Department of First Clinical Medical College, Shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Shandong University of Traditional Chinese Medicine, Jinan 250355, China; Department of Neurology, Affiliated Hospital of shandong University of Traditional Chinese Medicine, Jinan 250014, China.
Phytomedicine. 2024 Nov;134:156012. doi: 10.1016/j.phymed.2024.156012. Epub 2024 Aug 31.
Major depressive disorder (MDD) is a severe mental health condition characterized by persistent depression, impaired cognition, and reduced activity. Increasing evidence suggests that gut microbiota (GM) imbalance is closely linked to the emergence and advancement of MDD, highlighting the potential significance of regulating the "Microbiota-Gut-Brain" (MGB) axis to impact the development of MDD. Natural products (NPs), characterized by broad biological activities, low toxicity, and multi-target characteristics, offer unique advantages in antidepressant treatment by regulating MGB axis.
This review was aimed to explore the intricate relationship between the GM and the brain, as well as host responses, and investigated the mechanisms underlying the MGB axis in MDD development. It also explored the pharmacological mechanisms by which NPs modulate MGB axis to exert antidepressant effects and addressed current research limitations. Additionally, it proposed new strategies for future preclinical and clinical applications in the MDD domain.
To study the effects and mechanism by which NPs exert antidepressant effects through mediating the MGB axis, data were collected from Web of Science, PubMed, ScienceDirect from initial establishment to March 2024. NPs were classified and summarized by their mechanisms of action.
NPs, such as flavonoids,alkaloids,polysaccharides,saponins, terpenoids, can treat MDD by regulating the MGB axis. Its mechanism includes balancing GM, regulating metabolites and neurotransmitters such as SCAFs, 5-HT, BDNF, inhibiting neuroinflammation, improving neural plasticity, and increasing neurogenesis.
NPs display good antidepressant effects, and have potential value for clinical application in the prevention and treatment of MDD by regulating the MGB axis. However, in-depth study of the mechanisms by which antidepressant medications affect MGB axis will also require considerable effort in clinical and preclinical research, which is essential for the development of effective antidepressant treatments.
重度抑郁症（MDD）是一种严重的精神健康疾病，其特征为持续抑郁、认知受损和活动减少。越来越多的证据表明，肠道微生物群（GM）失衡与 MDD 的出现和发展密切相关，这凸显了调节“微生物群-肠道-大脑”（MGB）轴以影响 MDD 发展的重要性。天然产物（NPs）具有广泛的生物活性、低毒性和多靶点特点，通过调节 MGB 轴在抗抑郁治疗方面具有独特优势。
本综述旨在探讨 GM 与大脑以及宿主反应之间的复杂关系，研究 MGB 轴在 MDD 发展中的作用机制，探讨 NPs 通过调节 MGB 轴发挥抗抑郁作用的药理学机制，并解决当前研究的局限性。此外，还提出了新的策略，以用于未来 MDD 领域的临床前和临床应用。
为了研究 NPs 通过调节 MGB 轴发挥抗抑郁作用的效果和机制，从建库到 2024 年 3 月，我们通过 Web of Science、PubMed 和 ScienceDirect 收集数据。根据作用机制对 NPs 进行分类和总结。
黄酮类、生物碱类、多糖类、皂苷类、萜类等 NPs 可以通过调节 MGB 轴治疗 MDD。其机制包括平衡 GM、调节代谢物和神经递质（如 SCAFs、5-HT、BDNF）、抑制神经炎症、改善神经可塑性、增加神经发生。
NPs 具有良好的抗抑郁作用，通过调节 MGB 轴在预防和治疗 MDD 方面具有潜在的临床应用价值。然而，深入研究抗抑郁药物对 MGB 轴的影响机制也需要在临床和临床前研究中付出相当大的努力，这对于开发有效的抗抑郁治疗方法至关重要。
