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香叶醇通过调节 caspase-3、Bcl-2 和 Bax 的表达来改善高脂肪饮食/链脲佐菌素诱导的 2 型糖尿病大鼠的进展。

Geraniol ameliorates the progression of high fat-diet/streptozotocin-induced type 2 diabetes mellitus in rats via regulation of caspase-3, Bcl-2, and Bax expression.

机构信息

Department of Clinical Laboratories Sciences, College of Applied Medical Sciences at Al Qurayyat, Jouf University, Al Qurayyat, Saudi Arabia.

Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt.

出版信息

J Food Biochem. 2022 Jul;46(7):e14142. doi: 10.1111/jfbc.14142. Epub 2022 Mar 21.

DOI:10.1111/jfbc.14142
PMID:35312192
Abstract

The study was designed to evaluate the geraniol's effect on the kidney and liver damage triggered by a high-fat diet (HFD)/streptozotocin (STZ)-induced type 2 diabetes mellitus in rats. Firstly, in vitro inhibitory geraniol's effect against α-amylase and α-glucosidase activities was confirmed by in-silico molecular docking, which revealed higher binding affinity toward α-amylase than for α-glucosidase. The protective effect of geraniol with two separate doses (100 and 200 mg/kg b.wt) against diabetes' kidney and liver dysfunctions in Wistar rats was then evaluated. Results indicate that geraniol treatment for 6 weeks instigated a remarkable retrieval of the lipid profile, liver, and kidney function. Geraniol noticeably reinforced the antioxidant enzymes, parameters of oxidative stress of the kidney and liver in this type of diabetes. Also, geraniol treatment prompted a significant reduction in the expression levels of caspase-3 (Casp3) and Bax mRNA. In conclusion, geraniol ameliorates the progress of HFD/STZ-induced type 2 diabetes mellitus in rats via dependently upregulating the expression of Bcl-2 and downregulating Casp3 and Bax expression. PRACTICAL APPLICATIONS: Geraniol is a naturally occurring substantial acyclic monoterpenoid compound that has numerous pharmacological activities. The positive effect of geraniol in inhibiting in vitro diabetic markers by a silico molecular docking study was evidenced by illustrating the binding sites of geraniol with both α-amylase and α-glucosidase. This study also focused on the therapeutic impact of geraniol against the damage caused by high fat-diet/streptozotocin-induced type 2 diabetic complications in Wistar rats. Geraniol limits the oxidative stress of liver and kidney tissue, and it might be used as an antiapoptotic agent in type 2 diabetes.

摘要

这项研究旨在评估香叶醇对高脂肪饮食(HFD)/链脲佐菌素(STZ)诱导的 2 型糖尿病大鼠肾脏和肝脏损伤的影响。首先,通过计算机分子对接实验证实了香叶醇体外抑制α-淀粉酶和α-葡萄糖苷酶活性的作用,结果表明其对α-淀粉酶的结合亲和力高于对α-葡萄糖苷酶。然后评估了香叶醇(两种不同剂量,100 和 200mg/kg 体重)对 Wistar 大鼠糖尿病肾脏和肝脏功能障碍的保护作用。结果表明,香叶醇治疗 6 周可显著改善血脂谱、肝脏和肾脏功能。香叶醇显著增强了抗氧化酶的活性,改善了糖尿病状态下肾脏和肝脏的氧化应激参数。此外,香叶醇治疗还可显著降低 caspase-3(Casp3)和 Bax mRNA 的表达水平。总之,香叶醇通过独立地上调 Bcl-2 的表达和下调 Casp3 和 Bax 的表达,改善了 HFD/STZ 诱导的 2 型糖尿病大鼠的病情进展。实际应用:香叶醇是一种天然存在的非环状单萜化合物,具有多种药理学活性。计算机分子对接研究表明香叶醇具有抑制体外糖尿病标志物的积极作用,证明了香叶醇与α-淀粉酶和α-葡萄糖苷酶的结合部位。本研究还重点研究了香叶醇对 Wistar 大鼠高脂肪饮食/链脲佐菌素诱导的 2 型糖尿病并发症引起的损伤的治疗作用。香叶醇限制了肝和肾组织的氧化应激,它可能被用作 2 型糖尿病的抗凋亡剂。

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