In silico and in vivo study of anti-inflammatory activity of Morinda longissima (Rubiaceae) extract and phytochemicals for treatment of inflammation-mediated diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditionally, the plant Morinda longissima Y.Z.Ruan (Rubiaceae) is used by ethnic people in Vietnam for the treatment of liver diseases and hepatitis. AIM OF THE STUDY: The study was designed to assess the efficacy of the 95% ethanolic extract of Morinda longissima roots (MLE) in experimental immune inflammation. The phytochemical variation of root extract and the chemical structures of natural compounds were also investigated using HPLC-DAD-HR-MS analysis. MATERIALS AND METHODS: Three different doses (100, 200, and 300 mg/kg b.w.) of MLE were chosen to determine anti-inflammatory activity. The mice were given orally extracts and monitored their behavior and mortality for 14 days to evaluate acute toxicity. The volume of the paw and the histopathological evaluation were carried out. The polyphenolic phytoconstituents of MLE extract were identified using LC/MS analysis. The anti-inflammatory efficacy in silico and molecular docking simulations of these natural products were evaluated based on their cyclooxygenase (COX)-1 and 2 inhibitory effects. RESULTS: This investigation showed the 95% ethanolic extract of Morinda longissima roots was found non-toxic up to 2000 mg/kg dose level in an acute study, neither showed mortality nor treatment-related signs of toxicity in mice. Eight anthraquinones and anthraquinone glycosides of Morinda longissima roots were identified by HPLC-DAD-HR-MS analysis. In the in vivo experiments, MLE was found to possess powerful anti-inflammatory activities in comparison with diclofenac sodium. The highest anti-inflammatory activity of MLE in mice was observed at a dose of 300 mg/kg body weight. The in silico analysis showed that seven out the eight anthraquinones and anthraquinone glycosides possess a selectivity index RCOX-2/COX-1 lower than 1, indicating that these compounds are selective against the COX-2 enzyme in the following the order: rubiadin-3-methyl ether < morindone morindone-6-methyl ether < morindone-5-methyl ether < damnacanthol < rubiadin < damnacanthol-3-O-ß-primeveroside. The natural compounds with the best selectivity against the COX-2 enzyme are quercetin (9), rubiadin-3-methyl ether (7), and morindone (4), with RCOX2/COX1 ratios of 0.02, 0.03, and 0.19, respectively. When combined with the COX-2 protein in the MD research, quercetin and rubiadin-3-methyl ether greatly stabilized the backbone proteins and ligands. CONCLUSION: In conclusion, the anthraquinones and ethanolic extract of Morinda longissima roots may help fight COX-2 inflammation. To develop novel treatments for inflammatory disorders linked to this one, these chemicals should be investigated more in the future.

A simple nomogram for identifying individuals at high risk of undiagnosed diabetes in rural population.

AIMS: To sought for an easily applicable nomogram for detecting individuals at high risk of undiagnosed type 2 diabetes. METHODS: The development cohort included 2542 participants recruited randomly from a rural population in 2011.The glycemic status of subjects was determined using the fasting plasma glucose test and the oral glucose tolerance test. The Bayesian Model Average approach was used to search for a parsimonious model with minimum number of predictor and maximum discriminatory power. The corresponding prediction nomograms were constructed and checked for discrimination, calibration, clinical usefulness, and generalizability in nationwide population in 2012. RESULTS: The non-lab nomogram including waist circumference and systolic blood pressure was the most parsimonious with the area under receiver operating characteristic curve (AUC) of 0.71 (95 %CI = 0.64-0.76). Adding low-density lipoprotein cholesterol in the non-lab nomogram generated the lab-based nomogram with significantly improved AUC of 0.83 (0.78-0.87, P < 0.001). The nomograms had a positive net benefit at threshold probability between 0.01 and 0.15. Applying the non-lab nomogram to the national population yielded the AUC of 0.66 (0.63-0.70) and 0.68 (0.65-0.71) in the cohorts aged 40-64 and 30-69 years, respectively. CONCLUSIONS: The novel nomograms could help promote the early detection of undiagnosed diabetes in rural Vietnamese population.