Effects of Rosa roxburghii on insulin resistance in obese rats and its mechanisms

doi:10.12047/j.cjap.6328.2022.122

Abstract

Abstract: Objective: To investigate the effects of Rosa roxburghii on insulin resistance in obese rats and the regulation of phosphatidylinositol 3-kinase (PI3K)/ protein kinase Bβ(PKB_β/Akt2)/ glucose transporter 4(GLUT4) signaling pathway. Methods: Five-week-old male SD rats were randomly divided into normal control group (NC), model group (M), positive control group (PC), low-dose rosa roxburghii group (LD) and high-dose rosa roxburghii group (HD), with 10 rats in each group. The rats in the NC group were fed with normal diet, while those in the M, PC, LD and HD groups were fed with high-fat diet. From the 13th week, according to the dose standard of 6 ml/kg, rats in the LD group were intragastrically administered with 100 mg/kg Rosa roxburghii Tratt, the HD group were treated with 300 mg/kg Rosa roxburghii Tratt, the PC group were treated with 0.11 g/kg Chiglitazar sodium, and the NC and M groups were intragastrically administered with the same volume of normal saline. The body weight was measured every week until 20 weeks. The rats were sacrificed 24 h after the last experiment. Blood and skeletal muscle were collected. Serum total cholesterol (TC) and triglyceride (TG) contents were detected by colorimetric method, serum superoxide dismutase (SOD) activity was detected by xanthine oxidase method, serum malondialdehyde (MDA) content was detected by thiobarbituric acid method, blood glucose (FBG) value was detected by glucose oxidase method, insulin (FINS) content was detected by ELISA, and PI3K, Akt2, and GLUT4 protein and gene expressions were detected by Western blot and reverse transcription-polymerase chain reaction (RT-PCR). Results: Compared with the NC group, the body weight, serum MDA, TG, TC, FBG, FINS, HOMA-IR levels in the M group were significantly increased (P＜0.01), while SOD activity, PI3K、Akt2、GLUT4 protein and mRNA expression levels were significantly increased(P＜ 0.01). Compared with group M, the body weight, serum MDA, TG, TC, FBG, FINS, and HOMA-IR were decreased significantly in LD group, HD group and PC group (P＜0.05 or P＜0.01), while SOD activity, PI3K, Akt2, GLUT4 protein and mRNA expression levels were increased significantly (P＜0.05 or P＜0.01). Conclusion: Rosa roxburghii can improve insulin resistance in obese rats by antioxidant stress and up-regulating the expressions of PI3K, Akt2, and GLUT4 proteins and genes, which may be related to the PI3K/Akt2/GLUT4 signaling pathway.

Key words: Rosa roxburghii Tratt, fat, insulin resistance, PI3K/Akt2/GLUT4 signaling pathway

CLC Number:

R804.7

ZHANG Shuai-jun, ZHANG Jin, GUO Jin-ping, NIU Ying-peng. Effects of Rosa roxburghii on insulin resistance in obese rats and its mechanisms[J]. CJAP, 2022, 38(6): 670-675.

References

[1] 王睿, 魏日胞. 胰岛素抵抗评价方法及其干预手段的研究进展[J]. 中华临床医师杂志(电子版), 2013, 7(23): 10836-10838.
[2] 付阳洋, 刘佳敏, 卢小鸾, 等. 刺梨主要活性成分及药理作用研究进展[J]. 食品工业科技, 2020, 41(13): 328-335.
[3] Palmer NO, Bakos HW, Owens JA, et al. Diet and exer-cise in an obese mouse fed a high-fat diet improve meta-bolic health and reverse perturbed sperm function[J]. Am J Physiol Endocrinol Metab, 2012, 302(7): 768-780.
[4] Ileen LW, Han C, Morris J, et al. Role of Akt/protein kinase B in metabolism[J]. Trends Endocrin Met , 2002, 13(12): 444-451.
[5] 完建永, 张勇, 刘世强, 等. 运动对胰岛素抵抗大鼠肝脏BIM信号通路的影响[J]. 中国应用生理学杂志, 2020, 36(2): 115-118.
[6] 何诚. 实验动物学[M]. 北京: 中国农业大学出版社, 2013: 21-23.
[7] 张茁, 孙文, 刘铜华, 等. 山柰酚对2型糖尿病小鼠骨骼肌PI3K-AKT-GLUT4信号通路的影响[J]. 世界科学技术-中医药现代化, 2016, 18(7): 1139-1143.
[8] 张晓圆, 郭成成, 玉应香, 等. 高脂饲料诱导肥胖胰岛素抵抗大鼠模型的建立[J]. 北京大学学报(医学版), 2020, 52(3): 557-563.
[9] 林清, 石红欣, 刘月环, 等. 魔芋复方调控高脂饮食诱导肥胖大鼠脂质代谢及氧化应激作用研究[J]. 华南预防医学, 2020, 46(4): 338-341.
[10] 肖方喜, 孙晖, 陈璐璐. 高脂喂养诱导大鼠骨骼肌胰岛素抵抗的机制研究[J]. 华中科技大学学报(医学版), 2008, 37(3): 309-311.
[11] 袁清, 刘江华, 曾召林. 线粒体功能障碍在代谢性炎症中的作用[J]. 江苏大学学报(医学版), 2021, 31(5): 448-454.
[12] 刘颐轩, 宋桉, 王芸, 等. 氧化应激在肥胖及胰岛素抵抗中的作用研究进展[J]. 解放军医药杂志, 2014, 26(1): 99-101.
[13] 张艺博, 文静, 何燕. 长爪沙鼠氧化应激水平与血糖及胰岛素抵抗的相关性分析[J]. 医学信息, 2021, 34(12): 1-4.
[14] Venditti P, Di SL, Di MS. Mitochondrial metabolism of reactive oxygen species[J]. Mitochondrion, 2013, 13(2): 71-82.
[15] 周健, 秦浩, 李晓红, 等. 维生素C对镉负荷小鼠睾丸抗氧化功能的影响[J]. 中国应用生理学杂志, 2022, 38(3): 233-237.
[16] 谷峰, 宋淑珍, 罗勤慧, 等. SOD模拟酶对自由基的清除效能研究[J]. 解放军药学学报, 2004, 20(3): 191-194.
[17] Abel ED, Peroni O, Kim JK, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver[J]. Nature, 2001, 409: 729-733.
[18] Huang Y, Zhou TX, Zhang YR, et al. Antidiabetic activity of a flavonoid-rich extract from flowers of Wisteria sinensis in type 2 diabetic mice via activation of the IRS-1/PI3K/Akt/GLUT4 pathway[J]. J Funct Foods, 2021, 77(2): 1-12.
[19] Rosca MG, Vazquez EJ, Chen Q, et al. Oxidation of fatty acids is the source of increased mitochondrial reactive oxygen species production in kidney cortical tubules in early diabetes[J]. Diabetes, 2012, 61(8): 2074-2083.
[20] Hao JH, Tang Y, Liu XH, et al. Inhibiting PI3K leads to glucose metabolism disturbance in default mode network[J]. Brain Res Bull, 2021,170(5): 218-224.
[21] 郑书臣, 赵启韬, 桑晓宇, 等. 改善胰岛素抵抗的中药活性成分及作用机制研究进展[J]. 山东中医杂志, 2021, 40(1): 94-99.
[22] 汪磊. 刺梨多糖的分离纯化、降血糖作用及其对肠道微生态的影响[D]. 华南理工大学, 2019: 48-53.