Network Pharmacology and Molecular Docking Analysis on Pharmacological Mechanisms of Astragalus membranaceus in the Treatment of Gastric Ulcer.

BACKGROUND: Astragalus membranaceus (AM, family: Leguminosae) exerts significant therapeutic effect on gastric ulcer (GU); however, there are scarce studies on its molecular mechanism against GU. This study aims to explore the key ingredients, key targets, and potential mechanisms of AM in the treatment of GU by utilizing network pharmacology and molecular docking. METHODS: Several public databases were used to predict the targets of AM and GU, respectively, and the drug and disease targets were intersected to obtain the common targets. Next, the key ingredients and key targets were identified by constructing ingredient-target network and protein-protein-interaction (PPI) network. Gene Ontology biological processes (GOBP) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out on the common targets in order to ascertain the biological processes and signaling pathways involved. Finally, molecular docking was conducted to verify the binding affinity between the key ingredients and key targets. RESULTS: A total of 552 predicted targets were obtained from 23 screened active ingredients, of which 203 targets were the common targets with GU. Quercetin, kaempferol, and isorhamnetin were identified as the key ingredients by constructing ingredient-target network, and TP53, AKT1, VEGFA, IL6, TNF, CASP3, and EGFR were selected as the key targets by constructing PPI network. GOBP and KEGG pathway enrichment analysis suggested that the therapeutic effect of AM on GU involved multiple biological processes and signaling pathways related to inflammation, oxidative stress, apoptosis, cell proliferation, and angiogenesis. Molecular docking validation demonstrated that all key ingredients had good binding affinity with the key targets. CONCLUSION: This study revealed the key ingredients, key targets, and potential mechanisms of AM against GU, and these data may provide some crucial references for subsequent research and development of drugs for treating GU.

Protective effect of anisodamine in rats with glycerol-induced acute kidney injury.

BACKGROUND: Anisodamine is used for the treatment of reperfusion injury in various organs. In this study, we investigated the effectiveness and mechanisms of action of anisodamine in promoting recovery from glycerol-induced acute kidney injury (AKI). METHODS: We compared the protective effects of atropine and anisodamine in the rat model of glycerol-induced AKI. We examined signaling pathways involved in oxidative stress, inflammation and apoptosis, as well as expression of kidney injury molecule-1 (KIM-1). Renal injury was assessed by measuring serum creatinine and urea, and by histologic analysis. Rhabdomyolysis was evaluated by measuring creatine kinase levels, and oxidative stress was assessed by measuring malondialdehyde (MDA) and superoxide dismutase (SOD) levels in kidney tissues. Inflammation was assessed by quantifying interleukin 6 (IL-6) and CD45 expression. Apoptosis and necrosis were evaluated by measuring caspase-3 (including cleaved caspase 3) and RIP3 levels, respectively. RESULTS: Glycerol administration resulted in a higher mean histologic damage score, as well as increases in serum creatinine, urea, creatine kinase, reactive oxygen species (ROS), MDA, IL-6, caspase-3 and KIM-1 levels. Furthermore, glycerol reduced kidney tissue SOD activity. All of these markers were significantly improved by anisodamine and atropine. However, the mean histologic damage score and levels of urea, serum creatinine, creatine kinase, ROS and IL-6 were lower in the anisodamine treatment group compared with the atropine treatment group. CONCLUSION: Pretreatment with anisodamine ameliorates renal dysfunction in the rat model of glycerol-induced rhabdomyolytic kidney injury by reducing oxidative stress, the inflammatory response and cell death.

Protective role of Gentianella acuta on isoprenaline induced myocardial fibrosis in rats via inhibition of NF-κB pathway.

Gentianella acuta (Michx.) Hulten (G. acuta) has been widely used in Mongolian medicines for the treatment of cardiovascular diseases in Ewenki and Oroqen, Inner Mongolia autonomous region, China. The aim of this study was to investigate the effects and related mechanism of G. acuta on isoproterenol (ISO)-induced oxidative stress, fibrosis, and myocardial damage in rats. Male Sprague Dawley rats were randomly divided into the normal control group, ISO induced group and ISO+G. acuta treatment group. Rats were administered with ISO subcutaneously (5 mg/kg/day) for 7 days, and were orally administered simultaneously with aqueous extracts of G. acuta for 21 days. This investigation showed G. acuta treatment ameliorated cardiac structural disorder, excessive collagenous fiber accumulation and cardiac malfunction. Compared with the ISO induced model group, G. acuta treatment increased superoxide dismutase (SOD) activities and glutathione (GSH) level, prevented the rise of malondialdehyde (MDA), and decreased hydroxyproline contents in the heart tissues. Moreover, G. acuta reduced the expression of transforming growth factor ß1 (TGF-ß1) and connective tissue growth factor (CTGF), and inhibited the expression and activation of NF-κB-P65 in myocardial tissues. These results suggested that G. acuta protects against ISO-induced cardiac malfunction probably by preventing oxidative stress, and fibrosis, and the mechanism might be through inhibiting NF-κB pathway.

[Investigation of a compound, compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum on metabolic syndrome treatment III--controlling blood glucose].

Base on the improvement of compound FF16, compatibility of Rhodiola crenulata, Cordyceps militaris, and Rheum palmatum, on both insulin resistance and obesity, its effects on type 2 diabetes (T2DM ) was investigated here. The results showed that the levels of fasting and no-fasting blood glucose were controlled in the spontaneous type 2 diabetes KKAy mice; the impaired glucose tolerance (IGT)was improved by decreasing significantly the values of the glucose peaks and the area under the blood glucose-time curve (AUC ) after glucose-loading in glucose tolerance test (OGTT) in both high-fat-diet-induced pre-diabetes IRF mice and KKAy mice, respectively. The pancreatic histopathological analysis showed that the increased islet amount, the enlarged islet area, and the lipid accumulation in the pancreas were reversed by FF16 treatment in both IRF mice and KKAy mice. In the palmitate-induced RINm5f cell model, FF16 could effectively reduce the apoptosis and enhance the glucose-stimulated insulin secretion, respectively. In conclusion, FF16 could improve the T2DM by protecting the pancreatic beta-cells.