Deciphering the interactions of scopoletin and scopolin from Catunaregam nilotica roots against Naja nigricollis phospholipase A2 enzyme.

Catuneragam nilotica has been used in ethnomedicine to treat snakebite, inflammation, and diarrhea among others. The aim of this research is to isolate, and characterize potential potential phospholipase A 2 (PLA 2) inhibitors from the roots of C. nilotica. The plant material was collected, authenticated, and sequentially extracted using solvents of increasing polarity starting from n-hexane, ethyl acetate, and methanol. The extracts as reported in our previous work, were screened in vitro for their inhibitory activity against PLA 2 enzyme from N. nigricollis venom using acidimetric assay. In line with the bio-activity guided isolation, methanol extract (being the most active) was subjected to chromatographic separation using silica gel and sephadex LH-20 which resulted in the isolation and characterization of scopoletin, and scopolin; the compounds were able to inhibit the hydrolytic actions of PLA2 enzyme with percentage inhibition ranging from 67.82 to 100.00 % and 65.76–93.15 %, respectively while the standard Antisnake Venom (ASV) had 74.96–85.04 % after 10 min incubation at 37 °C. The molecular docking of the compounds against PLA 2 enzyme was performed using Auto Dock Vina while ADME-Tox analysis was evaluated using swissADME and ProTox-II online servers; The findings indicated that both compounds were able to bind to the active site of PLA 2 enzyme with high affinity (−6.5 to −6.2 kcal/mol) and they exhibited favorable drug-likeness and pharmacokinetic properties, and according to toxicity predictions, scopolin was found to be non-toxic (LD 50 of 5000 mg/kg) while scopoletin has a slight chance of being toxic (LD 50 of 3800 mg/kg). In conclusion, the findings of the research revealed that the roots of C. nilotica contains phytoconstituents with anti-PLA 2 enzyme activity and thus, validates the ethnomedicinal claim of the use of the plant as herbal therapy against N. nigricollis envenomation. [Display omitted] • Scopoletin and Scopolin were identified from the roots of Catuneragam nilotica. • Both compounds were able to inhibit the hydrolytic actions of PLA 2 enzyme from Naja nigricollis venom. • The compounds interacted with key amino acid residues such as HIS47 and ASP48 at the active site of PLA 2 with high affinity. • Scopoletin and Scopolin also exhibited favorable drug-like and pharmacokinetics properties. • The roots of C. nilotica contain active phytoconstituents with proven antisnake properties. [ABSTRACT FROM AUTHOR]