The pharmacological actions of Danzhi-xiaoyao-San on depression involve lysophosphatidic acid and microbiota-gut-brain axis: novel insights from a systems pharmacology analysis of a double-blind, randomized, placebo-controlled clinical trial

肠-脑轴 药理学 肠道菌群 抗抑郁药 自交轴蛋白 医学 生物 生物信息学 内科学 生物化学 溶血磷脂酸 受体 海马体
作者
Xiuqing Zhu,Shengwei Wu,Yufang Zhou,Tao Xiao,Liang Xia,Youtian Wang,Aixiang Xiao,Jianxiong Guo,Ming Zhang,Yuguan Wen,Dewei Shang,Lin Yu
出处
期刊:Journal of Biomolecular Structure & Dynamics [Taylor & Francis]
卷期号:42 (18): 9309-9324 被引量:4
标识
DOI:10.1080/07391102.2023.2251067
摘要

AbstractDanzhi-xiaoyao-San (DZXYS), a Traditional Chinese Medicine, plays an essential role in the clinical treatment of depression, but its mechanisms in humans remain unclear. To investigate its pharmacological effects and mechanisms as an add-on therapy for depression, we conducted a double-blind, placebo-controlled trial with depressed patients receiving selective serotonin reuptake inhibitors (SSRIs). Serum and fecal samples were collected for metabolomic and microbiome analysis using UHPLC-QTRAP-MS/MS and 16S rRNA gene sequencing technologies, respectively. Depression symptoms were assessed using the 24-item Hamilton Depression Scale. We employed network pharmacology, metabolomics, and molecular docking to identify potential targets associated with DZXYS. We also examined the correlation between gut microbes and metabolites to understand how DZXYS affects the microbiota-gut-brain axis. The results showed that DZXYS combined with SSRIs was more effective than SSRIs alone in improving depression. We identified 39 differential metabolites associated with DZXYS treatment and found seven upregulated metabolic pathways. The active ingredients quercetin and luteolin were docked to targets (AVPR2, EGFR, F2, and CDK6) associated with the enriched pathways 'pancreatic cancer' and 'phospholipase D signaling pathway', which included the metabolite lysophosphatidic acid [LPA(0:0/16:0)]. Additionally, we identified 32 differential gut microbiota species related to DZXYS treatment, with Bacteroides coprophilus and Ruminococcus gnavus showing negative correlations with specific metabolites such as L-2-aminobutyric acid and LPA(0:0/16:0). Our findings indicate that DZXYS's antidepressant mechanisms involve multiple targets, pathways, and the regulation of LPA and the microbiota-gut-brain axis. These insights from our systems pharmacology analysis contribute to a better understanding of DZXYS's potential pharmacological mechanisms in depression treatment.Communicated by Ramaswamy H. SarmaHIGHLIGHTSThis study presents a double-blind, randomized, placebo-controlled clinical trial comparing the clinical effects of Danzhi-xiaoyao-San (DZXYS) plus selective serotonin reuptake inhibitors (SSRIs) and SSRIs alone.This study is the first system pharmacology approach to integrate multi-omics and network pharmacology and examine the clinical pharmacological mechanisms of DZXYS as an add-on therapy for depression.This study highlights that regulation of lysophosphatidic acid (LPA) and the microbiota-gut-brain axis by DZXYS plays an essential role in its antidepressant mechanisms.Keywords: Danzhi-xiaoyao-Sandepressionlysophosphatidic acidmicrobiota-gut-brain axissystems pharmacologyclinical trialgut microbiotapharmacological mechanisms AcknowledgmentsWe thank International Science Editing (http://www.internationalscienceediting.com) for editing this manuscript.Disclosure statementThe authors declared there are no conflicts of interest for this study.Additional informationFundingThis work was supported by the National Natural Science Foundation of China (82004226, 81503475), China Postdoctoral Science Foundation (2020T130008ZX), Administration of Traditional Chinese and Tibetan Medicine of Qinghai Province (2016104), Natural Science Foundation of Guangdong Province (2021A1515011325, 2016A030313491), Science and Technology Plan Project of Guangdong Province (2019B030316001), Guangzhou municipal key discipline in medicine (2021–2023), and Guangzhou Municipal Science and Technology Project for Medicine and Healthcare (20201A011047, 20202A011016) Guangdong Provincial Hospital Association Pharmaceutical Research Special Foundation (2022YXKY11), Guangzhou Basic Research Program City-University (Institute) Joint Funding Project (SL2022A03J01499, 2023A03J0858).
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
2秒前
Jasper应助稳重向南采纳,获得10
3秒前
科研白白发布了新的文献求助10
3秒前
5秒前
5秒前
白昭完成签到,获得积分10
5秒前
qsy完成签到,获得积分10
6秒前
骆骆完成签到,获得积分10
7秒前
Fran07发布了新的文献求助10
9秒前
慕青应助咎星采纳,获得10
9秒前
9秒前
miao发布了新的文献求助10
10秒前
坦率的含海完成签到,获得积分10
11秒前
12秒前
13秒前
上官若男应助稳重向南采纳,获得10
13秒前
lzx应助painx采纳,获得10
13秒前
13秒前
丁璐完成签到,获得积分10
14秒前
哈尼发布了新的文献求助50
15秒前
15秒前
紫轩完成签到,获得积分10
16秒前
大魔王发布了新的文献求助10
16秒前
Learning完成签到,获得积分20
16秒前
16秒前
结实的秋凌完成签到,获得积分20
18秒前
橙子发布了新的文献求助20
18秒前
19秒前
坨坨发布了新的文献求助10
19秒前
大个应助流念采纳,获得10
19秒前
量子星尘发布了新的文献求助10
20秒前
科研发布了新的文献求助10
20秒前
domingo发布了新的文献求助10
21秒前
务实的菓完成签到 ,获得积分10
21秒前
zsy完成签到,获得积分10
22秒前
22秒前
whisper发布了新的文献求助10
22秒前
Ava应助稳重向南采纳,获得10
23秒前
快乐的夏岚完成签到,获得积分10
23秒前
Robert完成签到,获得积分10
23秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 360
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3971395
求助须知:如何正确求助?哪些是违规求助? 3516110
关于积分的说明 11180848
捐赠科研通 3251238
什么是DOI,文献DOI怎么找? 1795760
邀请新用户注册赠送积分活动 876012
科研通“疑难数据库(出版商)”最低求助积分说明 805228