MAPK domain inhibition: Validation of the anti-angiogenic effects of curcumin from Curcuma longa in NDEA model of liver carcinoma in Wistar rats

Abstract

Abstract 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.