Abstract
The neuroimmune and neuroendocrine systems are two critical biological systems in the pathogenesis of depression. Clinical and preclinical studies have demonstrated that the activation of the neuroinflammatory response of the immune system and hyperactivity of the hypothalamus–pituitary–adrenal (HPA) axis of the neuroendocrine system commonly coexist in patients with depression and that these two systems bidirectionally regulate one another through neural, immunological, and humoral intersystem interactions. The neuroendocrine-immune network poses difficulties associated with the development of antidepressant agents directed toward these biological systems for the effective treatment of depression. On the other hand, multidrug and multitarget Chinese Herbal Medicine (CHM) has great potential to assist in the development of novel medications for the systematic pharmacotherapy of depression. In this narrative essay, we conclusively analyze the mechanisms of action of CHM antidepressant constituents and formulas, specifically through the modulation of the neuroendocrine-immune network, by reviewing recent preclinical studies conducted using depressive animal models. Some CHM herbal constituents and formulas are highlighted as examples, and their mechanisms of action at both the molecular and systems levels are discussed. Furthermore, we discuss the crosstalk of these two biological systems and the systems pharmacology approach for understanding the system-wide mechanism of action of CHM on the neuroendocrine-immune network in depression treatment. The holistic, multidrug, and multitarget nature of CHM represents an excellent example of systems medicine in the effective treatment of depression.
Highlights
Depression is a persistent and recurring mental illness, affecting more than 264 million people of all ages worldwide
It is noteworthy that neuroinflammation in stress-induced animal models can be attenuated by the Corticotrophin Releasing Factor 1 (CRF1) antagonist, SSR125543 [192]. These findings have suggested that the release of CORT, adrenocorticotropic hormone (ACTH), and corticotrophin releasing factor (CRF) can be induced by proinflammatory cytokines and, proinflammatory cytokines can be regulated by the modulation of hypothalamus– pituitary–adrenal (HPA) axis hormones
Numerous empirical Chinese Herbal Medicine (CHM) antidepressant formulas are often used in clinical practice for the treatment of depression (Table 2)
Summary
Depression is a persistent and recurring mental illness, affecting more than 264 million people of all ages worldwide. Clinical studies have indicated that patients suffering from depression showed significantly higher levels of proinflammatory cytokines, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP), and inflammasome, than healthy people [6,20,21,22,23,24] These studies have shown that patients with chronic peripheral inflammatory diseases have a higher incidence of depression [25]. Several studies have reported that chronic unpredictable mild stress (CUMS) treatment elevated the proinflammatory or neuroinflammatory response of the immune system in the blood and brain [27,28,29], whereas the administration of endotoxins, such as lipopolysaccharide (LPS), caused depressive-like behaviors by activating the indoleamine 2,3-dioxygenase (IDO) pathway [30] or proinflammatory cytokines [31] These studies indicate that bidirectional communication exists between proinflammation or neuroinflammation and the CNS. These findings have provided evidence that the dysfunction of the neuroimmune system is involved in the pathogenesis of depression
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