A study on the effects of metacinnabar (β-HgS) on weight and appetite recovery in stressed mice

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.