Antibacterial and Antioxidant Molecule Isolated from Nepeta aristata Boiss Et Kotschy Ex Boiss plant: 1,5,9-Epideoxyloganic Acid

Abstract

1,5,9-Epideoxyloganic acid (ELA) was isolated from the methanol fraction of endemic Nepeta aristata crude methanol-chloroform by chromatographic methods (preparative-HPLC, silica, and sephadex column). The structure of ELA was determined with 1H NMR and 13C NMR spectrometry. Furthermore, the mass of the molecule was confirmed by mass spectrometry. ELA's antioxidant and antibacterial activities were examined and also compared to standards. ELA exhibited the best antibacterial activity with inhibition zone against K. pneumoniae (11.50 mm), S. aureus (10.00 mm), and also effective minimum inhibition concentration value against E. faecalis (8 µg/mL). The antioxidant properties of ELA were assessed with posphomolybdenium reducing, reducing power, metal chelating, H2O2, DPPH˙, ABTS˙⁺, and O2˙ˉ scavenging activities. The posphomolybdenium, O2˙ˉ, and H2O2 scavenging activities of ELA were found effective at 136.02±3.99, 3.54±0.26 and 9.67±1.26 µg/mL, respectively. As a result, the effective antioxidant and antimicrobial activity values of the ELA molecule may be a source that can be used in pharmacology in the future.

Keywords

• Nepeta aristata
• 1.5.9-epideoxyloganic acid
• Antibacterial activity
• antioxidant activity

References

1. Zhou, G.; Zhang, X.; Shah, M.; Che, Q.; Zhang, G.; Gu, Q.; Zhu, T.; Li, D., Polyhydroxy p-Terphenyls from a Mangrove Endophytic Fungus Aspergillus candidus LDJ-5. Mar. Drugs 2021, 19 (2), 82.
2. Wang, L.; Kuang, Z.; Zhang, D.; Gao, Y.; Ying, M.; Wang, T., Reactive oxygen species in immune cells: A new antitumor target. Biomed. pharmacother 2021, 133, 110978.
3. Çopuroğlu, Ö. Niğde Yöresindeki Bazı Endemik Bitki Türlerinin Antimikrobiyal Aktiviteleri. Yüksek Lisans Tezi, Niğde Üniversitesi,, 2013.
4. Temiz, A., Genel mikrobiyoloji uygulama teknikleri. Hatiboğlu Yayınevi: 2010.
5. Emori, T. G.; Gaynes, R. P., An overview of nosocomial infections, including the role of the microbiology laboratory. Clin. Microbiol. Rev. 1993, 6 (4), 428-442.
6. Essawi, T.; Srour, M., Screening of some Palestinian medicinal plants for antibacterial activity. J. Ethnopharmacol 2000, 70 (3), 343-349.
7. Hedge, I. C., Labiatae of South-West Asia: diversity, distribution and endemism. P. Roy. Soc. B-Biol. Sci 2011, 89, 23-35.
8. Dirmenci, T., A new subspecies of Nepeta (Lamiaceae) from Turkey. Bot. J. Linn. Soc. 2005, 147, 229-233.

9. Eser, F.; Altun, M.; Demirtas, I.; Behcet, L.; Aktas, E., Three new iridoids from the aerial parts of Nepeta teucriifolia Willd. and antiproliferative activities of extracts. Nat. Prod. Res. 2022, 1-10.
10. Süntar, I.; Nabavi, S. M.; Barreca, D.; Fischer, N.; Efferth, T., Pharmacological and chemical features of Nepeta L. genus: Its importance as a therapeutic agent. Phytother. Res. 2018, 32 (2), 185-198.
11. El-Moaty, H. I. A. In Essential oil and iridoide glycosides of Nepeta septemcrenata Erenb, 2010.
12. Aničić, N.; Gašić, U.; Lu, F.; Ćirić, A.; Ivanov, M.; Jevtić, B.; Dimitrijević, M.; Anđelković, B.; Skorić, M.; Nestorović Živković, J.; Mao, Y.; Liu, J.; Tang, C.; Soković, M.; Ye, Y.; Mišić, D., Antimicrobial and Immunomodulating Activities of Two Endemic Nepeta Species and Their Major Iridoids Isolated from Natural Sources. Pharmaceuticals (Basel) 2021, 14 (5).
13. Başar, Y.; Yenigün, S.; İpek, Y.; Behçet, L.; Gül, F.; Özen, T.; Demirtaş, İ., DNA protection, molecular docking, enzyme inhibition and enzyme kinetic studies of 1,5,9-epideoxyloganic acid isolated from Nepeta aristata with bio-guided fractionation. J. Biomol. Struct. Dyn. 2023, 1-14.
14. Yenigün, S.; Başar, Y.; İpek, Y.; Behçet, L.; Özen, T.; Demirtaş, İ., Determination of antioxidant, DNA protection, enzyme inhibition potential and molecular docking studies of a biomarker ursolic acid in Nepeta species. J. Biomol. Struct. Dyn. 2023, 1-18.
15. Mohamed, R.; Pineda, M.; Aguilar, M., Antioxidant capacity of extracts from wild and crop plants of the Mediterranean region. J. Food Sci. 2007, 72 (1), S059-S063.
16. Prieto, P.; Pineda, M.; Aguilar, M., Spectrophotometric quantitation of antioxidant capacity through the formation of a phosphomolybdenum complex: specific application to the determination of vitamin E. Anal. Biochem. 1999, 269 (2), 337-341.
17. Huang, D.; Ou, B.; Prior, R. L., The chemistry behind antioxidant capacity assays. J. Agric. Food Chem. 2005, 53 (6), 1841-1856.
18. Oyaizu, M., Studies on products of browning reaction. The Jpn. J. Nutr. Diet. 1986, 44 (6), 307-315.
19. Mukhopadhyay, D.; Dasgupta, P.; Roy, D. S.; Palchoudhuri, S.; Chatterjee, I.; Ali, S.; Dastidar, S. G., A Sensitive In vitro Spectrophotometric Hydrogen Peroxide Scavenging Assay using 1, 10-Phenanthroline. Free Radical Antioxidants 2016, 6 (1).
20. Utami, S.; Adityaningsari, P.; Sosiawan, I.; Endrini, S.; Sachrowardi, Q. R.; Laksono, S. P.; Nafik, S.; Arrahmani, B. C.; Afifah, E.; Widowati, W., Antioxidants and Anticholinesterase Activities of the Characterized Ethanolic of ripe Sesoot (Garcinia picrorrhiza Miq.) Fruit Extract (GpKar) and Xanthone. Trad. Med. J 2017, 22 (3), 160-165.
21. Blois, M. S., Antioxidant determinations by the use of a stable free radical. Nature 1958, 181 (4617), 1199-1200.
22. Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C., Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 1999, 26 (9-10), 1231-1237.
23. Dechayont, B.; Ruamdee, P.; Poonnaimuang, S.; Mokmued, K.; Chunthorng-Orn, J., Antioxidant and Antimicrobial Activities of Pogostemon cablin (Blanco) Benth. J. Bot. 2017, 2017.
24. Nishikimi, M.; Rao, N. A.; Yagi, K., The occurrence of superoxide anion in the reaction of reduced phenazine methosulfate and molecular oxygen. Biochem. Biophys. Res. Commun. 1972, 46 (2), 849-854.
25. Yang, J.; Guo, J.; Yuan, J., In vitro antioxidant properties of rutin. LWT - Food Sci. Technol. 2008, 41 (6), 1060-1066.
26. Dinis, T. C.; Madeira, V. M.; Almeida, L. M., Action of phenolic derivatives (acetaminophen, salicylate, and 5-aminosalicylate) as inhibitors of membrane lipid peroxidation and as peroxyl radical scavengers. Arch. Biochem. Biophys. 1994, 315 (1), 161-169.
27. Reller, L. B.; Weinstein, M.; Jorgensen, J. H.; Ferraro, M. J., Antimicrobial susceptibility testing: a review of general principles and contemporary practices. Clinical Infectious Diseases 2009, 49 (11), 1749-1755.
28. Andrews, J. M., Determination of minimum inhibitory concentrations. Clin. Infect. Dis. 2001, 48 (suppl_1), 5-16.
29. Barba, F. J.; de Souza Sant'Ana, A.; Orlien, V.; Koubaa, M., Innovative technologies for food preservation: Inactivation of spoilage and pathogenic microorganisms. Academic Press: 2017.
30. Gülçin, İ.; Bingöl, Z.; Taslimi, P.; Gören, A. C.; Alwasel, S. H.; Tel, A. Z., Polyphenol contents, potential antioxidant, anticholinergic and antidiabetic properties of mountain mint (Cyclotrichium leucotrichum). Chem. Biodiv. 2022, 19 (3), e202100775.
31. Durmaz, L.; Erturk, A.; Akyüz, M.; Polat Kose, L.; Uc, E. M.; Bingol, Z.; Saglamtas, R.; Alwasel, S.; Gulcin, İ., Screening of carbonic anhydrase, acetylcholinesterase, butyrylcholinesterase, and α-glycosidase enzyme inhibition effects and antioxidant activity of coumestrol. Molecules 2022, 27 (10), 3091.
32. Barba-Orellana, S.; Barba, F. J.; Quilez, F.; Cuesta, L.; Denoya, G. I.; Vieira, P.; Pinto, C. A.; Saraiva, J. A., Nutrition, public health, and sustainability: an overview of current challenges and future perspectives. In Agri-Food Industry Strategies for Healthy Diets and Sustainability, Elsevier: 2020; pp 3-50.
33. Tiwari, B. K.; Valdramidis, V. P.; O’Donnell, C. P.; Muthukumarappan, K.; Bourke, P.; Cullen, P., Application of natural antimicrobials for food preservation. J. Agric. Food Chem. 2009, 57 (14), 5987-6000.
34. Nikaido, H., Prevention of drug access to bacterial targets: permeability barriers and active efflux. Science 1994, 264 (5157), 382-388.
35. Vaara, M., Agents that increase the permeability of the outer membrane. Microbiol. Rev. 1992, 56 (3), 395-411.
36. Aničić, N.; Gašić, U.; Lu, F.; Ćirić, A.; Ivanov, M.; Jevtić, B.; Dimitrijević, M.; Anđelković, B.; Skorić, M.; Nestorović Živković, J., Antimicrobial and immunomodulating activities of two endemic Nepeta species and their major iridoids isolated from natural sources. Pharmaceuticals 2021, 14 (5), 414.