Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, No.138 XianLin Avenue, QiXia District, Nanjing, Jiangsu, China.
Institute of TCM-Related Comorbid Depression, Nanjing University of Chinese Medicine, No.138 XianLin Avenue, QiXia District, Nanjing, Jiangsu, China; Laboratory of Ethnopharmacology, Xiangya Hospital, Central South University, 410008 Changsha, China.
Phytomedicine. 2024 Jun;128:155324. doi: 10.1016/j.phymed.2023.155324. Epub 2023 Dec 30.
Researchers have not studied the integrity, orderly correlation, and dynamic openness of complex organisms and explored the laws of systems from a global perspective. In the context of reductionism, antidepressant development formerly focused on advanced technology and molecular details, clear targets and mechanisms, but the clinical results were often unsatisfactory.
MDD represents an aggregate of different and highly diverse disease subtypes. The co-occurrence of stress-induced nonrandom multimorbidity is widespread, whereas only a fraction of the potential clusters are well known, such as the MDD-FGID cluster. Mapping these clusters, and determining which are nonrandom, is vital for discovering new mechanisms, developing treatments, and reconfiguring services to better meet patient needs.
Acute stress 15-minute forced swimming (AFS) or CUMS protocols can induce the nonrandom MDD-FGID cluster. Multiple biological processes of rats with depression-like behaviours and gastrointestinal dysmobility will be captured under conditions of stress, and the Fructus Aurantii-Rhizoma Chuanxiong (ZQCX) decoction will be utilized to dock the MDD-FGID cluster.
METHODS/RESULTS: Here, Rhizoma Chuanxiong, one of the seven components of Chaihu-shugan-San, elicited the best antidepressant effect on CUMS rats, followed by Fructus Aurantii. ZQCX reversed AFS-induced depression-like behaviours and gastrointestinal dysmobility by regulating the glutamatergic system, AMPAR/BDNF/mTOR/synapsin I pathway, ghrelin signalling and gastrointestinal nitric oxide synthase. Based on the bioethnopharmacological analysis strategy, the determined meranzin hydrate (MH) and senkyunolide I (SI) by UPLC-PDA, simultaneously absorbed by the jejunum and hippocampus of rats, have been considered major absorbed bioactive compounds acting on behalf of ZQCX. Cotreatment with MH and SI at an equivalent dose in ZQCX synergistically replicated over 50.33 % efficacy of the parent formula in terms of antidepressant and prokinetic actions by modulating neuroinflammation and ghrelin signalling.
Brain-centric mind shifts require the integration of multiple central and peripheral systems and the elucidation of the underlying neurobiological mechanisms that ultimately contribute to novel therapeutic options. Ghrelin signalling and the immune system may partially underlie multimorbidity vulnerability, and ZQCX anchors stress-induced MDD-FGID clusters by docking them. Combining the results of micro details with the laws of the macro world may be more effective in finding treatments for MDD.
研究人员尚未从全局角度研究复杂生物体的整体性、有序相关性和动态开放性，并探索系统规律。在还原论的背景下，抗抑郁药的开发以前侧重于先进的技术和分子细节、明确的靶点和机制，但临床结果往往不尽如人意。
MDD 代表不同的、高度多样化的疾病亚型的总和。应激诱导的非随机多病共存普遍存在，而潜在的聚类只有一部分是众所周知的，例如 MDD-FGID 聚类。映射这些聚类并确定哪些是非随机的，对于发现新的机制、开发治疗方法以及重新配置服务以更好地满足患者需求至关重要。
急性应激 15 分钟强制游泳（AFS）或 CUMS 方案可诱导非随机 MDD-FGID 聚类。在应激条件下，将捕获具有抑郁样行为和胃肠道运动障碍的大鼠的多个生物学过程，并利用枳壳川芎汤（ZQCX）对接 MDD-FGID 聚类。
方法/结果：在这里，作为柴胡疏肝散的七种成分之一的川芎，对 CUMS 大鼠表现出最好的抗抑郁作用，其次是枳实。ZQCX 通过调节谷氨酸能系统、AMPA R/BDNF/mTOR/synapsin I 通路、胃饥饿素信号和胃肠道一氧化氮合酶，逆转 AFS 诱导的抑郁样行为和胃肠道运动障碍。基于生物民族药理学分析策略，UPLC-PDA 同时测定枳壳川芎汤中的芒柄花素水合物（MH）和川芎嗪 I（SI），这两种化合物被认为是枳壳川芎汤的主要吸收生物活性化合物，代表了枳壳川芎汤的作用。MH 和 SI 以相当于枳壳川芎汤的等效剂量共同处理，在抗抑郁和促动力作用方面协同复制了 50.33%以上的母体配方的功效，通过调节神经炎症和胃饥饿素信号。
以大脑为中心的思维转变需要整合多个中枢和外周系统，并阐明最终有助于新治疗选择的潜在神经生物学机制。胃饥饿素信号和免疫系统可能部分是多疾病易感性的基础，而 ZQCX 通过对接它们来锚定应激诱导的 MDD-FGID 聚类。将微观细节的结果与宏观世界的规律相结合，可能更有效地找到治疗 MDD 的方法。
