MICHELIA CHAMPACA MITIGATES NOISE STRESS-INDUCED OXIDATIVE AND BEHAVIORAL ALTERATIONS IN RAT BRAIN REGIONS

MICHELIA CHAMPACA MITIGATES NOISE STRESS-INDUCED OXIDATIVE AND BEHAVIORAL ALTERATIONS IN RAT BRAIN REGIONS MALATHI S VIDYASHREE HM RAVINDRAN RAJAN

Objectives: Noise is a globally prevalent environmental stressor known to contribute to a range of psychophysiological issues, including auditory defects and non-auditory disorders. The brain plays a central role in recognizing, interpreting, and responding to such stressors. The objective of the present study was to evaluate the anxiolytic, neuroprotective, and antioxidant effects of Michelia champaca in rats with noise-induced stress. Methods: Animals were exposed to noise stress (100 dB for 4 h/day) for 1 day and 30 days, after which endogenous free radical levels and antioxidant activities were assessed in discrete brain regions. Results: It demonstrated that noise exposure significantly (p<0.05) elevated free radical production and disrupted antioxidant status across various brain regions. Noise exposure also affected membrane bound enzymes. A marked decrease (p<0.05) was observed in the activities of Ca2⁺-ATPase, Mg2⁺-ATPase, and Na⁺/K⁺-ATPase. Behavioral assessments showed that noise exposed rats exhibited increased anxiety-like behaviors compared to controls. However, treatment with M. champaca (400 mg/kg body weight) effectively (p<0.05) mitigated these effects. The plant extract reduced free radical levels, restored antioxidant enzyme activities, and normalized the functions of membrane-bound enzymes, bringing them closer to control levels. Conclusion: The findings suggest that M. champaca possesses potent free radical scavenging and antioxidant properties, likely due to its phytochemical constituents. These properties contribute to its therapeutic potential in alleviating biochemical and behavioral abnormalities induced by noise stress.
08 07 2025 53 65 http://creativecommons.org/licenses/by/4.0 10.22159/ajpcr.2025v18i8.54836 https://journals.innovareacademics.in/index.php/ajpcr/article/view/54836 https://journals.innovareacademics.in/index.php/ajpcr/article/download/54836/32464 https://journals.innovareacademics.in/index.php/ajpcr/article/download/54836/32464 10.1254/jphs.FP0050127 1. Ravindran R, Rathinasamy SD, Samson J, Senthilvelan M. Noise-stress-induced brain neurotransmitter changes and the effect of Ocimum sanctum (Linn) treatment in albino rat’s. J Pharmacol Sci. 2005;98(4):354-60. doi: 10.1254/jphs.fp0050127, PMID 16113498 10.1016/j.freeradbiomed.2004.11.008 2. Endo T, Nakagawa T, Iguchi F, Kita T, Okano T, Sha SH, et al. Elevation of superoxide dismutase increases acoustic trauma from noise exposure. Free Radic Biol Med. 2005;38(4):492-8. doi: 10.1016/j. freeradbiomed.2004.11.008, PMID 15649651 10.1016/j.phrs.2005.07.007 3. Manikandan S, Devi RS. Antioxidant property of alphfa-asarone against noise-stress-induced changes in different regions of rat brain. Pharmacol Res. 2005;52(6):467-74. doi: 10.1016/j.phrs.2005.07.007, PMID 16140022 10.1016/S0300-483X(03)00153-7 4. Elsayed NM, Gorbunov NV. Interplay between high energy impulse noise (blast) and antioxidants in the lung. Toxicology. 2003;189(1-2):63-74. doi: 10.1016/s0300-483x(03)00153-7, PMID 12821283 5. Mercan U. Importance of free radicals in toxicology. YYUVet Fak Derg. 2004;15(1-2):91-6. 10.2174/1568026013394723 6. Contestabile A. Oxidative stress in neurodegeneration: Mechanism and therapeutic perspectives. Curr Top Med Chem. 2001;1(6):553-68. doi: 10.2174/1568026013394723, PMID 11895131 10.7883/yoken1952.50.9 7. Adhirai M, Selvam R. Effect of cyclosporin A on tissue lipid peroxidation and membrane bound phosphatases in hyperoxaluric rat and the protection by vitamin E pretreatment. Jpn J Med Sci Biol. 1997;50(1):9-17. doi: 10.7883/yoken1952.50.9, PMID 9354965 10.1146/annurev.physiol.65.092101.142558 8. Jorgensen PL, Hakansson KO, Karlish SJ. Structure and mechanism of Na,K-ATPase: Functional sites and their interactions. Annu Rev Physiol. 2003;65:817-49. doi: 10.1146/annurev.physiol.65.092101.142558, PMID 12524462 10.1023/A:1024988113978 9. Gamaro GD, Streck EL, Matté C, Prediger ME, Wyse AT, Dalmaz C. Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res. 2003;28(9):1339-44. doi: 10.1023/a:1024988113978, PMID 12938855 10.1016/0197-0186(92)90119-C 10. Hernández-R J, Na. Na+/K(+)-ATPase regulation by neurotransmitters. Neurochem Int. 1992;20(1):1-10. doi: 10.1016/0197-0186(92)90119-c, PMID 1363908 11. Devasagayam TP, Tilak JC. Boloor KK, Sane KS, Ghaskadbi SS, Lele RD. Free radicals and antioxidants in human health: Current status and future prospects. J Assoc Physicians India. 2004;52:794-804. 12. Kirtikar KR, Basu BD. Indian Medicinal Plants. Uttaranchal. 2nd ed., Vol. 8. Oriental Enterprises; 2001. p. 2604. 13. Sobhagini N, Soumit KB, Malaya KM. Ethano-medicobotanical survey of Kalahandi district of Orissa. Indian J Trad Knowl. 2004;3:72-9. 10.5580/1b0d 14. Dwajani S, Shanbhag TV. Michelia champaca: Wound healing activity in immuno suppressed Rats J Altern Med. 2009;7:6. 10.1016/S0367-326X(02)00248-4 15. Khan MR, Kihara M, Omoloso AD. Antimicrobial activity of Michelia champaca. Fitoterapia. 2002;73(7-8):744-8. doi: 10.1016/s0367- 326x(02)00248-4, PMID 12490248 10.4103/0253-7613.45151 16. Jarald EE, Joshi SB, Jain DC. Antidiabetic activity of flower buds of Michelia champaca Linn. Indian J Pharmacol. 2008;40(6):256-60. doi: 10.4103/0253-7613.45151, PMID 21279181 17. Vimala R, Nagarajan S, Alam M, Susan T, Joy S. Anti-inflammatory and antipyretic activity of Michelia champaca Linn., (White variety), Ixora brachiate Roxb. and Rhynchosia cana (Wild.) D.C. flower extract. Indian J Exp Biol. 1997;131(12):1310-4. 18. Hasan SM, Hossain MM, Akter R. Jamila M, Mazumder ME, Rahman S. DPPH free radical scavenging activity of some Bangladeshi medicinal plants. J Med Plants Res. 2009;3:875-9. 10.1016/j.jep.2006.08.002 19. Rangasamy O, Raoelison G, Rakotoniriana FE, Cheuk K, Urverg- Ratsimamanga S, Quetin-Leclercq J, et al. Screening for anti-infective properties of several medicinal plants of the Mauritians flora. J Ethnopharmacol. 2007;109(2):331-7. doi: 10.1016/j.jep.2006.08.002 10.1016/j.etap.2004.12.059 20. Samson J, Sheela Devi R, Ravindran R, Senthilvelan M. Effect of noise stress on free radical scavenging enzymes in brain. Environ Toxicol Pharmacol. 2005;20(1):142-8. doi: 10.1016/j.etap.2004.12.059, PMID 21783581 10.1111/j.1471-4159.1966.tb09873.x 21. Glowinski J, Iversen LL. Regional studies of catecholamines in the rat brain. I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H] dopa in various regions of the brain. J Neurochem. 1966;13(8):655-69. doi: 10.1111/j.1471-4159.1966.tb09873.x, PMID 5950056 10.1016/0003-2697(79)90738-3 22. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351-8. doi: 10.1016/0003-2697(79)90738-3, PMID 36810 10.1016/0003-2697(68)90092-4 23. Sedlack J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s reagent. Anal Biochem. 1968;25:192-205. 10.1016/0076-6879(90)86141-H 24. Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464-78. doi: 10.1016/0076- 6879(90)86141-h, PMID 1978225 10.1093/clinchem/41.6.892 25. Moshage H, Kok B, Huizenga JR, Jansen PL. Nitrite and nitrate determinations in plasma: A critical evaluation. Clin Chem. 1995;41(6 Pt 1):892-6. doi: 10.1093/clinchem/41.6.892, PMID 7768008 10.1016/0022-1759(80)90340-3 26. Pick E, Keisari Y. A simple colorimetric method for the measurement of hydrogen peroxide produced by cells in culture. J Immunol Methods. 1980;38(1-2):161-70. doi: 10.1016/0022-1759(80)90340-3, PMID 6778929 10.1111/j.1432-1033.1974.tb03714.x 27. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. J Biochem. 1974;47:469-74. 10.1016/0003-2697(72)90132-7 28. Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389-94. doi: 10.1016/0003-2697(72)90132-7, PMID 4556490 10.1126/science.179.4073.588 29. Rotruck JT, Pope AL, Ganther HE, Swanson AB, Hafeman DG, Hoekstra WG. Selenium: Biochemical role as a component of glutathione peroxidase. Science. 1973;179(4073):588-90. doi: 10.1126/ science.179.4073.588, PMID 4686466 30. Horn HD, Burns FH. Assay of glutathione reductase activity. In: Bergemeyer HV, editor. Methods of Enzymatic Analysis. New York: Academic Press; 1978. p. 142-6. 10.1016/0304-4165(79)90289-7 31. Moron MS, Difieree JW, Mannervik KB. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta. 1979;582:67-8. 10.1016/0076-6879(79)62181-X 32. Omaye ST, Turnbull JD, Sauberlich HE. Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol. 1979;62:3-11. 10.1016/S0076-6879(84)05019-9 33. Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol. 1984;105:138-47. doi: 10.1016/s0076-6879(84)05019-9, PMID 6727662 10.1016/0005-2736(73)90255-1 34. Bloj B, Morero RD, Farias RN, Trucco RE. Membrane lipid fatty acids and regulation of membrane-bound enzymes. Allosteric behaviour of erythrocyte Mg 2+ -ATPase, (Na + +K +)-ATPase and acetylcholinesterase from rats fed different fat-supplemented diets. Biochim Biophys Acta. 1973;311:67-79. 10.1016/0005-2736(83)90480-7 35. Hjerten S, Pan H. Purification and characterization of two forms of a low-affinity Ca2+-ATPase from erythrocyte membranes. Biochim Biophys Acta. 1983;728:281-8. 10.1016/0005-2736(82)90050-5 36. Ohnishi T, Suzuki T, Suzuki Y, Ozawa K. A comparative study of plasma membrane Mg2+ -ATPase activities in normal, regenerating and malignant cells. Biochim Biophys Acta. 1982;684:67-74. 37. Borriello A, Roberto R, Della Ragione F, Iolascon A. Proliferate and survive: Cell division cycle and apoptosis in human neuroblastoma. Haematologica. 2002;87(2):196-214. PMID 11836171 10.1016/j.bbr.2009.12.039 38. Salim S, Sarraj N, Taneja M, Saha K, Tejada-Simon MV, Chugh G. Moderate treadmill exercise prevents oxidative stress-induced anxiety-like behavior in rats. Behav Brain Res. 2010;208:545-52. 39. Bilkei-Gorzó A, Gyertyán I. Some doubts about the basic concept of hole-board test. Neurobiology (Bp). 1996;4(4):405-15. PMID 9200132 10.1006/exnr.1996.0154 40. McIntosh LJ, Sapolsky RM. Glucocorticoids increase the accumulation of reactive oxygen species and enhance adriamycin-induced toxicity in neuronal culture. Exp Neurol. 1996;141(2):201-6. doi: 10.1006/ exnr.1996.0154, PMID 8812153 41. Lopaczynski W, Zeisel SH. Antioxidants, programmed cell death, 10.1016/S0271-5317(00)00288-8 and cancer. Nutr Res. 2001;21(1-2):295-307. doi: 10.1016/S0271- 5317(00)00288-8 10.1016/S0899-9007(02)00916-4 42. Fang YZ, Yang S, Wu G. Free radicals, antioxidants, and nutrition. Nutrition. 2002;18(10):872-9. doi: 10.1016/s0899-9007(02)00916-4, PMID 12361782 10.2174/157015909787602823 43. Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 2009;7(1):65-74. doi: 10.2174/157015909787602823, PMID 19721819 44. Hacioglu G, Senturk A, Ince I, Alver A. Assessment of oxidative stress parameters of brain-derived neurotrophic factor heterozygous mice in acute stress model. Iran J Basic Med Sci. 2016;19(4):388-93. PMID 27279982 10.1016/j.cbi.2007.04.007 45. Anbuselvam C, Vijayavel K, Balasubramanian MP. Protective effect of Operculina turpethum against 7,12-dimethyl benz(a)anthracene induced oxidative stress with reference to breast cancer in experimental rats. Chem Biol Interact. 2007;168(3):229-36. doi: 10.1016/j. cbi.2007.04.007, PMID 17531963 10.29333/ejgm/82631 46. Demirel R, Mollaoğlu H, Yeşilyurt H, Üçok K, Ayçiçek A, Akkaya M, et al. Noise induces oxidative stress in rat. Eur J Gen Med. 2009;6(1):20-4. doi: 10.29333/ejgm/82631 10.2298/ABS0701029R 47. Radenovic L, Selakovic V, Janac B, Todorovic D. Effect of glutamate antagonists on nitric oxide production in rat brain following intra hippocampal injection. Arch Biol Sci (Beogr). 2007;59(1):29-36. doi: 10.2298/abs0701029r 10.3329/sjps.v4i1.8862 48. Wei LS, Wee W, Siong JY, Syamsumir DF. Characterization of antimicrobial, antioxidant, anticancer property and chemical composition of Michelia champaca seed and flower extracts. J Pharm Sci. 2011;4:19-24. 10.1016/j.biocel.2006.07.001 49. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 2007;39:44-84. doi: 10.1016/j. biocel.2006.07.001, PMID 16978905 10.1089/ars.2012.4644 50. Allen EM, Mieyal JJ. Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins. Antioxid Redox Signal. 2012;17(12):1748-63. doi: 10.1089/ars.2012.4644, PMID 22530666 51. Ahmad A, Rasheed N, Chand K, Maurya R, Banu N, Palit G. Restraint stress-induced central monoaminergic and oxidative changes in rats and their prevention by novel Ocimum sanctum compounds. Indian J Med Res. 2012;135(4):548-54. PMID 22664506 10.1007/BF00812068 52. Sabbadini RA, Dahms AS. Biochemical properties of isolated transverse tubular membranes. J Bioenerg Biomembr. 1989;21(2):163-213. doi: 10.1007/BF00812068, PMID 2473982 10.1111/j.1471-4159.1992.tb09415.x 53. Mata M, Hieber V, Beaty M, Clevenger M, Fink DJ. Activity-dependent regulation of Na+,K+-ATPase an isoform mRNA expression in vivo. J Neurochem. 1992;59(2):622-6. doi: 10.1111/j.1471-4159.1992. tb09415.x, PMID 1321232 10.1016/0006-8993(87)90414-8 54. Hernandez R, Na B. Brain Na+,K+-ATPase activity possibly regulated by a specific serotonin receptor. Brain Res. 1989;408:399-402. 10.1016/0165-0173(91)90011-V 55. Lees GJ. Inhibition of sodium-potassium-ATPase: A potentially ubiquitous mechanism contributing to central nervous system neuropathology. Brain Res Brain Res Rev. 1991;16(3):283-300. doi: 10.1016/0165-0173(91)90011-v, PMID 1665097 10.1111/j.1471-4159.2006.03907.x 56. Halliwell B. Oxidative stress and neurodegeneration: Where are we now? J Neurochem. 2006;97(6):1634-58. doi: 10.1111/j.1471- 4159.2006.03907.x, PMID 16805774 10.1016/S0006-3495(79)85264-9 57. Smejtek P, Paulis-Illangasekare M. Modification of ion transport in lipid bilayer membranes in the presence of 2,4-dichlorophenoxyacetic acid. I. Enhancement of cationic conductance and changes of the kinetics of nonactin-mediated transport of potassium. Biophys J. 1979;26(3):441-66. doi: 10.1016/S0006-3495(79)85264-9, PMID 263687 58. Hazarika A, Sarkar SN, Kataria M. Subacute toxicity of anilofos, a new organophosphorus herbicide in male rats: Effect on lipid peroxidation and ATPase activity. Indian J Exp Biol. 2001;39(11):1113-7. PMID 11906103 10.1006/phrs.2001.0842 59. Unlüçerçi Y, Koçak H, Seferoğlu G, BekpInar S. The effect of aminoguanidine on diabetes-induced inactivation of kidney Na(+),K(+)- ATPase in rats. Pharmacol Res. 2001;44(2):95-8. doi: 10.1006/phrs.2001.0842, PMID 11516257 10.1046/j.1432-1327.2000.01597.x 60. Dringen R, Gutterer JM, Hirrlinger J. Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem. 2000;267(16):4912-6. doi: 10.1046/j.1432-1327.2000.01597.x, PMID 10931173 10.1002/ptr.2983 61. Lee YJ, Suh KS, Choi MC, Chon S, Oh S, Woo JT, et al. Kaempferol protects HIT-T15 pancreatic beta cells from 2-deoxy-D-ribose-induced oxidative damage. Phytother Res. 2010;24(3):419-23. doi: 10.1002/ ptr.2983, PMID 19827031 10.1155/2014/249031 62. Ashafaq M, Varshney L, Khan MH, Salman M, Naseem M, Wajid S, et al. Neuromodulatory effects of hesperidin in mitigating oxidative stress in streptozotocin induced diabetes. BioMed Res Int. 2014;2014:249031. doi: 10.1155/2014/249031, PMID 25050332 10.3109/13880209.2014.982301 63. Al-Numair KS, Veeramani C, Alsaif MA, Chandramohan G. Influence of kaempferol, a flavonoid compound, on membrane-bound ATPases in streptozotocin-induced diabetic rats. Pharm Biol. 2015;53(9):1372-8. doi: 10.3109/13880209.2014.982301, PMID 25853957 10.4103/1463-1741.137048 64. Xue L, Zhang D, Yibulayin X, Wang T, Shou X. Effects of high frequency noise on female rat’s multi-organ histology. Noise Health. 2014;16(71):213-7. doi: 10.4103/1463-1741.137048, PMID 25033787 10.1002/neu.20025 65. Cook SC, Wellman CL. Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol. 2004;60(2):236-48. doi: 10.1002/neu.20025, PMID 15266654 10.1016/j.ejenta.2014.05.003 66. Abousetta A, Makhlouf NA, El-Beshbishy RA. The effects of concomitant Ginkgo intake on noise induced hippocampus injury. Possible auditory clinical correlate. Egypt J Ear Nose Throat Allied Sci. 2014;15(3):231-9. doi: 10.1016/j.ejenta.2014.05.003 10.4103/1463-1741.82961 67. Jáuregui-Huerta F, Garcıa-Estrada J, Ruvalcaba-Delgadillo Y, Trujillo X, Huerta M, Feria-Velasco A, et al. Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood. Noise Health. 2011;13(53):286-91. doi: 10.4103/1463-1741.82961, PMID 21768732 68. García-Segura LM. Hormones and Brain Plasticity. Vol. 17. Oxford: Oxford University Press; 2009. p. 170-1. doi: 10.1093/ acprof: oso/9780195326611.001.0001 10.7439/ijbar.v3i6.512 69. Dharini S. Effect of Acorus calamus Linn and its active principle on noise stress-induced changes on immune system. Int J Biomed Adv Res. 2012;3:494-501. 10.1016/j.neuroscience.2010.02.071 70. Kraus KS, Mitra S, Jimenez Z, Hinduja S, Ding D, Jiang H, et al. Noise trauma impairs neurogenesis in the rat hippocampus. Neuroscience. 2010;167(4):1216-26. doi: 10.1016/j.neuroscience.2010.02.071, PMID 20206235 10.1016/S0006-2952(03)00508-2 71. Higuchi Y. Chromosomal DNA fragmentation in apoptosis and necrosis induced by oxidative stress. Biochem Pharmacol. 2003;66(8):1527-35. doi: 10.1016/s0006-2952(03)00508-2, PMID 14555231 10.1038/jcbfm.2010.147 72. Liu D, Croteau DL, Souza-Pinto N, Pitta M, Tian J, Wu C, et al. Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions. J Cereb Blood Flow Metab. 2011;31(2):680-92. doi: 10.1038/jcbfm.2010.147, PMID 20736962 10.1016/S0891-5849(96)00571-0 73. Caraceni P, De Maria N, Ryu HS, Colantoni A, Roberts L, Maidt ML, et al. Proteins but not nucleic acids are molecular targets for the free radical attack during reoxygenation of rat hepatocytes. Free Radic Biol Med. 1997;23(2):339-44. doi: 10.1016/s0891-5849(96)00571-0, PMID 9199897 10.1016/j.physbeh.2011.06.018 74. Cheng L, Wang SH, Chen QC, Liao XM. Moderate noise induced cognition impairment of mice and its underlying mechanisms. Physiol Behav. 2011;104(5):981-8. doi: 10.1016/j.physbeh.2011.06.018, PMID 21726571 10.1016/S0378-5955(01)00391-4 75. Van Campen LE, Murphy WJ, Franks JR, Mathias PI, Toraason MA. Oxidative DNA damage is associated with intense noise exposure in the rat. Hear Res. 2002;164(1-2):29-38. doi: 10.1016/s0378- 5955(01)00391-4, PMID 11950522 10.1016/0891-5849(94)90246-1 76. Emerit I. Reactive oxygen species, chromosome mutation, and cancer: Possible role of clastogenic factors in carcinogenesis. Free Radic Biol Med. 1994;16(1):99-109. doi: 10.1016/0891-5849(94)90246-1, PMID 8300000 10.1093/humrep/15.6.1338 77. Barroso G, Morshedi M, Oehninger S. Analysis of DNA fragmentation, plasma membrane translocation of phosphatidylserine and oxidative stress in human spermatozoa. Hum Reprod. 2000;15(6):1338-44. doi: 10.1093/humrep/15.6.1338, PMID 10831565 10.3389/fnana.2017.00049 78. Frenzilli G, Ryskalin L, Ferrucci M, Cantafora E, Chelazzi S, Filippo S, et al. Loud noise exposure produces DNA, neurotransmitter and morphological damage within specific brain areas. Front Neuroanat. 2017;11(49):1-16. 10.1289/ehp.5847 79. Lenzi P, Frenzilli G, Gesi M, Ferrucci M, Lazzeri G, Fornai F, et al. DNA damage associated with ultrastructural alterations in rat myocardium after loud noise exposure. Environ Health Perspect. 2003;111(4):467-71. doi: 10.1289/ehp.5847, PMID 12676600 10.1289/ehp.7249 80. Frenzilli G, Lenzi P, Scarcelli V, Fornai F, Pellegrini A, Soldani P, et al. Effects of loud noise exposure on DNA integrity in rat adrenal gland. Environ Health Perspect. 2004;112(17):1671-2. doi: 10.1289/ehp.7249, PMID 15579411 10.22159/ijcpr.2024v16i3.4074 81. Lee YL, Yang JH, Mau JL. Antioxidant properties of water extracts from Monascus fermented soybeans. Food Chem. 2008;106(3):1128-37. doi: 10.1016/j.foodchem.2007.07.04782. Tiwari A. Comparative analysis of phytochemicals in acacia catechu bark extracts from Guna district, Madhya Pradesh. Int J Curr Pharm Res. 2024;16(3):76-81. doi: 10.22159/ijcpr.2024v16i3.4074 10.1016/S0955-2863(02)00255-3 83. Bub A, Watzl B, Blockhaus M, Briviba K, Liegibel U, Müller H, et al. Fruit juice consumption modulates antioxidative status, immune status, and DNA damage. J Nutr Biochem. 2003;14(2):90-8. doi: 10.1016/s0955-2863(02)00255-3, PMID 12667600 10.1093/carcin/18.9.1847 84. Pool-Zobel BL, Bub A, Müller H, Wollowski I, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: First results of a human intervention trial with carotenoid-rich foods. Carcinogenesis. 1997;18(9):1847-50. doi: 10.1093/carcin/18.9.1847, PMID 9328185 85. Pool-Zobel BL, Bub A, Liegibel UM, Treptow-van Lishaut S, Rech kemmer G. Mechanisms by which vegetable consumption reduces genetic damage in humans. Cancer Epidemiol Biomarkers Prev. 1998;7: 891–9. 10.1017/S0007114500001422 86. Brennan LA, Morris GM, Wasson GR, Hannigan BM, Barnett YA. The effect of vitamin C or vitamin E supplementation on basal and H2O2-induced DNA damage in human lymphocytes. Br J Nutr. 2000;84:195-202. 10.1080/10715760500525807 87. Hofer T, Karlsson HL, Möller L. DNA oxidative damage and strand breaks in young healthy individuals: A gender difference and the role of life style factors. Free Radic Res. 2006;40(7):707-14. doi: 10.1080/10715760500525807, PMID 16983997 10.22159/ijap.2021v13i5.41345 88. Abdallah M, Neseem DI, Elgazayerly ON, Abdelbary AA. Topical delivery of quercetin loaded transfersomes for wound treatment: In vitro and in vivo evaluation. Int J App Pharm. 2021;13(5):189-97. doi: 10.22159/ijap.2021v13i5.41345 10.22159/ijap.2021.v13s3.11 89. Idacahyati K, Nurdianti L, Husni SS, Gustaman F, Wulandari WT. Nephroprotective activity of ethanol extract of kirinyuh (Chromolaena odorata L.) in gentamicin induced nephrotoxicity in Wistar rats. Int J App Pharm. 2021;2021(13 Special Issue 3):53-6. doi: 10.22159/ ijap.2021.v13s3.11 10.1089/dna.2006.25.116 90. Kanakis CD, Tarantilis PA, Polissiou MG, Tajmir-Riahi HA. Interaction of antioxidant flavonoids with tRNA: Intercalation or external binding and comparison with flavonoid-D1A adducts. DNA Cell Biol. 2006;25(2):116-23. doi: 10.1089/dna.2006.25.116, PMID 16460235 10.1080/07391102.2005.10507038 91. Kanakis CD, Tarantilis PA, Polissiou MG, Diamantoglou S, Tajmir-Riahi HA. DNA interaction with naturally occurring antioxidant flavonoids quercetin, kaempferol, and delphinidin. J Biomol Struct Dyn. 2005;22(6):719-24. doi: 10.1080/07391102.2005.10507038, PMID 15842176 10.1016/j.snb.2005.12.014 92. Bi S, Qiao C, Song D, Tian Y, Gao D, Sun Y, et al. Study of interactions of flavonoids with DNA using acridine orange as a fluorescence probe. Sens Actuators B. 2006;119(1):199-208. doi: 10.1016/j. snb.2005.12.014 10.1016/j.jpba.2012.01.034 93. Hegde AH, Prashanth SN, Seetharamappa J. Interaction of antioxidant flavonoids with calf thymus DNA analyzed by spectroscopic and electrochemical methods. J Pharm Biomed Anal. 2012;63:40-6. doi: 10.1016/j.jpba.2012.01.034, PMID 22349882 10.1038/srep17574 94. Tawani A, Kumar A. Structural Insight into the interaction of Flavonoids with human telomeric sequence. Sci Rep. 2015;5:17574. doi: 10.1038/srep17574, PMID 26627543 10.1186/1756-9966-28-80 95. Seufi AM, Ibrahim SS, Elmaghraby TK, Hafez EE. Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/ antioxidant activity: Molecular and histological evidences. J Exp Clin Cancer Res. 2009;28(1):80. doi: 10.1186/1756-9966-28-80, PMID 19519916 10.1207/S15327914NC3402_6 96. Aherne SA, O’Brien NM. Protection by the flavonoids myricetin, quercetin, and rutin against hydrogen peroxide-induced DNA damage in Caco-2 and Hep G2 cells. Nutr Cancer. 1999;34(2):160-6. doi: 10.1207/S15327914NC3402_6, PMID 10578483 10.1111/j.1742-7843.2006.pto_382.x 97. Jin NZ, Zhu YP, Zhou JW, Mao L, Zhao RC, Fang TH, et al. Preventive effects of quercetin against benzo[a]pyrene-induced DNA damages and pulmonary precancerous pathologic changes in mice. Basic Clin Pharmacol Toxicol. 2006;98(6):593-8. doi: 10.1111/ j.1742-7843.2006.pto_382.x, PMID 16700823 10.1016/j.ejphar.2008.10.046 98. Silva JP, Gomes AC, Coutinho OP. Oxidative DNA damage protection and repair by polyphenolic compounds in PC12 cells. Eur J Pharmacol. 2008;601(1-3):50-60. doi: 10.1016/j.ejphar.2008.10.046, PMID 18996367 10.1038/srep24049 99. Srivastava S, Somasagara RR, Hegde M, Nishana M, Tadi SK, Srivastava M, et al. Quercetin, a natural flavonoid interacts with DNA, arrests cell cycle and causes tumor regression by activating mitochondrial pathway of apoptosis. Sci Rep. 2016;6:24049. doi: 10.1038/srep24049, PMID 27068577 10.1146/annurev.ge.29.120195.000441 100. Sancar A. DNA repair in humans. Annu Rev Genet. 1995;29(1):69-105. doi: 10.1146/annurev.ge.29.120195.000441 10.1016/j.pbb.2005.04.016 101. Mi XJ, Chen SW, Wang WJ, Wang R, Zhang YJ, Li WJ, et al. Anxiolytic-like effect of paeonol in mice. Pharmacol Biochem Behav. 2005;81(3):683-7. doi: 10.1016/j.pbb.2005.04.016, PMID 15970315 10.22159/ajpcr.2020.v13i1.35187 102. Keerthi Priya CS, Malathi S, Rajan R. Effect of sleep deprivation on reminiscence and apprehension behavior in Wistar albino rats. Asian J Pharm Clin Res. 2020;13(1):196-201. 10.4103/0253-7613.40487 103. Yadav AV, Kawale LA, Nade VS. Effect of Morus alba L. (mulberry) leaves on anxiety in mice. Indian J Pharmacol. 2008;40(1):32-6. doi: 10.4103/0253-7613.40487, PMID 21264159 10.1159/000063573 104. Kuloglu M, Atmaca M, Tezcan E, Gecici O, Tunckol H, Ustundag B. Antioxidant enzyme activities and malondialdehyde levels in patients with obsessive-compulsive disorder. Neuropsychobiology. 2002a;46(1):27-32. doi: 10.1159/000063573, PMID 12207144 10.1016/j.lfs.2007.05.001 105. Souza CG, Moreira JD, Siqueira IR, Pereira AG, Rieger DK, Souza DO, et al. Highly palatable diet consumption increases protein oxidation in rat frontal cortex and anxiety-like behavior. Life Sci. 2007;81(3):198-203. doi: 10.1016/j.lfs.2007.05.001, PMID 17574275 10.1096/fj.04-2400fje 106. Desrumaux C, Risold PY, Schroeder H, Deckert V, Masson D, Athias A, et al. Phospholipid transfer protein (PLTP) deficiency reduces brain vitamin E content and increases anxiety in mice. FASEB J. 2005;19(2):296-7. doi: 10.1096/fj.04-2400fje, PMID 15576481 10.1016/S0014-2999(98)00223-4 107. Takeda H, Tsuji M, Matsumiya T. Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol. 1998;350(1):21-9. doi: 10.1016/S0014- 2999(98)00223-4 10.1007/BF00414043 108. Nolan NA, Parkes MW. The effects of benzodiazepines on the behaviour of mice on a hole-board. Psychopharmacologia. 1973;29(3):277-86. doi: 10.1007/BF00414043, PMID 4702279 10.1016/j.bbr.2005.07.008 109. Hranilovic D, Cicin-Sain L, Bordukalo-Niksic T, Jernej B. Rats with constitutionally upregulated/downregulated platelet 5HT transporter: Differences in anxiety-related behavior. Behav Brain Res. 2005;165(2):271-7. doi: 10.1016/j.bbr.2005.07.008, PMID 16139900