• Ruhui Shen, Zhipeng Li, Huiyun Wang, Yongchao Wang, Xiaofang Li, Qian Yang, Yingjie Fu, Ming Li, and Li-Na Gao.
• College of Pharmacy, Binzhou Medical University, Yantai, Shandong 264003, P. R. China.
• Am. J. Chin. Med. 2023 Jan 1; 51 (8): 192719551927-1955.

AbstractDepression is a highly heterogeneous mental illness. Drug treatment is currently the main therapeutic strategy used in the clinic, but its efficacy is limited by the modulation of a single target, slow onset, and side effects. The gut-brain axis is of increasing interest because intestinal microenvironment disorders increase susceptibility to depression. In turn, depression affects intestinal microenvironment homeostasis by altering intestinal tissue structure, flora abundance and metabolism, hormone secretion, neurotransmitter transmission, and immune balance. Depression falls into the category of "stagnation syndrome" according to Traditional Chinese Medicine (TCM), which further specifies that "the heart governs the spirit and is exterior-interior with the small intestine". However, the exact mechanisms of the means by which the disordered intestinal microenvironment affects depression are still unclear. Here, we present an overview of how the Chinese materia medica (CMM) protects against depression by repairing intestinal microenvironment homeostasis. We review the past five years of research progress in classical antidepressant TCM formulae and single CMMs on regulating the intestinal microenvironment for the treatment of depression. We then analyze and clarify the multitarget functions of CMM in repairing intestinal homeostasis and aim to provide a new theoretical basis for CMM clinical application in the treatment of depression.

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