β-asarone protects against age-related motor decline via activation of SKN-1/Nrf2 and subsequent induction of GST-4

IF 9.1 2区医学 Q1 PHARMACOLOGY & PHARMACY

Pharmacological research Pub Date : 2024-10-02 DOI:10.1016/j.phrs.2024.107450

Ming Lei , Jiayu Wu , Yanheng Tan , Yang Shi , Wuyan Yang , Haijun Tu , Weihong Tan

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Abstract

Decelerating motor decline is important for promoting healthy aging in the elderly population. Acorus tatarinowii Schott is a traditional Chinese medicine that contains β-asarone as a pharmacologically active constituent. We found that β-asarone can decelerate motor decline in various age groups of Caenorhabditis elegans, while concurrently prolonging their lifespan and modulating synaptic transmission. To understand the mechanisms of its efficacy in motor improvement, we investigated and discovered that mitochondrial fragmentation, a marker for aging, is delayed after β-asarone treatment. Moreover, their efficacy is blocked by dysfunctional mitochondria. Corresponding to their role in regulating mitochondrial homeostasis, we found that SKN-1/Nrf2 and GST-4 are critical in the β-asarone treatment, and they appear to be activated via the insulin/IGF-1 signaling pathway. Well-developed intestinal microvilli are required for this process. Our study demonstrates the efficacy and mechanism of β-asarone treatment in age-related motor decline, contributing to the discovery of drugs for achieving healthy aging.

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β-asarone通过激活SKN-1/Nrf2和随后诱导GST-4防止与年龄相关的运动机能衰退

减缓运动机能衰退对促进老年人健康老龄化非常重要。唐菖蒲是一种传统中药，其药理活性成分为β-asarone。我们发现，β-asarone能减缓不同年龄组秀丽隐杆线虫的运动衰退，同时延长其寿命并调节突触传递。为了了解其改善运动能力的机制，我们研究发现，β-asarone 治疗后，衰老的标志物线粒体碎片会被延迟。此外，线粒体功能障碍也会阻碍其功效的发挥。与它们在调节线粒体平衡中的作用相对应，我们发现 SKN-1/Nrf2 和 GST-4 在 β-asarone 处理中起着关键作用，它们似乎是通过胰岛素/IGF-1 信号通路被激活的。这一过程需要发达的肠道微绒毛。我们的研究证明了β-asarone治疗老年性运动机能减退的疗效和机制，有助于发现实现健康老龄化的药物。

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来源期刊

Pharmacological research 医学-药学

CiteScore

18.70

自引率

3.20%

发文量

491

审稿时长

8 days

期刊介绍： Pharmacological Research publishes cutting-edge articles in biomedical sciences to cover a broad range of topics that move the pharmacological field forward. Pharmacological research publishes articles on molecular, biochemical, translational, and clinical research (including clinical trials); it is proud of its rapid publication of accepted papers that comprises a dedicated, fast acceptance and publication track for high profile articles.