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小檗碱富集提取物对链脲佐菌素诱导的代谢损伤治疗效果的生化研究

Biochemical Investigation of Therapeutic Efficacy of Berberine-Enriched Extract in Streptozotocin-Induced Metabolic Impairment.

作者信息

Akash Muhammad Sajid Hamid, Yaqoob Sahrish, Rehman Kanwal, Hussain Amjad, Chauhdary Zunera, Nadeem Ahmed, Shahzad Asif, Shah Muhammad Ajmal, Panichayupakaranant Pharkphoom

机构信息

Department of Pharmaceutical Chemistry, Government College University, Faisalabad 38000, Punjab, Pakistan.

Department of Pharmacy, The Women University, Multan 6000, Pakistan.

出版信息

ACS Omega. 2024 Mar 22;9(13):15677-15688. doi: 10.1021/acsomega.4c00696. eCollection 2024 Apr 2.

Abstract

Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups ( = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic β-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation.

摘要

代谢紊乱给全球健康带来了重大挑战,需要创新的治疗方法。本研究聚焦于富含小檗碱的提取物(BEE)在减轻链脲佐菌素(STZ)诱导的大鼠模型代谢损伤方面的多方面治疗潜力,并比较了BEE与小檗碱(BBR)和二甲双胍(MET)的效果,以全面评估它们对各种生化参数的影响。我们的研究表明,在改善代谢损伤方面,BEE的效果优于BBR和MET,使其成为治疗代谢紊乱的一个有潜力的候选药物。为此,将30只雄性Wistar大鼠分为五组(每组n = 6):对照组(CN)、STZ组、STZ + MET组、STZ + BBR组和STZ + BEE组。治疗持续4周,在此期间监测各种生化参数,包括空腹血糖(FBG)、血脂谱、炎症、肝肾功能生物标志物以及各种代谢酶的基因表达。STZ诱导的代谢损伤通过FBG水平升高和血脂谱紊乱得以体现。富含小檗碱的提取物有效调节了葡萄糖稳态,FBG水平的恢复证明了这一点,其效果优于BBR和MET。此外,BEE对胰岛素敏感性有显著影响,上调了碳水化合物代谢中的关键基因:GCK、IGF - 1和GLUT2。这突出了其在增强葡萄糖利用和胰岛素反应性方面的潜力。血脂异常是代谢紊乱中的常见现象,BEE有效控制了这一情况。该提取物在调节血脂谱方面表现出卓越的功效。此外,BEE具有显著的抗炎特性,在降低炎症生物标志物(IL - 6和TNF - α)水平方面超过了BBR和MET的效果,从而改善了胰岛素抵抗和全身炎症。肝肾功能生物标志物的恢复表明该提取物具有卓越的肝脏保护和肾脏保护作用,进一步突出了其在维持器官健康方面的潜力。此外,BEE具有强大的抗氧化特性,减少了肝组织匀浆中的氧化应激和脂质过氧化。胰腺的组织病理学检查强调了BEE的保护作用,保护并恢复了被STZ损伤的胰腺β细胞。这些综合证据表明BEE是治疗代谢紊乱的一个有潜力的候选药物,并提供了超越现有治疗方法的潜在益处。总之,我们的研究结果强调了BEE显著的治疗效果,并为进一步研究其作用机制、长期安全性和临床转化奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/21eb/10993375/f81b56787c50/ao4c00696_0001.jpg

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