The therapeutic potential of curculigoside in poststroke depression: a focus on hippocampal neurogenesis and mitochondrial function.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2024-07-16 DOI:10.1093/jpp/rgae091

Ning-Xi Zeng, Xin Chen, Xiao-Yan Yang, De-Sheng Chen, Mei Shen

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引用次数: 0

Abstract

Objectives: To investigate the effects and mechanism of curculigoside against poststroke depression (PSD).

Methods: In vivo, a PSD rat model was created by combining bilateral common carotid artery occlusion and chronic unpredictable mild stress stimulations. After 4-week modeling and intragastrically administration of curculigoside, the effects of curculigoside on behavior, hippocampal neurogenesis, and hippocampal mitochondrial oxidative phosphorylation (OxPhos) were investigated. In vitro, PSD-like primary neural stem cells (NSCs) model was established by oxygen-glucose deprivation/recovery (OGD/R) combing high-corticosterone (CORT) concentration, followed by treatment with curculigoside. The investigation subsequently examined the impact of curculigoside on mitochondrial OxPhos, proliferation, and differentiation of NSCs under OGD/R + CORT conditions.

Key findings: In vivo, PSD rats showed significantly depressive behaviors, dysfunctional neurogenesis in hippocampus, as well as decreased hippocampus adenosine triphosphate (ATP) levels, reduced electron transport chain complexes activity, and downregulates mitochondrial transcription factor A (TFAM) and PPAR-gamma coactivator 1 alpha (PGC-1α) expression in hippocampus. In vitro, OGD/R +CORT significantly injured the proliferation and differentiation, as well as impaired the mitochondrial OxPhos in NSCs. Curculigoside treatment was effective in improving these abnormal changes.

Conclusion: Curculigoside may repair hippocampal neurogenesis in PSD rats by enhancing hippocampal mitochondrial OxPhos, and has shown a great potential for anti-PSD.

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莪术苷对中风后抑郁症的治疗潜力：关注海马神经发生和线粒体功能。

目的：研究莪术甙对脑卒中后抑郁（PSD）的作用和机制：研究莪术苷对卒中后抑郁（PSD）的作用和机制：方法：结合双侧颈总动脉闭塞和慢性不可预知的轻度应激刺激，在体内建立 PSD 大鼠模型。方法：将双侧颈总动脉闭塞和慢性不可预测的轻度应激刺激结合起来，建立了 PSD 大鼠体内模型。经过 4 周的建模和胃内注射莪术苷后，研究了莪术苷对行为、海马神经发生和海马线粒体氧化磷酸化（OxPhos）的影响。在体外，通过氧-葡萄糖剥夺/恢复（OGD/R）结合高浓度皮质酮（CORT），建立了类似PSD的原代神经干细胞（NSCs）模型，然后用莪术甙治疗。随后，研究人员考察了在OGD/R + CORT条件下，莪术苷对线粒体OxPhos、NSCs增殖和分化的影响：在体内，PSD大鼠表现出明显的抑郁行为，海马神经发生功能障碍，海马三磷酸腺苷（ATP）水平下降，电子传递链复合物活性降低，海马线粒体转录因子A（TFAM）和PPAR-gamma辅激活因子1α（PGC-1α）表达下调。在体外，OGD/R +CORT 会显著损伤 NSCs 的增殖和分化，并损害线粒体 OxPhos。莪术甙能有效改善这些异常变化：结论：莪术苷可通过增强海马线粒体OxPhos来修复PSD大鼠的海马神经发生，在抗PSD方面具有巨大潜力。

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

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.