Comparison of Saffron (crocus sativus l.) and Atorvastatin for Anti-dyslipidaemic and Anti-Oxidant Effects in Dyslipidaemia Male Rat Models
Article Sidebar
Views | PDF/EPUB Downloads:
235
/ 98
/ 40
Main Article Content
Abstract
Dyslipidaemia is characterized by abnormal blood lipid profiles and is commonly treated with atorvastatin. However, its effectiveness may be reduced due to statin intolerance (SI). Saffron has gained interest as an alternative due to its potential lipid-modulating and antioxidant properties. This study aimed to compare the anti-dyslipidaemic and antioxidant effects of saffron extract and atorvastatin in male Wistar rats with dyslipidaemia. Thirty male Wistar rats (90 days old, 150–200 g) were divided into five groups. Group P1 received a standard diet, while groups P2–P5 were fed a high-fat diet (HFD) for 15 days to induce dyslipidaemia. Groups P3 and P4 received saffron extract at doses of 16 mg/200 g BW and 32 mg/200 g BW, respectively, while group P5 received atorvastatin at 0.2 mg/200 g BW. Lipid profiles (total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG)) were assessed on days 16 and 37. Serum malondialdehyde (MDA), an oxidative stress marker, was measured on day 37. Results showed that saffron extract at 32 mg/200 g BW/day significantly reduced TC, LDL, and TG levels, and increased HDL compared to the 16 mg/200 g BW/day dose. However, atorvastatin showed greater improvements in the lipid profile. Saffron at 32 mg/200 g BW/day also led to a greater reduction in serum MDA levels than doses of 16 mg/200 g BW/day and atorvastatin. Saffron demonstrated superior antioxidant activity, while its lipid-lowering effect was inferior to atorvastatin. Further research involving inflammatory biomarkers is needed to better elucidate its therapeutic potential.
Downloads
Article Details
Section
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
How to Cite
References
1. Diagnosis and Treatment: Risk Stratification in Children and Adolescents. J. Nutr Metab. 2022; 2022: 1–10. DOI: https://doi.org/10.1155/2022/4782344
2. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Lynne T Feranti S, Forman DE, Goldeberg R. Yeboah J. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019; 139(25): 1-4. DOI: https://doi.org/10.1161/CIR.0000000000000624
3. Du Z, Qin Y. Dyslipidemia and Cardiovascular Disease: Current Knowledge, Existing Challenges, and New Opportunities for Management Strategies. J. Clin Med. 2023; 12(1): 363. DOI: https://doi.org/10.3390/jcm12010363
4. Addisu B, Bekele S, Wube TB, Hirigo AT, Cheneke W. Dyslipidemia and its associated factors among adult cardiac patients at Ambo university referral hospital, Oromia region, west Ethiopia. BMC Cardiovasc Disord. 2023; 23(1): 321. DOI: https://doi.org/10.1186/s12872-023-03348-y
5. World Health Organization. Raised cholesterol [Online]. Geneva; 2023. [cited 2025 Jan 8]. Available from: https://www.who.int/data/gho/indicator-metadata-registry/imr-details/3236
6. Lin CF, Chang YH, Chien SC, Lin YH, Yeh HY. Epidemiology of Dyslipidemia in the Asia Pacific Region. Vol. 12, International Journal of Gerontology. Elsevier (Singapore) Pte Ltd; 2018: 2–6. DOI: https://doi.org/10.1016/j.ijge.2018.02.010
7. Nikos Pappan, Ayoola O. Awosika, Anis Rehman. Dyslipidemia. In: StatPearls. StatPearls Publishing; 2025: 10-15.
8. Berberich AJ, Hegele RA. A Modern Approach to Dyslipidemia. Endocr Rev. 2022; 43(4): 611–53. DOI: https://doi.org/10.1210/endrev/bnab037
9. Wengrofsky P, Lee J, N. Makaryus A. Dyslipidemia and Its Role in the Pathogenesis of Atherosclerotic Cardiovascular Disease: Implications for Evaluation and Targets for Treatment of Dyslipidemia Based on Recent Guidelines. In: Dyslipidemia. IntechOpen; 2020: 22-29. DOI: https://doi.org/10.5772/intechopen.85772
10. Gudisa Bereda. Pathophysiology and Management of Dyslipidemia. Biomed J Sci & Tech Res. 2022; 43(2): 34369–34375.
11. Udomkasemsab A, Prangthip P. High fat diet for induced dyslipidemia and cardiac pathological alterations in Wistar rats compared to Sprague Dawley rats. Clinica e Inves en Arterios. 2019; 31(2): 56–62. DOI: https://doi.org/10.1016/j.arteri.2018.09.004
12. Huang JK, Lee HC. Emerging Evidence of Pathological Roles of Very-Low-Density Lipoprotein (VLDL). Int J Mol Sci. 2022; 23(8): 4300. DOI: https://doi.org/10.3390/ijms23084300
13. Clemente-Suárez VJ, Redondo-Flórez L, Beltrán-Velasco AI, Martín-Rodríguez A, Martínez-Guardado I, Navarro-Jiménez E, Carmen C, José A. The Role of Adipokines in Health and Disease. Biomedicines. 2023; 11(5): 1290. DOI: https://doi.org/10.3390/biomedicines11051290
14. Vekic J, Stromsnes K, Mazzalai S, Zeljkovic A, Rizzo M, Gambini J. Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk. Biomedicines. 2023; 11(11): 2897. DOI: https://doi.org/10.3390/biomedicines11112897
15. Song Y, Liu J, Zhao K, Gao L, Zhao J. Cholesterol-induced toxicity: An integrated view of the role of cholesterol in multiple diseases. Cell Metab. 2022; 33(10): 1911–1925. DOI: https://doi.org/10.1016/j.cmet.2021.09.001
16. Bonacina F, Pirillo A, Catapano AL, Norata GD. HDL in Immune-Inflammatory Responses: Implications beyond Cardiovascular Diseases. Cells. 2021; 10(5): 1061. DOI: https://doi.org/10.3390/cells10051061
17. Esteve E, Ricart W, Fernández-Real JM. Dyslipidemia and inflammation: an evolutionary conserved mechanism. Clin Nutri. 2015; 24(1):16–31. DOI: https://doi.org/10.1016/j.clnu.2004.08.004
18. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update. Molecules. 2023; 28(16): 59-79.
19. Lankin VZ, Tikhaze AK, Melkumyants AM. Malondialdehyde as an Important Key Factor of Molecular Mechanisms of Vascular Wall Damage under Heart Diseases Development. Int J. Mol Sci. 2022; 24(1): 128. DOI: https://doi.org/10.3390/ijms24010128
20. Clemente GS, Antunes IF, Sijbesma JWA, Van Waarde A, Lammertsma AA, Dömling A. Atorvastatin Pharmacokinetics and Biodistribution in Healthy Female and Male Rats. Mol Pharm. 2021; 18(9): 3378–3386. DOI: https://doi.org/10.1021/acs.molpharmaceut.1c00305
21. Stillemans G, Paquot A, Muccioli GG, Hoste E, Panin N, Åsberg A, Jean LB, Vincent H, Laure E. Atorvastatin population pharmacokinetics in a real‐life setting: Influence of genetic polymorphisms and association with clinical response. Clin Transl Sci. 2022; 15(3): 667–679. DOI: https://doi.org/10.1111/cts.13185
22. Mangione CM, Barry MJ, Nicholson WK, Cabana M, Chelmow D, Coker TR, Esa MD, Katrina ED, Carlos RJ, Li L, Gbenga O. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. JAMA. 2022; 328(8): 746. DOI: https://doi.org/10.1001/jama.2022.13044
23. Chou R, Cantor A, Dana T, Wagner J, Ahmed AY, Fu R, Maros F. Statin Use for the Primary Prevention of Cardiovascular Disease in Adults. JAMA. 2022; 328(8): 754. DOI: https://doi.org/10.1001/jama.2022.12138
24. Bytyçi I, Penson PE, Mikhailidis DP, Wong ND, Hernandez A V, Sahebkar A, Paul DT, Mohsen M, Jacek R, Daniel P, Željko R, Peter PT, Maciej B. Prevalence of statin intolerance: a meta-analysis. Eur Heart J. 2022; 43(34): 3213–3223. DOI: https://doi.org/10.1093/eurheartj/ehac015
25. Cheeley MK, Saseen JJ, Agarwala A, Ravilla S, Ciffone N, Jacobson TA. NLA scientific statement on statin intolerance: a new definition and key considerations for ASCVD risk reduction in the statin intolerant patient. J. Clin Lipidol. 2022; 16(4): 361–375. DOI: https://doi.org/10.1016/j.jacl.2022.05.068
26. Danilov A, Frishman WH, Aronow WS. Antihyperlipidemic Treatment Options in Statin Resistance and Intolerance. Cardiol Rev. 2024; 32(1): 51–56. DOI: https://doi.org/10.1097/CRD.0000000000000498
27. Mesi O, Lin C, Ahmed H, Cho LS. Statin intolerance and new lipid-lowering treatments. Cleve Clin J Med. 2021; 88(7): 381–387. DOI: https://doi.org/10.3949/ccjm.88a.20165
28. Ezati P, Khan A, Rhim JW, Roy S, Hassan ZU. Saffron: Perspectives and Sustainability for Active and Intelligent Food Packaging Applications. Food Bioproc Tech. 2023; 16(6): 1177–1196. DOI: https://doi.org/10.1007/s11947-022-02949-3
29. Abd Rahim IN, Mohd Kasim NA, Isa MR, Nawawi H. A Systematic Review on the Effect of Saffron Extract on Lipid Profile in Hyperlipidaemic Experimental Animal Models. Malay J. of Med Sci. 2022; 29(4): 14–27. DOI: https://doi.org/10.21315/mjms2022.29.4.3
30. Zhang A, Shen Y, Cen M, Hong X, Shao Q, Chen Y, Zheng B. Polysaccharide and crocin contents, and anti-oxidant activity of saffron from different origins. Ind Crops Prod. 2019; 133: 111–117.
31. Mansouri A, Reiner Ž, Ruscica M, Tedeschi-Reiner E, Radbakhsh S, Bagheri Ekta M, Amirhossein S. Anti-oxidant Effects of Statins by Modulating Nrf2 and Nrf2/HO-1 Signaling in Different Diseases. J Clin Med. 2022; 11(5): 1313. DOI: https://doi.org/10.3390/jcm11051313
32. World Health Organization. Standards and Operational Guidance for Ethics Review of Health-Related Research with Human Participants [Online]. Geneva; 2011 [cited 2025 Jan 8]. Available from: https://www.who.int/publications/i/item/9789241502948
33. Council for International Organizations of Medical Sciences. International Ethical Guidelines for Health-related Research involving Humans. Geneva: CIOMS; 2016: 125-128.
34. Gradel AKJ, Holm SK, Byberg S, Merkestein M, Hogendorf WFJ, Lund ML, Buijink JA, Damgaard J, Lykkesfeldt J,
Holst B. The dietary regulation of LEAP2 depends on meal composition in mice. FASEB Journal. 2023; 37(6): 29-33. DOI: https://doi.org/10.1096/fj.202201828R
35. Boudjeko T, Ngomoyogoli JEK, Woguia AL, Yanou NN. Partial characterization, antioxidative properties and hypolipidemic effects of oilseed cake of Allanblackia floribunda and Jatropha curcas. BMC Comp and Alter Med. 2013; 13(352): 2–9. DOI: https://doi.org/10.1186/1472-6882-13-352
36. Hoshyar R, Hosseinian M, Naghandar MR, Hemmati M, Zarban A, Amini Z, Valavi M, Beyki MZ, Mehrpour O. Anti-dyslipidemic properties of saffron: Reduction in the associated risks of atherosclerosis and insulin resistance. Iran Red Crescent Med J. 2016; 18(12). DOI: https://doi.org/10.5812/ircmj.36226
37. Nair A, Jacob S. A simple practice guide for dose conversion between animals and human. J Basic Clin Pharm. 2016; 7(2): 27-33. DOI: https://doi.org/10.4103/0976-0105.177703
38. Ahloy-Dallaire J, Klein JD, Davis JK, Garner JP. Automated monitoring of mouse feeding and body weight for continuous health assessment. Lab Anim. 2020; 53(4): 342–51. DOI: https://doi.org/10.1177/0023677218797974
39. Perwito Sari D, Susilo I, Khotib J. Mechanism of Alpha Lipoic Acid on Reducing MDA Level and MCP-1 Expression. Folia Med Indo. 2016; 254–9.
40. Romano E, Cataldo PG, Iramain MA, Castillo M V., Manzur ME, Antonia Brandán S. Identification of cholesterol in different media by using the FT-IR, FT-Raman and UV–visible spectra combined with DFT calculations. J. Mol Liq. 2024; 403: 124879. DOI: https://doi.org/10.1016/j.molliq.2024.124879
41. Patil V, Hardikar H, Joshi S, Tembe S. Optical detection of total cholesterol based on a dye-displacement method. Spectrochim Acta A Mol Biomol Spectrosc. 2023; 293: 1224-1225. DOI: https://doi.org/10.1016/j.saa.2023.122425
42. Ulilalbab A, Maskanah E. Red Rosella (Hibiscus sabdariffa Linn.) Petal Brew is Able to Reduce the Sprague Dawley MDA Rate in Rats Exposed to Waste Cooking Oil. Folia Medica Indonesiana. 2018; 54(3): 167. DOI: https://doi.org/10.20473/fmi.v54i3.10005
43. Merino de Paz N, Carrillo-Palau M, Hernández-Camba A, Abreu-González P, de Vera-González A, González-Delgado A, et al. Association of Serum Malondialdehyde Levels with Lipid Profile and Liver Function in Patients with Inflammatory Bowel Disease. Anti-oxidants. 2024; 13(10): 1171. DOI: https://doi.org/10.3390/antiox13101171
44. Mendonca D, Papini R. Negative-pressure wound therapy : a snapshot of the evidence The management of deep sternal wound infections using vacuum assisted closure TM ( V . A . C . Ò ) therapy Die Behandlung tief reichender sternaler Wundinfektionen und der Einsatz einer. Int Wound J. 2016; 3(4): 261–71. DOI: https://doi.org/10.1111/j.1742-481X.2006.00266.x
45. Mala FA. Basic Statistics and Epidemiology: A Practical Guide (5th ed). New York: Technometrics; 2022. 578–579 p. DOI: https://doi.org/10.1080/00401706.2022.2126657
46. Gouda MA. Common Pitfalls in Reporting the Use of SPSS Software. Medical Principles and Practice. 2015; 24(3): 300–300. DOI: https://doi.org/10.1159/000381953
47. IBM Corp. IBM SPSS Statistics for Macintosh. Version 24.0. [Online]. New York: IBM Corp; 2024 [cited 2025 Jan 10]. Available from: https://www.ibm.com/products/spss-statistics.
48. Mah MS, Cao E, Anderson D, Escott A, Tegegne S, Gracia G, et al. High-fat feeding drives the intestinal production and assembly of C 16:0 ceramides in chylomicrons. Sci Adv. 2024; 10(34): 55-59. DOI: https://doi.org/10.1126/sciadv.adp2254
49. Michalski MC, Le Barz M, Vors C. Metabolic impact of dietary lipids: towards a role of unabsorbed lipid residues? OCL. 2021; 28:9. DOI: https://doi.org/10.1051/ocl/2020058
50. Vergès B. Intestinal lipid absorption and transport in type 2 diabetes. Diabetologia. 2022; 65(10): 1587–1600. DOI: https://doi.org/10.1007/s00125-022-05765-8
51. Gugliucci A. Triglyceride-Rich Lipoprotein Metabolism: Key Regulators of Their Flux. J Clin Med. 2023; 12(13): 4399. DOI: https://doi.org/10.3390/jcm12134399
52. Feingold KR. Introduction to Lipids and Lipoproteins. Dartmouth S, editor. NCBI. 2024; 1–10.
53. Ullah R, Rauf N, Nabi G, Yi S, Yu-Dong Z, Fu J. Mechanistic insight into high-fat diet-induced metabolic inflammation in the arcuate nucleus of the hypothalamus. Vol. 142, Biomed and Phar. Elsevier Masson; 2021: 88-91 . DOI: https://doi.org/10.1016/j.biopha.2021.112012
54. Cunha LF, Ongaratto MA, Endres M, Barschak AG. Modelling hypercholesterolaemia in rats using high cholesterol diet. Vol. 102, International Journal of Experimental Pathology. Blackwell Publishing Ltd; 2021: 74–79. DOI: https://doi.org/10.1111/iep.12387
55. Okoro EU. Tnfɑ‐induced ldl cholesterol accumulation involve elevated ldlr cell surface levels and sr‐b1 downregulation in human arterial endothelial cells. Int J Mol Sci. 2021; 22(12). DOI: https://doi.org/10.3390/ijms22126236
56. Singh, Nain. A Mini-Review on Hyperlipidemia: Common Clinical Problem. Inter Cardio J. 2018; 04(03). DOI: https://doi.org/10.21767/2471-8157.100080
57. Duan Y, Gong K, Xu S, Zhang F, Meng X, Han J. Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics. Signal Transduct Target Ther. 2022; 7(1): 265. DOI: https://doi.org/10.1038/s41392-022-01125-5
58. Kianbakht S, Hashem Dabaghian F. Anti-obesity and anorectic effects of saffron and its constituent crocin in obese Wistar rat. Journal of Medicinal Plants. 2015; 14(53):25–33.
59. Zhang A, Shen Y, Cen M, Hong X, Shao Q, Chen Y, Zheng B. Polysaccharide and crocin contents, and anti-oxidant activity of saffron from different origins. Ind Crops Prod. 2019; 133:111–117. DOI: https://doi.org/10.1016/j.indcrop.2019.03.009
60. Zhang Y, Fei F, Zhen L, Zhu X, Wang J, Li S. Sensitive analysis and simultaneous assessment of pharmacokinetic properties of crocin and crocetin after oral administration in rats. Journal of Chromato B. 2017; 1044–1045:1–7. DOI: https://doi.org/10.1016/j.jchromb.2016.12.003
61. Xing B, Li S, Yang J, Lin D, Feng Y, Lu J, Li S, Zhu H. Phytochemistry, pharmacology, and potential clinical applications of saffron: A review. J. Ethno pharmacol. 2021; 281:114-125. DOI: https://doi.org/10.1016/j.jep.2021.114555
62. Hosseini A, Razavi BM, Hosseinzadeh H. Pharmacokinetic Properties of Saffron and its Active Components. Euro J Drug Met and Phar. Springer-Verlag France. 2018; 383–390. DOI: https://doi.org/10.1007/s13318-017-0449-3
63. Rahim INA, Kasim NAM, Isa MR, Nawawi H. A Systematic Review on the Effect of Saffron Extract on Lipid Profile in Hyperlipidaemic Experimental Animal Models. Malay J. of Med Sci. 2022; 29: 14–27.
64. Shafiee M, Aghili Moghaddam NS, Nosrati M, Tousi M, Avan A, Ryzhikov M. Saffron against Components of Metabolic Syndrome: Current Status and Prospective. J Agric Food Chem. 2017; 65(50): 10837–10843. DOI: https://doi.org/10.1021/acs.jafc.7b03762
65. Zamani M, Zarei M, Nikbaf-Shandiz M, Gholami F, Hosseini AM, Nadery M, Shiraseb F, Asbaghi O. The effects of saffron supplementation on cardiovascular risk factors in adults: A systematic review and dose-response meta-analysis. Front Nutr. 2022; 8: 9-16. DOI: https://doi.org/10.3389/fnut.2022.1055517
66. Aryaeian N, Alipour R, Jafari Karegar S, Soleimani M, Hosseini A, Hekmatdoost A. Saffron effects on liver enzymes, anti-oxidant capacity, insulin, inflammation and
genes expression of lipolysis and lipogenesis in a rat model of non-alcoholic fatty liver disease. Clin Nutri Open Sci. 2024; 53: 95–107. DOI: https://doi.org/10.1016/j.nutos.2023.12.004
67. Vakili S, Savardashtaki A, Amin M, Moghaddam M, Nowrouzi PS, Shirazi MK. The effects of saffron consumption on lipid profile, liver enzymes, and oxidative stress in male hamsters with high fat diet. Trends in Pharm Sci. 2017; 54-59.
68. Khan TJ, Ahmed YM, Zamzami MA, Mohamed SA, Khan I, Baothman OAS, Mehanna MG, Yasir M. Effect of atorvastatin on the gut microbiota of high fat diet-induced hypercholesterolemic rats. Sci Rep. 2018; 8(1): 662. DOI: https://doi.org/10.1038/s41598-017-19013-2
69. Ji G, Zhao X, Leng L, Liu P, Jiang Z. Comparison of Dietary Control and Atorvastatin on High Fat Diet Induced Hepatic Steatosis and Hyperlipidemia in Rats. Lipids Health Dis. 2019; 10(1): 23. DOI: https://doi.org/10.1186/1476-511X-10-23
70. Bedi O, Dhawan V, Sharma PL, Kumar P. Pleiotropic effects of statins: new therapeutic targets in drug design. Vol. 389, Naunyn-Schmiedeberg’s Archives of Pharmacology. Springer Verlag; 2016: 695–712. DOI: https://doi.org/10.1007/s00210-016-1252-4
71. Lennernäs H. Clinical Pharmacokinetics of Atorvastatin. Clin Pharmacokinet. 2018;42(13): 1141–1160. DOI: https://doi.org/10.2165/00003088-200342130-00005
72. Kiran S, Rakib A, Kodidela S, Kumar S, Singh UP. High-Fat Diet-Induced Dysregulation of Immune Cells Correlates with Macrophage Phenotypes and Chronic Inflammation in Adipose Tissue. Cells. 2022; 11(8): 1327. DOI: https://doi.org/10.3390/cells11081327
73. Salunke M. Estimation of Serum Malondialdehyde as a Marker of Lipid Peroxidation in Medical Students Undergoing Examination - induced Psychological Stress. J Sci Soc 2018; 137–139. DOI: https://doi.org/10.4103/jss.JSS_13_17
74. Yekti R, Bukhari A, Jafar N, Thaha AR. Measurement of Malondialdehyde (MDA) as a good Indicator of Lipid Peroxidation. Int J of Allied Med Sci and Clin. Research. 2018; 60-80.
75. Cordiano R, Di Gioacchino M, Mangifesta R, Panzera C, Gangemi S, Minciullo PL. Malondialdehyde as a Potential Oxidative Stress Marker for Allergy-Oriented Diseases: An Update. Molecules. 2023; 28(16): 59-79. DOI: https://doi.org/10.3390/molecules28165979
76. Huang J, Yancey PG, Tao H, Borja MS, Smith LE, Kon V, Davies SS, Linton MF. Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity. Nutrients. 2020;12(7): 1937. DOI: https://doi.org/10.3390/nu12071937
77. Hardiany NS, Sucitra S, Paramita R. Profile of malondialdehyde (MDA) and catalase specific activity in plasma of elderly woman. Health Sci J of Indo. 2020;10(2):132–136. DOI: https://doi.org/10.22435/hsji.v12i2.2239
78. Tajaddini A, Roshanravan N, Mobasseri M, Haleem Al‐qaim Z, Hadi A, Aeinehchi A, Azar PSM, Ostadrahimi A. The effect of saffron (Crocus sativus L.) on glycemia, lipid profile, and anti-oxidant status in patients with type‐2 diabetes mellitus: A randomized placebo‐controlled trial. Phyto Research. 2023; 37(2):388–398. DOI: https://doi.org/10.1002/ptr.7600
79. Su X, Li XY, Zhang YJ, Liu YS, Yuan C, Yang F, Liu C, Chen HW, Xiong XJ, Gao YH, Xing YW. Cardioprotective effect
of saffron total glycoside tablets in patients with breast cancer receiving anthracycline-based chemotherapy: Study protocol for a multicentre, randomised, parallel, double-blind, placebo-controlled clinical trial. Ann Palliat Med. 2021; 10(7):8283–8291. DOI: https://doi.org/10.21037/apm-21-444
80. Mashmoul M, Azlan A, Khaza’Ai H, Yusof BNM, Noor SM. Saffron: A natural potent anti-oxidant as a promising anti-obesity drug. Anti-oxidants. MDPI; 2013; 2: 293–308. DOI: https://doi.org/10.3390/antiox2040293
81. Kumar N, Neeraj. Polysaccharide-based component and their relevance in edible film/coating: a review. Nutr Food Sci. 2019; 49(5): 793–823. DOI: https://doi.org/10.1108/NFS-10-2018-0294
82. Zinellu A, Mangoni AA. A Systematic Review and Meta-Analysis of the Effect of Statins on Glutathione Peroxidase,
Superoxide Dismutase, and Catalase. Anti-oxidants. 2021; 10(11): 1841. DOI: https://doi.org/10.3390/antiox10111841
83. Altinoz E, Cetinavci D, Abdulkareem Aljumaily SA, Elbe H, Cengil O, Bicer Y. Crocin, the compound of the dried stigma of Crocus sativus L (saffron), restores doxorubicin-induced disturbances in kidney functioning, oxidative stress, inflammation, renal tissue morphology and TGF-β signalling pathways. Nat Prod Res. 2024; 1–14. DOI: https://doi.org/10.1080/14786419.2024.2344180
84. German CA, Liao JK. Understanding the molecular mechanisms of statin pleiotropic effects. Arch of Toxi. 2023; 97: 1529–1545. DOI: https://doi.org/10.1007/s00204-023-03492-6
85. Zhang Q, Dong J, Yu Z. Pleiotropic use of statins as non-lipid-lowering drugs. Inter J of Bio Scie. 2020; 16: 2704–11. DOI: https://doi.org/10.7150/ijbs.42965
86. Izzuddin A, Ridwan M, Iskandar CD, Purnawarman A, Husna F, Nurkhalis N, Yafi DA, Fajri F, Fitriani F. Anti-Atherosclerotic Effect of Nigella sativa L. in High-Fat diet Fed Wistar Rats. Trop J Nat Prod Res. 2024; 8(12): 9632 – 9636 DOI: https://doi.org/10.26538/tjnpr/v8i12.41
87. Melasari WP, Suharjono S, Samsulhadi W. Effect of Atorvastatin in Lipid Profile Changes and Inflammation Marker TNF-alpha on Diabetes Patient with Dyslipidemia. Folia Medi Indo. 2021; 57(1): 6-10. DOI: https://doi.org/10.20473/fmi.v57i1.26326