Chinese Herbal Medicine for the Treatment of Depression: Effects on the Neuroendocrine-Immune Network

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.

Keywords: Chinese herbal medicine; HPA axis; depression; neuroendocrine system; neuroendocrine-immune network; neuroimmune system; neuroinflammation.

Figure 1

The neuroendocrine-immune network in the pathogenesis of depression. In response to stress, the peripheral or neuroimmune system activates the release of HPA axis hormones, whereas the stress-induced hyperactivation of the HPA axis also stimulates a proinflammatory or neuroinflammatory response. Intersystem crosstalk occurs at many levels through neural, immunological, and humoral interactions and subsequently results in the dysfunction of the central nervous system (CNS) in the pathogenesis of depression.

Figure 2

Several representative CHM constituents that have been demonstrated to exert antidepressant activity, specifically by mediating the neuroimmune system.

Figure 3

Several representative CHM constituents that have been demonstrated to exhibit antidepressant-like activities through their action on HPA axis hormone receptors.

Figure 4

Several representative CHM constituents that have been shown to produce antidepressant effects through their actions on the neuroendocrine-immune network.