Natural products for the treatment of stress-induced depression: Pharmacology, mechanism and traditional use

Depression, one of the most common psychiatric disorders, is the fourth leading cause of long-term disability worldwide. A series of causes triggered depression, including psychological stress and conflict, as well as biological derangement, among which stress has a pivotal role in the development of depression. Traditional herbal medicine has been used for the treatment of various disorders including depression for a long history with multi-targets, multi-levels and multi-ways, attracting great attention from scholars. Recently, natural products have been commercialized as antidepressants which have become increasingly popular in the world health drug markets. Major research contributions in ethnopharmacology have generated and updated vast amount of data associated with natural products in antidepressant-like activity.This review aims to briefly discuss the pathological mechanism, animal models of stress-induced depression, traditional use of herbal medicines and especially recapitulate the natural products with antidepressant activity and their pharmacological functions and mechanism of action, which may contribute to a better understanding of potential therapeutic effects of natural products and the development of promising drugs with high efficacy and low toxicity for the treatment of stress-induced depression.The contents of this review were sourced from electronic databases including PubMed, Sci Finder, Web of Science, Science Direct, Elsevier, Google Scholar, Chinese Knowledge On frastructure (CNKI), Wan Fang, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM). Additional information was collected from Yao Zhi website (https://db.yaozh.com/). Data were obtained from April 1992 to June 2021. Only English language was applied to the search. The search terms were 'stress-induced depression', 'pathological mechanism' in the title and 'stress', 'depression', 'animal model' and 'natural products' in the whole text.Stress-induced depression is related to the monoaminergic system, hypothalamic-pituitary-adrenal (HPA) axis, neuronal plasticity and a series of inflammatory factors. Four main types of animal models of stress-induced depression were represented. Fifty-eight bioactive phytochemical compounds, fifty-six herb medicines and five formulas from traditional Chinese medicine were highlighted, which exert antidepressant effects by inhibiting monoamine oxidase (MAO) reaction, alleviating dysfunction of the HPA axis and nerve injury, and possessing anti-inflammatory activities.Natural products provide a large number of compounds with antidepressant-like effects, and their therapeutic impacts has been highlighted for a long time. This review summarized the pathological mechanism and animal models of stress-induced depression, and the natural products with antidepressant activity in particular, which will shed light on the action mechanism and clinical potential of these compounds. Natural products also have been a vital and promising source for future antidepressant drug discovery.