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

References

• SmithK. Mental health: a world of depression. Nature. 2014;515(7526):181. doi:10.1038/515180a25391942
   PubMedGoogle Scholar
• MonteggiaLM, MalenkaRC, DeisserothK. Depression: the best way forward. Nature. 2014;515(7526):200–201. doi:10.1038/515200a25391955
   PubMed Web of Science ®Google Scholar
• HuangY, WangY, WangH, et al. Prevalence of mental disorders in China: a cross-sectional epidemiological study. Lancet Psychiatry. 2019;6(3):211–224. doi:10.1016/s2215-0366(18)30511-x30792114
   PubMed Web of Science ®Google Scholar
• KirschI, JakobsenJC. Network meta-analysis of antidepressants. Lancet (London, England). 2018;392(10152):1010. doi:10.1016/s0140-6736(18)31799-9
   Web of Science ®Google Scholar
• FournierJC, DeRubeisRJ, HollonSD, et al. Antidepressant drug effects and depression severity: a patient-level meta-analysis. JAMA. 2010;303(1):47–53. doi:10.1001/jama.2009.194320051569
   PubMed Web of Science ®Google Scholar
• OrgetaV, TabetN, NilforooshanR, et al. Efficacy of antidepressants for depression in alzheimer’s disease: systematic review and meta-analysis. J Alzheimers Dis. 2017;58(3):725–733. doi:10.3233/jad-16124728505970
   PubMed Web of Science ®Google Scholar
• PapakostasGI, JacksonWC, RafeyanR, et al. Inadequate response to antidepressant treatment in major depressive disorder. J Clinl Psychiatry. 2020;81(3):OT19037COM5. doi:10.4088/jcp.Ot19037com5
   Web of Science ®Google Scholar
• YangL, ShergisJL, DiYM, et al. Managing depression with bupleurum chinense herbal formula: a systematic review and meta-analysis of randomized controlled trials. J Altern Compl Med. 2020;26(1):8–24. doi:10.1089/acm.2019.0105
   Web of Science ®Google Scholar
• QiuJ, HuSY, ShiGQ, et al. Changes in regional cerebral blood flow with Chaihu-Shugan-San in the treatment of major depression. Pharmacogn Mag. 2014;10(40):503–508. doi:10.4103/0973-1296.14177525422553
   PubMed Web of Science ®Google Scholar
• ChenXQ, LiCF, ChenSJ, et al. The antidepressant-like effects of Chaihu Shugan San: dependent on the hippocampal BDNF-TrkB-ERK/Akt signaling activation in perimenopausal depression-like rats. Biomed Pharmacother. 2018;105:45–52. doi:10.1016/j.biopha.2018.04.03529843044
   PubMed Web of Science ®Google Scholar
• SunKH, JinY, MeiZG, et al. Antidepressant-like effects of chaihu shugan powder () on rats exposed to chronic unpredictable mild stress through inhibition of endoplasmic reticulum stress-induced apoptosis. Chin J Integr Med. 2021;27(5):353–360. doi:10.1007/s11655-020-3228-y32572775
   PubMed Web of Science ®Google Scholar
• LiuY, MaS, QuR. SCLM, total saponins extracted from Chaihu-jia-longgu-muli-tang, reduces chronic mild stress-induced apoptosis in the hippocampus in mice. Pharm Biol. 2010;48(8):840–848. doi:10.3109/1388020090329615420673169
   PubMed Web of Science ®Google Scholar
• ZhangQ, YuH, QiJ, et al. Natural formulas and the nature of formulas: exploring potential therapeutic targets based on traditional Chinese herbal formulas. PLoS One. 2017;12(2):e0171628. doi:10.1371/journal.pone.017162828182702
   PubMed Web of Science ®Google Scholar
• KibbleM, SaarinenN, TangJ, et al. Network pharmacology applications to map the unexplored target space and therapeutic potential of natural products. Nat Prod Rep. 2015;32(8):1249–1266. doi:10.1039/c5np00005j26030402
   PubMed Web of Science ®Google Scholar
• XuJ, GuanZ, WangX, et al. Network pharmacology and experimental evidence identify the mechanism of astragaloside IV in oxaliplatin neurotoxicity. Drug Des Devel Ther. 2021;15:99–110. doi:10.2147/dddt.S262818
   PubMed Web of Science ®Google Scholar
• PanossianAG, EfferthT, ShikovAN, et al. Evolution of the adaptogenic concept from traditional use to medical systems: pharmacology of stress- and aging-related diseases. Med Res Rev. 2021;41(1):630–703. doi:10.1002/med.2174333103257
   PubMed Web of Science ®Google Scholar
• LiuYY, HuD, FanQQ, et al. Mechanism of chaihu shugan powder () for treating depression based on network pharmacology. Chin J Integr Med. 2020;26(12):921–928. doi:10.1007/s11655-019-3172-x31630361
   PubMed Web of Science ®Google Scholar
• JiangY, ZhongM, LongF, et al. Network pharmacology-based prediction of active ingredients and mechanisms of lamiophlomis rotata (benth.) kudo against rheumatoid arthritis. Front Pharmacol. 2019;10:1435. doi:10.3389/fphar.2019.0143531849678
   PubMed Web of Science ®Google Scholar
• RuJ, LiP, WangJ, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminform. 2014;6:13. doi:10.1186/1758-2946-6-1324735618
   PubMed Web of Science ®Google Scholar
• LiuH, WangJ, ZhouW, et al. Systems approaches and polypharmacology for drug discovery from herbal medicines: an example using licorice. J Ethnopharmacol. 2013;146(3):773–793. doi:10.1016/j.jep.2013.02.00423415946
   PubMed Web of Science ®Google Scholar
• FengSH, ZhaoB, ZhanX, et al. Danggui buxue decoction in the treatment of metastatic colon cancer: network pharmacology analysis and experimental validation. Drug Des Devel Ther. 2021;15:705–720. doi:10.2147/dddt.S293046
   PubMed Web of Science ®Google Scholar
• GfellerD, GrosdidierA, WirthM, et al. SwissTargetPrediction: a web server for target prediction of bioactive small molecules. Nucleic Acids Res. 2014;42(WebServer issue):W32–W38. doi:10.1093/nar/gku29324792161
   PubMed Web of Science ®Google Scholar
• GfellerD, MichielinO, ZoeteV. Shaping the interaction landscape of bioactive molecules. Bioinformatics. 2013;29(23):3073–3079. doi:10.1093/bioinformatics/btt54024048355
   PubMed Web of Science ®Google Scholar
• WangY, ZhangS, LiF, et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics. Nucleic Acids Res. 2020;48(D1):D1031–D1041. doi:10.1093/nar/gkz98131691823
   PubMed Web of Science ®Google Scholar
• PiñeroJ, Ramírez-AnguitaJM, Saüch-PitarchJ, et al. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 2019;48(D1):D845–D855. doi:10.1093/nar/gkz1021
   Web of Science ®Google Scholar
• WishartDS, FeunangYD, GuoAC, et al. DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018;46(D1):D1074–D1082. doi:10.1093/nar/gkx103729126136
   PubMed Web of Science ®Google Scholar
• SzklarczykD, MorrisJH, CookH, et al. The STRING database in 2017: quality-controlled protein-protein association networks, made broadly accessible. Nucleic Acids Res. 2017;45(D1):D362–D368. doi:10.1093/nar/gkw93727924014
   PubMed Web of Science ®Google Scholar
• JiaoX, ShermanBT, Huang daW, et al. DAVID-WS: a stateful web service to facilitate gene/protein list analysis. Bioinformatics. 2012;28(13):1805–1806. doi:10.1093/bioinformatics/bts25122543366
   PubMed Web of Science ®Google Scholar
• WangC, ChenY, WangY, et al. Inhibition of COX-2, mPGES-1 and CYP4A by isoliquiritigenin blocks the angiogenic Akt signaling in glioma through ceRNA effect of miR-194-5p and lncRNA NEAT1. J Exp Clinl Cancer Res. 2019;38(1):371. doi:10.1186/s13046-019-1361-2
   Web of Science ®Google Scholar
• SongH, ParkJ, ChoiK, et al. Ginsenoside Rf inhibits cyclooxygenase-2 induction via peroxisome proliferator-activated receptor gamma in A549 cells. J Ginseng Res. 2019;43(2):319–325. doi:10.1016/j.jgr.2018.11.00730976170
   PubMed Web of Science ®Google Scholar
• YoungJY, BerrisfordJ, ChenM. wwPDB biocuration: on the front line of structural biology. Nat Methods. 2021;18(5):431–432. doi:10.1038/s41592-021-01137-z33963335
   PubMed Web of Science ®Google Scholar
• BurleySK, BermanHM, BhikadiyaC. Protein data bank: the single global archive for 3D macromolecular structure data. Nucleic Acids Res. 2019;47(D1):D520–D528. doi:10.1093/nar/gky94930357364
   PubMed Web of Science ®Google Scholar
• LiuH, QiuF, BianB, et al. Integrating qualitative and quantitative assessments of Yougui pill, an effective traditional Chinese medicine, by HPLC-LTQ-Orbitrap-MSn and UPLC-QqQ-MS/MS. Anal Methods. 2017;9(23):3485–3496. doi:10.1039/c7ay00259a
   Web of Science ®Google Scholar
• SunHY, LiQ, LiuYY, et al. Xiao-Yao-San, a Chinese medicine formula, ameliorates chronic unpredictable mild stress induced polycystic ovary in rat. Front Physiol. 2017;8:729. doi:10.3389/fphys.2017.0072929018356
   PubMed Web of Science ®Google Scholar
• SuWJ, ZhangY, ChenY, et al. NLRP3 gene knockout blocks NF-κB and MAPK signaling pathway in CUMS-induced depression mouse model. Behav Brain Res. 2017;322(Pt A):1–8. doi:10.1016/j.bbr.2017.01.01828093255
   PubMed Web of Science ®Google Scholar
• ZhaoM, TangX, GongD, et al. Bungeanum improves cognitive dysfunction and neurological deficits in D-Galactose-induced aging mice via activating PI3K/Akt/Nrf2 signaling pathway. Front Pharmacol. 2020;11:71. doi:10.3389/fphar.2020.0007132158388
   PubMed Web of Science ®Google Scholar
• LiL, YuAL, WangZL, et al. Chaihu-Shugan-San and absorbed meranzin hydrate induce anti-atherosclerosis and behavioral improvements in high-fat diet ApoE (-/-) mice via anti-inflammatory and BDNF-TrkB pathway. Biomed Pharmacother. 2019;115:108893. doi:10.1016/j.biopha.2019.10889331022598
   PubMed Web of Science ®Google Scholar
• GaoC, DuQ, LiW, et al. Baicalin modulates APPL2/Glucocorticoid receptor signaling cascade, promotes neurogenesis, and attenuates emotional and olfactory dysfunctions in chronic corticosterone-induced depression. Mol Neurobiol. 2018;55(12):9334–9348. doi:10.1007/s12035-018-1042-829675572
   PubMed Web of Science ®Google Scholar
• LiuMY, YinCY, ZhuLJ, et al. Sucrose preference test for measurement of stress-induced anhedonia in mice. Nature Protoco. 2018;13(7):1686–1698. doi:10.1038/s41596-018-0011-z
   PubMed Web of Science ®Google Scholar
• IñiguezSD, RiggsLM, NietoSJ, et al. Social defeat stress induces a depression-like phenotype in adolescent male c57BL/6 mice. Stress. 2014;17(3):247–255. doi:10.3109/10253890.2014.91065024689732
   PubMed Web of Science ®Google Scholar
• SahuP, MudgalJ, AroraD, et al. Cannabinoid receptor 2 activation mitigates lipopolysaccharide-induced neuroinflammation and sickness behavior in mice. Psychopharmacology. 2019;236(6):1829–1838. doi:10.1007/s00213-019-5166-y30666359
   PubMed Web of Science ®Google Scholar
• SteruL, ChermatR, ThierryB, et al. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985;85(3):367–370. doi:10.1007/bf004282033923523
   PubMed Web of Science ®Google Scholar
• WalkerAK, BudacDP, BisulcoS, et al. NMDA receptor blockade by ketamine abrogates lipopolysaccharide-induced depressive-like behavior in C57BL/6J mice. Neuropsychopharmacology. 2013;38(9):1609–1616. doi:10.1038/npp.2013.7123511700
   PubMed Web of Science ®Google Scholar
• LiuW, LiuJ, HuangZ, et al. Possible role of GLP-1 in antidepressant effects of metformin and exercise in CUMS mice. J Affect Disord. 2019;246:486–497. doi:10.1016/j.jad.2018.12.11230599373
   PubMed Web of Science ®Google Scholar
• ChenD, WeiL, LiuZR, et al. Pyruvate Kinase M2 Increases Angiogenesis, Neurogenesis, and Functional Recovery Mediated by Upregulation of STAT3 and focal adhesion kinase activities after ischemic stroke in adult mice. Neurotherapeutics. 2018;15(3):770–784. doi:10.1007/s13311-018-0635-229869055
   PubMed Web of Science ®Google Scholar
• WeiL, FraserJL, LuZY, et al. Transplantation of hypoxia preconditioned bone marrow mesenchymal stem cells enhances angiogenesis and neurogenesis after cerebral ischemia in rats. Neurobiol Dis. 2012;46(3):635–645. doi:10.1016/j.nbd.2012.03.00222426403
   PubMed Web of Science ®Google Scholar
• XuX, ZhangW, HuangC, et al. A novel chemometric method for the prediction of human oral bioavailability. Int J Mol Sci. 2012;13(6):6964–6982. doi:10.3390/ijms1306696422837674
   PubMed Web of Science ®Google Scholar
• TaoW, XuX, WangX, et al. Network pharmacology-based prediction of the active ingredients and potential targets of Chinese herbal Radix Curcumae formula for application to cardiovascular disease. J Ethnopharmacol. 2013;145(1):1–10. doi:10.1016/j.jep.2012.09.05123142198
   PubMed Web of Science ®Google Scholar
• QiuJ, HuSY, ZhangCH, et al. The effect of Chaihu-Shugan-San and its components on the expression of ERK5 in the hippocampus of depressed rats. J Ethnopharmacol. 2014;152(2):320–326. doi:10.1016/j.jep.2014.01.00424486208
   PubMed Web of Science ®Google Scholar
• YangJL, LinXG, PanY, et al. Critical roles of mTOR Complex 1 and 2 for T follicular helper cell differentiation and germinal center responses. eLife. 2016;5:e17936. doi:10.7554/eLife.1793627690224
   PubMed Web of Science ®Google Scholar
• JainAN. Surflex: fully automatic flexible molecular docking using a molecular similarity-based search engine. J Med Chem. 2003;46(4):499–511. doi:10.1021/jm020406h12570372
   PubMed Web of Science ®Google Scholar
• Tunc-OzcanE, PengCY, ZhuY, et al. Activating newborn neurons suppresses depression and anxiety-like behaviors. Nat Commun. 2019;10(1):3768. doi:10.1038/s41467-019-11641-831434877
   PubMed Web of Science ®Google Scholar
• BoldriniM, GalfalvyH, DworkAJ, et al. Resilience is associated with larger dentate gyrus, while suicide decedents with major depressive disorder have fewer granule neurons. Bioll Psychiatry. 2019;85(10):850–862. doi:10.1016/j.biopsych.2018.12.022
   Web of Science ®Google Scholar
• KaregeF, PerroudN, BurkhardtS, et al. Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims. Neuropsychobiology. 2011;63(4):224–231. doi:10.1159/00032214521422769
   PubMed Web of Science ®Google Scholar
• XianYF, IpSP, LiHQ, et al. Isorhynchophylline exerts antidepressant-like effects in mice via modulating neuroinflammation and neurotrophins: involvement of the PI3K/Akt/GSK-3β signaling pathway. FASEB J. 2019;33(9):10393–10408. doi:10.1096/fj.201802743RR31233346
   PubMed Web of Science ®Google Scholar
• GuoLT, WangSQ, SuJ, et al. Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K/AKT/FoxO1 pathway. J Neuroinflammation. 2019;16(1):95. doi:10.1186/s12974-019-1474-831068207
   PubMed Web of Science ®Google Scholar
• PardoM, AbrialE, JopeRS, et al. GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation. Genes Brain Behav. 2016;15(3):348–355. doi:10.1111/gbb.1228326749572
   PubMed Web of Science ®Google Scholar
• WangYH, ChernCM, LiouKT, et al. Ergostatrien-7,9(11),22-trien-3β-olfrom Antrodia camphorata ameliorates ischemic stroke brain injury via downregulation of p65NF-κ-B and caspase 3, and activation of Akt/GSK3/catenin-associated neurogenesis. Food Funct. 2019;10(8):4725–4738. doi:10.1039/c9fo00908f31304955
   PubMed Web of Science ®Google Scholar
• FangK, LiHR, ChenXX, et al. Quercetin alleviates LPS-induced depression-like behavior in rats via regulating bdnf-related imbalance of copine 6 and TREM1/2 in the hippocampus and PFC. Front Pharmacol. 2019;10:1544. doi:10.3389/fphar.2019.0154432009956
   PubMed Web of Science ®Google Scholar
• MerzougS, ToumiML, TahraouiA. Quercetin mitigates Adriamycin-induced anxiety- and depression-like behaviors, immune dysfunction, and brain oxidative stress in rats. Naunyn Schmiedebergs Arch Pharmacol. 2014;387(10):921–933. doi:10.1007/s00210-014-1008-y24947870
   PubMed Web of Science ®Google Scholar
• GaoW, WangW, PengY, DengZ. Antidepressive effects of kaempferol mediated by reduction of oxidative stress, proinflammatory cytokines and up-regulation of AKT/β-catenin cascade. Metab Brain Dis. 2019;34(2):485–494. doi:10.1007/s11011-019-0389-530762138
   PubMed Web of Science ®Google Scholar
• CrupiR, PaternitiI, AhmadA, et al. Effects of palmitoylethanolamide and luteolin in an animal model of anxiety/depression. CNS Neurol Disord Drug Targets. 2013;12(7):989–1001. doi:10.2174/1871527311312999008423844686
   PubMed Web of Science ®Google Scholar