ABSTRACT
Objective::To identify the active constituents of Paidu Qingzhi tablets by UPLC-Q-TOF-MS technique, and to reveal its potential targets and molecular mechanisms by network pharmacology. Method::Chromatography separation was achieved on an ACQUITY UPLC HSS T3 column (2.1 mm×100 mm, 1.8 μm) with mobile phase consisted of 0.1% formic acid aqueous solution and acetonitrile for gradient elution (0-17 min, 95%-5%A; 17-17.01 min, 5%-95%A; 17.01-20 min, 95%A), the flow rate was 0.3 mL·min-1, the column temperature was 40 ℃. Data acquisition was carried out in electrospray ionization (ESI) under the negative ion mode, the scanning range was 50-1 200.Ingredients in Paidu Qingzhi tablets were identified according to reference substance, relative molecular weight, mass spectrometric cleavage rule and literature information. Multiple databases were used to retrieve the targets of these identified ingredients and related diseases treated by the tablets, and metabolic pathways. A visual network of " herbs-compounds-targets-pathways-diseases" was constructed by Cytoscape 3.7.1. Result::A total of 33 active compounds in methanol extract of Paidu Qingzhi tablets were identified by UPLC-Q-TOF-MS, including 27 compounds from Rhei Radix et Rhizoma, 4 compounds from Panacis Quinquefolii Radix, 2 compounds from Ophiopogonis Radix. Totally 18 direct targets and 58 indirect targets corresponding to 31 ingredients were obtained, 7 metabolic pathways including steroid hormone biosynthesis pathway, arachidonic acid metabolic pathway, insulin signaling pathway were strongly correlated with the treatment of hyperlipidemia, acne and simple obesity by Paidu Qingzhi tablets. Conclusion::Ingredients of Paidu Qingzhi tablets are revealed by UPLC-Q-TOF-MS, based on these identified ingredients, targets and related metabolic pathways are visualized by network pharmacology. The current research can provide theoretical basis for quality control and clinical application of Paidu Qingzhi tablets.
ABSTRACT
OBJECTIVE: To investigate the biomolecular anti-diabetes mechanism and its complications of celastrol based on bioinformatics database. METHODS: The related genes of celastrol were obtained from the bioinformatics database, the cross-related genes of celastrol and diabetes mellitus were searched by Veen diagram software, the protein-protein interaction network was constructed by STRING software, the related KEGG pathway was identified by the DAVID software and KOBAS software, and the molecular network of anti-diabetes "compound-target gene-pathway-disease" was further constructed by R program software. RESULTS: There were 50 genes related to diabetes in celastrol, and 11 related pathways (P<0.001), which mainly affected the AGE-RAGE signaling pathway in diabetic complications. The mechanism was to regulate AGE-RAGE-NF-κB axis by inhibiting NF-κB, which reduced the production of downstream inflammatory effectors, insulin resistance and fibrotic damage. CONCLUSION: Celastrol can improve the symptoms of diabetes and its complications by regulating the AGE-RAGE-NF-κB axis-related signaling pathway, which is expected to be a potential drug for the treatment of diabetes and its complications.
ABSTRACT
OBJECTIVE: To explore the synergistic molecular network mechanism of Chinese medicine ingredients and glibenclamide from Xiaoke pill for the treatment of diabetes mellitus. METHODS: After obtained diabetic-related genes of Xiaoke pill, STRING software was used to construct biomolecular network, DAVID software was used to identify KEGG pathways, Cytoscape software was used to construct the network for Xiaoke pill ingredients-key target-disease related pathway. RESULTS: The results showed that Xiaoke pill targeted 123 diabetic-related genes. Glibenclamide mainly affected pathways involved in type 2 diabetes, whereas Chinese medicine ingredients from Xiaoke pill was associated with inflammatory-related pathways such as TNF, Jak-STAT, NF-kB and cytokine pathway, islet β cell-related pathways such as PI3K/Akt, mTOR and MAPK pathway, AGE-RAGE and metabolic pathways. By combining Chinese medicine ingredients and glibenclamide, Xiaoke pill widely targeted diabetic-related pathways. CONCLUSION: It indicates that Xiaoke pill, a combination of traditional Chinese and Western medicine, can prevente diabetes and diabetic syndrome possibly by improving insulin resistance and protecting β cells and inhibiting inflammatory response.