Exploration of the mechanism of regulating uterus peristaltic wave by Shoutai Sijunzi Decoction based on network pharmacology
XU Ting1 GUAN Ronghua2 ZHUANG Yuan1 CAO Huabin1
1. Ambulatory Surgical Center, Jiangxi Maternal and Child Health Hospital, Jiangxi Province, Nanchang 330006, China
2. Reproductive Medicine Center, North Guangdong People's Hospital, Guangdong Province, Shaoguan 512000, China
Abstract：Objective To explore the potential target and mechanism of the regulation of uterus peristaltic wave by Shoutai Sijunzi Decoction based on network pharmacology and molecular docking techniques. Methods Based on Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicines Integrated Database (TCMID), the active ingredients and targets of Shoutai Sijunzi Decoction were screened. At the same time, Gencards and DrugBank databases were used to mine the relevant targets of uterus peristaltic waves, and the potential targets of regulating abnormal endometrial peristalsis waves were obtained after the intersections were taken. The protein interaction network of potential target was constructed using the STRING platform, and the "drug-active ingredients-intersection target-disease" network was constructed using Cytoscape software. The "clusterProfiler" package was used for gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. PyMOL and AuTo Dock software were used to verify the molecular docking between the core target and the active component monomer. Results A total of 594 targets of Shoutai Sijunzi Decoction were retrieved, 90 targets of uterus peristaltic wave correlation, and 33 intersection targets were obtained. Kaempferol, β-sitosterol, quercetin, isorhamnetin and 7-methoxy-2-methyl isoflavones were the main active monomers of tetraphanoides, and nitric oxide synthase 3 (NOS3), transient receptor potential vanilloid subtype (TRPV1), prostaglandin-endoperoxide synthase 2 (PTGS2), caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 1 (PTGS1) were the core action targets. The KEGG pathway was mainly concentrated in neuroactive ligand-receptor interaction, calcium signaling pathway, 5-hydroxytryptaminergic synapse, renin secretion, inflammatory mediators regulation of transient receptor potential (TRP) channels, cyclic guanosinc monophosphate-protein kinase G (cGMP-PKG) signaling pathway and relaxin signaling pathway. Molecular docking showed that kaempferol, β-sitosterol, quercetin, isorhamnetin and 7-methoxy-2-methyl isoflavone could stably bind to the core target. Conclusion Shoutai Sijunzi Decoction may target core genes such as NOS3, TRPV1, PTGS2, CASP3 and PTGS1 to regulate the neuroactive ligand-receptor interaction, calcium signaling pathway, 5-hydroxytryptaminergic synapse, renin secretion, inflammatory mediators regulation of TRP channel, cGMP-PKG signaling pathway and relaxin signaling pathway. It plays the role of regulating the uterus peristaltic wave.
Revuelta MP，Hidalgo A，Cantabrana B.Involvement of cAMP and beta-adrenoceptors in the relaxing effect elicited by flavonoids on rat uterine smooth muscle[J].J Auton Pharmacol，1999，19（6）：353-358.
[8]
Revuelta MP，Cantabrana B，Hidalgo A.Mechanisms involved in kaempferol-induced relaxation in rat uterine smooth muscle[J].Life Sci，2000，67（3）：251-259.
Begum S，Sultana I，Siddiqui BS，et al.tructure and spasmolytic activity of eucalyptanoic acid from Eucalyptus camaldulensis var obtusa and synthesis of its active derivative from oleanolic acid[J].J Nat Prod，2002，65（12）：1939- 1941.
[12]
Lanuzza F，Occhiuto F，Monforte MT，et al.Antioxidant Phytochemicals of Opuntia ficus-indica （L.） Mill.Cladodes with Potential Anti-spasmodic Activity[J].Pharmacogn Mag，2017， 13（Suppl 3）：S424-S429.
Fleming I.Molecular mechanisms underlying the activation of eNOS[J].Pflügers Arch，2010，459（6）：793-806.
[15]
Qin SL，Liu SL，Wang RR.Protective effect of capsaicin on against myocardial ischemia-reperfusion injury of rat in vivo[J].Sichuan Da Xue Xue Bao Yi Xue Ban，2008，39（4）：550-554.
[16]
Brighton PJ，McDonald J，Taylor AH，et al.Characterization of anandamide-stimulated cannabinoid receptor signaling in human ULTR myometrial smooth muscle cells[J].Mol Endocrinol，2009，23（9）：1415-1427.
Xie WL，Chipman JG，Robertson DL，et al.Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing[J].Proc Natl Acad Sci U S A，1991，88（7）：2692-2696.
[19]
Ingles J，Simpson A，Kyathanahalli C，et al.Preconditioning the uterine unfolded protein response maintains non-apoptotic Caspase 3-dependent quiescence during pregnancy[J].Cell Death Dis，2018，9（10）：933.
[20]
Jiang B，Zhang Y，She C，et al.X-ray irradiation has positive effects for the recovery of peripheral nerve injury maybe through the vascular smooth muscle contraction signaling pathway[J].Environ Toxicol Pharmacol，2017，54（3）：177-183.
[21]
Okaty BW，Commons KG，Dymecki SM.Embracing diversity in the 5-HT neuronal system[J].Nat Rev Neurosci，2019，20（7）：397-424.
Kohler R，Brakemeier S，Kühn M，et al.Expression of ryanodine receptor type 3 and TRP channels in endothelial cells：comparison of in situ and cultured human endothelial cells[J].Cardiovasc Res，2001，51（1）：160-168.
Olaf B，Bettina B，Richard I.Phosphodiesterase 4 inhibition synergizes with relaxin signaling to promote decidualization of human endometrial stromal cells[J].J Clin Endocrinol Metab，2004，89（1）：324-334.
[27]
Palejwala S，Tseng L，Wojtczuk A，et al.Relaxin gene and protein expression and its regulation of procollagenase and vascular endothelial growth factor in human endometrial cells[J].Biol Reprod，2002，66（6）：1743-1748.
京公网安备 11010502046607号