INSIGHTS INTO THE MOLECULAR AND BIOCHEMICAL ROLE OF QUINIC ACID IN ALLEVIATING ETHANOL-INDUCED LIVER TOXICITY IN A RAT MODEL: EXPLORING OXIDATIVE STRESS, INFLAMMATION, AND APOPTOSIS SIGNALING PATHWAYS

Authors

  • GURUSAMY MUTHUKARUPPIAH Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Cuddalore, Tamil Nadu, India
  • NADANAM SARAVANAN Department of Biochemistry, Government Medical College and Hospital, Cuddalore, Tamil Nadu, India.

DOI:

https://doi.org/10.22159/ajpcr.2024v18i01.52854

Keywords:

antioxidants, ethanol, lipid peroxidation, liver disease, quinic acid

Abstract

Objective: The study aimed to evaluate the effects of quinic acid, a natural bioactive compound, on tissue and circulatory antioxidant status, lipid peroxidation, and its anti-apoptotic and anti-inflammatory mechanisms in ethanol-induced hepatotoxicity in rats.

Methods: The rats were divided into four groups. Groups 1 and 4 were administered isocaloric glucose. Groups 2 and 3 received 30% ethanol at a dose of 5 g/kg body weight daily. In addition, Groups 3 and 4 were treated with quinic acid (50 mg/kg body weight) dissolved in 2% dimethyl sulfoxide.

Results: The results demonstrated significantly elevated levels of tissue thiobarbituric acid reactive substances (TBARS), conjugated dienes (CD), and lipid hydroperoxides (LOOH), along with significantly reduced enzymatic and non-enzymatic antioxidant activities, including superoxide dismutase (SOD), catalase (CAT), and glutathione-related enzymes such as glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione-S-transferase (GST), as well as reduced levels of glutathione (GSH), Vitamin C, and Vitamin E in ethanol-treated rats compared to the control group. Administration of quinic acid to rats with ethanol-induced liver injury significantly reduced the levels of TBARS, LOOH, and CD while markedly increasing the activity of SOD, CAT, GPx, GR, GST, and levels of GSH, Vitamin C, and Vitamin E in liver tissues compared to untreated ethanol-exposed rats. In addition, ethanol-treated rats showed increased mast cell accumulation, which was reduced by quinic acid treatment, along with elevated expressions of inflammatory and apoptotic markers, including Bax, Caspase-9, tumor necrosis factor-alpha, Nuclear factor kappa B, and interleukin-6, and a decreased expression of Bcl2 in the liver. Quinic acid supplementation in ethanol-fed rats reversed these ethanol-induced changes. Immunohistochemical studies further supported these findings.

Conclusion: Quinic acid, with its antioxidant, anti-inflammatory, and anti-apoptotic properties, may offer a therapeutic option for protecting against ethanol-induced hepatotoxicity

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References

Dguzeh U, Haddad NC, Smith KT, Johnson JO, Doye AA, Gwathmey JK, et al. Alcoholism: A multi-systemic cellular insult to organs. Int J Environ Res Public Health. 2018;15(6):1083. doi: 10.3390/ ijerph15061083, PMID 29843384

Rehm J, Shield KD. Global burden of alcohol use disorders and alcohol liver disease. Biomedicines. 2019;7(4):99. doi: 10.3390/ biomedicines7040099, PMID 31847084

Tuma DJ, Casey CA. Dangerous byproducts of alcohol breakdown- -focus on adducts. Alcohol Res Health. 2003;27(4):285-90. PMID 15540799

Teschke R. Alcoholic liver disease: Alcohol metabolism, cascade of molecular mechanisms, cellular targets, and clinical aspects. Biomedicines. 2018;6(4):106. doi: 10.3390/biomedicines6040106, PMID 30424581

Rodriguez FD, Coveñas R. Biochemical mechanisms associating alcohol use disorders with cancers. Cancers (Basel). 2021;13(14):3548. doi: 10.3390/cancers13143548, PMID 34298760

Laranjinha J, Nunes C, Ledo A, Lourenço C, Rocha B, Barbosa RM. The peculiar facets of nitric oxide as a cellular messenger: From disease-associated signaling to the regulation of brain bioenergetics and neurovascular coupling. Neurochem Res. 2021;46(1):64-76. doi: 10.1007/s11064-020-03015-0, PMID 32193753

Chambers PA. Light and nutrients in the control of aquatic plant community structure. II. In situ observations. J Ecol. 1987;75(3):621-8. doi: 10.2307/2260194

Rodella U, Honisch C, Gatto C, Ruzza P, D’Amato Tóthová J. Antioxidant nutraceutical strategies in the prevention of oxidative stress related eye diseases. Nutrients. 2023;15(10):22. doi: 10.3390/ nu15102283, PMID 37242167

Namachivayam A, Valsala Gopalakrishnan AV. Effect of lauric acid against ethanol-induced hepatotoxicity by modulating oxidative stress/apoptosis signalling and HNF4α in Wistar albino rats. Heliyon. 2023;9(11):e21267. doi: 10.1016/j.heliyon.2023.e21267, PMID 37908709

Contreras-Zentella ML, Villalobos-García D, Hernández-Muñoz R. Ethanol metabolism in the liver, the induction of oxidant stress, and the antioxidant defense system. Antioxid. 2022 Jun 26;11(7):1258. doi: 10.3390/antiox11071258

Tripathi R, Gupta R, Sahu M, Srivastava D, Das A, Ambasta RK, et al. Free radical biology in neurological manifestations: Mechanisms to therapeutics interventions. Environ Sci Pollut Res Int. 2022;29(41):62160–62207. doi: 10.1007/s11356-021-16693-2, PMID 34617231

Tan HK, Yates E, Lilly K, Dhanda AD. Oxidative stress in alcohol-related liver disease. World J Hepatol. 2020;12(7):332-49. doi: 10.4254/ wjh.v12.i7.332, PMID 32821333

Elmore S. Apoptosis: A review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. doi: 10.1080/01926230701320337, PMID 17562483

Brown JM, Wilson TM, Metcalfe DD. The mast cell and allergic diseases: Role in pathogenesis and implications for therapy. Clin Exp Allergy. 2008;38(1):4-18. doi: 10.1111/j.1365-2222.2007.02886.x, PMID 18031566

Osna NA, Ganesan M, Seth D, Wyatt TA, Kidambi S, Kharbanda KK. Second hits exacerbate alcohol-related organ damage: An update. Alcohol Alcohol. 2021;56(1):8-16. doi: 10.1093/alcalc/agaa085, PMID 32869059

Aristri MA, Lubis MA, Iswanto AH, Fatriasari W, Sari RK, Antov P, et al. Bio-based polyurethane resins derived from tannin: Source, synthesis, characterisation, and application. Forests. 2021;12(11):1516. doi: 10.3390/f12111516

Wang L, Pan X, Jiang L, Chu Y, Gao S, Jiang X, et al. The biological activity mechanism of chlorogenic acid and its applications in food industry: A review. Front Nutr. 2022;9:943911. doi: 10.3389/ fnut.2022.943911, PMID 35845802

Zamani‐Garmsiri F, Emamgholipour S, Rahmani Fard S, Ghasempour G, Jahangard Ahvazi R, Meshkani R. Polyphenols: Potential anti‐inflammatory agents for treatment of metabolic disorders. Phytother Res. 2022;36(1):415-32. doi: 10.1002/ptr.7329, PMID 34825416

Benali T, Bakrim S, Ghchime R, Benkhaira N, El Omari N, Balahbib A, et al. Pharmacological insights into the multifaceted biological properties of quinic acid. Biotechnol Genet Eng Rev. 2022;40:3408-37.

Nam SY, Han NR, Rah SY, Seo Y, Kim HM, Jeong HJ. Anti-inflammatory effects of Artemisia scoparia and its active constituent, 3, 5-dicaffeoyl-epi-quinic acid against activated mast cells. Immunopharmacol Immunotoxicol. 2018;40(1):52-8. doi: 10.1080/08923973.2017.1405438, PMID 29172841

Singh SK, Thakur K, Sharma V, Saini M, Sharma D, Vishwas S, et al. Exploring the multifaceted potential of chlorogenic acid: Journey from nutraceutical to nanomedicine. South Afr J Bot. 2023;159:658-77.

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

Jiang Y, Liu BW. LOOH, CD, TBARS and REM kinetic changes during oxidation of high density lipoproteins induced by Cu(2+) in vitro. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai). 1999;31(3):325-7. PMID 12136188

Rao KS, Recknagel RO. Early onset of lipoperoxidation in rat liver after carbon tetrachloride administration. Exp Mol Pathol. 1968;9(2):271-8. doi: 10.1016/0014-4800(68)90041-5, PMID 4952076

Kakkar R, Kalra J, Mantha SV, Prasad K. Lipid peroxidation and activity of antioxidant enzymes in diabetic rats. Mol Cell Biochem. 1995;151(2):113-9. doi: 10.1007/BF01322333, PMID 8569756

Sinha AK. Colorimetric assay of catalase. Anal Biochem. 1972;47(2):389- 94. doi: 10.1016/0003-2697(72)90132-7, PMID 4556490

Eyer P, Podhradský D. Evaluation of the micromethod for determination of glutathione using enzymatic cycling and Ellman’s reagent. Anal Biochem. 1986;153(1):57-66. doi: 10.1016/0003-2697(86)90061-8, PMID 3963383

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

Carlberg I, Mannervik B. Glutathione reductase. Methods Enzymol. 1985;113:484-90. doi: 10.1016/s0076-6879(85)13062-4, PMID 3003504

Habig WH, Pabst MJ, Jakoby WB. Glutathione S-transferases: The first enzymatic step in mercapturic acid formation. J Biol Chem. 1974;249(22):7130-9. doi: 10.1016/S0021-9258(19)42083-8, PMID 4436300

Roe JH, Kuether CA. The determination of ascorbic acid in whole blood and urine through the 2, 4-dinitrophenylhydrazine derivative of dehydroascorbic acid. J Biol Chem. 1943;147(2):399-407. doi: 10.1016/S0021-9258(18)72395-8

Baker H, Handelman GJ, Short S, Machlin LJ, Bhagavan HN, Dratz EA, et al. Comparison of plasma α and γ tocopherol levels following chronic oral administration of either all-rac-α-tocopheryl acetate or RRR- α-tocopheryl acetate in normal adult male subjects. Am J Clin Nutr. 1986;43(3):382-7. doi: 10.1093/ajcn/43.3.382, PMID 3953477

Khan MW, Keshavarzian A, Gounaris E, Melson JE, Cheon EC, Blatner NR, et al. PI3K/AKT signaling is essential for communication between tissue-infiltrating mast cells, macrophages, and epithelial cells in colitis-induced cancer. Clin Cancer Res. 2013;19(9):2342-54. doi: 10.1158/1078-0432.CCR-12-2623, PMID 23487439

Elshopakey GE, Elazab ST. Cinnamon aqueous extract attenuates diclofenac sodium and oxytetracycline mediated hepato-renal toxicity and modulates oxidative stress, 9cell apoptosis, and inflammation in male albino rats. Vet Sci. 2021;8(1):9. doi: 10.3390/vetsci8010009, PMID 33418920

Moslemi M, Jannat B, Mahmoudzadeh M, Ghasemlou M, Abedi AS. Detoxification activity of bioactive food compounds against ethanol‐induced injuries and hangover symptoms: A review. Food Sci Nutr. 2023;11(9):5028-40. doi: 10.1002/fsn3.3520, PMID 37701198

Chauhan SS, Ojha S, Mahmood A. Neurotoxicity of fluoride in ethanol fed rats: Role of oxidative stress, mitochondrial dysfunction and neurotransmitters. Indian J Exp Biol (IJEB). 2022;58(01):14-22.

Clarke N, Ferrar J, Pechey E, Ventsel M, Pilling MA, Munafò MR, et al. Impact of health warning labels and calorie labels on selection and purchasing of alcoholic and non‐alcoholic drinks: A randomized controlled trial. Addiction. 2023;118(12):2327-41. doi: 10.1111/ add.16288, PMID 37528529

Ratheesh M, Jose SP, Sheethal S, Sandya S, Jagmag T, Tilwani J. Ameliorating effect of essential phospholipids enriched with virgin coconut oil (Phoscoliv®) on alcohol induced liver toxicity: Possible role in oxidative stress and cellular leakage. J Nutr Food Sci. 2021;11:797.

Engwa GA, EnNwekegwa FN, Nkeh-Chungag BN. Free radicals, oxidative stress-related diseases and antioxidant supplementation. Altern Ther Health Med. 2022;28(1):114-28. PMID 32827401

Sabitha R, Nishi K, Gunasekaran VP, Agilan B, David E, Annamalai G, et al. p-coumaric acid attenuates alcohol exposed hepatic injury through MAPKs, apoptosis and Nrf2 signaling in experimental models. Chem Biol Interact. 2021;321:109044.

Ding Y, Li X, Liu Y, Wang S, Cheng D. Protection mechanisms underlying oral administration of chlorogenic acid against cadmium-induced hepatorenal injury related to regulating intestinal flora balance. J Agric Food Chem. 2021;69(5):1675-83. doi: 10.1021/acs. jafc.0c06698, PMID 33494608

Singh H, Singh R, Singh A, Singh H, Singh G, Kaur S, et al. Role of oxidative stress in diabetes-induced complications and their management with antioxidants. Arch Physiol Biochem. 2023;130:616-41.

Islam MN, Rauf A, Fahad FI, Emran TB, Mitra S, Olatunde A, et al. Superoxide dismutase: An updated review on its health benefits and industrial applications. Crit Rev Food Sci Nutr. 2022;62(26):7282-300. doi: 10.1080/10408398.2021.1913400, PMID 33905274

Nilsson R, Liu NA. Nuclear DNA damages generated by reactive oxygen molecules (ROS) under oxidative stress and their relevance to human cancers, including ionizing radiation-induced neoplasia part I: Physical, chemical and molecular biology aspects. Rad Med Prot. 2020;1(3):140-52. doi: 10.1016/j.radmp.2020.09.002

Thilagavathi R, Begum SS, Varatharaj SD, Balasubramaniam AK, George JS, Selvam C. Recent insights into the hepatoprotective potential of medicinal plants and plant‐derived compounds. Phytother Res. 2023;37(5):2102-18. doi: 10.1002/ptr.7821, PMID 37022281

Chaudhary P, Janmeda P, Docea AO, Yeskaliyeva B, Abdull Razis AF, Modu B, et al. Oxidative stress, free radicals and antioxidants: Potential crosstalk in the pathophysiology of human diseases. Front Chem. 2023;11:1158198. doi: 10.3389/fchem.2023.1158198, PMID 37234200

Dey S, Nandi A, Das S, Sinha SK, Dey SK. Nicotine and chromium co-exposure lead to hepatotoxicity in male albino rats. J Stress Physiol Biochem. 2023;19(3):24-34.

Yu J, Zhao Y, Xu L, Li W, Zhang H, Ping F, et al. Liraglutide attenuates hepatic oxidative stress, inflammation, and apoptosis in streptozotocin-induced diabetic mice by modulating the Wnt/β- catenin signaling pathway. Mediators Inflamm. 2023;2023:8974960. doi: 10.1155/2023/8974960, PMID 36756089

Wang C, Gong B, Peng D, Liu Y, Wu Y, Wei J. Agarwood extract mitigates alcoholic fatty liver in C57 mice via anti-oxidation and anti-inflammation. Mol Med Rep. 2023;28(5):1-10. doi: 10.3892/ mmr.2023.13097, PMID 37772395

Barzan M, Heydari M, Mirshekari-Jahangiri H, Firouzi H, Dastan M, Najafi M, et al. Carvacrol exerts anti-inflammatory, anti-oxidative stress and hepatoprotective effects against diclofenac-induced liver injury in male rats. Int J Prev Med. 2023;14:61. doi: 10.4103/ijpvm. ijpvm_178_21, PMID 37351047

Roy Z, Bansal R, Siddiqui L, Chaudhary N. Understanding the role of free radicals and antioxidant enzymes in human diseases. Curr Pharm Biotechnol. 2023;24(10):1265-76. doi: 10.2174/138920102466622112 1160822, PMID 36411571

Krishnamurthy HK, Pereira M, Jayaraman V, Krishna K, Wang T, Bei K, et al. Oxidative Stress: Mechanisms, Quantification and Its Role in Human Aging. ScienceOpen [Preprints]; 2024.

Asghar F, Shakoor B, Murtaza B, Butler IS. An insight on the different synthetic routes for the facile synthesis of O/S-donor carbamide/thiocarbamide analogs and their miscellaneous pharmacodynamic applications. J Chem. 2023;44(1):90-147. doi: 10.1080/17415993.2022.2119085

Bayır H, Dixon SJ, Tyurina YY, Kellum JA, Kagan VE. Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney. Nat Rev Nephrol. 2023;19(5):315-36. doi: 10.1038/s41581-023-00689-x, PMID 36922653

Najafi A, Asadi E, Benson JD. Ovarian tissue cryopreservation and transplantation: A review on reactive oxygen species generation and antioxidant therapy. Cell Tissue Res. 2023;393(3):401-23. doi: 10.1007/ s00441-023-03794-2, PMID 37328708

Bazabang SA, Makena W, Rilwan HB, Onimisi OB, Buba HS, Jerome VK. Citrullus lanatus methanol seed extract exhibits antioxidant and anti-inflammatory potential against ethanol-induced kidney damage in Wistar rats. Comp Clin Pathol. 2023;32(5):733-42. doi: 10.1007/s00580-023-03479-w

Shamsabadi S, Nazer Y, Ghasemi J, Mahzoon E, Baradaran Rahimi VB, Ajiboye BO, et al. Promising influences of zingerone against natural and chemical toxins: A comprehensive and mechanistic review. Toxicon. 2023;233:107247. doi: 10.1016/j.toxicon.2023.107247, PMID 37562703

Dasgupta T, Manickam V. Benzydamine hydrochloride ameliorates ethanol-induced inflammation in RAW 264.7 macrophages by stabilizing redox homeostasis. Asian Pac J Trop Biomed. 2024;14(2):73- 81. doi: 10.4103/apjtb.apjtb_823_23

Chiang FF, Huang SC, Yu PT, Chao TH, Huang YC. Oxidative stress induced by chemotherapy: Evaluation of glutathione and its related antioxidant enzyme dynamics in patients with colorectal cancer. Nutrients. 2023;15(24):5104. doi: 10.3390/nu15245104, PMID 38140363

Boulebd H, Carmena-Bargueño M, Pérez-Sánchez H. Exploring the antioxidant properties of caffeoylquinic and feruloylquinic acids: A computational study on hydroperoxyl radical scavenging and xanthine oxidase inhibition. Antioxidants (Basel). 2023;12(9):1669. doi: 10.3390/antiox12091669, PMID 37759973

Rai GK, Rai NP, Rathaur S, Kumar S, Singh M. Expression of rd29A: AtDREB1A/CBF3 in tomato alleviates drought-induced oxidative stress by regulating key enzymatic and non-enzymatic antioxidants. Plant Physiol Biochem. 2013;69:90-100. doi: 10.1016/j. plaphy.2013.05.002, PMID 23728392

Murugan P. Modulatory effect of tetrahydrocurcumin compared curcumin in oxidative stress induced lipid peroxidation in type 2 diabetes: Systemic review TJP. Rom J Dia Nutrn Metab Dis. 2023;30:675-91.

Srivastava S, Dubey RS. Manganese-excess induces oxidative stress, lowers the pool of antioxidants and elevates activities of key antioxidative enzymes in rice seedlings. Plant Growth Regul. 2011;64(1):1-16. doi: 10.1007/s10725-010-9526-1

Niki E. Role of vitamin E as a lipid-soluble peroxyl radical scavenger: In vitro and in vivo evidence. Free Radic Biol Med. 2014;66:3-12. doi: 10.1016/j.freeradbiomed.2013.03.022, PMID 23557727

Satapathy T, Banjare B, Sahu H. A comprehensive analysis of Cestrum nocturnum: Its phytochemical composition, pharmacological applications and toxicity profile in the context of traditional medicinal practices. J Drug Deliv Ther. 2024 Sep 1;14(9). Doi: 10.22270/jddt.v14i9.6771

Batiha GE, Beshbishy AM, Ikram M, Mulla ZS, El-Hack ME, Taha AE, et al. The pharmacological activity, biochemical properties, and pharmacokinetics of the major natural polyphenolic flavonoid: Quercetin. Foods. 2020;9(3):374. doi: 10.3390/foods9030374, PMID 32210182

Nisar A, Jagtap S, Vyavahare S, Deshpande M, Harsulkar A, Ranjekar P, et al. Phytochemicals in the treatment of inflammation-associated diseases: The journey from preclinical trials to clinical practice. Front Pharmacol. 2023;14:1177050. doi: 10.3389/fphar.2023.1177050, PMID 37229273

Sobhani M, Farzaei MH, Kiani S, Khodarahmi R. Immunomodulatory; anti-inflammatory/antioxidant effects of polyphenols: A comparative review on the parental compounds and their metabolites. Food Rev Int. 2020;37:759-811.

Clifford MN, Jaganath IB, Ludwig IA, Crozier A. Chlorogenic acids and the acyl-quinic acids: Discovery, biosynthesis, bioavailability and bioactivity. Nat prod rep. 2017;34(12):1391-421. doi: 10.1039/C7NP00030H.

Bahuguna A, Bharadwaj S, Bajpai VK, Shukla S, Won DW, Park I, et al. Insights into cyclooxygenase-2 inhibition by isolated bioactive compounds 3-caffeoyl-4-dihydrocaffeoyl quinic acid and isorhamnetin 3-O-β-D-glucopyranoside from Salicornia herbacea. Phytomedicine. 2021;90:153638. doi: 10.1016/j.phymed.2021.153638, PMID 34275700

Wan YM, Li ZQ, Zhou Q, Liu C, Wang MJ, Wu HX, et al. Mesenchymal stem cells alleviate liver injury induced by chronic-binge ethanol feeding in mice via release of TSG6 and suppression of STAT3 activation. Stem Cell Res Ther. 2020;11(1):24.

Sun L, Wen S, Li Q, Lai X, Chen R, Zhang Z, et al. L-theanine relieves acute alcoholic liver injury by regulating the TNF-α/NF-κB signaling pathway in C57BL/6J mice. J Funct Foods. 2021;86:104699. doi: 10.1016/j.jff.2021.104699

Nanji AA, Khettry U, Sadrzadeh SM. Lactobacillus feeding reduces endotoxemia and severity of experimental alcoholic liver (disease). Proc Soc Exp Biol Med. 1994;205(3):243-7. doi: 10.3181/00379727- 205-43703, PMID 8171045

Tsukamoto H, Horne W, Kamimura S, Niemelä O, Parkkila S, Ylä- Herttuala S, et al. Experimental liver cirrhosis induced by alcohol and iron. J Clin Invest. 1995;96(1):620-30. doi: 10.1172/JCI118077, PMID 7615836

Torres-Rodríguez ML, García-Chávez E, Berhow M, De Mejia EG. Anti-inflammatory and anti-oxidant effect of Calea urticifolia lyophilized aqueous extract on lipopolysaccharide-stimulated RAW 264.7 macrophages. J Ethnopharmacol. 2016;188:266-74. doi: 10.1016/j.jep.2016.04.057, PMID 27139571

Nanji AA, Jokelainen K, Rahemtulla A, Miao L, Fogt F, Matsumoto H, et al. Activation of nuclear factor kappa B and cytokine imbalance in experimental alcoholic liver disease in the rat. Hepatology. 1999;30(4):934-43. doi: 10.1002/hep.510300402, PMID 10498645

Jokelainen K, Reinke LA, Nanji AA. NF-Kappab activation is associated with free radical generation and endotoxemia and precedes pathological liver injury in experimental alcoholic liver disease. Cytokine. 2001;16(1):36-9. doi: 10.1006/cyto.2001.0930, PMID 11669585

Hämäläinen M, Nieminen R, Vuorela P, Heinonen M, Moilanen E. Anti-inflammatory effects of flavonoids: Genistein, kaempferol, quercetin, and daidzein inhibit STAT-1 and NF-κB activations, whereas flavone, isorhamnetin, naringenin, and pelargonidin inhibit only NF- κB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophages. Mediators Inflamm. 2007;2007:45673. doi: 10.1155/2007/45673, PMID 18274639

Shi J, Levinson DF, Duan J, Sanders AR, Zheng Y, Pe’Er I, et al. Common variants on chromosome 6p22. 1 are associated with schizophrenia. Nature. 2009;460(7256):753-7. doi: 10.1038/nature08192, PMID 19571809

Jang JH, Surh YJ. Potentiation of cellular antioxidant capacity by Bcl- 2: Implications for its antiapoptotic function. Biochem Pharmacol. 2003;66(8):1371-9. doi: 10.1016/s0006-2952(03)00487-8, PMID 14555211

Shimizu S, Eguchi Y, Kosaka H, Kamiike W, Matsuda H, Tsujimoto Y. Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL. Nature. 1995;374(6525):811-3. doi: 10.1038/374811a0, PMID 7723826

Amstad PA, Yu G, Johnson GL, Lee BW, Dhawan S, Phelps DJ. Detection of caspase activation in situ by fluorochrome-labeled caspase inhibitors. BioTechniques. 2001;31(3):608-16. doi: 10.2144/01313pf01, PMID 11570504

Sharifipour M, Izadpanah E, Nikkhoo B, Zare S, Abdolmaleki A, Hassanzadeh K, et al. A new pharmacological role for donepezil: Attenuation of morphine-induced tolerance and apoptosis in rat central nervous system. J Biomed Sci. 2014;21:1

Published

07-01-2025

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GURUSAMY MUTHUKARUPPIAH, and NADANAM SARAVANAN. “INSIGHTS INTO THE MOLECULAR AND BIOCHEMICAL ROLE OF QUINIC ACID IN ALLEVIATING ETHANOL-INDUCED LIVER TOXICITY IN A RAT MODEL: EXPLORING OXIDATIVE STRESS, INFLAMMATION, AND APOPTOSIS SIGNALING PATHWAYS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 18, no. 1, Jan. 2025, pp. 30-38, doi:10.22159/ajpcr.2024v18i01.52854.

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