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.

Study of Antidepressant-Like Effects of Albiflorin and Paeoniflorin Through Metabolomics From the Perspective of Cancer-Related Depression

“…From the perspective of TCM, the model rats not only present the endocrine-immune system disorders caused by the deficiency of yin blood in the liver meridian, but also show changes in the neuroendocrine system disorders caused by the stagnation of liver qi. This is also consistent with the view that the pathogenesis of depression is involved in the neuroendocrine-immune network (41,42). In this paper, pharmacological studies showed that depression-like behavioral deficits in model groups and the lowered or increased levels of the peripheral hemogram, HPA axis, and organ index were ameliorated by AF and PF.…”

“…AF and PF could significantly increase the thymus index and spleen index, improving the abnormal immune function of the body. With increasing bloodbrain barrier permeability, peripheral cytokines can be actively transported into the CNS, subsequently, followed by a reduction in serotonin neurotransmission and the activation of the HPA axis (41). As the hub of the neuroendocrine network, the HPA axis plays an important role in the pathogenesis of depression, with the dysregulation of the HPA axis (48), increasing extracellular glutamate levels and glutamate neurotransmission, and then impacting hippocampal neurogenesis, and through glucocorticoids, the HPA axis is involved in anti-inflammatory, pro-inflammatory and other immune regulatory processes (49).…”

Antidepressant Potential of Quercetin and its Glycoside Derivatives: A Comprehensive Review and Update

“…As a flavonol with numerous biological activities, quercetin has different pharmacological effects such as antidepression, anti-cancer, antioxidant, anti-fibrosis, and antiinflammatory (Reyes-Farias and Carrasco-Pozo, 2019;Ou et al, 2020;Alshammari et al, 2021). Many studies have suggested the protection of mature neurons in the hippocampus, improvement of HPA axis dysfunction, anti-inflammatory, and anti-oxidative stress were involved in the antidepressant effects of quercetin (Sun et al, 2007;Bicca et al, 2021;El-Haroun et al, 2021;Han et al, 2021;Li et al, 2021;Sun et al, 2021), which also encompasses hippocampal neurogenesis promotion through direct and indirect effects (Chan et al, 2018;Rahvar et al, 2018;Wang et al, 2021a;Ma et al, 2021). Hence, quercetin has multiple targets and pathways compared to other antidepressants (Figure 3).…”

“…This paradoxical phenomenon reminds us to be more cautious in future. First of all, as numerous studies in vivo have confirmed that quercetin could act on multiple targets in depression treatment (El-Haroun et al, 2021;Han et al, 2021;Li et al, 2021), the top priority of in vitro studies is not to prove whether quercetin has new targets in treating depression, but to reveal the mechanisms of the proved targets through more scientific models and methods. Besides, based on the difficulties to distinguish the non-specifically and therapeutically irrelevant effects (Baell, 2016), it is necessary to review the false positives and related mechanisms of quercetin, in order to guide researchers to select appropriate cells, culture mediums, control groups and evaluation methods.…”

Dissecting the molecular mechanisms underlying the antidepressant activities of herbal medicines through the comprehensive review of the recent literatures

“…Indeed, anti-inflammatory drugs like celecoxib could effectively relieve the symptoms of depression ( 94 ). Many herbal medicines are well-documented for anti-inflammatory properties and potential in the treatment of depression in the inflammatory model of depression ( 95 ). Crocus sativus L. (Saffron) is an important medicinal ingredient and also a common spice in North African, Mediterranean, and Middle Eastern countries.…”