In Vivo Bioactivities of Hoya parasitica (Wall.) and In Silico Study against Cyclooxygenase Enzymes.

Hoya parasitica (Wall.) is extensively used in traditional medicine for the treatment of various diseases including rheumatism, kidney problems, jaundice, urinary tract disorders, fever, and pain. The present study was designed to explore new lead compound(s) to alleviate pain, pyresis, and diarrhea from methanol, ethyl acetate, and n-hexane extracts of H. parasitica (Wall.) leaves (MHP, EAHP, and NHP, respectively). Analgesic activity of the extracts was assessed through acetic acid induced writhing, tail immersion, and hot plate tests while brewer's yeast-induced pyrexia test was employed for the assessment of antipyretic activity. Besides, castor oil and magnesium sulfate induced diarrheal tests were utilized for the evaluation of antidiarrheal properties. Moreover, in silico study of the isolated compounds was undertaken to seek out best-fit phytoconstituent(s) against cyclooxygenase enzymes. MHP revealed substantial antioxidant activities in different in vitro assays compared to EAHP and NHP. In the acetic acid-induced writhing test, among the extracts, MHP (400 mg/kg) revealed maximum 74.15 ± 1% inhibition of writhing comparable to that of standard (85.77 ± 1.39%). Again, in tail immersion and hot plate tests, higher doses of all the test samples exhibited a significant increase of latent period in a time-dependent manner. In brewer yeast-induced pyrexia test, at 3rd and 4th hour of treatment, significant (P < 0.05) antipyretic action was found in the test samples. In both castor oil and magnesium induced diarrheal tests, MHP at 400 mg/kg showed the highest percent inhibition of diarrhea (68.62 ± 4.74 and 64.99 ± 2.90, respectively). Moreover, molecular docking analysis corroborated the results of the present study. The findings of the present study supported the traditional uses of this plant for the alleviation of pain and fever. Furthermore, hoyasterone was found to be the most effective lead compound as cyclooxygenase enzyme inhibitor.

Investigations of AGEs' inhibitory and nephroprotective potential of ursolic acid towards reduction of diabetic complications.

In diabetes, interactions between AGEs (advanced glycation end products) and RAGEs (receptors of AGEs) are responsible for chronic complications and the current work reports the potential of ursolic acid as a RAGE inhibitor. The three-dimensional crystal structure of RAGE was first docked with target molecules by 'AutodockVina' using GROMOS 96 4381 parameters. Druggability and pharmacokinetic properties were calculated from the SwissADME server. In vitro bovine serum albumin (BSA)-glucose fluorescence and BSA-methylglyoxal fluorescence assays were also performed. Finally, alloxan-induced diabetic mice were administered ursolic acid and metformin standards (at 1, 50, 100 mg/kg) for 50 days. Blood glucose levels, several blood parameters, blood lipid profiles, supernatants of homogenized kidney and plasma of mice were examined. In the computational study, ursolic acid showed greater binding affinity (-7.5 kcal/mol) for RAGE with an ADMET profiles and lead-likeness compared to metformin as a standard antidiabetic. In the in vitro fluorescence assays, the IC50 value for ursolic acid was much less than that of metformin standard. During the in vivo study, significant reduction in the levels of blood glucose, HbA1C (glycated hemoglobin), creatinine, uric acid, BUN (blood urea nitrogen), AST (aspartate aminotransferase), ALT (alanine aminotransferase), ALP (alkaline phosphatase) were observed in the ursolic acid and metformin-treated mice. Substantial inhibition of AGEs' formation in the plasma and kidney were also detected. Finally, the histopathological examinations of the kidney revealed reversal of cellular necrosis. Hence, ursolic acid is proved to be a potent AGE inhibitory agent in managing the diabetic complications.