Equol can improve depression by inhibiting excessive activation of the hypothalamic-pituitary-adrenal axis

Depression, also known as major depressive disorder, is characterized by persistent and significant feelings of sadness, reduced interest or pleasure in activities, and low energy levels. It may also include early symptoms such as slow reaction, slowed thinking, and decreased memory, although these can vary among individuals [1]. According to the Chinese National Mental Health Report, the detection rate of high depression risk in the eastern and northeastern regions of China is significantly lower than in the central and western regions. There are also significant differences in depression and anxiety levels among different age groups [2]. The 2019 China Mental Health Survey showed a lifetime prevalence of depression in China to be 6.8% and a 12-month prevalence of 3.6%. The lifetime prevalence of major depressive disorder was 3.4%, while the 12-month prevalence was 2.1% [1]. With the increasing pace of life and growing stress, the global incidence of depression has been steadily increasing, making it the fourth leading cause of disease that threatens human health [3]

In our previous article, we briefly discussed the antidepressant effects of Equol. Howdoes Equol, a secondary metabolite of soy isoflavones with estrogenic-like effects, antioxidant properties, anti-inflammatory effects, and neuroactivity, specifically exert its antidepressant effects? In this article, I will share relevant research and lead you to a deeper understanding of the specific mechanisms of Equol in treating depression.

Recent studies have found that stressful life events are significant triggering factors for depression, and the main cause of depression is chronic, low-intensity, long-term daily stress. The Chronic Restraint Stress (CRS) model, which uses behavioral restraintto induce psychological stress in animals (Figure 3), is a commonly used method for establishing animal models of emotional and cognitive impairments.

In order to evaluate the antidepressant efficacy of Equol, researchers used a 28-day, 10-hour/day restraint method to induce depression in mice and randomly divided them into five groups based on body weight: blank control group, model group, low-dose Equol group, medium-dose Equol group, and high-dose Equol group. The study found that Equol intervention can improve depressive behavior induced by chronic restraint stress in mice and exhibits antidepressant activity. It can achieve this by regulating the HPA axis function and relieving neuroinflammation, among other mechanisms [3]. The results are as follows:

Equol does not affect the spontaneous activity of model mice.

The elevated levels of pro-inflammatory cytokines can also increase CORT release. Under stress stimulation, the body's immune cells are rapidly activated and release inflammatory factors, leading to the formation of more pro-inflammatory mediators. The sympathetic nervous system and HPA axis are rapidly activated to regulate peripheral inflammatory response, ultimately leading to the occurrence of neuroinflammation. The sustained activation of the HPA axis in regulating inflammatory response exacerbates depression.

Studies have shown that Equol can improve depression by inhibiting excessive activation of the hypothalamic-pituitary-adrenal axis, suppressing neuroinflammation, upregulating neurotransmitters, and balancing oxidative stress.

参考:

[1] https://baike.baidu.com/item/%E6%8A%91%E9%83%81%E7%97%87/90924#6-3

[2] 傅小兰，张侃，陈雪峰，陈祉妍.中国国民心理健康发展报告（2019～2020）[M].北京:社会科学文献出版社.2021.

[3] 韦震, 高荣静, 张瑛毓, 孙晶, 卢聪, & 王凤忠. (2022). 雌马酚对慢性束缚致抑郁小鼠模型的改善作用及机制研究. 大豆科学(001), 041.

 https://www.namr.org.cn/Ldesc/1_202