Guangzhou Key Laboratory of Formula-Pattern of Traditional Chinese Medicine, School of Traditional Chinese Medicine, Jinan University, Guangzhou 510632, Guangdong Province, China.
College of Pharmacy, Jinan University, Guangzhou 510632, Guangdong Province, China.
J Integr Med. 2022 Sep;20(5):442-452. doi: 10.1016/j.joim.2022.07.003. Epub 2022 Jul 25.
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.
抑郁和代谢紊乱具有重叠的心理社会和病理生理原因。目前的研究集中在脂联素在调节共同的生物学机制中的可能作用上。逍遥散（XYS）是一种经典的中药复方，已广泛用于治疗抑郁症，并能缓解脂质或葡萄糖代谢紊乱等代谢紊乱。然而，XYS 改善抑郁样行为以及改善小鼠代谢功能障碍的能力及其潜在机制尚不清楚。
采用慢性社会挫败应激（CSDS）建立动物抑郁模型。通过灌胃给予 XYS 和氟西汀进行药物干预。通过社会互动试验、旷场试验、强迫游泳试验和高架十字迷宫试验分析抑郁样行为。采用口服葡萄糖耐量试验测定血糖水平。通过免疫荧光、组织病理学和 Western blot 验证某些分子的参与。体外，将下丘脑原代神经元暴露于高葡萄糖中以诱导神经元损伤，通过细胞计数试剂盒-8 试验评估 XYS 的神经保护作用。免疫荧光和 Western blot 用于评估 XYS 对脂联素受体 1（AdipoR1）、腺苷 5'-单磷酸激活蛋白激酶（AMPK）、乙酰辅酶 A 羧化酶（ACC）等相关蛋白的影响。
XYS 改善了 CSDS 诱导的抑郁样行为和小鼠葡萄糖耐量损伤，并增加了血清脂联素水平。XYS 还恢复了表现出抑郁样行为的小鼠下丘脑神经元中的尼氏体，并降低了神经元形态损伤的程度。体内和体外研究表明，XYS 增加了下丘脑神经元中 AdipoR1 的表达。
脂联素可能是连接抑郁和代谢紊乱的关键调节剂；调节下丘脑 AdipoR1/AMPK/ACC 通路在 XYS 治疗抑郁症中起重要作用。
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