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Journal of Integrative Medicine ›› 2022, Vol. 20 ›› Issue (5): 442-452.doi: 10.1016/j.joim.2022.07.003

• Original Experimental Research • Previous Articles     Next Articles

Xiaoyao San, a Chinese herbal formula, ameliorates depression-like behavior in mice through the AdipoR1/AMPK/ACC pathway in hypothalamus

Kai-rui Tanga, Xiao-wei Moa, Xing-yi Zhoua, Yue-yue Chena, Dong-dong Liua, Liang-liang Heb, Qing-yu Maa, Xiao-juan Lia, Jia-xu Chena   

  1. a. Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China
    b. College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province, China
  • Online:2022-09-15 Published:2022-08-23
  • Contact: Xiao-juan Li, Jia-xu Chen,


Depression and metabolic disorders have overlapping psychosocial and pathophysiological causes. Current research is focused on the possible role of adiponectin in regulating common biological mechanisms. Xiaoyao San (XYS), a classic Chinese medicine compound, has been widely used in the treatment of depression and can alleviate metabolic disorders such as lipid or glucose metabolism disorders. However, the ability of XYS to ameliorate depression-like behavior as well as metabolic dysfunction in mice and the underlying mechanisms are unclear.


An in vivo animal model of depression was established by chronic social defeat stress (CSDS). XYS and fluoxetine were administered by gavage to the drug intervention group. Depression-like behaviors were analyzed by the social interaction test, open field test, forced swim test, and elevated plus maze test. Glucose levels were measured using the oral glucose tolerance test. The involvement of certain molecules was validated by immunofluorescence, histopathology, and Western blotting. In vitro, hypothalamic primary neurons were exposed to high glucose to induce neuronal damage, and the neuroprotective effect of XYS was evaluated by cell counting kit-8 assay. Immunofluorescence and Western blotting were used to evaluate the influences of XYS on adiponectin receptor 1 (AdipoR1), adenosine 5’-monophosphate-activated protein kinase (AMPK), acetyl-coenzyme A carboxylase (ACC) and other related proteins.


XYS ameliorated CSDS-induced depression-like behaviors and glucose tolerance impairment in mice and increased the level of serum adiponectin. XYS also restored Nissl bodies in hypothalamic neurons in mice that exhibited depression-like behaviors and decreased the degree of neuronal morphological damage. In vivo and in vitro studies indicated that XYS increased the expression of AdipoR1 in hypothalamic neurons.


Adiponectin may be a key regulator linking depression and metabolic disorders;  regulation of the hypothalamic AdipoR1/AMPK/ACC pathway plays an important role in treatment of depression by XYS.

Key words: Depression, Xiaoyao San, Chronic social defeat stress, Adiponectin, Adiponectin receptor 1, Glucose metabolism disorders

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