Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, 810008, China; School of Psychology, Chengdu Medical College, Chengdu, 610500, China; University of Chinese Academy of Sciences, 19(A) yuquan road, Beijing, 10049, China.
Qinghai Provincial Key Laboratory of Tibetan Medicine Pharmacology and Safety Evaluation, Northwest Institute of Plateau Biology, Chinese Academy of Science, Xining, 810008, China.
J Ethnopharmacol. 2024 Dec 5;335:118663. doi: 10.1016/j.jep.2024.118663. Epub 2024 Aug 9.
Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (β-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which β-HgS restores appetite and weight in stressed mice remains unclear.
The objective of this study is to assess the efficacy of β-HgS in ameliorating weight loss and appetite suppression induced by pressure stimulation in mice, as well as elucidate its potential mechanisms of action.
The present study employed chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) as experimental models to simulate environmental stress encountered in daily life. Subsequently, a series of experiments were conducted, including behavior tests, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, as well as metabolomics analysis of hippocampal and intestinal contents.
Dysregulation of glycerophospholipid metabolism may represent the principal pathway underlying reduced appetite, body weight, neurotransmitter and appetite hormone levels, heightened inflammatory response, hippocampal and rectal tissue damage, as well as altered composition of intestinal microbiota in stressed mice. Following intervention with SER and β-HgS in stressed mice, the deleterious effects induced by stress can be ameliorated, in which the medium-dose β-HgS exhibited superior performance.
The aforementioned research findings suggest that the stress-induced decrease in appetite and body weight in mice may be associated with dysregulation in glycerophospholipid metabolism connecting the gut-brain axis. β-HgS exhibits potential in ameliorating depressive-like symptoms in mice subjected to stress, while concurrently restoring their body weight and appetite without inducing excessive augmentation. Its therapeutic effect may also be attributed to its ability to modulate glycerophospholipid metabolism status and exert influence on the gut-brain axis.
抑郁症是一种普遍的应激障碍，但将应激与食欲和体重减轻联系起来的潜在生理机制仍难以捉摸。虽然大多数抗抑郁药与体重增加和食欲增加有关，但舍曲林（SER）发生这些副作用的风险较低。天然辰砂（β-HgS）是藏药左泰的主要成分，已被证明可以增强小鼠对外界应激的适应能力，而不会导致体重或食欲过度增加。然而，β-HgS 恢复应激小鼠食欲和体重的确切生理途径尚不清楚。
本研究旨在评估β-HgS 改善压力刺激诱导的小鼠体重减轻和食欲抑制的功效，并阐明其潜在的作用机制。
本研究采用慢性束缚应激（CRS）和慢性不可预测轻度应激（CUMS）作为实验模型，模拟日常生活中遇到的环境应激。随后进行了一系列实验，包括行为测试、直肠和海马病理切片的 HE 染色、抑郁相关生物标志物的检测、肠道菌群多样性分析以及海马和肠道内容物的代谢组学分析。
甘油磷脂代谢失调可能是应激导致食欲、体重、神经递质和食欲激素水平降低、炎症反应增强、海马和直肠组织损伤以及肠道微生物群落组成改变的主要途径。在应激小鼠中用 SER 和β-HgS 干预后，应激引起的有害作用可以得到改善，其中中剂量β-HgS 表现出更好的效果。
上述研究结果表明，应激诱导的小鼠食欲和体重下降可能与连接肠-脑轴的甘油磷脂代谢失调有关。β-HgS 具有改善应激小鼠抑郁样症状的潜力，同时恢复其体重和食欲，而不会引起过度增加。其治疗效果可能还归因于它调节甘油磷脂代谢状态和对肠-脑轴的影响。
