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在高脂饮食和注射链脲佐菌素的大鼠中,[具体物质]的抗糖尿病活性可能是通过调节胰岛素信号通路、炎性细胞因子和脂肪细胞因子来介导的。

Antidiabetic activity of is possibly mediated through modulation of insulin signaling pathway, inflammatory cytokines and adipocytokines in high fat diet and streptozotocin-administered rats.

作者信息

Mehdi Shumaila, Mehmood Malik Hassan, Ahmed Mobeen Ghulam, Ashfaq Usman Ali

机构信息

Department of Pharmacology, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, Pakistan.

Department of Biotechnology and Bioinformatics, Faculty of Life Sciences, Government College University, Faisalabad, Pakistan.

出版信息

Front Pharmacol. 2023 Apr 6;14:1085013. doi: 10.3389/fphar.2023.1085013. eCollection 2023.

Abstract

Medicinal plants play a key role in protection of chronic non-communicable ailments like diabetes, hypertension and dyslipidemia. 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, -coumaric acid, -coumaric acid and ferulic acid. The efficacy of has not been established yet in diabetes. This study has been planned to assess the antidiabetic activity of in high fat diet and streptozotocin (HFD/STZ)-induced diabetes using animals. Administration of aqueous methanolic extract of (AMEBB) and berbamine (Berb) for 8 weeks caused a dose dependent marked ( < 0.01) rise in serum insulin and HDL levels with a significant decline ( < 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 ( < 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 ( < 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 and berbamine in diabetes.

摘要

药用植物在预防糖尿病、高血压和血脂异常等慢性非传染性疾病方面发挥着关键作用。阿勒特(小檗科)传统上用于治疗糖尿病、肝脏问题、伤口、关节炎、感染、肿胀和肿瘤。已知它富含多种植物成分,包括小檗胺、黄连素、槲皮素、没食子酸、咖啡酸、香草酸、苯甲酸、绿原酸、丁香酸、对香豆酸、反式对香豆酸和阿魏酸。其在糖尿病方面的疗效尚未确定。本研究计划使用动物评估阿勒特水甲醇提取物(AMEBB)和小檗胺(Berb)对高脂饮食和链脲佐菌素(HFD/STZ)诱导的糖尿病的抗糖尿病活性。与仅给予HFD/STZ的大鼠相比,给予AMEBB和Berb 8周导致血清胰岛素和高密度脂蛋白水平呈剂量依赖性显著升高(P<0.01),而血糖、甘油三酯、糖化血红蛋白(HbA1c)、胆固醇、低密度脂蛋白、肝功能和肾功能水平显著下降(P<0.01)。AMEBB和Berb还调节了炎症生物标志物(TNF-α、IL-6)和脂肪细胞因子(瘦素、脂联素和趋化素)。AMEBB(150mg/kg和300mg/kg)和Berb(80mg/kg和160mg/kg)处理的大鼠胰腺(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)中的过氧化氢酶水平(单位/mg)显著升高(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)中的超氧化物歧化酶水平(单位/mg)也显著升高,而与仅给予HFD/STZ喂养的大鼠的数据相比,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)中的血清丙二醛水平(nmol/g)显著降低(P<0.01)。胰腺、肝脏、肾脏、心脏和主动脉的组织病理学研究显示,AMEBB和Berb处理的大鼠恢复了正常组织结构。当评估候选基因的mRNA表达时,AMEBB和Berb显示IRS-1、SIRT1、GLUT-4上调,ADAM17下调。这些发现表明,AMEBB和Berb具有抗糖尿病活性,可能是由于其对氧化应激、葡萄糖代谢、炎症生物标志物和脂肪细胞因子水平的影响。IRS-1、SIRT1、GLUT-4的进一步上调和ADAM17的下调,证明了其对葡萄糖稳态、胰岛素抵抗和慢性炎症标志物的潜在影响。因此,本研究为阿勒特和小檗胺在糖尿病中的药用提供了支持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f4b/10117783/0d432139de57/fphar-14-1085013-g001.jpg

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