Zhi Zi Chi decoction (Gardeniae fructus and semen Sojae Praeparatum) attenuates anxious depression via modulating microbiota–gut–brain axis in corticosterone combined with chronic restraint stress‐induced mice

Abstract

BackgroundThe microbiota–gut–brain axis plays a critical role in neuropsychiatric disorders, particularly anxious depression, and attracts more attention gradually. Zhi Zi Chi decoction (ZZCD) consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr, is a classic formula in clinic and widely applied in anxiety and depression treatment. However, the underlying mechanisms of regulating microbiota–gut–brain axis in the treatment of anxious depression by oral administration of ZZCD remain elusive.Materials and MethodsIn this project, we clarified the origin and preparation methods of the Gardenia jasminoides J. Ellis and Glycine max (L.) Merr and examined the chemical ingredients of ZZCD by liquid chromatograph mass spectrometer. Then, corticosterone combined with chronic restraint stress was applied to establish an anxious depression model. After treated with ZZCD standard decoction, based on enzyme‐linked immunosorbent assay (ELISA), 16S rRNA technology, high‐throughput sequencing, quantitative RT‐PCR and fecal microbiota transplantation (FMT), the multiple associations between nucleus accumbens and intestinal flora in anxious depression mice were determined to clarify the mechanism of ZZCD in the treatment of anxiety and depression disorder.ResultsWe found various substances with antidepressant and antianxiety properties in ZZCD such as rosiridin and oleanolic acid. ZZCD could alleviate depressive and anxiety behaviors in anxious depression mice via regulating the disturbance of gut microbiota. Meanwhile, the bioactive compounds of ZZCD might directly active on neurodevelopment and neuroimmune‐related genes. Furthermore, the secretion of prolactin and estrogen, and interfering with mitogen‐activated protein kinase (MAPK) and tumor necrosis factor (TNF) signaling pathways were mainly involved in the multi‐target therapeutic effects of ZZCD against anxiety and depression.ConclusionsThese findings suggested that ZZCD exerts antidepressant effects pleiotropically through modulating the microbiota‐gut‐brain.

Microbiome Metabolomic Analysis of the Anxiolytic Effect of Baihe Dihuang Decoction in a Rat Model of Chronic Restraint Stress

“…Therefore, the gut microbiota, metabolites, and neuroinflammation are key factors in the development of anxiety disorders through the MGB. [19][20][21] These findings offer novel insights into the mechanisms of BBD.…”

Current landscape of fecal microbiota transplantation in treating depression

“…Additionally, ZZCD, consisting of Gardenia jasminoides J. Ellis and Glycine max (L.) Merr is also extensively utilized for addressing anxiety and depression (99). Tian et al used corticosterone combined with chronic constraint stress to establish the model of anxiety and depression, and transplanted fecal intestinal flora of the ZZCD group into anxious and depressed mice (100). ZZCD exerted an influence on and participated in the neuroactive ligand/receptor interaction process, regulated the HPA axis, influenced the secretion of prolactin and estrogen, interfered with MAPK and TNF signaling pathways, and reduced inflammation levels, thus contributing to inhibiting anxiety and depression.…”