DNA protection, molecular docking, enzyme inhibition and enzyme kinetic studies of 1,5,9-epideoxyloganic acid isolated from Nepeta aristata with bio-guided fractionation

Abstract

1,5,9-epideoxyloganic acid (ELA) was isolated from the aerial parts of endemic Nepeta aristata Boiss Et Kotschy Ex Boiss crude extract (methanol:chloroform) using silica gel (hexane, chloroform, ethyl acetate, and methanol) and sephadex LH-20 (65% methanol-35% chloroform) columns. Activity-guided isolation was performed on methanol sub-fractions with DNA protection and enzyme inhibitory activities, and then the ELA was purified by prep-HPLC. The ELA structure, bio-guided isolate, was determined via ¹H NMR, ¹³C NMR, and MS spectrometry. ELA's enzyme inhibition and DNA protection activities were investigated and compared with standard drugs. The inhibition capacity of ELA against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), urease, carbonic anhydrase (CA), α-glucosidase, α-amylase, lipase, and tyrosinase enzymes was evaluated by kinetic and molecular docking results. The ELA displayed the best inhibitory activity on AChE, BChE, α-glucosidase, urease, α-amylase, and tyrosinase with IC₅₀ values of 2.53 ± 0.27, 3.75 ± 0.11, 3.98 ± 0.07, 4.40 ± 0.01, 6.43 ± 0.54 and 7.39 ± 0.00 µg/mL, respectively. ELA acted as a competitive inhibitor against BChE and α-glucosidase and a non-competitive inhibitor against AChE. The ELA’s binding affinity values on AChE, BChE, and α-glucosidase were −7.70, −8.50, and −8.30 kcal/mol, respectively. DNA protection activity of the ELA molecule was determined as 57.53% for form I and 53.57% for form II. In conclusion, the inhibitory activity of ELA demonstrated its effectiveness in terms of its suitability in the pharmaceutical industry.

Communicated by Ramaswamy H. Sarma

Keywords:

• 1,5,9-epideoxyloganic acid
• activity-guided isolation
• enzyme inhibition
• DNA protection activity
• molecular docking

Acknowledgments

We thank TUBITAK (The Scientific and Technological Research Council of Turkey) for providing financial support (Project Number: 119Z442).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBİTAK, Project No: 119Z442).