INCREASED SUSCEPTIBILITY TO GASTRIC ULCERATION IN DIABETIC RATS: SYNERGISTIC EFFECT OF QUERCETIN AND PIOGLITAZONE
DOI:
https://doi.org/10.22159/ijap.2026v18i1.54668Keywords:
Diabetic ulcers, Insulin resistance, Pioglitazone, Quercetin, Antioxidant levelsAbstract
Objective: This research delves into the potential therapeutic benefits of quercetin, a prominent flavonoid, in addressing diabetes and associated ulcers, emphasizing its synergistic effects with oral hypoglycemic agent, pioglitazone.
Methods: Sprague-Dawley rats received a high-fat diet and 35 mg/kg streptozotocin to mimic human diabetic condition. These rats were exposed to drug (indomethacin) and alcohol induced gastric ulceration, to study the flavonoid’s effect alone and in combination with pioglitazone (low doses) in type 2 diabetes enhanced gastric mucosa sensitivity towards ulcerogenic insults.Quercetin and pioglitazone administered alone and in combination over eight-week period.OGTT, antioxidant status was estimated at the end of the study. Ulcer score and index were also determined by using respective standards.
Results: Monotherapy of pioglitazone (low dose) and quercetin exhibited limited effectiveness in increasing insulin sensitivity and ulcer prevention. Blood sample analyses, unveiled elevated antioxidant levels in the combination group compared to monotherapy. Notably, low dose combinations of quercetin and pioglitazone effectively displayed better healing-promoting properties. The combination of low doses of quercetin and pioglitazone demonstrated superior efficacy in ameliorating resistance towards insulin, physiological restoration, and prevention of stomach ulcers in diabetic rats.
Conclusion: The synergistic effects of quercetin and pioglitazone at low doses offers promising avenues for slowing the progression of diabetic gastric ulcers by enhancing antioxidant levels and maintaining physiological balance.Our findings open new possibilities for innovative treatment strategies in the realm of diabetes and related complications.
References
1. Tashima K, Korolkiewicz R, Kubomi M, Takeuchi K. Increased susceptibility of gastric mucosa to ulcerogenic stimulation in diabetic rats—role of capsaicin-sensitive sensory neurons. Br J Pharmacol. 1998 Aug;124(7):1395–1402. doi: 10.1038/sj.bjp.0701974, PMID 9723950, PMCID PMC1565532. Available from: https://pubmed.ncbi.nlm.nih.gov/9723950/. [Last accessed on 15 Aug 2025].
2. Vador N, Jagtap AG, Damle A. Vulnerability of Gastric Mucosa in Diabetic Rats, Its Pathogenesis and Amelioration by Cuminum cyminum. Indian J Pharm Sci. 2012;74(5):387–396. doi: 10.4103/0250-474X.108413, PMID 23716866. Available from: https://pubmed.ncbi.nlm.nih.gov/23716866/. [Last accessed on 15 Aug 2025].
3. Goldin E, Ardite E, Elizalde JI, Odriozola A. Gastric mucosal damage in experimental diabetes in rats: role of endogenous glutathione. Gastroenterology. 1997;112:855–863. doi: 10.1053/gast.1997.v112.pm9041247, PMID 9041247. Available from: https://pubmed.ncbi.nlm.nih.gov/9041247/. [Last accessed on 15 Aug 2025].
4. Brzozowska I, Targosz A, Sliwowski Z, Kwiecien S, Drozdowicz D. Healing of chronic gastric ulcers in diabetic rats treated with native aspirin, nitric oxide (NO)-derivative of aspirin and cyclooxygenase (COX)-2 inhibitor. J Physiol Pharmacol. 2004;55:773–790. PMID 15613743. Available from: https://pubmed.ncbi.nlm.nih.gov/15613743/. [Last accessed on 15 Aug 2025].
5. Ommurugan B, Rao V. Pharmacotherapy of Peptic Ulcer Disease and Latest Research. In: Gastritis – New Approaches and Treatments. Edited by Bruna Maria Roesler. IntechOpen; 2019. Published 19 August 2019. doi: 10.5772/intechopen.86386. Available from: https://www.intechopen.com/chapters/68625. [Last accessed on 15 Aug 2025].
6. Chandra P, Kaleem M, Sachan N, Pathak R, Alanazi AS, Alsaif NA, Alsanea S, Alsuwayt B, Alanazi MM, Kabra A. Gastroprotective evaluation of Medicago sativa L. (Fabaceae) on diabetic rats. Saudi Pharm J. 2023;31(11):101815. doi: 10.1016/j.jsps.2023.101815, PMID 37860685. Available from: https://pubmed.ncbi.nlm.nih.gov/37860685/. [Last accessed on 15 Aug 2025].
7. Perdichizzi G, Bottari M, Pallio S, Fera MT, Carbone M, Barresi G. Gastric infection by Helicobacter pylori and antral gastritis in hyperglycemic obese and in diabetic subjects. New Microbiol. 1996;19:149–154. Available from: https://pubmed.ncbi.nlm.nih.gov/
8. Takehara K, Tashima K, Takeuchi K. Alterations in duodenal bicarbonate secretion and mucosal susceptibility to acid in diabetic rats. Gastroenterology. 1997 Feb;112(2):418–428. doi: 10.1053/gast.1997.v112.pm9024295, PMID 9024295. Available from: https://pubmed.ncbi.nlm.nih.gov/9024295/. [Last accessed on 15 Aug 2025].
9. Begum AN, Terao J. Protective effect of quercetin against cigarette tar extract-induced impairment of erythrocyte deformability. J NutrBiochem. 2002;13(5):265–272. doi: 10.1016/S0955-2863(01)00219-4, PMID 12015156. Available from: https://pubmed.ncbi.nlm.nih.gov/12015156/. [Last accessed on 15 Aug 2025].
10. Janisch KM, Williamson G, Needs P, Plumb GW. Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res. 2004;38(8):877–884. doi: 10.1080/10715760410001728415, PMID 15493462. Available from: https://pubmed.ncbi.nlm.nih.gov/15493462/. [Last accessed on 15 Aug 2025].
11. Benherlal PS, Arumughan C. Chemical composition and in vitro antioxidant studies on Syzygiumcumini fruit. J Sci Food Agric. 2007 Nov;87(14):2560–2569. doi: 10.1002/jsfa.2957, PMID 20836162. Available from: https://pubmed.ncbi.nlm.nih.gov/20836162/. [Last accessed on 15 Aug 2025].
12. Segovia GR, Quintanar JL, Salinas E. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol. 2008;43(Suppl):S441–S447. doi: 10.1007/s00535-008-2184-7. Available from: https://doi.org/10.1007/s00535-008-2184-7. [Last accessed on 15 Aug 2025].
13. Brzozowski T, Konturek PC, Pajdo R, Kwiecien S, Konturek S, Targosz A, Hahn EG. Agonist of peroxisome proliferator-activated receptor γ (PPAR-γ): a new compound with potent gastroprotective and ulcer healing properties. Inflammopharmacology. 2005;13(1-3):317–330. doi: 10.1163/156856005774423908, PMID 16259750. Available from: https://pubmed.ncbi.nlm.nih.gov/16259750/. [Last accessed on 15 Aug 2025].
14. Sivri B. Trends in peptic ulcer pharmacotherapy. Fundam Clin Pharmacol. 2004 Feb;18(1):23–31. doi: 10.1111/j.1472-8206.2004.00203.x, PMID 14748750. Available from: https://pubmed.ncbi.nlm.nih.gov/14748750/. [Last accessed on 15 Aug 2025].
15. Boj-Carceller D. Proton pump inhibitors: impact on glucose metabolism. Endocrine. 2013;43(1):22–32. doi: 10.1007/s12020-012-9755-3. Available from: https://www.ncbi.nlm.nih.gov/pubmed/?term=10.1007/s12020-012-9755-3. [Last accessed on 15 Aug 2025].
16. Rooman I, Lardon J, Bouwens L. Gastrin stimulates beta-cell neogenesis and increases islet mass from transdifferentiated but not from normal exocrine pancreas tissue. Diabetes. 2002 Mar;51(3):686–690. doi: 10.2337/diabetes.51.3.686, PMID 11872667. Available from: https://pubmed.ncbi.nlm.nih.gov/11872667/. [Last accessed on 15 Aug 2025].
17. Bodvarsdottir TB, Hove KD, Gotfredsen CF, Pridal L, Vaag A, Karlsen AE, Petersen JS. Treatment with a proton pump inhibitor improves glycaemic control in Psammomys obesus, a model of type 2 diabetes. Diabetologia. 2010 Oct;53(10):2220–2223. doi: 10.1007/s00125-010-1825-6, PMID 20585936. Available from: https://pubmed.ncbi.nlm.nih.gov/20585936/. [Last accessed on 15 Aug 2025].
18. Prem Kumar N, Annamalai AR, Thakur RS. Antinociceptive property of Emblica officinalisGaertn(Amla) in high fat diet-fed/low-dose streptozotocin-induced diabetic neuropathy in rats. Indian J Exp Biol. 2009 Sep;47(9):737–742. PMID 19957886. Available from: https://pubmed.ncbi.nlm.nih.gov/19957886/. [Last accessed on 15 Aug 2025].
19. Basavarajappa GM, Prem Kumar N, Abdulrahim Alabdulsalam A, Afzal Haq Asif A, Shekharappa HT, Md Khalid Anwer M, Nagaraja S. Improved renoprotection in diabetes with combination therapy of Coccinia indica leaf extract and low-dose pioglitazone. Separations. 2020;7(4):58. doi: 10.3390/separations7040058. Available from: https://doi.org/10.3390/separations7040058. [Last accessed on 15 Aug 2025].
20. Jonnalagadda A, Karthik KM, Prem Kumar N. Combined effect of Syzygiumcumini seed kernel extract with oral hypoglycemics in diabetes-induced increase in susceptibility to ulcerogenic stimuli. J Diabetes Metab. 2012;4(1):236. Available from: https://www.iomcworld.com/open-access/combined-effect-of-syzygium-cumini-seed-kernel-extract-with-oral-hypoglycemics-2155-6156.1000236.pdf. [Last accessed on 15 Aug 2025].
21. Sahoo PK, Padhy KM, Pradhan D, Tripathy G, Bhoi R, Pattanayak S, Sahoo SK. Antidiabetic and antioxidant activity of ethanolic extract of Sapindustrifoliatus Linn. Int J Pharma Bio Sci. 2010;1(2):1–8. Available from: https://www.cabidigitallibrary.org/doi/full/10.5555/20113372253. [Last accessed on
22. Kennard MR, Nandi M, Chapple S, King AJ. The glucose tolerance test in mice: Sex, drugs and protocol. Diabetes Obes Metab. 2022;24(11):2241–2252. doi: 10.1111/dom.14811, PMID 35815375. Available from: https://pubmed.ncbi.nlm.nih.gov/35815375/. [Last accessed on 15 Aug 2025]
23. Vogel HG, Vogel H. Drug discovery and evaluation: Pharmacological assays. Springer-Verlag: Berlin – New York; 1997. ix + 486 p. DOI: 10.1007/978-3-540-70995-4. Available from: https://link.springer.com/referencework/10.1007/978-3-540-70995-4. [Last accessed on 15 Aug 2025]
24. Majumdar B, Chaudhuri SGR, Ray A, Bandyopadhyay SK. Effect of ethanol extract of Piper betle Linn leaf on healing of NSAID-induced experimental ulcer – a novel role of free radical scavenging action. Indian J Exp Biol. 2003;41(4):311–315. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC4250642/. [Last accessed on 15 Aug 2025]
25. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with Folin phenol reagent. J Biol Chem. 1951;193(1):265–275. PMID 14907713. Available from: https://pubmed.ncbi.nlm.nih.gov/14907713/. [Last accessed on 15 Aug 2025]
26. Elstner EF, Heupel A. Inhibition of nitrite formation from hydroxylammonium chloride: a simple assay for superoxide dismutase. Anal Biochem. 1976 Feb;70(2):616–620. doi: 10.1016/0003-2697(76)90488-7, PMID 817618. Available from: https://pubmed.ncbi.nlm.nih.gov/817618/. [Last accessed on 15 Aug 2025]
27. Eva ML. Mechanism of pH-dependent hydrogen peroxide cytotoxicity in vitro. Arch Biochem Biophys.1988;365:362–372. Available from: https://pubmed.ncbi.nlm.nih.gov/3421711/. [Last accessed on 15 Aug 2025]
28. Vogel WH, Schölkens BA, Sandow J. Drug Discovery and Evaluation: Pharmacological Assays. 2nd ed. Springer-Verlag: Berlin; 2002. Available from: https://link.springer.com/referencework/10.1007/3-540-29837-1. [Last accessed on 15 Aug 2025]
29. Brzozowski T, Konturek PC, Konturek SJ, Kwiecien S, Pajdo R, Brzozowska I, Hahn EG. Involvement of endogenous cholecystokinin and somatostatin in gastroprotection induced by intraduodenal fat. J Clin Gastroenterol. 1998;27 Suppl1:S125–S137. doi: 10.1097/00004836-199800001-00020, PMID 9872509. Available from: https://pubmed.ncbi.nlm.nih.gov/9872509/. [Last accessed on 15 Aug 2025]
30. Ajeigbe KO, Olaleye SB, Oladejo EO, Olayanju AO. Effect of folic acid supplementation on oxidative gastric mucosa damage and acid secretory response in the rat. Indian J Pharmacol. 2011 Sep;43(5):578–581. doi: 10.4103/0253-7613.84976, PMID 22022004, PMCID PMC3195131. Available from: https://pubmed.ncbi.nlm.nih.gov/22022004/. [Last accessed on 15 Aug 2025]
31. Yokotani K, Murakami Y, Okada S, Wang M, Nakamura K. Histamine H₃ receptor–mediated inhibition of endogenous acetylcholine release from the isolated, vascularly perfused rat stomach. Eur J Pharmacol. 2000 Mar 24;392(1–2):23–29. doi: 10.1016/S0014-2999(00)00085-6, PMID 10748268. Available from: https://pubmed.ncbi.nlm.nih.gov/10748268/. [Last accessed on 15 Aug 2025]
32. Sarosiek J, Rourk RM, Piascik R, Namiot Z, Hetzel DP, McCallum RW. The effect of esophageal mechanical and chemical stimuli on salivary mucin secretion in healthy individuals. Am J Med Sci. 1994 Jul;308(1):23–31. doi: 10.1097/00000441-199407000-00006, PMID 8010333. Available from: https://pubmed.ncbi.nlm.nih.gov/8010333/. [Last accessed on 15 Aug 2025]
33. Mæhre HK, Dalheim L, Edvinsen GK, Elvevoll EO, Jensen IJ. Protein Determination—Method Matters. Foods. 2018;7(1):5. doi: 10.3390/foods7010005. Available from: https://doi.org/10.3390/foods7010005. [Last accessed on 15 Aug 2025]
34. Engelbrecht I, Horn S, Giesy JP, Pieters R. Determining superoxide dismutase content and catalase activity in mammalian cell lines. MethodsX. 2023;11:102395. doi: 10.1016/j.mex.2023.102395. Available from: https://doi.org/10.1016/j.mex.2023.102395. [Last accessed on 15 Aug 2025]
35. Mishra P, Singh U, Pandey CM, Mishra P, Pandey G. Application of Student's t-test, analysis of variance, and covariance. Ann Card Anaesth. 2019 Oct–Dec;22(4):407–411. doi: 10.4103/aca.ACA_94_19, PMID 31621677, PMCID PMC6813708. Available from: https://pubmed.ncbi.nlm.nih.gov/31621677/. [Last accessed on 15 Aug 2025]
36. Sakai M, Oimomi M, Kasuga M. Experimental studies on the role of fructose in the development of diabetic complications. Kobe J Med Sci. 2002 Dec;48(5–6):125–136. PMID 12594356. Available from: https://pubmed.ncbi.nlm.nih.gov/12594356/, and PDF at: https://www.med.kobe-u.ac.jp/journal/contents/48/125.pdf. [Last accessed on 15 Aug 2025]
37. Reed MJ, Meszaros K, Entes LJ, Claypool MD, Pinkett JG, Gadbois TM, et al. A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat. Metabolism. 2000;49(11):1390–1394. doi: 10.1016/S0026-0495(00)51653-9. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0026049500516539. [Last accessed on 15 Aug 2025]
38. Ahmad M, Qureshi R, Arshad M. Traditional herbal remedies used for the treatment of diabetes from District Attock (Pakistan). Pak J Bot. 2009;41(6):2777–2782. Available from: https://www.pakbs.org/pjbot/abstracts/41(6)/13.html. [Last accessed on 15 Aug 2025]
39. Shinde J, Taldone T, Barletta M, Kunaparaju N, Hu B, Kumar S, Placido J, Zito SW. α-Glucosidase inhibitory activity of Syzygiumcumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats. Carbohydr Res. 2008;343(7):1278–1281. doi: 10.1016/j.carres.2008.03.003. Available from: https://www.scirp.org/reference/referencespapers?referenceid=1990601. [Last accessed on 15 Aug 2025]
40. Adewole SO, Caxton-Martins EA, Ojewole JAO. Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats. Afr J Tradit Complement Altern Med. 2006 Aug;4(1):64–74. doi: 10.4314/ajtcam.v4i1.31196, PMID 20162074, PMCID PMC2816429. Available from: https://pubmed.ncbi.nlm.nih.gov/20162074/, full text PDF at: https://pmc.ncbi.nlm.nih.gov/articles/PMC2816429/. [Last accessed on 15 Aug 2025]
41. Youl E, Bardy G, Magous R, Cros G, Sejalon F, Virsolvy A, Richard S, Quignard JF, Gross R, Petit P. Quercetin potentiates insulin secretion and protects INS-1 pancreatic β-cells against oxidative damage via the ERK1/2 pathway. Br J Pharmacol. 2010 Oct;161(4):799–814. doi: 10.1111/j.1476-5381.2010.00910.x, PMID 20860660, PMCID PMC2992896. Available from: https://pubmed.ncbi.nlm.nih.gov/20860660/. [Last accessed on 15 Aug 2025]
42. Choi HN, Jeong SM, Huh GH, Kim JI. Quercetin ameliorates insulin sensitivity and liver steatosis partly by increasing adiponectin expression in ob/ob mice. Food Sci Biotechnol. 2015;24(1):273–279. doi: 10.1007/s10068-015-0036-9. Available from: https://link.springer.com/article/10.1007/s10068-015-0036-9. [Last accessed on 15 Aug 2025]
43. Gohlke A, Ingelmann CJ, Nürnberg G, Weitzel JM, Hammon HM, Görs S, Starke A, Wolffram S, Metges CC. Influence of 4-week intraduodenal supplementation of quercetin on performance, glucose metabolism, and mRNA abundance of genes related to glucose metabolism and antioxidative status in dairy cows. J Dairy Sci. 2013;96(11):6986–7000. doi: 10.3168/jds.2013-6852. Available from: https://www.sciencedirect.com/science/article/pii/S0022030213006449. [Last accessed on 15 Aug 2025]
44. Khaleel EF, Mostafa DG, Abdel-Aleem GA. Gastroprotective effect of flavonoid quercetin and coenzyme Q10 in indomethacin-induced gastric ulcers in normal and diabetic rats. J Dent Med Sci. 2015 Dec;14(12):58–71. DOI: 10.9790/0853-141245871. Available from: https://www.iosrjournals.org/iosr-jdms/papers/Vol14-issue12/Version-4/K0141245871.pdf. [Last accessed on 15 Aug 2025]
45. Moreira L, Costa T, Correia-Branco A, Faria A, Martel F, Keating E. Quercetin and epigallocatechin gallate inhibit glucose uptake and metabolism by breast cancer cells by an estrogen receptor-independent mechanism. Exp Cell Res. 2013;319(13):1784–1795. doi: 10.1016/j.yexcr.2013.05.010. Available from: https://www.sciencedirect.com/science/article/pii/S001448271300195X. [Last accessed on 15 Aug 2025]
46. Danya R, Arya AD, Nisha P, Jayamurthy P. Quercetin, a lead compound against Type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front Pharmacol. 2017;8:336. doi: 10.3389/fphar.2017.00336. Available from: https://pubmed.ncbi.nlm.nih.gov/28642704/. [Last accessed on 15 Aug 2025]
47. Kim JH, Kang MJ, Choi HN, Jeong SM, Lee YM, Kim JI. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutr Res Pract. 2011 Apr;5(2):107–111. doi: 10.4162/nrp.2011.5.2.107, PMID 21556223, PMCID PMC3085798. Available from: https://pubmed.ncbi.nlm.nih.gov/21556223/. [Last accessed on 15 Aug 2025]
48. Joshi MC, Dorababu M, Prabha T. Effects of Pterocarpus marsupium on NIDDM-induced rat gastric ulceration and mucosal offensive and defensive factors. Indian J Pharmacol. 2004 Oct;36(5):296–302. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991700/. [Last accessed on 15 Aug 2025]
49. Mahmoud SA, Elkhoely A, El-Sayed EK, Ahmed AAE. Enhanced upregulation of SIRT1 via pioglitazone and ligustrazine confers protection against ethanol-induced gastric ulcer in rats. Naunyn-Schmiedeberg’s Arch Pharmacol. 2024;397:6177–6195. doi: 10.1007/s00210-024-03026-6. Available from: https://pubmed.ncbi.nlm.nih.gov/38441571/. [Last accessed on 15 Aug 2025]
50. Brzozowski T, Konturek PC, Pajdo R, Kwiecien S, Konturek S, Targosz A, Hahn EG. Agonist of peroxisome proliferator-activated receptor gamma (PPAR-γ): a new compound with potent gastroprotective and ulcer healing properties. Inflammopharmacology. 2005;13(1-3):317–330. doi: 10.1163/156856005774423908, PMID 16259750. Available from: https://pubmed.ncbi.nlm.nih.gov/16259750/. [Last accessed on 15 Aug 2025]
51. Konturek PC, Brzozowski T, Kania J, Konturek SJ, Kwiecien S, Pajdo R, Hahn EG. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, accelerates gastric ulcer healing in rat. Eur J Pharmacol. 2003;472(3):213–220. doi: 10.1016/S0014-2999(03)02280-2, PMID 12871756. Available from: https://pubmed.ncbi.nlm.nih.gov/12871756/. [Last accessed on 15 Aug 2025]
52. Dhanya R, Arya AD, Nisha P, Jayamurthy P. Quercetin, a lead compound against Type 2 diabetes ameliorates glucose uptake via AMPK pathway in skeletal muscle cell line. Front Pharmacol. 2017;8:336. doi: 10.3389/fphar.2017.00336. Available from: https://pubmed.ncbi.nlm.nih.gov/28642704/. [Last accessed on 15 Aug 2025]
53. Fryer LGD, Parbu-Patel A, Carling D. The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem. 2002;277(28):25226–25232. doi: 10.1074/jbc.M202489200, PMID 11994296. Available from: https://pubmed.ncbi.nlm.nih.gov/11994296/. [Last accessed on 15 Aug 2025]
54. Dorababu M, Joshi MC, Bhawani G, Mohan Kumar M, Chaturvedi A, Goel RK. Effect of aqueous extract of neem (Azadirachta indica) leaves on offensive and defensive gastric mucosal factors in rats. Indian J Physiol Pharmacol. 2006;50(2):241–249. Available from: https://pubmed.ncbi.nlm.nih.gov/17092040/. [Last accessed on 15 Aug 2025]
55. Yoshizumi M, Tsuchiya K, Suzaki Y, Kirima K, Kyaw M. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway. Biochem Biophys Res Commun. 2002;293(2):458–465. doi: 10.1016/S0006-291X(02)00225-X. PMID 12054670. Available from: https://pubmed.ncbi.nlm.nih.gov/12054670/. [Last accessed on 15 Aug 2025]
56. Begum AN, Terao J. Protective effect of quercetin against cigarette tar extract-induced impairment of erythrocyte deformability. J NutrBiochem. 2002;13(5):265–272. doi: 10.1016/S0955-2863(01)00219-4, PMID 12015156. Available from: https://pubmed.ncbi.nlm.nih.gov/12015156/. [Last accessed on 15 Aug 2025]
57. Janisch KM, Williamson G, Needs P, Plumb GW. Properties of quercetin conjugates: modulation of LDL oxidation and binding to human serum albumin. Free Radic Res. 2004;38(8):877–884. doi: 10.1080/10715760410001728415, PMID 15493462. Available from: https://pubmed.ncbi.nlm.nih.gov/15493462/. [Last accessed on 15 Aug 2025]
58. Benherlal PS, Arumughan C. Chemical composition and in vitro antioxidant studies on Syzygiumcumini fruit. J Sci Food Agric. 2007 Nov;87(14):2560–2569. doi: 10.1002/jsfa.2957, PMID 20836162. Available from: https://pubmed.ncbi.nlm.nih.gov/20836162/. [Last accessed on 15 Aug 2025]
59. González-Segovia R, Quintanar JL, Salinas E. Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol. 2008;43 Suppl6:S441–S447. doi: 10.1007/s00535-008-2184-7, PMID 18600388. Available from: https://pubmed.ncbi.nlm.nih.gov/18600388/. [Last accessed on 15 Aug 2025]
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