RESUMEN
We identified the effective components and the underlying mechanisms of Quince (Cydonia oblonga Mill, COM) extract against atherosclerosis. The effective components of COM extract were identified with UHPLC-Q-TOF-MS/MS. Network pharmacology was performed. A rat model of atherosclerosis induced by high-fat emulsion combined with vitamin D3 was established. The anti-atherosclerosis effect of COM extract was evaluated from various aspects such as blood lipid regulation, anti-oxidative stress, anti-inflammatory response, and vascular protection function. We identified 14 serum components of COM extract using UHPLC-Q-TOF-MS/MS. Through prediction, 573 targets were obtained, among which 224 targets were atherosclerosis specific targets. The key targets included GSK3ß, ESR1, EGFR, and HSP90AA1. The key signaling pathway was PI3K-Akt signaling pathway. Pharmacodynamics analysis showed that COM extract reduced the levels of TC, TG, and LDL-C as well as ALT and AST, while increased the level of HDL-C. Mechanistically, COM extract significantly increased serum SOD and GSH-Px activities, but decreased MDA content in atherosclerosis rats, showing antioxidant effects. Meanwhile, COM extract significantly down-regulated the levels of pro-inflammatory factors IL-1ß, IL-6, TNF-α and CRP, but up-regulated anti-inflammatory factor IL-10. Additionally, COM extract increased the levels of NO, eNOS, and 6-keto-PGF1α; whereas, decreased the levels of ET-1 and TXB2. Furthermore, COM extract significantly inhibited the mRNA and protein levels of EGFR, p-PI3K, p-AKT, GSK-3ß, Bax, and Caspase-3 as well as the Bax/Bcl-2 ratio. Conclusively, COM extract exerts hypolipidemic, anti-oxidative, anti-inflammatory, anti-thrombotic and vascular endothelium protective effects on atherosclerosis rat model, which may be related to the inhibition of EGFR/PI3K/AKT/GSK-3ß signaling pathway.
Asunto(s)
Aterosclerosis , Rosaceae , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Fosfatidilinositol 3-Quinasas/metabolismo , Espectrometría de Masas en Tándem , Proteína X Asociada a bcl-2 , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Receptores ErbBRESUMEN
Cydonia oblonga Mill. (COM), mature fruit of genus Rosaceae, is consumed as a kind of traditional Chinese medicinal herb. Previous studies have shown that the components in COM extract have antioxidant, anti-inflammatory, blood pressure-lowering, blood lipid-lowering, antithrombotic, and other biological activities. However, the quality markers (Q-markers) of atherosclerosis (AS) have not been elucidated. The Q-marker is based on the five core principles of traceability, transferability, specificity, measurability, validity, and prescription dispensing. In this study, the quality markers of quince were investigated by applying the ultraperformance liquid chromatography-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) method and network pharmacology method to highlight the three core elements which are, respectively, traceability transmission, measurability, and validity. At the first step, 72 components were identified by applying the ultraperformance liquid chromatography-time-of-flight mass spectrometry (UHPLC/Q-TOF-MS/MS) method. In the next step, 46 candidate components of COM anti-AS were obtained by network pharmacology, and then, 27 active components were filtered with the molecular docking assay. Finally, the 27 active components were intersected with 10 active components obtained by mass transfer and traceable quality markers. Four anti-AS Q-markers of COM were identified, including caffeic acid, chlorogenic acid, ellagic acid, and vanillic acid, which provided a reference for the quality control of quince. The methods and strategies can also be applied to other traditional Chinese medicines and their compound preparations, providing new ideas on the quantitative evaluation and identification of quality markers.
Asunto(s)
Medicamentos Herbarios Chinos , Rosaceae , Biomarcadores , Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Simulación del Acoplamiento Molecular , Farmacología en Red , Espectrometría de Masas en Tándem/métodosRESUMEN
ABSTRACT: This study investigates the active components and mechanism of Shufeng Jiedu Capsules (SFJDC) against novel coronavirus through network pharmacology and molecular docking.The TCMSP, TCMID, and BATMAN-TCM databases were used to retrieve the components of SFJDC. The active components were screened by ADME (absorption, distribution, metabolism, and excretion) parameters, and identified by Pubchem, Chemical Book, and ChemDraw softwares. The molecular docking ligands were constructed. SARS Coronavirus-2 Major Protease (SARS-CoV-2-Mpro) and angiotension converting enzyme 2 (ACE2) were used as molecular docking receptors. AutoDock software was used for molecular docking. Cytoscape 3.7.1 software was used to generate an herbs-active components-targets network. Gene Ontology gene function and Kyoto Encyclopedia of Genes and Genomes signal pathway analysis were performed by DAVID data.A total of 1244 components were identified from SFJDC, and 210 active components were obtained. Among them, 97 active components were used as docking ligands to dock with SARS-CoV-2-Mpro and ACE2. There were 48 components with good binding activity to SARS-CoV-2-Mpro. Ten active components (including 7-Acetoxy-2-methylisoflavone, Kaempferol, Quercetin, Baicalein, Glabrene, Glucobrassicin, Isoglycyrol, Wogonin, Petunidin, and Luteolin) combined with SARS-CoV-2-Mpro and ACE2 simultaneously. Among them, Kaempferol, Wogonin, and Baicalein showed higher binding activity. The herbs-active components-targets network contained 7 herbs, 10 active components, and 225 targets. The 225 target targets were involved in 653 biological processes of Gene Ontology analysis and 130 signal pathways (false discovery rate ≤ 0.01) of Kyoto Encyclopedia of Genes and Genomes analysis.The active components of SFJDC (such as Kaempferol, Wogonin, and Baicalein) may combine with ACE2 and act on multiple signaling pathways and targets to exert therapeutic effect on novel coronavirus.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Simulación del Acoplamiento Molecular/métodos , Farmacología en Red , SARS-CoV-2/efectos de los fármacos , Enzima Convertidora de Angiotensina 2 , Humanos , Quempferoles , Ligandos , SARS-CoV-2/genéticaRESUMEN
Background: Ocimum basilicum L. (OBL) is mainly used to treat neurological diseases in China. The preliminary work of this group showed that OBL improves cognitive impairment in Alzheimer's disease (AD). However, the underlying pharmacological mechanism remains unclear. Methods: The components of OBL were compiled by literature search, and their active ingredients were screened by online database. The drug targets of OBL in the treatment of AD were predicted and analyzed using information derived from sources such as the SwissTargetPrediction tool. And through the network visual analysis function of Cytoscape software and protein-protein interaction analysis (PPI), the core targets of OBL treatment of AD are predicted. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were employed to analyze the related signaling pathways affected by OBL. Moreover, AutoDock software was used to assess the potential binding affinity between the core targets and the active compounds. Subsequently, in vivo experiment was conducted to verify the findings of network pharmacology. Results: A total of 35 active compounds and 188 targets of OBL were screened, of which 43 common targets were related to AD. The active compounds of 35 OBLs induced 118 GO and 78 KEGG. The results of PPI and network topology parameter analysis show that targets such as MAPK1, GSK3B, NR3C2, ESR1, and EGFR are known as the core targets for the treatment of AD by OBL and are docked with the active ingredients of OBL. Molecular docking results suggest that diterbutyl phthalate (DBP) may be the main active component of OBL for the treatment of AD. Flow cytometry analysis results showed that apoptosis decreased with increasing DBP dose. In addition, DBP significantly decreased the levels of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) in the supernatant of Aß 25-35-induced injury HT22 cell cultures, and it can be speculated that DBP has the ability to protect the stability of injured neuronal cells and improve the permeability of cell membranes, thus stabilizing the intracellular environment. Mechanistically, DBP may increase the mRNA levels of AKT, GSK-3ß, etc. in AD cell models and regulate the phosphorylation of AKT/GSK-3ß pathway-related. Conclusions: Conclusively, our study suggests that DBP, the main active component of OBL, has potential in the prevention or treatment of AD.
Asunto(s)
Enfermedad de Alzheimer , Medicamentos Herbarios Chinos , Ocimum basilicum , Dibutil Ftalato , Glucógeno Sintasa Quinasa 3 beta , Proteínas Proto-Oncogénicas c-akt , Enfermedad de Alzheimer/tratamiento farmacológico , Simulación del Acoplamiento Molecular , Farmacología en RedRESUMEN
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. At present, the incidence rate of PD is increasing worldwide, there is no effective cure available so far, and currently using drugs are still limited in efficacy due to serious side effects. Acteoside (ACT) is an active ingredient of many valuable medicinal plants, possesses potential therapeutic effects on many pathological conditions. In this study, we dissected the neuroprotection effects of ACT on PD and its potential molecular mechanism in our PD model pathology based on network pharmacology prediction and experimental assays. Network pharmacology and bioinformatics analysis demonstrated that ACT has 381 potential targets; among them 78 putative targets associated with PD were closely related to cellular autophagy and apoptotic processes. Our experimental results showed that ACT exerted significant neuroprotection effects on Rotenone (ROT) -induced injury of neuronal cells and Drosophila melanogaster (D. melanogaster). Meanwhile, ACT treatment induced autophagy in both neuronal cell lines and fat bodies of D. melanogaster. Furthermore, ACT treatment decreased ROT induced apoptotic rate and reactive oxygen species production, increased mitochondrial membrane potentials in neuronal cells, and promoted clearance of α-synuclein (SNCA) aggregations in SNCA overexpressed cell model through the autophagy-lysosome pathway. Interestingly, ACT treatment significantly enhanced mitophagy and protected cell injury in neuronal cells. Taken together, ACT may represent a potent stimulator of mitophagy pathway, thereby exerts preventive and therapeutic effects against neurodegenerative diseases such as PD by clearing pathogenic proteins and impaired cellular organelles like damaged mitochondria in neurons.