Evidence map›Paper›PMID 34385814›Full record

ArticleDrug design, development and therapy2021

Network Pharmacology and Experimental Evidence: PI3K/AKT Signaling Pathway is Involved in the Antidepressive Roles of Chaihu Shugan San.

Shan Zhang, Yujia Lu, Wei Chen, Wei Shi, Qian Zhao, Jingjie Zhao, Li Li

Open access · goldAbstract read
In one paragraph

Article in Drug design, development and therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 51 citations in OpenAlex.

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  15. Frontiers in pharmacology · 2024
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Shan ZhangDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.ORCID 0000-0001-8089-1314
Yujia LuDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Wei ChenExperimental and Translational Research Center, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Wei ShiDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Qian ZhaoDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Jingjie ZhaoDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Li LiDepartment of Traditional Chinese Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People's Republic of China.
Capital Medical University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveChaihu Shugan San (CSS) is a common antidepressant prescription in traditional Chinese medicines. However, its active ingredients and mechanisms are unknown. The aim of this study was to explore the potential active ingredients and pharmacological mechanisms of CSS for the treatment of major depressive disorder (MDD).

methodsActive compounds in CSS were screened using the Traditional Chinese Medicine Systems Pharmacology database. Compound-related targets were retrieved using the SwissTargetPrediction database. MDD-related targets were determined using DisGeNET, Therapeutic Target Database and DrugBank databases. The common targets of active compounds in CSS and MDD were retained to construct a compound-MDD target network. Then, functional enrichment analysis and protein-protein interaction analysis were performed to identify hub targets and explore the underlying molecular mechanisms. Finally, hub-targeted genes and pathways were validated by Western blotting and immunofluorescence using chronic unpredictable mild stress (CUMS) mice with or without CSS treatment. The affinities between the active compounds in CSS and hub-targeted genes were evaluated by molecular docking.

resultsNetwork pharmacology analysis revealed 24 potential targets for treatment of MDD by CSS. Functional enrichment analysis showed that PI3K/AKT signaling pathway was likely to be evidently affected by CSS in the treatment of MDD. In vivo experiments showed that CSS could improve depressive-like behaviors and promote neurogenesis in CUMS mice. Furthermore, CSS could increase phosphorylated (p) PI3K/PI3K and pAKT/AKT levels and decrease the pGSK3β/GSK3β level in the hippocampus of CUMS mice. The active compounds mainly included quercetin and luteolin, which showed good docking scores targeting the PI3K protein.

conclusionThis network pharmacological and experimental study highlights that the PI3K/AKT pathway is the potential mechanism by which CSS is involved in MDD treatment. Quercetin, luteolin, and kaempferol are probable active compounds in CSS, and these results might provide valuable guidance for further studies of MDD treatment.

Indexed as

AnimalsAntidepressive AgentsDisease Models, AnimalHippocampusMajor Depressive DisorderMaleMedicine, Chinese TraditionalMiceMice, Inbred C57BLMolecular Docking SimulationNetwork PharmacologyPhosphatidylinositol 3-KinasePlant ExtractsProto-Oncogene Proteins c-aktSignal TransductionAntidepressive Agentschaihu-shugan-sanPhosphatidylinositol 3-KinasePlant ExtractsProto-Oncogene Proteins c-aktChaihu Shugan Sanmajor depressive disordernetwork pharmacologyPI3K/AKT signaling pathway

Identifiers

PMID34385814
PMCPMC8353879
OpenAlexW3187697657

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.