Effects of Pomegranate Peel and Atorvastatin on the Inflammatory Factors and the Glucose Transport 4 in 3T3-L1 Cell Line

Document Type : Original Article (s)


1 MSc Student, Department of Experimental Sciences, Dezful Branch, Islamic Azad University, Dezful, Iran

2 Assistant Professor, Department of Experimental Sciences, Dezful Branch, Islamic Azad University, Dezful, Iran



Background: Pomegranate peel extract (PPE) exhibits biological activities with potential therapeutic applications. In this research, the antioxidant properties of the combination of atorvastatin and PPE, and the effect of this combination on the regulation of inflammatory factors and the gene pathway of glucose transport regulation (GLUT4) in tissue fibroblast cells (3T3-L1).
Methods: This research was done in a descriptive-analytical way. The percentage of cell survival after treatment with suitable concentrations of aqueous extract of pomegranate peel (AEPP) and atorvastatin drug was obtained. The amount of inflammatory cytokines IL-1, IL-6, and TNF-α in the supernatant solution of treated cells was measured using the ELISA method. Then the antioxidant activity and GLUT4 expression were measured using real-time PCR.
Findings: The highest antioxidant capacity is related to the combination of AEPP with atorvastatin. Also, the level of IL-1, TGF-B, and IL-6 cytokines increased. Furthermore, atorvastatin significantly increased the level of GLUT4 in adipocytes compared to the combination of atorvastatin and AEPP concentration, as well as AEPP alone.
Conclusion: The results showed that the combined use of AEPP and Atorvastatin can improve the efficiency of antioxidant pathways in the cell and significantly reduce the level of reactive oxygen. In addition, atorvastatin has a greater effect on regulating the function of inflammatory factors and the adipose glucose transporter 4 (GLUT4) regulatory gene pathway than the combination of atorvastatin and AEPP concentrations. However, more studies are needed in this area.


Atousa Moradzadegan: PubMed, Google Scholar


Main Subjects

  1. Tang F. Metabolic profiling of complex mixtures using novel NMR-based approaches and chemometrics: Pomegranate juice as a case study [Thesis]. Columbus, OH: Graduate Program in Food Science and Technology: The Ohio State University; 2020.
  2. Noormohammadi Z, Fasihee A, Homaee-Rashidpoor S, Sheidai M, Baraki SG, Mazooji A, rt al. Genetic variation among Iranian pomegranates ('Punica granatum'L.) using RAPD, ISSR and SSR markers. Australian Journal of Crop Science 2012; 6(2): 268-75.
  3. Bassiri-Jahromi S. Punica granatum (Pomegranate) activity in health promotion and cancer prevention. Oncol Rev 2018; 12(1).
  4. Khan MS, Ahmad I. Herbal medicine: current trends and future prospects. New Look to Phytomedicine 2019; 3-13.
  5. Vučić V, Grabež M, Trchounian A, Arsić A. Composition and potential health benefits of pomegranate: a review. Curr Pharm Des 2019; 25(16): 1817-27.
  6. Wong TL, Strandberg KR, Croley CR, Fraser SE, Venkata KC, Fimognari C, et al. Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention. Semin Cancer Biol 2021; 73: 265-93.
  7. . Kalaycıoğlu Z, Erim FB. Total phenolic contents, antioxidant activities, and bioactive ingredients of juices from pomegranate cultivars worldwide. Food chemistry. 2017;221:496-507.
  8. Kojadinovic MI, Arsic AC, Debeljak‐Martacic JD, Konic‐Ristic AI, Kardum ND, Popovic TB, et al. Consumption of pomegranate juice decreases blood lipid peroxidation and levels of arachidonic acid 22in women with metabolic syndrome. J Sci Food Agric 2017; 97(6): 1798-804.
  9. Razani Z, Dastani M, Kazerani HR. Cardioprotective effects of pomegranate (Punica granatum) juice in patients with ischemic heart disease. Phytother Res 2017; 31(11): 1731-8.
  10. Kim JM, Jo YJ, Hahn D. Physicochemical properties, bioactive composition and antioxidant activities of noni fruit juices from different regions of cultivation. Korean J Food Preserv 2017; 24(7): 1000-6.
  11. Turgut SS, Soyer A, Işıkçı F. Effect of pomegranate peel extract on lipid and protein oxidation in beef meatballs during refrigerated storage. Meat Sci 2016; 116: 126-32.
  12. Sadeghi-Kiakhani M, Tehrani-Bagha AR, Gharanjig K, Hashemi E. Use of pomegranate peels and walnut green husks as the green antimicrobial agents to reduce the consumption of inorganic nanoparticles on wool yarns. J Clean Prod 2019; 231: 1463-73.
  13. Gullón P, Astray G, Gullón B, Tomasevic I, Lorenzo JM. Pomegranate peel as suitable source of high-added value bioactives: Tailored functionalized meat products. Molecules 2020; 25(12): 2859.
  14. Paul A, Radhakrishnan M. Pomegranate seed oil in food industry: Extraction, characterization, and applications. Trends in Food Science & Technology 2020; 105: 273-83.
  15. Kahramanoglu I, Usanmaz S. Pomegranate production and marketing. Boca Raton, FL: C RC Press; 2016.
  16. Vincent L, Anushma PL, Vasugi C, Rekha A, Shiva B. Genetic Resources of tropical fruits. In: Rajasekharan P, Rao V. Editors. Conservation and Utilization of Horticultural Genetic Resources. Berlin, Germany: Springer; 2019. p. 79-116.
  17. Hussain SZ, Naseer B, Qadri T, Fatima T, Bhat TA. Pomegranate (Punica granatum)—Morphology, Taxonomy, Composition and Health Benefits. In: Hussain SZ, Naseer B, Qadri T, Fatima T, Ahmad Bhat T. Editors. Fruits Grown in Highland Regions of the Himalayas: Nutritional and Health Benefits. Cham: Springer International Publishing; 2021. p. 131-44.
  18. Stohs SJ, Badmaev V. A review of natural stimulant and non‐stimulant thermogenic agents. Phytother Res 2016; 30(5): 732-40.
  19. Okumuş E, Bakkalbaşı E, Javidipour I, Meral R, Ceylan Z. A novel coating material: Ellagitannins-loaded maltodextrin and lecithin-based nanomaterials. Food Bioscience 2021; 42: 101158.
  20. Saltiel AR. New perspectives into the molecular pathogenesis and treatment of type 2 diabetes. Cell 2001; 104(4): 517-29.
  21. Abo-Saif MA, Ragab AE, Ibrahim AO, Abdelzaher OF, Mehanyd AB, Saber-Ayad M, El-Feky OA. Pomegranate peel extract protects against the development of diabetic cardiomyopathy in rats by inhibiting pyroptosis and downregulating LncRNA-MALAT1. Front Pharmacol 2023; 14: 1166653.
  22. Özcan ÖU, Güleç S. Heterozygous familial hypercholesterolemia. Turk Kardiyol Dern Ars 2014; 42(2): 10-18.
  23. Mphahlele RR, Fawole OA, Makunga NP, Opara UL. Effect of drying on the bioactive compounds, antioxidant, antibacterial and antityrosinase activities of pomegranate peel. BMC Complement Altern Med 2016; 16: 143.
  24. Kumar N. Study on physico-chemical and antioxidant properties of pomegranate peel. J Pharmacogn Phytochem 2018; 7(3): 2141-7.
  25. Baradaran Rahimi V, Ghadiri M, Ramezani M, Askari VR. Antiinflammatory and anti‐cancer activities of pomegranate and its constituent, ellagic acid: Evidence from cellular, animal, and clinical studies. Phytotherapy research 2020; 34(4): 685-720.
  26. Colombo E, Sangiovanni E, Dell'Agli M. A review on the anti-inflammatory activity of pomegranate in the gastrointestinal tract. Evid Based Complement Alternat Med 2013; 2013: 247145.
  27. Ahmed D, Sharma M, Mukerjee A, Ramteke PW, Kumar V. Improved glycemic control, pancreas protective and hepatoprotective effect by traditional poly-herbal formulation “Qurs Tabasheer” in streptozotocin induced diabetic rats. BMC Complement Altern Med 2013; 13: 10.
  28. van Gerwen J, Shun-Shion AS, Fazakerley DJ. Insulin signalling and GLUT4 trafficking in insulin resistance. Biochem Soc Trans 2023; 51(3): 1057-69.
  29. Zhang X, Du L, Zhang W, Yang M, Chen L, Hou C, Li J. Pomegranate peel polyphenols alleviate insulin resistance through the promotion of insulin signaling pathway in skeletal muscle of metabolic syndrome rats. Food Sci Hum Wellness 2022; 11(4): 1076-85.
Volume 42, Issue 758
2nd Week, May
May and June 2024
Pages 132-139
  • Receive Date: 04 September 2023
  • Revise Date: 10 June 2024
  • Accept Date: 12 June 2024