口腔粘膜下纤维化(OSMF)是一种潜在的恶性疾病,没有永久性的治疗方法,由于三端子而影响生活质量。计算药理学加速了用于治疗不治之症的候选药物的发现。本研究旨在筛选具有基于吸收的药物相似特性的奇迹草本植物积雪草的化合物,分布,新陈代谢,和排泄(ADME)特性。通过网络药理学鉴定了这些筛选的化合物对OSMF的药理作用,基因本体论,途径富集分析,分子对接,和模拟。虚拟筛选后鉴定出15种药物样配体,即积雪草酸,山奈酚,槲皮素,木犀草素,芹菜素,Bayogenin,没食子酸,异硫氰酸,madecassic酸,马草酸,空钠酸,终止醇酸,儿茶素,表儿茶素,还有诺比林.预测了配体的850个潜在靶标,对与OSMF相关的354种蛋白质进行了分析。化合物途径分析和疾病途径分析鉴定了53种常见蛋白质。GO富集分析确定了472个生物过程术语,76个分子功能项,和44个蜂窝组件术语。途径富集分析预测142条KEGG途径,35Biocarta途径,和236个靶蛋白的反应组通路。分析显示,该草药靶向纤维化的关键事件,如炎症,氧化应激,凋亡,胶原蛋白沉积,和上皮-间质转化。将常见的53种蛋白质用于蛋白质-蛋白质相互作用(PPI)网络分析,这揭示了4种与植物化合物相互作用的关键蛋白;转化生长因子-β1(TGF-β1),母亲反对十食截瘫-3(SMAD-3),丝裂原活化蛋白激酶-1(MAPK-1)和原癌基因酪氨酸蛋白激酶(SRC)。分子对接显示所有配体对靶蛋白具有良好的结合亲和力。Bayogenin对MAPK-1的结合亲和力最高(-9.7kcal/mol),然后是异硫氰酸对SRC蛋白(-9.3kcal/mol)。Madasiatic酸对SMAD-3(-7.6kcal/mol)和TGF-β1(-7.1kcal/mol)具有最高的结合亲和力。分子动力学模拟证明了Bayogenin和MAPK复合物的稳定配体蛋白相互作用,异硫氰酸和SRC复合物。这项计算机模拟研究首次确定了积雪草及其目标分子中存在的潜在植物化学物质,这可能是逆转OSMF的原因。
Oral submucous fibrosis (OSMF) is a potentially malignant disorder with no permanent cure that affects the quality of life due to trismus. Computational pharmacology has accelerated the discovery of drug candidates for the treatment of incurable diseases. The present study aimed to screen the compounds of the miracle herb Centella asiatica with drug-likeness properties based on the absorption, distribution, metabolism, and excretion (ADME) properties. The pharmacological actions of these screened compounds against OSMF were identified by network pharmacology, gene ontology, pathway enrichment analysis, molecular docking, and simulation. Fifteen drug-like ligands were identified after virtual screening viz; asiatic acid, kaempferol, quercetin, luteolin, apigenin, bayogenin, gallic acid, isothankunic acid, madecassic acid, madasiatic acid, arjunolic acid, terminolic acid, catechin, epicatechin, and nobiletin. 850 potential targets were predicted for the ligands, which were analyzed against 354 proteins associated with OSMF. Compound pathway analysis and disease pathway analysis identified 53 common proteins. The GO enrichment analysis identified 472 biological process terms, 76 molecular function terms, and 44 cellular component terms. Pathway enrichment analysis predicted 142 KEGG pathways, 35 Biocarta pathways, and 236 Reactome pathways for the target proteins. The analysis revealed that the herb targets crucial events of fibrosis such as inflammation, oxidative stress, apoptosis, collagen deposition, and epithelial-mesenchymal transition. The common 53 proteins were used for protein-protein interaction (PPI) network analysis, which revealed 4 key proteins interacting with the phytocompounds viz; transforming growth factor-β1 (TGF-β1), mothers against decapentaplegic-3 (SMAD-3), mitogen-activated protein kinase-1 (MAPK-1) and proto-oncogene tyrosine-protein kinase (SRC). Molecular docking revealed that all ligands had a good binding affinity to the target proteins. Bayogenin had the highest binding affinity towards MAPK-1 (-9.7 kcal/mol), followed by isothankunic acid towards SRC protein (-9.3 kcal/mol). Madasiatic acid had the highest binding affinity to SMAD-3 (-7.6 kcal/mol) and TGF-β1 (-7.1 kcal/mol). Molecular dynamics simulation demonstrated stable ligand protein interactions of bayogenin and MAPK complex, isothankunic acid and SRC complex. This in silico study is the first to identify potential phytochemicals present in Centella asiatica and their target molecules, which might be responsible for reversing OSMF.