Exploring enzyme inhibition and antioxidant activities of different Salvia L. species with phenolic profiling and molecular docking

Abstract

Salvia L. is one of the largest genera belonging to the Lamiaceae family and is a plant species of great importance in perfumery, pharmaceutical, and food industry. Salvia species have a large usage as their extracts and essential oils among people in many areas. There are about 900 species belonging to the genus Salvia in the world, and they are generally distributed in the North, and South Americas as well as South-West Asia continents. Looking at its traditional uses, the genus has widely used in various disorders, such as stomach problems, cold, and sore throat, as well as for carminative, wound healing, and memory enhancer. Salvia species is rich in phytochemical contents, especially important bioactive secondary metabolites such as polyphenolics, phenolic acids, terpenes, and flavonoids. In this study, antioxidant activities (TPC, TFC, DPPH, and ABTS) and enzyme inhibition (cholinesterase and tyrosinase) capacities of ten different Salvia species were evaluated by microplate reader at 1 mg/mL concentration. When the results were evaluated, S. tomentosa water (241.20 ± 1.45 mg GA/ g) and MeOH (227.01 ± 3.85 mg GA/ g) extracts were found to have the highest total phenol content over gallic acid equivalent. S. cilicia DCM (166.70 ± 9.06 mg QE/g) and EtOAC (174.97 ± 3.29 mg QE/g) extracts were found to have the highest total flavonoid concentration in terms of quercetin equivalent. All Salvia species demonstrated antioxidant effects using the DPPH and ABTS methods, except for the DCM extracts of S. caespitosa, S. adenocaulon, and S. tomentosa. Notably, the DCM extract of S. tomentosa (86.86 % ± 3.51) exhibited strong inhibitory activity against AChE. The EtOAc extract of S. sclarea (98.38 % ± 1.91) showed the highest inhibitory activity against BChE.. Molecular docking studies have been conducted on the components that are highly concentrated in the extracts, showing inhibition of cholinesterase and tyrosinase enzymes with the respective enzymes. The molecular docking results of sinapinic acid and rutin compounds against acetylcholinesterase, Apigenin, kaempferol, and quercetin against butyrylcholinesterase, and gallic acid and salicylic acid against tyrosinase have been examined. It has been found that all compounds bound to the enzymes and that pi bonds and hydrogen bonds were present in the ligand-protein interactions. The stabilities of the complexes retreived from the docking were assessed through molecular dynamics (MD) simulation analysis. The MD simulation study pointed out the formation of stable complexes between the enzyme structures and ligands that had higher binding affinity in the docking. The ADMET analysis of the investigated compounds were conducted. The compounds (except rutin) exhibited favorable pharmacokinetic properties, including high gastrointestinal absorption and compliance with Lipinski’s rules, while in silico toxicity predictions suggested acceptable safety profiles. According to our works, it is predicted that Salvia species may be a potential drug candidate in the field of development of new formulations for cognitive disorders and dermatological problems.