧诱导HepG2肝癌细胞糖代谢的影响及机制研究[J]. 中药新药与临床药理,2023,34(5):636-645.
17 KHAMZINA L, VEILLEUX A, BERGERON S, et al. Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: Possible involvement in obesity-linked insulin resistance[J]. Endocrinology,2005, 146(3): 1473-1481. doi:10.1210/en.2004-0921
18 WANG Y, BAI C, RUAN Y, et al. Coordinative metabolism of glutamine carbon and nitrogen in proliferating cancer cells under hypoxia[J]. Nat Commun,2019, 10(1): 1-14. doi:10.1038/s41467-018-08033-9
19 YUN J K, KESTER M. Regulatory role of sphingomyelin metabolites in hypoxia-induced vascular smooth muscle cell proliferation[J]. Arch Biochem Biophys,2002, 408(1): 78-86. doi:10.1016/s0003-9861(02)00526-x
20 SUN K, ZHANG Y, D′ALESSANDRO A, et al. Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia[J]. Nat Commun, 2016, 7(1): 1-13. doi:10.1038/ncomms12086
21 VAN DER VEEN J N, LINGRELL S, VANCE D E. The membrane lipid phosphatidylcholine is an unexpected source of triacylglycerol in the liver[J]. J Biol Chem, 2012, 287(28): 23418-23426. doi:10.1074/jbc.m112.381723
22 VAN DER VEEN J N, KENNELLY J P, WAN S, et al. The critical role of phosphatidylcholine and hosphatidylethanolamine metabolism in health and disease[J]. Biochim Biophys Acta Biomembr, 2017, 1859(9): 1558-1572. doi:10.1016/j.bbamem.2017.04.006
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