Antidyslipidaemic effect of Ipomoea batatas L. extract with increased PCSK-9 levels in atherosclerotic rats
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I Wayan Putu Sutirta Yasa
https://orcid.org/0000-0003-2494-1553
I Made Jawi
https://orcid.org/0000-0002-1748-2179
Agung Nova Mahendra
https://orcid.org/0000-0003-3960-3792
Putu Angga Wiradana
https://orcid.org/0000-0002-0139-8781
I Gede Widhiantara
https://orcid.org/0000-0003-0498-525X
Abstract
Atherosclerosis is the largest cause of mortality worldwide, and Low-Density Lipoprotein (LDL) is a primary risk factor for this illness. The purpose of this research was to determine the effect of purple sweet potato (Ipomoea batatas L.) extract on cholesterol, LDL, PCSK9, and MDA levels in rats fed a high-cholesterol diet. This true experimental study used a randomised pre-test-post-test control group design. Wistar rats were randomly assigned to three groups. Purple sweet potato extract (PSPE) was prepared by 24-hour maceration with 70% ethanol. All rats were fed a high-cholesterol diet for 14 days, followed by pre-test measurements of cholesterol, LDL, PCSK9, and MDA on day 15. Rats were then randomly divided into control (no treatment), PSPE (200 mg/day), and Simvastatin (0.9 mg/kg BW) groups. After one month of treatment, post-test analyses were performed for all parameters. The results showed an increase in serum cholesterol, LDL and MDA levels in rats fed a high-cholesterol diet (p<0.05) compared to the PSPE and Simvastatin groups. The high-cholesterol diet also resulted in a significant (p<0.05) decrease in PCSK9 when compared to the PSPE and Simvastatin groups. In the PSPE group there was a decrease in cholesterol, LDL, and MDA, and PSPE (p<0.05) compared to the control group. In the Simvastatin group, the increase in PCSK9 was very low compared to the PSPE group. PSPE has antidyslipidaemic activity by reducing total cholesterol status, LDL, and oxidative stress while promoting PCSK-9 function. Further research is still needed to provide a comprehensive understanding of the mechanism of action of PSPE as an antioxidant source in patients with atherosclerosis.
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Copyright (c) 2026 I Wayan Putu Sutirta Yasa, I Made Jawi, Agung Nova Mahendra, Putu Angga Wiradana, I Gede Widhiantara
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References
Tsai CL, Chang YH, Su CH, Wu YJ, Yeh HI, Lin CF. Real-world data on the prescription of proprotein convertase subtilisin/kexin type 9 inhibitors in high-risk patients in a tertiary medical center. J Formos Med Assoc. 2022;121(9):1877-1880. https://doi.org/10.1016/j.jfma.2021.11.007
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O; ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111-188. https://doi.org/10.1093/eurheartj/ehz455
Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino J, Forman DE, Goldberg R, Heidenreich PA, Hlatky MA, Jones DW, Lloyd-Jones D, Lopez-Pajares N, Ndumele CE, Orringer CE, Peralta CA, Saseen JJ, Smith SC Jr, Sperling L, Virani SS, 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):e1082-e1143. https://doi.org/10.1161/cir.0000000000000625
Giugliano RP, Pedersen TR, Saver JL, Sever PS, Keech AC, Bohula EA, Murphy SA, Wasserman SM, Honarpour N, Wang H, Lira Pineda A, Sabatine MS; FOURIER Investigators. Stroke prevention with the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) inhibitor evolocumab added to statin in high-risk patients with stable atherosclerosis. Stroke. 2020;51(5):1546-1554. https://doi.org/10.1161/strokeaha.119.027759
Abifadel M, Varret M, Rabès JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derré A, Villéger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154-6. https://doi.org/10.1038/ng1161
Chaudhary R, Garg J, Shah N, Sumner A. PCSK9 inhibitors: A new era of lipid lowering therapy. World J Cardiol. 2017;9(2):76-91. https://doi.org/10.4330/wjc.v9.i2.76
Dijk W, Cariou B. Efficacy and safety of proprotein convertase subtilisin/kexin 9 inhibitors in people with diabetes and dyslipidaemia. Diabetes Obes Metab. 2019;21 Suppl 1:39-51. https://doi.org/10.1111/dom.13636
Nozue T. Lipid Lowering Therapy and Circulating PCSK9 Concentration. J Atheroscler Thromb. 2017;24(9):895-907. https://doi.org/10.5551/jat.rv17012
Page MM, Watts GF. Emerging PCSK9 inhibitors for treating dyslipidaemia: buttressing the gaps in coronary prevention. Expert Opin Emerg Drugs. 2015;20(2):299-312. https://doi.org/10.1517/14728214.2015.1035709
di Mauro G, Zinzi A, Scavone C, Mascolo A, Gaio M, Sportiello L, Ferrajolo C, Rafaniello C, Rossi F, Capuano A. PCSK9 inhibitors and neurocognitive adverse drug reactions: Analysis of individual case safety reports from the eudravigilance database. Drug Saf. 2021;44(3):337-349. https://doi.org/10.1007/s40264-020-01021-3
Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004;117(11):823-9. https://doi.org/10.1016/j.amjmed.2004.07.041
Muldoon MF, Barger SD, Ryan CM, Flory JD, Lehoczky JP, Matthews KA, Manuck SB. Effects of lovastatin on cognitive function and psychological well-being. Am J Med. 2000;108(7):538-46. https://doi.org/10.1016/s0002-9343(00)00353-3
Page MM, Watts GF. PCSK9 inhibitors - mechanisms of action. Aust Prescr. 2016;39(5):164-167. https://doi.org/10.18773/austprescr.2016.060
Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Wang Y, Li Z, Liu J, Jiang JD. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins. Nat Med. 2004;10(12):1344-51. https://doi.org/10.1038/nm1135
Widhiantara IG, Putri Permatasari AAA, Sutirta Yasa IWP. Spermatogenic and Leydig Cells Induced Hyperlipidemia: A Review. Res J Pharm Technol. 2021;14(10):5573–8. https://doi.org/10.52711/0974-360X.2021.00971
Boachie R, Yao S, Udenigwe CC. Molecular mechanisms of cholesterol-lowering peptides derived from food proteins. Curr Opin Food Sci. 2018;20:58–63. https://doi.org/10.1016/j.cofs.2018.03.006
Zanoni C, Aiello G, Arnoldi A, Lammi C. Hempseed peptides exert hypocholesterolemic effects with a statin-like mechanism. J Agric Food Chem. 2017;65(40):8829-8838. https://doi.org/10.1021/acs.jafc.7b02742
Subawa AAN, Jawi IM, Sutirta-Yasa IWP, Sumardika IW, Mahendra AN. Therapeutic effects of Ipomoea batatas L. extract-containing capsule and simvastatin combination versus simvastatin in dyslipidemic patients. Biomed Pharmacol J. 2022;15(2):635–41. https://dx.doi.org/10.13005/bpj/2402
Yustiantara PS, Warditiani NK, Sari PMNA, Dewi NLKAA, Ramona Y, Jawi IM, et al. Determination of TLC fingerprint biomarker of Ipomoea batatas (L.) Lam leaves extracted with ethanol and its potential as antihyperglycemic agent. Pharmacia. 2021;68(4):907–17. https://doi.org/10.3897/pharmacia.68.e71334
Subawa AAN, Yasa IWPS, Jawi IM, Mahendra AN. Antioxidant and hypolipidemic effects of Ipomoea batatas L and Pandanus conoideus Lam combination on rats fed with high cholesterol diet. Open Access Maced J Med Sci [Internet]. 2021;9(A):473–6. https://doi.org/10.3889/oamjms.2021.6390
Widhiantara IG, Permatasari AAAP, Rosiana IW, Wiradana PA, Widiastini LP, Jawi IM. Antihypercholesterolemic and antioxidant effects of Blumea balsamifera L. leaf extracts to maintain luteinizing hormone secretion in rats induced by high-cholesterol diets. Indones Biomed J. 2021;13(4):396–402. https://doi.org/10.18585/inabj.v13i4.1694
O’Connell EM, Lohoff FW. Proprotein convertase subtilisin/kexin type 9 (PCSK9) in the brain and relevance for neuropsychiatric disorders. Front Neurosci [Internet]. 2020;14:609. https://doi.org/10.3389/fnins.2020.00609
Schulz R, Schlüter K-D, Laufs U. Molecular and cellular function of the proprotein convertase subtilisin/kexin type 9 (PCSK9). Basic Res Cardiol. 2015;110(2):4. https://doi.org/10.1007/s00395-015-0463-z
Xia X, Peng Z, Gu H, Wang M, Wang G, Zhang D. Regulation of PCSK9 Expression and function: mechanisms and therapeutic implications. Front Cardiovasc Med. 2021;8: 764038. https://doi.org/10.3389/fcvm.2021.764038
Anesi A, Di Minno A, Calcaterra I, Cavalca V, Tripaldella M, Porro B, Di Minno MND. An untargeted lipidomic analysis reveals depletion of several phospholipid classes in patients with familial hypercholesterolemia on treatment with evolocumab. Biomedicines. 2021;9(12):1941. https://doi.org/10.3390/biomedicines9121941
Mbikay M, Sirois F, Simoes S, Mayne J, Chrétien M. Quercetin-3-glucoside increases low-density lipoprotein receptor (LDLR) expression, attenuates proprotein convertase subtilisin/kexin 9 (PCSK9) secretion, and stimulates LDL uptake by Huh7 human hepatocytes in culture. FEBS Open Bio. 2014;4:755-62. https://doi.org/10.1016/j.fob.2014.08.003
Li X, Hu X, Pan T, Dong L, Ding L, Wang Z, Song R, Wang X, Wang N, Zhang Y, Wang J, Yang B. Kanglexin, a new anthraquinone compound, attenuates lipid accumulation by activating the AMPK/SREBP-2/PCSK9/LDLR signalling pathway. Biomed Pharmacother. 2021;133:110802. https://doi.org/10.1016/j.biopha.2020.110802
Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109(9):1125-31. https://doi.org/10.1172/JCI15593
Li S, Cao H, Shen D, Jia Q, Chen C, Xing SL. Quercetin protects against ox‑LDL‑induced injury via regulation of ABCAl, LXR‑α and PCSK9 in RAW264.7 macrophages. Mol Med Rep. 2018;18(1):799-806. https://doi.org/10.3892/mmr.2018.9048
Mbikay M, Mayne J, Sirois F, Fedoryak O, Raymond A, Noad J, Chrétien M. Mice fed a high-cholesterol diet supplemented with quercetin-3-glucoside show attenuated hyperlipidemia and hyperinsulinemia associated with differential regulation of PCSK9 and LDLR in their liver and pancreas. Mol Nutr Food Res. 2018;62(9):e1700729. https://doi.org/10.1002/mnfr.201700729
Nasruddin NI, Novi Silvia Hardiany, Wiji Lestari. Flavonoid intake and its correlation to malondialdehyde serum among reproductive-aged women with obesity. World Nutr J. 2022;5(2):8–17. https://doi.org/10.25220/WNJ.V05.i2.0003
Wahyuningtyas AP, Putri DP, Maharani N, Al-Baarri AN. Flavonoid fraction from chayote (Sechium edule (Jacq.) Sw) leaves reduced malondialdehyde (MDA) and tumor necrosis factor-α (TNF-α) in hyperuricemic rats. Nutr Food Sci. 2022;52(2):366–78. https://doi.org/10.1108/NFS-04-2021-0134
Lee M-C, Velayutham M, Komatsu T, Hille R, Zweier JL. Measurement and characterization of superoxide generation from xanthine dehydrogenase: A redox-regulated pathway of radical generation in ischemic tissues. Biochemistry. 2014;53(41):6615–23. https://doi.org/10.1021/bi500582r
Wang W, Ge T, Chen X, Mao Y, Zhu Y. Advances in the Protective Mechanism of NO, H2S, and H2 in Myocardial Ischemic Injury. Front Cardiovasc Med. 2020;7. https://doi.org/10.3389/fcvm.2020.588206
Widhiantara IG, Jawi IM. Phytochemical composition and health properties of Sembung plant (Blumea balsamifera): A review. Vet World. 2021;14(5):1185-1196. https://doi.org/10.14202/vetworld.2021.1185-1196
Guerra JA, Molina M, Abad MJ, Villar AM, Paulina B. Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids isolated from Tanacetum microphyllum. Int Immunopharmacol. 2006 Nov;6(11):1723-8. https://doi.org/10.1016/j.intimp.2006.07.012
Ribeiro D, Freitas M, Lima JL, Fernandes E. Proinflammatory pathways: The modulation by flavonoids. Med Res Rev. 2015;35(5):877-936. https://doi.org/10.1002/med.21347
Khamis AA, Salama AF, Kenawy ME, Mohamed TM. Regulation of hepatic hydroxy methyl glutarate - CoA reductase for controlling hypercholesterolemia in rats. Biomed Pharmacother. 2017;95:1242-1250. https://doi.org/10.1016/j.biopha.2017.09.071
Nhoek P, Chae HS, Masagalli JN, Mailar K, Pel P, Kim YM, Choi WJ, Chin YW. Discovery of flavonoids from Scutellaria baicalensis with inhibitory activity against PCSK 9 expression: Isolation, Synthesis and their biological evaluation. Molecules. 2018;23(2):504. https://doi.org/10.3390/molecules23020504
Kim E, Kim YM, Ahn J, Chae HS, Chin YW, Kim J. Prenylated flavonoid glycosides with PCSK9 mRNA expression inhibitory activity from the aerial parts of Epimedium koreanum. Molecules. 2021;26(12):3590. https://doi.org/10.3390/molecules26123590
Mayeka JG, Atilaw Y, Shadrack DM, Sarnyai F, Csala M, Németh K, Nyandoro SS, Tamási V, Erdelyi M, Munissi JJE. Flavonoids from the leaves of monanthotaxis filipes modulate pcsk9 and ldlr. Sci Afr. 2025;28: e02709. https://doi.org/10.1016/j.sciaf.2025.e02709