Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats

sundaram, ramalingam; Ayyakkannu, Purushothaman; Ranganathan, Sundhararajan; Packirisamy, Meenatchi

doi:10.14744/ijmb.2020.60352

Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats

Purushothaman AYYAKKANNU, (Affiliated to the University of Madras, Department of Biochemistry, Mohamed Sathak College of Arts and Science, Chennai, India)

Ramalingam SUNDARAM, (Affiliated to the University of Madras, Department of Biochemistry, Mohamed Sathak College of Arts and Science, Chennai, India)

Meenatchi PACKİRİSAMY, (Affiliated to the University of Madras, Department of Biochemistry, Mohamed Sathak College of Arts and Science, Chennai, India)

Sundhararajan RANGANATHAN (Affiliated to the Tamilnadu Dr. MGR Medical University, Department of Pharmacy, Mohamed Sathak A. J. College of Pharmacy, Sholinganallur, Chennai, India)

International Journal of Medical Biochemistry

0 0

Yıl: 2021 Cilt: 4 Sayı: 1 Sayfa Aralığı: 1 - 7 Metin Dili: İngilizce DOI: 10.14744/ijmb.2020.60352 İndeks Tarihi: 05-06-2021

Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats

Öz:

Objectives: Hypercholesterolemia is a serious health concern throughout the world. It is the key risk factor for cardiovascular disease (CVD). The aim of this study was to investigate the antihypercholesterolemic potential of fraxetin onhypercholesterolemic rats given a high-fat diet (HFD).Methods: A total of 24 male albino Wistar rats weighing 180-200 g were used in this study and were divided into 4groups: Control (Group 1), hypercholesterolemia-induced (Group 2), hypercholesterolemia-induced and treated withfraxetin (75 mg/kg) (Group 3), and hypercholesterolemia-induced and treated with simvastatin (10 mg/kg) (Group 4).The plasma lipid profile, status of enzymatic and non-enzymatic antioxidants, and the levels of oxidative stress markersof all groups were analyzed.Results: The plasma level of total cholesterol, triglycerides, very low-density lipoprotein, and low-density lipoproteincholesterol were significantly increased, and the level of high-density lipoprotein cholesterol was significantly decreased in the hypercholesterolemic rats in comparison with the normal, control rats. Oral administration of fraxetinsignificantly (p<0.05) reversed these altered parameters to near-normal levels. In addition, fraxetin treatment significantly (p<0.05) increased the status of antioxidants with a concomitant reduction in oxidative stress markers. Oil red Ostaining of the thoracic aorta revealed widespread deposition of lipid droplets in the hypercholesterolemic rats (Group2), whereas the hypercholesterolemic rats treated with fraxetin or simvastatin showed only scattered droplets of fat.The effect of fraxetin on various biochemical parameters was comparable to that of simvastatin.Conclusion: The results of this study indicated that the lipid-lowering potential of fraxetin at the dosage of 75 mg/kg was comparable to that of the antihypercholesterolemic drug simvastatin. Further studies on the molecularmechanism of action of fraxetin are warranted and in progress in our laboratory at the time of writing.

Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık

1. WHO report 2019. Available at: https://www.who.int/en/ news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) Accessed Nov 20, 2020.
2. World Heart Day. Scale up prevention of heart attack and stroke. WHO, 2017. Avalable at: https://www.who.int/cardiovascular_diseases/world-heart-day/en/. Accessed Dec 17, 2019.
3. Ibrahim MA, Asuka E, Jialal I. Hypercholesterolemia. Florida: StatPearls Publishing LLC; 2020.
4. Phan BA, Toth PP. Dyslipidemia in women: etiology and management. Int J Womens Health 2014;6:185−94. [CrossRef]
5. Sizar O, Khare S, Jamil RT, Talati R. Statin Medications. Florida: StatPearls Publishing LLC. Available at: https://www.ncbi.nlm. nih.gov/books/NBK430940/. Accessed Feb 4, 2020.
6. Jukema JW, Cannon CP, de Craen AJ, Westendorp RG, Trompet S. The controversies of statin therapy: weighing the evidence. J Am Coll Cardiol 2012;60(10):875−81. [CrossRef]
7. Durrington P. Dyslipidaemia. Lancet 2003;362(9385):717−31.
8. Liu ZL, Liu JP, Zhang AL, Wu Q, Ruan Y, Lewith G, et al. Chinese herbal medicines for hypercholesterolemia. Cochrane Database Syst Rev 2011;(7):CD008305. [CrossRef]
9. Tejada S, Martorell M, Capo X, Tur JA, Pons A, Sureda A. Coumarin and Derivates as Lipid Lowering Agents. Curr Top Med Chem 2017;17(4):391−8. [CrossRef]
10. Taşdemir E, Atmaca M, Yıldırım Y, Bilgin HM, Demirtaş B, Obay BD, et al. Influence of coumarin and some coumarin derivatives on serum lipid profiles in carbontetrachloride-exposed rats. Hum Exp Toxicol 2017;36(3):295−301. [CrossRef]
11. Thuong PT, Pokharel YR, Lee MY, Kim SK, Bae K, Su ND, Oh WK, Kang KW. Dual anti-oxidative effects of fraxetin isolated from Fraxinus rhinchophylla. Biol Pharm Bull 2009;32(9):1527−32.
12. Mo Z, Li L, Yu H, Wu Y, Li H. Coumarins ameliorate diabetogenic action of dexamethasone via Akt activation and AMPK signaling in skeletal muscle. J Pharmacol Sci 2019;139(3):151−7.
13. Suresh C, Dixit Pk. Antioxidant and antiapoptotic effects of fraxetin against lead induced toxicity in human neuroblastoma cells. Org Med Chem Int J 2018;5(1):1−6. [CrossRef]
14. Purushothaman A, Sundaram R. Lipid lowering efficacy of fraxetin, a coumarin derivative on high fat diet-induced hypercholesterolemic rats. Bangladesh J Pharmacol 2020;15:96−8.
15. Xie W, Xing D, Sun H, Wang W, Ding Y, Du L. The effects of Ananas comosus L. leaves on diabetic-dyslipidemic rats induced by alloxan and a high-fat/high-cholesterol diet. Am J Chin Med 2005;33(1):95−105. [CrossRef]
16. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18(6):499−502. [CrossRef]
17. Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 1974;47(3):469−74. [CrossRef]
18. Sinha AK. Colorimetric assay of catalase. Anal Biochem 1972;47(2):389−94. [CrossRef]
19. 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.
20. 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. [CrossRef]
21. Desai ID. Vitamin E analysis methods for animal tissues. Methods Enzymol 1984;105:138-47. [CrossRef] 22. Moron MS, Depierre JW, Mannervik B. Levels of glutathione, glutathione reductase and glutathione S-transferase activities in rat lung and liver. Biochim Biophys Acta 1979 4;582(1):67−78. [CrossRef]
23. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979;95(2):351−8. [CrossRef]
24. Jiang ZY, Hunt JV, Wolff SP. Ferrous ion oxidation in the presence of xylenol orange for detection of lipid hydroperoxide in low density lipoprotein. Anal Biochem 1992;202(2):384−9.
25. Wolff SP. Ferrous oxidation in presence of ferric ion indicator xylenol orange for measurement of hydroperoxides. Methods Enzymol 1994;233:182−9. [CrossRef]
26. Tziomalos K, Athyros VG, Karagiannis A, Kolovou GD, Mikhailidis DP. Triglycerides and vascular risk: insights from epidemiological data and interventional studies. Curr Drug Targets 2009;10(4):320−7. [CrossRef]
27. Chien KL, Hsu HC, Su TC, Chen MF, Lee YT, Hu FB. Apolipoprotein B and non-high density lipoprotein cholesterol and the risk of coronary heart disease in Chinese. J Lipid Res 2007;48(11):2499−505. [CrossRef]
28. Berliner JA, Heinecke JW. The role of oxidized lipoproteins in atherogenesis. Free Radic Biol Med 1996;20(5):707−27. [CrossRef]
29. Shi H, Liu KJ. Cerebral tissue oxygenation and oxidative brain injury during ischemia and reperfusion. Front Biosci 2007;12:1318−28. [CrossRef]
30. Kaur J, Sarika A, Bhawna S, Thakur LC, Gambhir J, Prabhu KM. Role of Oxidative Stress in Pathophysiology of Transient Ischemic Attack and Stroke. Int J Biol Med Res 2011;2(3):611−5.
31. Kelly PJ, Morrow JD, Ning M, Koroshetz W, Lo EH, Terry E, et al. Oxidative stress and matrix metalloproteinase-9 in acute ischemic stroke: the Biomarker Evaluation for Antioxidant Therapies in Stroke (BEAT-Stroke) study. Stroke 2008;39(1):100−4.
32. Domínguez C, Delgado P, Vilches A, Martín-Gallán P, Ribó M, Santamarina E, et al. Oxidative stress after thrombolysis-induced reperfusion in human stroke. Stroke 2010;41(4):653−60.
33. Seet RC, Lee CY, Chan BP, Sharma VK, Teoh HL, Venketasubramanian N, et al. Oxidative damage in ischemic stroke revealed using multiple biomarkers. Stroke 2011;42(8):2326−9. [CrossRef]
34. Janssen AM, Bosman CB, van Duijn W, Oostendorp-van de Ruit MM, Kubben FJ, Griffioen G, et al. Superoxide dismutases in gastric and esophageal cancer and the prognostic impact in gastric cancer. Clin Cancer Res 2000;6(8):3183−92.
35. Talas ZS, Ozdemir I, Yilmaz I, Gok Y. Antioxidative effects of novel synthetic organoselenium compound in rat lung and kidney. Ecotoxicol Environ Saf 2009;72(3):916−21. [CrossRef]
36. Weydert CJ, Waugh TA, Ritchie JM, Iyer KS, Smith JL, Li L, et al. Overexpression of manganese or copper-zinc superoxide dismutase inhibits breast cancer growth. Free Radic Biol Med 2006;41(2):226−37. [CrossRef]
37. Valenzuela A. The biological significance of malondialdehyde determination in the assessment of tissue oxidative stress. Life Sci 1991;48(4):301−9. [CrossRef]
38. Appelros P, Terént A. Characteristics of the National Institute of Health Stroke Scale: results from a population-based stroke cohort at baseline and after one year. Cerebrovasc Dis 2004;17(1):21−7. [CrossRef]
39. Du J, Martin SM, Levine M, Wagner BA, Buettner GR, Wang SH, et al . Mechanisms of ascorbate-induced cytotoxicity in pancreatic cancer. Clin Cancer Res 2010;16(2):509−20. [CrossRef]
40. Anoopkumar-Dukie S, Walker RB, Daya S. A sensitive and reliable method for the detection of lipid peroxidation in biological tissues. J Pharm Pharmacol 2001;53(2):263−6. [CrossRef]
41. Rao AV, Shaha C. Role of glutathione S-transferases in oxidative stress-induced male germ cell apoptosis. Free Radic Biol Med 2000;29(10):1015−27. [CrossRef]
42. Esterbauer H, Zollner H, Schaua RJ. Aldehydes formed by lipid peroxidation: mechanisms of formation, occurrences and determination. In: Vigo-Pelfrey C, editor. Membrance lipid peroxidation. Florida: CRC Press; 1990. p. 239−83.

APA	Ayyakkannu P, sundaram r, Packirisamy M, Ranganathan S (2021). Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. , 1 - 7. 10.14744/ijmb.2020.60352
Chicago	Ayyakkannu Purushothaman,sundaram ramalingam,Packirisamy Meenatchi,Ranganathan Sundhararajan Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. (2021): 1 - 7. 10.14744/ijmb.2020.60352
MLA	Ayyakkannu Purushothaman,sundaram ramalingam,Packirisamy Meenatchi,Ranganathan Sundhararajan Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. , 2021, ss.1 - 7. 10.14744/ijmb.2020.60352
AMA	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. . 2021; 1 - 7. 10.14744/ijmb.2020.60352
Vancouver	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. . 2021; 1 - 7. 10.14744/ijmb.2020.60352
IEEE	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S "Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats." , ss.1 - 7, 2021. 10.14744/ijmb.2020.60352
ISNAD	Ayyakkannu, Purushothaman vd. "Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats". (2021), 1-7. https://doi.org/10.14744/ijmb.2020.60352

APA	Ayyakkannu P, sundaram r, Packirisamy M, Ranganathan S (2021). Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. International Journal of Medical Biochemistry, 4(1), 1 - 7. 10.14744/ijmb.2020.60352
Chicago	Ayyakkannu Purushothaman,sundaram ramalingam,Packirisamy Meenatchi,Ranganathan Sundhararajan Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. International Journal of Medical Biochemistry 4, no.1 (2021): 1 - 7. 10.14744/ijmb.2020.60352
MLA	Ayyakkannu Purushothaman,sundaram ramalingam,Packirisamy Meenatchi,Ranganathan Sundhararajan Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. International Journal of Medical Biochemistry, vol.4, no.1, 2021, ss.1 - 7. 10.14744/ijmb.2020.60352
AMA	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. International Journal of Medical Biochemistry. 2021; 4(1): 1 - 7. 10.14744/ijmb.2020.60352
Vancouver	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats. International Journal of Medical Biochemistry. 2021; 4(1): 1 - 7. 10.14744/ijmb.2020.60352
IEEE	Ayyakkannu P,sundaram r,Packirisamy M,Ranganathan S "Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats." International Journal of Medical Biochemistry, 4, ss.1 - 7, 2021. 10.14744/ijmb.2020.60352
ISNAD	Ayyakkannu, Purushothaman vd. "Fraxetin supplementation lowers plasma lipids and enhances antioxidant status in high-fat diet-induced hypercholesterolemic rats". International Journal of Medical Biochemistry 4/1 (2021), 1-7. https://doi.org/10.14744/ijmb.2020.60352