Chronic inflammation of the central nervous system (CNS) is critical to the pathogenesis of neuropsychiatric disorders (NPDs) that affect the global population. Current therapeutics for NPDs are limited to relieving symptoms and induce many adverse effects. Therefore, the discovery of novel therapeutic agents from natural sources is urgently needed. Intriguingly, the immune responses of peripheral organs are closely linked through the molecular communication between resident and blood-borne cellular components, which shape the neuroinflammatory phenotypes of NPDs. Since the gut and spleen are the two largest immunological organs of the body, the brain-gut-microbiome and brain-spleen axes have been implicated in the connection between the CNS and the peripheral immune system. Accordingly, it has been proposed that the local CNS inflammation observed in NPDs is regulated via the manipulation of the systemic immune system by targeting the gut and spleen. Additionally, the complexity of the signalling network underlying the communication between the CNS and the systemic immune system suggests a strong potential for treating NPDs through a polypharmacological approach. The close association between systemic immunity and the homeostasis of the CNS points to the concept of repurposing interventions for systemic immune disorders to treat NPDs. Notably, natural products represent a promising source of such effective compounds due to both their pharmacological potency and safety. This review discusses the complex implications of dysregulated systemic immunity mediated by the brain-spleen and brain-gut-microbiome axes in NPDs, such as Alzheimer's disease, Parkinson's disease, schizophrenia and major depressive disorder. In addition, the potential of repurposing natural product-based bioactive compounds for treating NPDs via modulating systemic immune disorders is intensively discussed.

中文翻译：

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基于天然产物的外周免疫系统的多药理学调节，用于治疗神经精神疾病。

中枢神经系统（CNS）的慢性炎症对于影响全球人口的神经精神疾病（NPD）的发病机理至关重要。当前用于NPD的疗法仅限于缓解症状并引起许多不良反应。因此，迫切需要从天然来源发现新型治疗剂。有趣的是，周围器官的免疫反应通过驻留和血液传播的细胞成分之间的分子通讯紧密相连，从而形成了NPD的神经炎症表型。由于肠道和脾脏是人体两个最大的免疫器官，因此，中枢神经系统和周围免疫系统之间的联系牵涉到脑肠微生物群和脑脾轴。因此，已经提出，通过靶向肠道和脾脏，通过操纵全身免疫系统来调节在NPD中观察到的局部CNS炎症。此外，CNS和全身免疫系统之间通信基础的信号网络的复杂性表明，通过多药理学方法治疗NPD的潜力很大。全身免疫和中枢神经系统内在平衡之间的紧密联系指出了重新采用针对全身免疫疾病的干预措施来治疗NPD的概念。值得注意的是，天然产物由于其药理效力和安全性而代表了此类有效化合物的有希望的来源。这篇评论讨论了NPD中脑脾和脑肠道微生物组轴介导的系统免疫失调的复杂影响，如阿尔茨海默氏病，帕金森氏病，精神分裂症和重度抑郁症。此外，深入讨论了通过调节全身性免疫疾病来重新利用基于天然产物的生物活性化合物治疗NPD的潜力。