Modulatory Effects of Clitoria ternatea Extract on TNF-α Protein and Gys Gene Expression in Diabetic–Dyslipidemic Rats
DOI:
https://doi.org/10.15395/mkb.v58.4608Keywords:
diabetes mellitus, dyslipidemia, glycogen, plant extracts, tumor necrosis factorAbstract
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia resulting from impaired insulin secretion or insulin action. Dyslipidemia is a common complication of DM and is associated with an increased risk of cardiovascular disease. Although pharmacological therapies are widely used, their long-term use is often limited by adverse effects, highlighting the need for safer alternative therapeutic approaches. The butterfly pea (Clitoria ternatea L.) has been reported to possess antidiabetic and antioxidant properties; however, evidence regarding its effects on inflammatory mediators such as TNF-α and Gys gene expression in diabetic–dyslipidemic conditions remains limited. This study aimed to evaluate the modulatory effects of C. ternatea extract (CTE) on TNF-α expression and Gys gene expression in diabetic–dyslipidemic rats. This experimental study was conducted from July to September 2021 in Bogor and Bandung, Indonesia. Diabetic–dyslipidemic rats were attained by inducing streptozotocin (STZ) and a high fat diet (HFD). CTE was administered at doses of 200, 400, and 800 mg/kg body weight. Glibenclamide, simvastatin, and their combination were administered to diabetic rats as a comparison group. The immunohistochemistry assay was conducted to quantify liver TNF-α protein expression, and liver and muscle’s Gys genes were determined by quantitative qRT-PCR. Results showed 800 mg/kg BW CTE had a positive effect on decreasing TNF-α expression and elevating liver and femoral muscle Gys expression. Butterfly pea extract has the potential as an antidiabetic by regulating TNF-α and Gys gene.
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1. Sapra A, Bhandari P. Diabetes mellitus. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551501 Accessed January 10, 2022.
2. Swargiary A, Swargiary A, Narzary B, Dey K, Brahma D. Computational screening of phytochemicals as DPP-4 inhibitors for treating type 2 diabetes. J Ethnopharmacol Toxicol. 2024;2(2):44–55. doi:10.37446/jet/rsa/2.2.2024.44-55
3. Schofield JD, Liu Y, Rao-Balakrishna P, Malik RA, Soran H. Diabetes dyslipidemia. Diabetes Ther. 2016;7(2):203–19. doi:10.1007/s13300-016-0167-x
4. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A. Costus ignus: Insulin plant and its preparations as remedial approach for diabetes mellitus. Int J Mol Sci. 2020;21(1):1–34. doi:10.13040/IJPSR.0975-8232.13(4).1551-58
5. Oguis GK, Gilding EK, Jackson MA, Craik DJ. Butterfly pea (Clitoria ternatea), a cyclotide-bearing plant with applications in agriculture and medicine. Front Plant Sci. 2019;10:645. doi:10.3389/fpls.2019.00645
6. Gew LT, Teoh WJ, Lein LL, Lim MW, Cognet P, Aroua MK. Glycerol-based extracts of Clitoria ternatea (Butterfly Pea Flower) with enhanced antioxidant potential. PeerJ Anal Chem. 2024;6:e30. doi:10.7717/peerj-achem.30
7. Gunawan O, Putranto RP, Subandono J, Budiastuti VI. The effect of butterfly pea extract on blood glucose levels in white rats with metabolic syndrome model. Smart Med J. 2023;6(1):14. doi:10.13057/smj.v6i1.67934
8. Afrianto WF, Tamnge F, Hasanah LN. Review: A relation between ethnobotany and bioprospecting of edible flower Butterfly Pea (Clitoria ternatea) in Indonesia. Asian J Ethnobiol. 2020;3(2):51–61. doi:10.13057/asianjethnobiol/y030202
9. Johan L, Darsono L, Widowati W, Rusmana D, Tiono H, Onggowidjaja P, et al. Anti-diabetes mellitus potential of butterfly pea flower (Clitoria ternatea L.) extract based on antioxidant and inhibition of α-amylase and α-glucosidase activities. Med Plants. 2024a;16(2):267–73. doi:10.5958/0975-6892.2024.00040.1
10. Widowati W, Darsono L, Lucianus J, Setiabudi E, Obeng SS, Stefani S, et al. Butterfly pea flower (Clitoria ternatea L.) extract displayed antidiabetic effect through antioxidant, anti-inflammatory, lower hepatic GSK-3β, and pancreatic glycogen on diabetes mellitus and dyslipidemia rat. J King Saud Univ Sci. 2023;35(4):102579. doi:10.1016/j.jksus.2023.102579
11. Gondokesumo ME, Pardjianto B, Handono K, Sumitro SB, Widowati W, Wismandanu O, et al. Garcinia mangostana extract enhances skin epithelialization in rat-induced burn injury. Pak Vet J. 2019;39(3):365–70. doi:10.29261/pakvetj/2019.059
12. Kurniati NF, Garmana AN, Sakinah LN. The effect of ethanol extract of Punica granatum Linn. leaves on lipid profiles of dyslipidemic rat. Pharm Sci Res. 2021;8(2):86–92. doi:10.7454/psr.v8i2.1106
13. Widowati W, Lucianus J, Darsono L, Onggowidjaja P, Tiono H, Nindya FS, et al. Antidiabetic and hepatoprotective effects of butterfly pea flower (Clitoria ternatea L.) extract through antioxidant and anti-inflammatory mechanisms in diabetic–dyslipidemic rats. Heliyon. 2024;10:e29812. doi:10.1016/j.heliyon.2024.e29812
14. Widowati W, Wargasetia TL, Zakaria TM, Marthania M, Akbar RATPP, Gunadi MS, et al. Antioxidant activity of TEMON (Clitoria ternatea and Citrus sp.) as an infused herbal tea. Majalah Obat Tradisional. 2022;27(1):32–40. doi:10.22146/mot.71628
15. Lusiana D, Widowati W, Lucianus J, Setiabudi E, Obeng SS, Stefani S, et al. The ethanolic extract of Clitoria ternatea L. flower attenuates SMADs and REGs regulation in dyslipidemia and diabetes mellitus rat model. Nat Prod Sci. 2023;29(4):193–9. doi:10.20307/nps.2023.29.4.193
16. Afifah E, Mozef T, Sandra F, Arumwardana S, Rihibiha DD, Nufus H, et al. Induction of matrix metalloproteinases in chondrocytes by interleukin IL-1β as an osteoarthritis model. J Math Fundam Sci. 2019;51(2):103–11. doi:10.5614/j.math.fund.sci.2019.51.2.1
17. Lydia W, Nasution MS, Lubis DA. The differences of TNF-α levels and BMI in diabetic patients with pulmonary tuberculosis after intensive phase of tuberculosis treatment. J Endocrinol Trop Med Infect Dis (JETROMI). 2020;2(2):87–95. doi:10.32734/jetromi.v2i2.3873
18. Akash MSH, Rehman K, Liaqat A. Tumor necrosis factor-alpha: Role in development of insulin resistance and pathogenesis of type 2 diabetes mellitus. J Cell Biochem. 2018;119(1):105–10. doi:10.1002/jcb.26174
19. Alzamil H. Elevated serum TNF-α is related to obesity in type 2 diabetes mellitus and is associated with glycemic control and insulin resistance. J Obes. 2020;2020:5076858. doi: 10.1155/2020/5076858
20. Liu Y, Wang Q, Wu K, Sun Z, Tang Z, Li X, et al. Anthocyanins’ effects on diabetes mellitus and islet transplantation. Crit Rev Food Sci Nutr. 2023;63(33):12102–25. doi:10.1080/10408398.2022.2098464
21. Taylor R. Aetiology of type 2 diabetes: an experimental medicine odyssey. Diabetologia. 2025;68:1375–1389. doi:10.1007/s00125-025-06428-0
22. Mir MM, Jeelani M, Alharthi MH, Rizvi SF, Sohail SK, Wani JI, et al. Unraveling the mystery of insulin resistance: From principle mechanistic insights and consequences to therapeutic interventions. Int J Mol Sci. 2025;26(6):2770. doi:10.3390/ijms26062770
23. Sullivan MA, Forbes JM. Glucose and glycogen in the diabetic kidney: Heroes or villains?. EBioMedicine. 2019;47:590–7. doi: 10.1016/j.ebiom.2019.07.067
24. Sanad FAA, Ahmed SF, El-Tantawy WH. Antidiabetic and hypolipidemic potentials of Solidago virgaurea extract in alloxan-induced diabetes type 1. Arch Physiol Biochem. 2022;128(3):716–23. doi:10.1080/13813455.2020.1722705
25. Johan L, Darsono L, Widowati W, Rusmana D, Tiono H, Onggowidjaja P, et al. Antidiabetic potential of Clitoria ternatea flowers against pancreatic ratio, protein expression of α-amylase, and gene expression of pancreatic glucagon in diabetic rats. Med Plants. 2024b;16(1):99–106. doi:10.5958/0975-6892.2024.00011.X
26. Philip P, Darsono L, Widowati W, Onggowidjaja P, Kusuma HSW. Potency of Clitoria ternatea L. Ethanol Extract Against IFNγ and GLUT4 Protein in Type 2 Diabetes Mellitus Rat Model. J Nat Remedies. 2024;24(2):155–63. doi:10.18311/jnr/2024/32205
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