Reactive Oxygen Species Scavenging and Anti-Proliferative Potential of Veratric Acid: An in vitro Approach

http://www.doi.org/10.26538/tjnpr/v7i4.28

Authors

  • Shanmugam M Sivasankaran Department of Chemistry and Biosciences, Srinivasa Ramanujan Centre, Kumbakonam - 612 001, Tamilnadu, India
  • Sahul H.S. Abdulla Department of Chemistry and Biosciences, Srinivasa Ramanujan Centre, Kumbakonam - 612 001, Tamilnadu, India
  • Chakravarthy Elanchezhiyan Department of Zoology, Annamalai University, Annamalainagar-608002, Tamilnadu, India
  • Manoharan Pethanasamy Department of Chemistry and Biosciences, Srinivasa Ramanujan Centre, Kumbakonam - 612 001, Tamilnadu, India
  • Saravanan Surya Department of Chemistry and Biosciences, Srinivasa Ramanujan Centre, Kumbakonam - 612 001, Tamilnadu, India
  • Azhamuthu Theerthu Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608002, Tamilnadu, India
  • Harish Krishnan Department of Biochemistry and Biotechnology, Annamalai University, Annamalainagar-608002, Tamilnadu, India

Keywords:

Apoptosis, Cell viability, Reactive oxygen species, Veratric acid

Abstract

Medicinal plants and their bioactive constituents play a vital role in the prevention of oxidative stress mediated diseases such as cancer and diabetes mellitus. The aim of this study is to investigate the reactive oxygen species (ROS) scavenging and anti-proliferative potential of veratric acid in vitro. The study analysed the antioxidant potential of veratric acid using in vitro free radical scavenging assays. The anti-proliferative potential of veratric acid was assessed by utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, mitochondrial membrane potential (MMP) changes, intracellular ROS generation measurement and by determining the morphological alterations using Acridine orange/Ethidium bromide (Ao/EtBr) staining in the subline of Keratin-forming tumour cell line HeLa (KB). Veratric acid showed a good antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), superoxide and hydroxyl radicals and the effect was found to be much comparable to that of the reference drug, ascorbic acid. Veratric acid significantly reduced the cell viability of KB cells and IC50 was 80 μg/ml. Veratric acid reduced the cell viability by generating excess ROS through activation of MMP depolarization and by inducing the apoptotic cell death of KB cells. The in vitro antioxidant and antiproliferative effect of veratric acid could be used further to validate its anti-carcinogenic potential using ideal experimental animal models. 

References

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021; 71(3):209-249.

Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A, Visser O, Bray F. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018; 103:356-387.

Alkadi H. A Review on Free Radicals and Antioxidants. Infect Disord Drug Targets. 2020; 20(1):16-26.

Sharma GN, Gupta G, Sharma P. A Comprehensive Review of Free Radicals, Antioxidants, and Their Relationship with Human Ailments. Crit Rev Eukaryot Gene Expr. 2018; 28(2):139-154.

Durai P, Manoharan S, Suresh K, Elanchezhiyan C, Durgarao V, Hemavardhini R. Vincamine Reduces Cell Viability of KB and Hep-2 Cancer Cells Through its Apoptotic Potential. Trop J Nat Prod Res. 2022; 6(9):1420-1425.

Selvasundaram R, Manoharan S, Buddhan R, Neelakandan M, Murali Naidu R. Chemopreventive potential of esculetin in 7,12-dimethylbenz(a)anthracene-induced hamster buccal pouch carcinogenesis. Mol Cell Biochem. 2018; 448(1-2):145-153.

Manimaran A, Manoharan S. Tumor Preventive Efficacy of Emodin in 7,12-Dimethylbenz[a]Anthracene-Induced Oral Carcinogenesis: a Histopathological and Biochemical Approach. Pathol Oncol Res. 2018; 24(1):19-29.

Ngozi P Okolie, Falodun A and Oluseyi Davids. Evaluation of the antioxidant activity of root extract of pepper fruit (Dennetia tripetala), and its potential for the inhibition of Lipid peroxidation. Afri J Trad Complem and Altern Med 2014; 11(3):221-227.

Odion EE, Falodun A and Adelusi SA. Total flavonoid, Total Phenolic and antioxidant potential of root bark extract and fractions of from Cola rostrata (Sterculiaceae) K. Schum. University of Benin 2013; J. Sci. Tech 1 (2): 38 - 42.

Egharevba E, Chukwuemeke-Nwani P, Eboh U, Okoye E, Bolanle IO, Oseghale IO, Imieje VO, Erharuyi O, Falodun A. Antioxidant and Hypoglycaemic Potentials of the Leaf Extracts of Stachytarphyta jamaicensis (Verbenaceae). Trop J Nat Prod Res. 2019; 3(5):170-174.

Qi JH, Dong FX. The relevant targets of anti-oxidative stress: a review. J Drug Target. 2021; 29(7):677-686.

Shaban N, Elanchezhiyan C, Manoharan S. Modulating Effect of Vincamine on the Oxidative Stress Markers and Lipid Profile in High Fat Diet and Streptozotocin-Induced Type 2 Diabetic Rats. Trop J Nat Prod Res.2022; 6(4):546-551.

Toczewska J, Konopka T. Activity of enzymatic antioxidants in periodontitis: A systematic overview of the literature. Dent Med Probl. 2019; 56(4):419-426.

Engel N, Falodun A, Kühn J, Kragl U, Langer P, Nebe B. Pro-apoptotic and anti-adhesive effects of four African plant extracts on the breast cancer cell line MCF-7. BMC Complement Altern Med. 2014; 14:334

Lee KE, Park JE, Jung E, Ryu J, Kim YJ, Youm JK, Kang S. A study of facial wrinkles improvement effect of veratric acid from cauliflower mushroom through photo-protective mechanisms against UVB irradiation. Arch Dermatol Res. 2016; 308(3):183-92.

Yu Q, Chen S, Tang H, Zhang X, Tao R, Yan Z, Shi J, Guo W, Zhang S. Veratric acid alleviates liver ischemia/reperfusion injury by activating the Nrf2 signaling pathway. Int Immunopharmacol. 2021; 101(Pt B):108294.

Saravanakumar M, Raja B. Veratric acid, a phenolic acid attenuates blood pressure and oxidative stress in L-NAME induced hypertensive rats. Eur J Pharmacol. 2011; 671(1-3):87-94.

Raja B, Saravanakumar M, Sathya G. Veratric acid ameliorates hyperlipidemia and oxidative stress in Wistar rats fed an atherogenic diet. Mol Cell Biochem. 2012; 366(1-2):21-30.

Choi WS, Seo YB, Shin PG, Kim WY, Lee SY, Choi YJ, Kim GD. Veratric acid inhibits iNOS expression through the regulation of PI3K activation and histone acetylation in LPSstimulated RAW264.7 cells. Int J Mol Med. 2015; 35(1):202-10.

Choi WS, Shin PG, Lee JH, Kim GD. The regulatory effect of veratric acid on NO production in LPS-stimulated RAW264.7 macrophage cells. Cell Immunol. 2012; 280(2):164-70.

Ran X, Chao S, Jun-Gang Z, Yun H, Kuan-Bing C, Wen-Jun S. Protective effect of veratric acid on lipopolysaccharideinduced acute lung injury in mice. Eur J Pharmacol. 2014; 740:227-32.

Palko-Łabuz A, Gliszczyńska A, Skonieczna M, Poła A, Wesołowska O, Środa-Pomianek K. Conjugation with Phospholipids as a Modification Increasing Anticancer Activity of Phenolic Acids in Metastatic Melanoma-In vitro and In Silico Studies. Int J Mol Sci. 2021; 22(16):8397

Vaughan L, Glänzel W, Korch C, Capes-Davis A. Widespread Use of Misidentified Cell Line KB (HeLa): Incorrect Attribution and Its Impact Revealed through Mining the Scientific Literature. Cancer Res. 2017; 77(11):2784-2788.

Blois MS. Antioxidant determinations by the use of a stable free radical. Nature. 1958; 181(4617):1199-200.

Miller NJ, Castelluccio C, Tijburg L, Rice-Evans C. The antioxidant properties of theaflavins and their gallate esters- -radical scavengers or metal chelators?. FEBS Lett. 1996; 392(1):40-44.

Halliwell B, Gutteridge JM, Aruoma OI. The deoxyribose method: a simple "test-tube" assay for determination of rate constants for reactions of hydroxyl radicals. Anal Biochem. 1987;165(1):215-219

Nishikimi M, Appaji N, 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.

Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63.

Rastogi RP, Singh SP, Häder DP, Sinha RP. Detection of reactive oxygen species (ROS) by the oxidant-sensing probe 2',7'-dichlorodihydrofluorescein diacetate in the cyanobacterium Anabaena variabilis PCC 7937. Biochem Biophys Res Commun. 2010; 397(3):603-7.

Scaduto RC Jr, Grotyohann LW. Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J. 1999; 76(1 Pt 1):469-77.

Baskić D, Popović S, Ristić P, Arsenijević NN. Analysis of cycloheximide-induced apoptosis in human leukocytes: fluorescence microscopy using annexin V/propidium iodide versus acridin orange/ethidium bromide. Cell Biol Int. 2006; 30(11):924-32

Baldisserotto A, Demurtas M, Lampronti I, Tacchini M, Moi D, Balboni G, Vertuani S, Manfredini S, Onnis V. In-Vitro Evaluation of Antioxidant, Anti-proliferative and PhotoProtective Activities of Benzimidazolehydrazone Derivatives. Pharmaceuticals. 2020; 13(4):68.

Munteanu IG, Apetrei C. Analytical Methods Used in Determining Antioxidant Activity: A Review. Int J Mol Sci. 2021; 22(7):3380.

Gulcin İ. Antioxidants and antioxidant methods: an updated overview. Arch Toxicol. 2020; 94(3):651-715.

Biondi R, Brancorsini S, Poli G, et al. Detection and scavenging of hydroxyl radical via D-phenylalanine hydroxylation in human fluids. Talanta. 2018; 181:172-181.

Schweikl H, Godula M, Petzel C, Bolay C, Hiller KA, Buchalla W. Critical role of superoxide anions and hydroxyl radicals in HEMA-induced apoptosis. Dent Mater. 2017; 33(1):110-118.

Kaneyuki T, Noda Y, Traber MG, Mori A, Packer L. Superoxide anion and hydroxyl radical scavenging activities of vegetable extracts measured using electron spin resonance. Biochem Mol Biol Int. 1999; 47(6):979-89.

Bozdağ-Dündar O, Gürkan S, Aboul-Enein HY, Kruk I, Kładna A. Scavenging of superoxide anion radical and hydroxyl radical by novel thiazolyl-thiazolidine-2,4-dione compounds. Luminescence. 2009; 24(3):194-201.

Published

2023-05-01

How to Cite

Sivasankaran, S. M., Abdulla, S. H., Elanchezhiyan, C., Pethanasamy, M., Surya, S., Theerthu, A., & Krishnan, H. (2023). Reactive Oxygen Species Scavenging and Anti-Proliferative Potential of Veratric Acid: An in vitro Approach: http://www.doi.org/10.26538/tjnpr/v7i4.28. Tropical Journal of Natural Product Research (TJNPR), 7(4), 2837–2843. Retrieved from https://tjnpr.org/index.php/home/article/view/1894