PMID- 33849116 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20211204 IS - 2224-5839 (Electronic) IS - 2224-5820 (Linking) VI - 10 IP - 3 DP - 2021 Mar TI - Network pharmacology study on the mechanism of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel for anxiety disorders. PG - 3313-3327 LID - 10.21037/apm-21-531 [doi] AB - BACKGROUND: Although anxiety disorders are one of the most common mental illness in population, antianxiety drugs often only have single action targets, require long-term use, and are associated with many adverse reactions and dependencies. Professor Yan Zhaojun from Shandong Provincial Hospital of Traditional Chinese Medicine (TCM) has applied the modified Renshu Powder, a TCM formula, to treat anxiety disorders, with satisfactory outcomes. Here, we investigated the mechanism of action of two core herbs (prepared Rehmannia root and Chinese arborvitae kernel) in the Renshu Powder in the treatment of anxiety disorders by using network pharmacology approaches. METHODS: Candidate compounds of the herb pair of prepared Rehmannia root-Chinese arborvitae kernel were extracted via the Traditional Chinese Medicine Systems Pharmacology (TCMSP) platform. The targets of action of the main compounds were collected using the SwissTargetPrediction database. Targets associated with anxiety disorders were retrieved from DisGeNET, Online Mendelian Inheritance in Man (OMIM), DrugBank, GeneCards, and Comparative Toxicogenomics Database (CTD) databases. The compound-target interaction network was constructed by Cytoscape 3.7.2 software, and the protein-protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) platform. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses the data by using Metascape. RESULTS: The main active compounds of the herb pair included arachidonic acid, stigmasterol, and beta-sitosterol. The key targets included Nitric Oxide Synthase 3 (NOS3), Epidermal growth factor (EGF), Prostaglandin-Endoperoxide Synthase 2 (PTGS2), Caspase 3 (CASP3), Mitogen-Activated Protein Kinase 1 (MAPK1), Peroxisome proliferator-activated receptor gamma (PPARG), RELA Proto-Oncogene, NF-KB Subunit (RELA), Estrogen Receptor 1 (ESR1), Solute Carrier Family 6 Member 4 (SLC6A4), and Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN). Anxiety disorder-related GO analysis mainly involved synaptic signaling, neurotransmitter receptor activity, and G protein-coupled neurotransmitter receptor activity. The KEGG pathways involved neuroactive ligand-receptor interaction, serotonergic synapse, PI3K/AKT/mTOR signaling pathway, and MAPK signaling pathway. CONCLUSIONS: The mechanism of action of the prepared Rehmannia root-Chinese arborvitae kernel in treating anxiety disorders involves multiple ingredients, multiple targets, and pathways. FAU - Liu, Pu-Lin AU - Liu PL AD - College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Song, An-Ran AU - Song AR AD - College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Dong, Cheng-Da AU - Dong CD AD - College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Chu, Qian AU - Chu Q AD - College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Xu, Bao-Lin AU - Xu BL AD - College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Liu, Jian-Min AU - Liu JM AD - Department of Psychosomatic Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. FAU - Yan, Zhao-Jun AU - Yan ZJ AD - Department of Psychosomatic Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China. 361257818@163.com. LA - eng PT - Journal Article PL - China TA - Ann Palliat Med JT - Annals of palliative medicine JID - 101585484 RN - 0 (Drugs, Chinese Herbal) RN - 0 (MAS1 protein, human) RN - 0 (Proto-Oncogene Mas) RN - 0 (SLC6A4 protein, human) RN - 0 (Serotonin Plasma Membrane Transport Proteins) SB - IM MH - Anxiety Disorders/drug therapy/genetics MH - China MH - *Drugs, Chinese Herbal/therapeutic use MH - Humans MH - Phosphatidylinositol 3-Kinases MH - Proto-Oncogene Mas MH - *Rehmannia MH - Serotonin Plasma Membrane Transport Proteins MH - *Thuja OTO - NOTNLM OT - Chinese arborvitae kernel OT - Prepared Rehmannia root OT - anxiety disorders OT - mechanism of action OT - network pharmacology EDAT- 2021/04/15 06:00 MHDA- 2021/05/15 06:00 CRDT- 2021/04/14 01:00 PHST- 2021/01/27 00:00 [received] PHST- 2021/03/23 00:00 [accepted] PHST- 2021/04/14 01:00 [entrez] PHST- 2021/04/15 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] AID - 10.21037/apm-21-531 [doi] PST - ppublish SO - Ann Palliat Med. 2021 Mar;10(3):3313-3327. doi: 10.21037/apm-21-531.