In Silico Prediction of the Anti-Depression Mechanism of a Herbal Formula (Tiansi Liquid) Containing Morinda officinalis and Cuscuta chinensis

Abstract

Purpose: Depression is a sickening psychiatric condition that is prevalent worldwide. To manage depression, the underlying modes of antidepressant effect of herbals are important to be explored for the development of natural drugs. Tiansi Liquid is a traditional Chinese medicine (TCM) that is prescribed for the management of depression, however its underlying mechanism of action is still uncertain. The purpose of this study was to systematically investigate the pharmacological mode of action of a herbal formula used in TCM for the treatment of depression. Methods: Based on literature search, an ingredients-targets database was developed for Tiansi Liquid, followed by the identification of targets related to depression. The interaction between these targets was evaluated on the basis of protein-protein interaction network constructed by STITCH and gene ontology (GO) enrichment analysis using ClueGO plugin. Results: As a result of literature search, 57 components in Tiansi Liquid formula and 106 potential targets of these ingredients were retrieved. A careful screening of these targets led to the identification of 42 potential targets associated with depression. Ultimately, 327 GO terms were found by analysis of gene functional annotation clusters and abundance value of these targets. Most of these terms were found to be closely related to depression. A significant number of protein targets such as IL10, MAPK1, PTGS2, AKT1, APOE, PPARA, MAPK1, MIF, NOS3 and TNF-α were found to be involved in the functioning of Tiansi Liquid against depression. Conclusions: The findings elaborate that Tiansi Liquid can be utilized to manage depression, however, multiple molecular mechanisms of action could be proposed for this effect. The observed core mechanisms could be the sensory perception of pain, regulation of lipid transport and lipopolysaccharide-mediated signaling pathway.

Keywords: Cytoscape; STITCH; Tiansi Liquid; biological effects; depression; mechanism of action; molecular targets.

Figure 1

Factors contributing to the pathophysiology of depression.

Figure 2

Flow chart presentation of systematic procedure utilized in this study.

Figure 3

Action view of the protein network of Tiansi Liquid targets. Action type is represented by colored edges, as described here: activation () inhibition (), binding (), catalysis (-), phenotype (), posttranslational modification (), reaction () and transcriptional regulation (). Action effects are shown by following signs: Positive (), negative () and unspecified (). Note: MIF—macrophage migration inhibitory factor; MAPK1—mitogen-activated protein kinase 1; HMOX1—heme oxygenase (decycling) 1; PON2—paraoxonase 2; CCND1—cyclin D1; CSN1S1—casein alpha s1; APOE—apolipoprotein E; NR1H2—nuclear receptor subfamily 1, group H, member 2; PPARA—peroxisome proliferator-activated receptor alpha; UCP1—uncoupling protein 1; STK17B—serine/threonine kinase 17b; AKT1—v-akt murine thymoma viral oncogene homolog 1; EGFR—epidermal growth factor receptor; NOS3—nitric oxide synthase 3; ACHE—Acetylcholinesterase; IL8—interleukin 8; CASP3—caspase 3; ADIPOQ—adiponectin, C1Q; NOS2—nitric oxide synthase 2; PRKCD—protein kinase C; NR1I2—nuclear receptor subfamily 1, group I, member 2; FDPS—farnesyl diphosphate synthase; MAPK8—mitogen-activated protein kinase 8; COMT—catechol-O-methyltransferase; NPY1R—neuropeptide Y receptor Y1; PTGS2—prostaglandin-endoperoxide synthase 2; MCL1—myeloid cell leukemia sequence 1 (BCL2 -related); DHCR24—24-dehydrocholesterol reductase; RUNX2—runt-related transcription factor 2; ALOX5—arachidonate 5-lipoxygenase; PRNP—prion protein; RPS6KA3—ribosomal protein S6 kinase, 90 kDa, polypeptide 3; CDK1—cyclin-dependent kinase 1; KDM1A—lysine (K)-specific demethylase 1A; NR1H3—nuclear receptor subfamily 1, group H, member 3; MAPK9—mitogen-activated protein kinase 9; IL10—interleukin 10; BDNF—brain-derived neurotrophic factor; RGS6—regulator of G-protein signaling 6; S1PR2—Sphingosine 1-phosphate receptor 2; CCNB1—cyclin B1; CDK4—cyclin-dependent kinase 4; JUN—jun proto-oncogene; MTOR—mechanistic target of rapamycin; CDK6—cyclin-dependent kinase 6; SHC1—SHC transforming protein 1; GRB2—growth factor receptor-bound protein 2; RCOR1—REST corepressor 1; CCNA2—cyclin A2; STAT3—signal transducer and activator of transcription 3.

Figure 4

Retrieval of functionally grouped networks for the candidate targets of Tiansi Liquid, obtained via ClueGO, with terms as nodes associated. Each group is represented by only the label of the most significant term. The node size indicates the term enrichment significance. Functionally associated groups partially overlap.

Figure 5

Mechanistic effect of Tiansi Liquid against depression.