Hesperidin Exerts Anxiolytic-like Effects in Rats with Streptozotocin- Induced Diabetes via PKA/CREB Signaling.

IF 2.4 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Current molecular pharmacology Pub Date : 2023-01-01 DOI:10.2174/1573413718666220314140848

Xia Zhu, Haiyan Liu, Zongli Deng, Chuanzhi Yan, Yaowu Liu, Xiaoxing Yin

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引用次数: 5

Abstract

Background: The mechanisms underlying synaptic injury and anxiety-like behavioral changes caused by diabetes and the strategies to reverse these changes are not well understood.

Objectives: This study examined the neuroprotective effects of hesperidin on anxiety-like behaviors in diabetic rats and investigated the underlying mechanisms from the perspective of the PKA/CREB pathway.

Methods: Rats with streptozotocin-induced diabetes were treated orally with hesperidin (50 and 150 mg/kg) for 10 weeks. The elevated plus maze (EPM), hole board test (HBT), and marbleburying test (MBT) were used to assess anxiety-like behaviors. We further examined the effects of hesperidin on the PKA/CREB pathway in vivo and in vitro.

Results: The results show that supplementation with hesperidin exerted anxiolytic effects on the diabetic rats, as evidenced by increased percentages of open arm entries and time spent in the open arms in the EPM; decreased numbers of hole visits in the HBT; decreased numbers of marbles buried; and increased expression of PKA, CREB, BDNF, and synaptic proteins in the amygdala and hippocampus of diabetic rats. Hesperidin was found to reverse the imbalance in the PKA/CREB/BDNF pathway. In vitro, we found that the PKA inhibitor H89 reversed the protective effects of hesperidin against cell injury and reversed the HG-induced expression of PKA, pCREB/CREB, and BDNF.

Conclusion: Our results demonstrated that hesperidin could ameliorate the anxiety-like behaviors of diabetic rats and that activating the PKA/CREB/BDNF pathway contributed to the beneficial effects. This study may provide important insights into the mechanisms underlying anxiety-like behaviors in diabetes and identify new therapeutic targets for clinical treatment.

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橙皮苷通过PKA/CREB信号传导对链脲霉素诱导的糖尿病大鼠发挥抗焦虑作用。

背景:糖尿病引起的突触损伤和焦虑样行为改变的机制以及逆转这些变化的策略尚不清楚。目的:研究橙皮苷对糖尿病大鼠焦虑样行为的神经保护作用，并从PKA/CREB通路的角度探讨其机制。方法:采用橙皮苷50、150 mg/kg口服治疗链脲佐菌素所致糖尿病大鼠10周。采用高架迷宫法(EPM)、孔板法(HBT)和大理石掩埋法(MBT)评估焦虑样行为。我们进一步在体内和体外研究了橙皮苷对PKA/CREB通路的影响。结果:橙皮苷对糖尿病大鼠有一定的抗焦虑作用，表现为大鼠EPM中张开臂进入率和张开臂时间的增加;HBT井眼次数减少;埋藏的弹珠数量减少;糖尿病大鼠杏仁核和海马中PKA、CREB、BDNF和突触蛋白的表达增加。橙皮苷被发现可以逆转PKA/CREB/BDNF通路的失衡。在体外，我们发现PKA抑制剂H89逆转了橙皮苷对细胞损伤的保护作用，逆转了hg诱导的PKA、pCREB/CREB和BDNF的表达。结论:橙皮苷可以改善糖尿病大鼠的焦虑样行为，其作用机制可能与激活PKA/CREB/BDNF通路有关。本研究可能为糖尿病焦虑样行为的潜在机制提供重要见解，并为临床治疗提供新的治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Current molecular pharmacology Pharmacology, Toxicology and Pharmaceutics-Drug Discovery

CiteScore

4.90

自引率

3.70%

发文量

112

期刊介绍： Current Molecular Pharmacology aims to publish the latest developments in cellular and molecular pharmacology with a major emphasis on the mechanism of action of novel drugs under development, innovative pharmacological technologies, cell signaling, transduction pathway analysis, genomics, proteomics, and metabonomics applications to drug action. An additional focus will be the way in which normal biological function is illuminated by knowledge of the action of drugs at the cellular and molecular level. The journal publishes full-length/mini reviews, original research articles and thematic issues on molecular pharmacology. Current Molecular Pharmacology is an essential journal for every scientist who is involved in drug design and discovery, target identification, target validation, preclinical and clinical development of drugs therapeutically useful in human disease.