How effective are herbal remedies and natural products in the treatment of psychological disorders?

Depression, a common illness severely limiting psychosocial functioning and diminishing quality of life, affects 350 million people worldwide according to the World Health Organization (WHO) (Malhi and Mann, 2018; Smith, 2014). Moreover, depression is one of the most serious neuropsychiatric disorders accounting for 40.5% of all disability-adjusted life years caused by mental pathologies (Whiteford et al., 2016). Risk factors for occurrence of depression including genetic, immunological and environmental, among which stress is a significant trigger for the onset of depression. Study noted patients with depression experienced 2.5 times more stressors than normal individuals, and 80% of depression cases were preceded by stressful events (Hammen, 2005). Numerous researches revealed prolonged exposure to stress increased vulnerability to anxiety, depression and other mood disorders, accompanying by metabolic syndrome, cardio cerebrovascular disease, memory disorders, cognition, learning disorders and even structural changes in different parts of brain (Seo et al., 2017).

The pathological mechanism of depression is subject to sharply divided opinions. A considerable finding in psychoneuroendocrinology of stress-induced depression is the change of the HPA axis, characterizing elevated levels of corticosterone (CORT) and adrenocorticotrophic hormone (ACTH) in serum (Weger and Sandi, 2018). Moreover, various evidence demonstrates that the increased activity of proinflammatory cytokines has played an important role in stress-induced depression (Lindqvist et al., 2017). Another leading hypothesis on the neurobiological basis of stress-induced depression is the monoamine hypothesis, which contends decreased level of serotonin (5-HT) and norepinephrine (NE) (Charney, 1998). Increasing evidence indicates brain-derived neurotrophic factor (BDNF) controls the process of neurogenesis, which reflects the neuroplasticity hypothesis in stress-induced depression (D'Sa and Duman, 2002). Furthermore, some authorities maintain just as firmly that oxidative stress causes the oxidation of proteins and cell degeneration, relating to the occurrence of depression.

Animal models contribute to understanding the pathological mechanism and drug discovery of diseases. Stress-induced depression related animal models are established on chronic and inescapable stress paradigms. We describe four animal stress models as possible models for human depression. The paradigms, behavioral correlates to depression and potential underlying neurobiological mechanisms were discussed to facilitate possible future therapies for depression. For example, as the most commonly used and effective rodent model of depression, CUMS paradigm is widely applied to evaluate depressive-like behavior (Antoniuk et al., 2019).

Synthesized agents including selective 5-HT reuptake inhibitors (SSRIs), MAO inhibitors, tricyclic antidepressants (TCAs) and atypical antidepressants have been widely clinical used in patients with depression (Duman and Voleti, 2012). Unfortunately, only one-third of patients have beneficial treatment response to these agents complicating by serious adverse side effects of nausea, vomiting, sleep disruption, sedation, sexual dysfunction and weight gain (David and Gourion, 2016; Thanacoody and Thomas, 2005). Thus, it is urgent to seek safer and more effective alternatives against depression.

Traditional medicine such as traditional Chinese medicine, traditional African medicine and Islamic medicine, is widely used to treat mental disorders in Europe or other countries and areas of the world (Kpobi et al., 2019; Mitha, 2020; Qu et al., 2019; Sarris et al., 2011). In support, hypericin, a class of natural flavonoids product that act as the main pharmacologically active components of Hypericum perforatumis (also known as St. John's wort), has been discovered as a novel antidepressant to amelioration depression and is available as an over-the-counter herbal medicine in the United States. In addition, a St. John's wort dietary supplement with antidepressant activity is currently produced. Moreover, Chinese herbal formulas such as Gan-Mai-Da-Zao Decotion, Xiao-Yao-San and Chai-Hu-Shu-Gan-San, have been proved to be effective in treating and improving depressive-like symptoms (Jun et al., 2014; Sun et al., 2018; Yuan et al., 2020).

Several animal experiments and randomized clinical trials have been performed to validate the anti-depressive effects of many herbal medicines or natural products. These investigations provide a scientific rationale and research direction to support the traditional use of herbal medicines. To better understand the potential therapeutic effects of natural products and develop a promising drug with high efficacy and low toxicity for the treatment of stress-induced depression, more and more scientific investigations regard to the research for natural products with antidepressant activities should be carried out. This review summarized the pathological mechanism and animal models of stress-induced depression, and a various of natural products with antidepressant effects, which confirmed the therapeutic potential of natural products and provided a reference for the further development of antidepressants.

Pathological mechanism of stress-induced depression

Stress can be either a triggering or aggravating factor for many diseases and pathological conditions, exerting destructive effects on central nervous system (CNS) and thus leading to memory, cognitive and learning disorders. Moreover, it affects the function of immune system through modulating processes in the CNS and neuroendocrine system, leading to a deleterious effect on cardiovascular system, gastrointestinal (GI) system and endocrine system (Yaribeygi et al., 2017). These changes may

Animal models of stress-induced depression

Establishment of animal models perfectly recapitulating the symptoms of depression is extremely difficult as animals not only lack consciousness of themselves, consideration of others, self-regulatory and self-reflection but also hallmarks of depression such as depressed mood, low self-esteem or suicidality (McArthur and Borsini, 2006). Three eligibility criteria sets for a desirable animal model included face validity, construct validity and predictive validity (Willner, 1984). The stress

Natural products with antidepressant activities

Various active ingredients from natural products are observed to play an important and indispensable role in prevention and treatment of mental disorders (Olfson et al., 2002; Williams et al., 1999), which have attracted increasing attention and may be ideal alternatives for depression treatment. Structural diversity and extensive pharmacological effects are characteristic of natural products, which are not common in synthetic anti-depressant drugs.

Chinese medicine formulas with antidepressant effects

Chinese medicine formulas (TCMFs), in which the interaction of various medicines can improve efficacy and reduce toxicity, have been clinically used for thousands of years in China. Recently, treatment with Chinese medicine formulas against depression is becoming favorable among scholars and researchers. Numerous studies have shown the antidepressant effects of TCMFs focused on regulating monoamines, reestablishing neuronal plasticity, alleviating HPA axis dysfunction and abnormal regulation of

Traditional use of natural products for depression

Among the rich and diverse medicinal plants, herbal medicine is one of the oldest with a history of more than 2000 years. With great structural diversity and extensive biological activity, natural products have been the most productive source of leads for new drugs. As early as the Swiss physician Paracelsus (ca. 1493–1541), traditional European medicine has used Hypericum perforatum L. for centuries as a treatment for psychiatric disorders including neuralgia, anxiety, neurosis and depression (

Toxicological information of natural products

Since the US Congress passed the Dietary Supplement Health and Education Act, the retail sales of herbal products, a subcategory of dietary supplements, have increased by 83% from 2008 to 2018 ($4.8 to $8.8 billion) (Gaston et al., 2020). Although natural products show good and unique effects in the treatment of depression, the duality of drugs, as one of the basic laws of drug action, can likewise be found in natural products. Natural products not only have a good effect on disease prevention,

Conclusions

Stress-induced depression is a prevalent and persistent mental disorder leading to heavy socioeconomic burden and higher suicide rates. Numerous studies have demonstrated that stress-induced depression was in high relationship with the monoaminergic system, HPA axis, neuronal plasticity and a series of inflammatory factors (Farahani et al., 2015). Stress-induced experimental animal models can recapitulate depressive symptoms, analyze the effects of novel antidepressants, and guide the

Author's contributions

Wei Dai collated documents and wrote the manuscript; Xiaolei Sun helped to perform the arrangement of tables and pictures; Kunmiao Feng contributed to the documents download and queried; Lingchuan Xu, Dan Jia and Ting Han contributed significantly to analysis and manuscript preparation.

Declaration of competing interest

The authors declare that they do not have any conflict of interest.

Acknowledgments

This work was supported by National Natural Science Foundation of China (No. 81872953 and 82174091) and Shanghai Pujiang Program (No. 18PJD061).

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