Berberis brandisiana的抗糖尿病活性可能是通过调节胰岛素信号通路、炎症因子和脂肪细胞因子在高脂饮食和链脲霉素处理的大鼠中介导的。
Antidiabetic activity of Berberis brandisiana is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats.
发表日期:2023
作者:
Shumaila Mehdi, Malik Hassan Mehmood, Mobeen Ghulam Ahmed, Usman Ali Ashfaq
来源:
ARTHRITIS RESEARCH & THERAPY
摘要:
药用植物在保护像糖尿病、高血压和血脂异常这样的慢性非传染性疾病方面发挥着关键作用。隆脉小檗(学名为Berberis brandisiana Ahrendt,小檗科)传统上被用于治疗糖尿病、肝脏问题、伤口、关节炎、感染、肿胀和肿瘤等疾病。据了解,它还富含多种植物化学成分,包括伯巴明、小檗碱、槲皮素、没食子酸、咖啡酸、香草酸、苯甲酸、绿原酸、紫草酸、对香豆酸、间香豆酸和阿魏酸。然而,隆脉小檗在治疗糖尿病方面的有效性尚未确定。本研究计划使用动物模型评估高脂饮食和链脲佐菌素(HFD/STZ)诱导的糖尿病中隆脉小檗的降糖活性。给予隆脉小檗水甲醇提取物(AMEBB)和伯巴明(Berb)治疗8周后,血清胰岛素和高密度脂蛋白水平明显升高(p <0.01),血糖、甘油三酯、糖基化血红蛋白(HbA1c)、胆固醇、低密度脂蛋白、肝功能测定和肾功能测定的水平显著下降(p <0.01),与仅接受HFD/STZ治疗的大鼠相比。AMEBB和Berb还调节了炎症生物标志物(TNF-α,IL-6)和脂肪细胞素(瘦素、脂联素和化合物A)的水平。AMEBB(150毫克/千克和300毫克/千克)和Berb(80毫克/千克和160毫克/千克)治疗的大鼠胰腺(42.4 ± 0.24,47.4 ± 0.51)、(38.2 ± 0.583,48.6 ± 1.03)和肝脏(52 ± 1.41,63.2 ± 0.51)、(57.2 ± 0.58,61.6 ± 1.24)中过氧化氢酶水平(单位/毫克)明显升高(p <0.001),超氧化物歧化酶水平(单位/毫克)明显升高(p <0.001),胰腺(34.8 ± 1.46,38.2 ± 0.58)、(33.2 ± 0.80,40.4 ± 1.96)和肝脏(31.8 ± 1.52,36.8 ± 0.96)、(30 ± 0.70,38.4 ± 0.81),同时与仅接受HFD/STZ治疗的大鼠相比,血清饱和度丙二醛水平(nmol/g)在胰腺(7.34 ± 0.17,6.22 ± 0.22)、(7.34 ± 0.20,6.34 ± 0.11)和肝脏(9.08 ± 0.31,8.18 ± 0.29)、(9.34 ± 0.10,8.86 ± 0.24)中显著下降(p <0.01)。胰腺、肝脏、肾、心脏和主动脉的组织病理学研究显示,AMEBB和Berb治疗的大鼠恢复了正常的组织结构。当考察候选基因的mRNA表达时,AMEBB和Berb显示了IRS-1,SIRT1,GLUT-4的上调和ADAM17的下调。这些发现表明,AMEBB和Berb具有降糖作用,可能是由于其对氧化应激、葡萄糖代谢、炎症和脂肪细胞素水平的影响。进一步的IRS-1、SIRT1、GLUT-4的上调和ADAM17的下调,证明了它对葡萄糖稳态、胰岛素抵抗和慢性炎症标志物的潜在影响。因此,本研究支持隆脉小檗和伯巴明在糖尿病中药用的应用。版权所有 © 2023 Mehdi, Mehmood, Ahmed and Ashfaq.
Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. Berberis brandisiana Ahrendt (Berberidaceae) is traditionally used to treat diabetes, liver problems, wounds, arthritis, infections, swelling and tumors. It is also known to be enriched with multiple phytoconstituents including berbamine, berberine, quercetin, gallic acid, caffeic acid, vanillic acid, benzoic acid, chlorogenic acid, syringic acid, p-coumaric acid, m-coumaric acid and ferulic acid. The efficacy of B. brandisiana has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of B. brandisiana in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of B. brandisiana (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked (p < 0.01) rise in serum insulin and HDL levels with a significant decline (p < 0.01) in glucose, triglycerides, glycosylated hemoglobin (HbA1c), cholesterol, LDL, LFTs and RFTs levels when compared with only HFD/STZ-administered rats. AMEBB and Berb also modulated inflammatory biomarkers (TNF-α, IL-6) and adipocytokines (leptin, adiponectin and chemerin). AMEBB (150 mg/kg and 300 mg/kg) and Berb (80 mg/kg and 160 mg/kg) treated rats showed a marked increase (p < 0.001) in catalase levels (Units/mg) in pancreas (42.4 ± 0.24, 47.4 ± 0.51), (38.2 ± 0.583, 48.6 ± 1.03) and liver (52 ± 1.41, 63.2 ± 0.51), (57.2 ± 0.58, 61.6 ± 1.24) and superoxide dismutase levels (Units/mg) in pancreas (34.8 ± 1.46, 38.2 ± 0.58), (33.2 ± 0.80, 40.4 ± 1.96) and liver (31.8 ± 1.52, 36.8 ± 0.96), (30 ± 0.70, 38.4 ± 0.81),respectively while a significant (p < 0.01) decrease in serum melondialdehyde levels (nmol/g) in pancreas (7.34 ± 0.17, 6.22 ± 0.22), (7.34 ± 0.20, 6.34 ± 0.11) and liver (9.08 ± 0.31,8.18 ± 0.29), (9.34 ± 0.10, 8.86 ± 0.24) compared to the data of only HFD/STZ-fed rats. Histopathological studies of pancreas, liver, kidney, heart and aorta revealed restoration of normal tissue architect in AMEBB and Berb treated rats. When mRNA expressions of candidate genes were assessed, AMEBB and Berb showed upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17. These findings suggest that AMEBB and Berb possess antidiabetic activity, possibly due to its effect on oxidative stress, glucose metabolism, inflammatory biomarkers and adipocytokines levels. Further upregulation of IRS-1, SIRT1, GLUT-4 and downregulation of ADAM17, demonstrated its potential impact on glucose homeostasis, insulin resistance and chronic inflammatory markers. Thus, this study provides support to the medicinal use of B. brandisiana and berbamine in diabetes.Copyright © 2023 Mehdi, Mehmood, Ahmed and Ashfaq.