No abstract

Type II diabetes is an endemic disease and is responsible for approximately 90% to 95% of diabetes cases. The pathophysiological distortions are majorly β-cell dysfunction, insulin resistance, and long-term inflammation, which all progressively unsettle the control of blood glucose levels and trigger microvascular and macrovascular complications. The diverse pathological disruptions which patients with type II diabetes mellitus exhibit precipitate the opinion that different antidiabetic agents, administered in combination, might be required to curb this menace and maintain normal blood glucose. To this end, natural compounds were screened to identify small molecular weight compounds with inhibitory effects on protein tyrosine phosphatase 1B (PTP1B), dipeptidyl-peptidase-4 (DPP-4), and α-amylase. From the result, the top 5 anthocyanins with the highest binding affinity are reported herein. Further ADMET profiling showed moderate pharmacokinetic profiles for these compounds as well as insignificant toxicity. Cyanidin 3-(p-coumaroyl)-diglucoside-5-glucoside (−15.272 kcal/mol), cyanidin 3-O-(6ʺ-malonyl-3ʺ-glucosyl-glucoside) (−9.691 kcal/mol), and delphinidin 3,5-O-diglucoside (−12.36 kcal/mol) had the highest binding affinities to PTP1B, DPP-4, and α-amylase, respectively, and can be used in combination to control glucose fluctuations. However, validations must be carried out through further in vitro and in vivo tests.

Objectives This study employed MAPK domain inhibition as an anti-angiogenic scaffold and further validate the anti-angiogenic effects of the lead phytochemicals, curcumin from ethanolic extract of curcuma longa (EECL) in N-nitrosodiethylamine (NDEA) model of liver cancer in Wistar rats.Methods One hundred and twenty Wistar rats comprising of sixty male and female rats were randomly selected into twelve groups (n = 5): group A (100 mg/kg NDEA + 200 mg/kg EECL), group B (100 mg/kg NDEA + 400 mg/kg EECL), group C (100 mg/kg NDEA + 600 mg/kg EECL), group D (100 mg/kg NDEA + 200 mg/kg pure curcumin), group E (100 mg/kg NDEA + 100 mg/kg sylibon 140), group F (100 mg/kg NDEA), group G (200 mg/kg pure curcumin), group H (100 mg/kg DMSO), group I (200 mg/kg EECL), group J (400 mg/kg EECL), group K (600 mg/kg EECL), group L (control) at the end of 42 days of the experiment period. The lead phytochemicals, curcumin from EECL were isolated and subjected to Gas Chromatography-Mass Spectrometry for characterization. The anti-angiogenic potentials of the curcumin isolates were validated through molecular docking and the expression of antiangiogenic related mRNA.Results The binding of Co-crystallized, curcumin and cis-sesquisabinene hydrate, to the binding site led to the conformation with binding energies of -15.15 kcal/mol, -7.212 kcal/mol, and − 6.361 kcal/mol respectively. Treatment with 200 mg/kg and 400 mg/kg significantly (p < 0.05) downregulated the expression of MAPK and Vascular endothelial growth factor mRNAs in the hepatocyte tumour, while the Alpha Fero Protein and Interleukin-10 mRNA was significantly (p < 0.05) upregulated.Conclusion Ethanolic extract of Curcumin longa possessed anti-angiogenic and anti-proliferating prospective against MAPK domain inhibition.