Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression

Gao, Fang-Yuan; Chen, Xuefeng; Cui, Li-Xun; Zhai, Yujia; Liu, Jialin; Gao, Congcong; Fang, Yichao; Huang, Taohong; Wen, Jing; Zhou, Tingting

doi:10.1016/j.jep.2022.115934

Cited by 8 publications

(5 citation statements)

References 37 publications

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“…In addition, the abundance of Firmicutes was significant higher in FLX-and TGM-treated mice group compared to CUMS and Control mice group. Zhi-zi-chi decoction ameliorated the dysbiosis of depression-induced pathogenic bacteria Bacteroidota and increased the abundance of beneficial probiotics Firmicutes at the phylum and genus level, which are closely related to the production of β-glucosidase and sulfotransferases [58]. Moreover, in accorded with the aforementioned studies that suggested overabundance or depletion of specific phyla may contribute to depression.…”

Section: Discussionsupporting

confidence: 56%

“…Specific operational taxonomic units of Bacteroidetes positively associated with depression [52][53][54][55][56], while Firmicutes depletion and increased Bacteroidetes, Proteobacteria, and Actinobacteria occur in depression [56][57]. The antidepressant effect of Zhi-zi-chi decoction (decoction of Gardenia jasminoides Ellis，ZZCD) was promoted due to the increased exposures and reduced eliminations of anti-depressive compounds, especially geniposide, under the depression state [58]. In the current study, the abundance of Bacteroidetes was not found differ between CUMS and Control groups, but it was lower in both FLX and TGM treatment groups.…”

Section: Discussionmentioning

confidence: 99%

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Effect of L-theanine combined with geniposide on depression-like behavior induced by the chronic unpredictable mild stress (CUMS) in mice

Yu,

Zhu,

Jiang

et al. 2024

Food Science and Human Wellness

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Depression is a prevalent mental disorder with limited effective treatments, posing a significant global issue. This study explored L-theanine and geniposide, key components in "food-medicine homology" materials, to determine if their combination (TG) could alleviate depression-like behaviors and hippocampal neuronal damage in a chronic unpredictable mild stress (CUMS) mouse model. Male C57BL/6J mice were divided into control, CUMS model, and CUMS+TG groups with varying doses. The CUMS group displayed depression-like behaviors, including reduced activity and sucrose preference. TG treatment partially reversed these changes, significantly increasing antioxidant enzyme activities, decreasing pro-inflammatory cytokine levels, and improving neuromodulator levels. RNA-seq analysis identified the transthyretin (TTR) gene, upregulated in the model group but downregulated after TG treatment. TG treatment modulated intestinal microbiota composition compared to the CUMS group, including increased Firmicutes, reduced Bacteroidetes and Prevotella, and variable changes in Bifidobacterium abundance. In conclusion, our study indicates that CUMS exposure upregulates stress hormones and TTR expression, associated with neuroinflammation, oxidative stress, monoamine depletion, depression-like behaviors, and intestinal microbiota dysbiosis. TG treatment alleviates these effects and modulates intestinal microbiota, suggesting L-theanine and geniposide's potential as a novel depression therapy.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Effect of L-theanine combined with geniposide on depression-like behavior induced by the chronic unpredictable mild stress (CUMS) in mice

Yu,

Zhu,

Jiang

et al. 2024

Food Science and Human Wellness

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“…In this study, five prototypes comprising caffeic acid, genipin, altechromone A, rhein methylester and rhein, as well as eight metabolites including the glucose and sulfate conjugation products of feruloyl quinic acid and the glucose conjugation product of rhein methylester, were identified in intestine tissue. Genipin is not only a prototype but also a metabolite converted from genipin 1‐gentiobioside and geniposide via intestinal bacterial‐produced glycosidase (Gao et al, 2023). Genipin has demonstrated effectiveness in various liver injuries (Fan et al, 2020).…”

Section: Resultsmentioning

confidence: 99%

An UHPLC–QTOF–MS‐based strategy for systematic profiling of chemical constituents and associated in vivo metabolites of a famous traditional Chinese medicine formula, Yinchenhao decoction

Wang,

Ouyang,

Cao

et al. 2023

Biomedical Chromatography

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Yinchenhao decoction (YCHD), a famous traditional Chinese medicine formula, has been applied for relieving jaundice in China for more than 1800 years. However, the material basis for YCHD is still unclear, and the chemical composition and metabolism characteristic in vivo are undefined, making the potential effective constituents and mechanism of action unclear. Herein, an ultrahigh‐performance liquid chromatography coupled with quadrupole time‐of‐flight mass spectrometry (UHPLC–QTOF–MS)‐based strategy was applied for the chemical profiling of YCHD, as well as their in vivo prototypes and global metabolites that defined the metabolome. Our results showed that a total of 139 chemicals were identified in YCHD, including 28 organic acids, 12 monoterpenoids, five diterpenes, three triterpenoids, 17 iridoids, 23 anthraquinones, 26 flavonoids, four coumarins and 21 other types. Moreover, 58 prototypes and 175 metabolites were found in rat biological samples after oral administration of YCHD; those distributed in plasma, liver, intestine and feces were suggested to be potentially effective substances. Oxidation, hydrogenation, decarboxylation and conjugations with methyl, sulfate and glucuronate were considered as the predominant metabolic pathways in vivo. In conclusion, this is a systemic study of chemical constituents and in vivo metabolome profiles of YCHD, contributing to the material basis understanding and further mechanism research.

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“…Genipin and genipin sulfate conjugates were detected in negative electrospray ionization in the full scan mode at m/z 200–600. The MS parameters were as follows: capillary voltage at 3500 V, nebulizing gas pressure at 35 psi, drying gas at 11 L/min, drying gas temperature at 350°C and fragment voltage at 120 V. The UPLC‐MS chromatograms and concentration determination of the effective fraction of ZZCD extract are shown in Figure S1 and Table S1 24 …”

Section: Methodsmentioning

confidence: 99%

“…The UPLC-MS chromatograms and concentration determination of the effective fraction of ZZCD extract are shown in Figure S1 and Table S1. 24…”

Section: Identification Of Zzcd Extract Using Uplc-msmentioning

confidence: 99%

Zhi‐zi‐chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter

Zou,

Sugimoto,

Zhao

et al. 2024

J Cellular Molecular Medi

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Traditional Chinese medicine, particularly Zhi‐zi‐chi decoction (ZZCD), is gaining recognition as a potential treatment for depression. This study aimed to uncover the molecular mechanisms behind ZZCD's antidepressant effects, focusing on lncRNA Six3os1 and histone H3K4 methylation at the BDNF promoter. Network pharmacology and in vivo experiments were conducted to identify ZZCD targets and evaluate its impact on depression‐related behaviours and neuron injury. The role of Six3os1 in recruiting KMT2A to the BDNF promoter and its effects on oxidative stress and neuron injury were investigated. ZZCD reduced depression‐like behaviours and neuron injury in mice subjected to chronic stress. It upregulated Six3os1, which facilitated KMT2A recruitment to the BDNF promoter, leading to increased histone H3K4 methylation and enhanced BDNF expression. ZZCD also inhibited CORT‐induced neuron injury, inflammatory response and oxidative stress in vitro. ZZCD's antidepressant properties involve Six3os1 upregulation, which exerts neuroprotective effects by inhibiting oxidative stress and neuron injury, thereby alleviating depressive symptoms. Targeting Six3os1 upregulation may offer a potential therapeutic intervention for depression.

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Gut microbiota mediates the pharmacokinetics of Zhi-zi-chi decoction for the personalized treatment of depression

Cited by 8 publications

References 37 publications

Effect of L-theanine combined with geniposide on depression-like behavior induced by the chronic unpredictable mild stress (CUMS) in mice

Effect of L-theanine combined with geniposide on depression-like behavior induced by the chronic unpredictable mild stress (CUMS) in mice

An UHPLC–QTOF–MS‐based strategy for systematic profiling of chemical constituents and associated in vivo metabolites of a famous traditional Chinese medicine formula, Yinchenhao decoction

Zhi‐zi‐chi decoction mitigates depression by enhancing lncRNA Six3os1 expression and promoting histone H3K4 methylation at the BDNF promoter

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