State Key Laboratory Cultivation Base for TCM Quality and Efficacy, Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, Nanjing, China.
Department of Traditional Chinese Medicine, Xiamen University, China.
Behav Brain Res. 2021 Feb 1;398:112898. doi: 10.1016/j.bbr.2020.112898. Epub 2020 Sep 6.
The burden of depression is enormous, and numerous studies have found that major depressive disorder (MDD) induces cardiovascular disorders (CVD) and functional dyspepsia (FD). Excitingly, meranzin hydrate (MH), an absorbed bioactive compound of Aurantii Fructus Immaturus, reverses psychosocial stress-induced mood disorders, gastrointestinal dysfunction and cardiac disease. Pharmacological methods have repeatedly failed in antidepressant development over the past few decades, but repairing aberrant neural circuits might be a reasonable strategy. This article aimed to explore antidepressant-like effects and potential mechanisms of MH in a rat model of unpredictable chronic mild stress (UCMS). Utilizing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we sought to find reliable neurocircuits or a dominant brain region revealing the multiple effects of MH. The results show that compared with UCMS rats, MH (10 mg/kg/day for 1 week i.g.)-treated rats exhibited decreased depression-like behaviour; increased expression of brain-derived neurotrophic factor (BDNF) in the hippocampal dentate gyrus; and normalized levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and acylated ghrelin (AG). Additionally, the UCMS-induced rise in BOLD activation in the reward system was attenuated after MH treatment. A literature search shown that nucleus accumbens (NAc) and hypothalamus of the reward system might reveal multiple effects of MH on MDD-FD-CVD comorbidity. Further research will focus on the role of these two brain regions in treating depression associated with comorbidities.
抑郁症的负担是巨大的，许多研究发现，重度抑郁症（MDD）可导致心血管疾病（CVD）和功能性消化不良（FD）。令人兴奋的是，枳实素水合物（MH），酸橙未成熟果实的一种被吸收的生物活性化合物，可逆转社会心理应激引起的情绪障碍、胃肠功能障碍和心脏病。在过去的几十年中，药理学方法在抗抑郁药的开发中一再失败，但修复异常的神经回路可能是一种合理的策略。本文旨在探讨 MH 在不可预测性慢性轻度应激（UCMS）大鼠模型中的抗抑郁样作用及其潜在机制。利用血氧水平依赖（BOLD）功能磁共振成像（fMRI），我们试图找到可靠的神经回路或主导大脑区域，揭示 MH 的多种作用。结果表明，与 UCMS 大鼠相比，MH（10mg/kg/天，灌胃 1 周）治疗的大鼠表现出抑郁样行为减少；海马齿状回中脑源性神经营养因子（BDNF）表达增加；促肾上腺皮质激素（ACTH）、皮质酮（CORT）和酰化生长素释放肽（AG）水平正常化。此外，MH 治疗后，UCMS 诱导的奖励系统中 BOLD 激活升高得到减弱。文献检索表明，奖励系统的伏隔核（NAc）和下丘脑可能揭示 MH 对 MDD-FD-CVD 共病的多种作用。进一步的研究将集中在这两个大脑区域在治疗与共病相关的抑郁症中的作用。
