Ginseng Extract: Multi-Targeted Antidepressant Effects Mediated by Active Compounds

General Description

Ginseng extract, derived from the ginseng herb, is a valuable component in traditional Chinese medicine. It contains active ingredients such as ginsenosides, ginseng polysaccharides, and ginseng polypeptides, which contribute to its beneficial effects. Ginseng extract has been found to have antidepressant properties through various mechanisms. It modulates monoamine neurotransmitters, normalizes the hypothalamic-pituitary-adrenal axis, regulates gonadal hormones, enhances brain-derived neurotrophic factor expression, and exhibits anti-inflammatory effects. These mechanisms collectively contribute to its antidepressant effects. Overall, ginseng extract offers potential therapeutic benefits for individuals suffering from depression and related neurological disorders.

Figure 1. Ginseng extract

Active ingredients

Ginseng extract is derived from the ginseng herb, which has been used in traditional Chinese medicine for centuries. It is known for its ability to improve mental state and modulate neurological diseases such as insomnia, depression, anxiety, and neurasthenia. Ginseng is classified into different species, including Panax ginseng, Panax quinquefolium L., and Panax notoginseng. Panax ginseng, also known as Asian ginseng, is primarily cultivated in northeast China, Korea, Japan, and eastern Russia. It is considered to have the greatest tonic effect and is recommended for individuals who are physically weak and infirm, preferably taken in winter. Panax quinquefolium L., or American ginseng, is mainly produced in the United States, Canada, and other countries. It is milder in nature and suitable for most people and can be consumed throughout the year. Panax notoginseng is grown in specific regions of China, including Jilin, Guangxi, and Yunnan. Each type of ginseng undergoes different processing methods, resulting in white ginseng, sugar ginseng, and red ginseng. Modern studies have revealed that Ginseng extract contains various active ingredients, including ginsenosides, ginseng polypeptides, and ginseng polysaccharides. Ginsenosides are considered the major active compounds responsible for Ginseng extract's physiological effects on the nervous system, cardiovascular system, and immune system. They can be classified into three main types: protopanaxadiols (PPDs), protopanaxatriols (PPTs), and oleanolic acids. Ginseng polysaccharides, another key component, exhibit biological activities such as immune regulation, anti-cancer, antidepression, and anti-oxidation. They are composed of ginseng neutral sugars and ginseng acid pectin. The antidepressant effects of Ginseng extract have been confirmed through clinical applications and experimental studies. Studies have shown that ginseng extract can improve depression-like behaviors and regulate neurotransmitters in animal models. Overall, ginseng extract contains a wide range of active ingredients that contribute to its pharmacological effects and medical applications, making it a valuable herb in traditional medicine. ¹

Antidepressant mechanisms

Ginseng extract has been found to have antidepressant effects through various mechanisms. One of the main mechanisms is its impact on monoamine neurotransmitters, such as serotonin (5-HT), noradrenaline (NA), and dopamine (DA). Depression is associated with reduced function of these neurotransmitters, and ginsenosides have been shown to mitigate changes in their levels. For example, ginseng fruit saponins can increase 5-HT levels in serum and platelets. Ginsenoside Rb1, found in ginseng root, significantly upregulates the levels of 5-HT, 5-HIAA, NA, and DA in the brain. These effects are similar to those of commonly used antidepressants. Another mechanism involves the hypothalamic-pituitary-adrenal (HPA) axis, which is dysregulated in depression. Ginsenosides, such as Rg1, Rh1, Rg3, and Rb1, have been found to normalize the HPA axis by improving cortisol and testosterone levels, as well as modulating glucocorticoid receptor (GR) levels in the brain. They also protect neurons from toxicity associated with stress hormones. Additionally, ginseng extract can regulate the gonadal hormones, such as estrogen and progesterone, which play a role in depression. Ginseng extract affects the neurotrophic factor called brain-derived neurotrophic factor (BDNF), which is associated with neurogenesis and neural survival. Reduced BDNF levels have been observed in the brains and serum of depressed individuals. Ginseng extract, particularly ginsenoside Rg1, has been shown to increase BDNF expression in various animal models of depression. It also enhances CREB phosphorylation, which is involved in BDNF signaling pathways. Other ginsenosides, such as Rg2 and Rg5, also regulate the BDNF/TrkB pathway. Furthermore, ginseng extract has anti-inflammatory properties that can modulate the neuroimmune system. Inflammatory cytokine disorders have been linked to depression, and ginseng extract can reduce the production of proinflammatory cytokines. It inhibits neuroinflammation by regulating microglia and astrocyte activation, thereby preventing neuronal damage. These effects are mediated by various signaling pathways, such as AMPK, PI3K/Akt, NF-κB, and PPAR. In conclusion, ginseng extract exerts its antidepressant effects through multiple mechanisms, including modulation of monoamine neurotransmitters, normalization of the HPA axis, regulation of neurotrophic factors like BDNF, and modulation of the neuroimmune system. ²

Reference

1. Zheng M, Xin Y, Li Y, et al. Ginsenosides: a potential neuroprotective agent. Biomed Res Int. 2018;2018: 8174345.

2. Jin Y, Cui R, Zhao L, Fan J, Li B. Mechanisms of Panax ginseng action as an antidepressant. Cell Prolif. 2019;52(6):e12696.

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