Sacha inchi (Plukenetia volubilis L.) Oil Ameliorates Hypertensive and Vascular Remodeling in Nitric Oxide Synthase Inhibitor-Induced Hypertensive Rats

Main Article Content

Pakaporn Sa-nguanpong
Anatcha Thongsit
Jhantanipa Boonsang
Anjaree Inchan
Worasak Kaewkong
Wanthanee Hanchang
Krongkarn Chootip
Tippaporn Bualeong


Sacha inchi (SI) oil possesses a wealth of vital polyunsaturated fatty acids (PUFA), vitamin E (including γ- and δ-tocopherols), and beneficial antioxidants like phenolic compounds, making it highly recommended for promoting heart health. Therefore, our ambition was to analyze the potential anti-hypertensive effect of SI oil on cardiovascular remodeling in nitric oxide synthase inhibitor-induced hypertensive rats. Hypertension was provoked in male Sprague-Dawley rats by daily handling of L-NAME through their drinking water at a dose of 40 mg/kg for three weeks. The rats were then administrated with L-NAME in drinking water plus SI oil 0.5, 1.0, 2.0 ml/kg/day or captopril 5 mg/kg/day which was delivered via oral gavage for 5 weeks. All rats had their tail cuff blood pressure measured weekly. Upon completion of the experiment, the measurement of direct blood pressure was conducted by cannulating the common carotid artery. Plasma nitric oxide metabolites (NOx), levels of the adhesion molecule VCAM-I, cardiac histopathology, fibrosis in cardiac muscle, and aorta were also investigated. SI oil at 2.0 ml/kg administered once daily for 5 weeks significantly reduced SBP, DBP, MAP, and decreased VCAM-I and fibrosis in hypertensive rats. Furthermore, SI oil also mitigated endothelial dysfunction by enhancing the vascular response to acetylcholine (ACh) in aortic rings. Taken together, these results indicated that SI oil attenuated blood pressure and improved vascular dysfunction. However, the protective effect of SI oil will be further studied because the damage to organs from hypertension is difficult to restore after pathological damage has occurred.



Download data is not yet available.

Article Details

Research Articles


Organization WH. Guideline for the pharmacological treatment of hypertension in adults. World Health Organization; 2021.

Collins R, Peto R, MacMahon S, Godwin J, Qizilbash N, Hebert P, et al. Blood pressure, stroke, and coronary heart disease: part 2, short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet. 1990; 335(8693):827-838.

Wright Jr JT, Bakris G, Greene T, Agodoa LY, Appel LJ, Charleston J, et al. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288(19):2421-2431.

Van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006;444(7121):875-880.

World Health Organization (WHO). Guideline for the pharmacological treatment of hypertension in adults: summary. 2022 [cited 2023 May 10]. Available from:

Kebadnew M, Tensaykahsay. Factors associated with hypertension among age groups of 18 years and above in Southwestern, Ethiopia, 2020: A community based cross-sectional study. DEIB. 2020;17(7):202-208.

Laher I. Systems biology of free radicals and antioxidants. Springer; 2014.

Copstead-Kirkhorn L-EC, Banasik JL. Pathophysiology-E-Book. Elsevier Health Sciences; 2014.

Paravicini TM, Touyz RM. Redox signaling in hypertension. Cardiovasc Res. 2006;71(2):247-258.

Tousoulis D, Stefanadis C. Biomarkers in cardiovascular diseases. CRC Press; 2013.

Schulman IH, Zhou MS, Raij L. Interaction between nitric oxide and angiotensin II in the endothelium: role in atherosclerosis and hypertension. J Hypertens Suppl. 2006;24(1):S45-50.

Maneesai P, Bunbupha S, Potue P, Berkban T, Kukongviriyapan U, Kukongviriyapan V, et al. Hesperidin prevents nitric oxide deficiency-induced cardiovascular remodeling in rats via suppressing TGF-β1 and MMPs protein expression. Nutrients. 2018;10(10):1549.

Pechánová O, Bernátová I, Babál P, Martínez MC, Kyselá S, Stvrtina S, et al. Red wine polyphenols prevent cardiovascular alterations in L-NAME-induced hypertension. J Hypertens. 2004;22(8):1551-1559.

Bunbupha S, Prachaney P, Kukongviriyapan U, Kukongviriyapan V, Welbat JU, Pakdeechote P. Asiatic acid alleviates cardiovascular remodelling in rats with L‐NAME‐induced hypertension. Clin Exp Pharmacol. 2015;42(11):1189-1197.

Bernátová I, Pechánová O, Babál P, Kyselá S, Stvrtina S, Andriantsitohaina R. Wine polyphenols improve cardiovascular remodeling and vascular function in NO-deficient hypertension. Am J Physiol Heart. 2002;282(3):H942-H948.

Pechanova O, Simko F. The role of nuclear factor kappa B and nitric oxide interaction in heart remodelling. J Hypertens. 2010;28:S39-S44.

Liu T, Zhang L, Joo D, Sun S-C. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017;2(1):17023.

Harrison DG, Gongora MC. Oxidative stress and hypertension. Med Clin. 2009;93(3):621-635.

Chirinos R, Zuloeta G, Pedreschi R, Mignolet E, Larondelle Y, Campos D. Sacha inchi (Plukenetia volubilis): A seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity. Food Chem. 2013;141(3):1732-1739.

Mhd Rodzi NAR, Lee LK. Sacha Inchi (Plukenetia volubilis L.): recent insight on phytochemistry, pharmacology, organoleptic, safety and toxicity perspectives. Heliyon. 2022;8(9):e10572.

Simopoulos AP. The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother. 2002;56(8):365-379.

DiNicolantonio JJ, O'Keefe J. The importance of maintaining a low omega-6/omega-3 ratio for reducing the risk of autoimmune diseases, asthma, and allergies. Mo Med. 2021;118(5):453-459.

Simopoulos AP. The omega-6/omega-3 fatty acid ratio, genetic variation, and cardiovascular disease. Asia Pac J Clin Nutr. 2008;17 Suppl 1:131-134.

Gutiérrez LF, Rosada LM, Jiménez Á. Chemical composition of Sacha Inchi (Plukenetia volubilis L.) seeds and characteristics of their lipid fraction. Grasas Aceites. 2011;62(1):76-83.

Maurer NE, Hatta-Sakoda B, Pascual-Chagman G, Rodriguez-Saona LE. Characterization and authentication of a novel vegetable source of omega-3 fatty acids, sacha inchi (Plukenetia volubilis L.) oil. Food Chem. 2012;134(2):1173-1180.

Goyal A, Tanwar B, Kumar Sihag M, Sharma V. Sacha inchi (Plukenetia volubilis L.): An emerging source of nutrients, omega-3 fatty acid and phytochemicals. Food Chem. 2022;373:131459.

Cisneros FH, Paredes D, Arana A, Cisneros-Zevallos L. Chemical composition, oxidative stability and antioxidant capacity of oil extracted from roasted seeds of Sacha-inchi (Plukenetia volubilis L.). J Agric Food Chem. 2014;62(22):5191-5197.

Fanali C, Dugo L, Cacciola F, Beccaria M, Grasso S, Dacha M, et al. Chemical characterization of Sacha inchi (Plukenetia volubilis L.) oil. J Agric Food Chem. 2011;59(24):13043-13049.

Liu Q, Xu Y-K, Zhang P, Na Z, Tang T, Shi Y. Chemical composition and oxidative evolution of Sacha Inchi (Plukentia volubilis L.) oil from Xishuangbanna (China). Grasas Aceites. 2014;65(1):e012.

Chasquibol NA, del Aguila C, Yácono JC, Guinda Á, Moreda W, Gómez-Coca RB, et al. Characterization of glyceridic and unsaponifiable compounds of Sacha Inchi (Plukenetia huayllabambana L.) oils. J Agric Food Chem. 2014;62(41):10162-10169.

Zanqui AB, da Silva CM, de Morais DR, Santos JM, Ribeiro SAO, Eberlin MN, et al. Sacha inchi (Plukenetia volubilis L.) oil composition varies with changes in temperature and pressure in subcritical extraction with n-propane. Ind Crops Prod. 2016;87:64-70.

Xuan TD, Gangqiang G, Minh TN, Quy TN, Khanh TD. An overview of chemical profiles, antioxidant and antimicrobial activities of commercial vegetable edible oils marketed in Japan. Foods. 2018;7(2): 21.

Brogden RN, Todd PA, Sorkin EM. Captopril. An update of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in hypertension and congestive heart failure. Drugs. 1988;36(5):540-600.

Inchan A, Pathomwichaiwat T, Bualeong T, Tipratchadaporn S, Chootip K. Anti-hypotensive effect of “Yahom Navakot” in rats with orthostatic hypotension. J Tradit Complement Med. 2022;12(2):180-189.

Ribeiro MO, Antunes E, de Nucci G, Lovisolo SM, Zatz R. Chronic inhibition of nitric oxide synthesis. A new model of arterial hypertension. J Hypertens. 1992;20(3):298-303.

Bernátová I, Pechánová Og, Kristek F. Mechanism of structural remodelling of the rat aorta during long-term NG-nitro-L-arginine methyl ester treatment. J Pharmacol. 1999;81(1):99-106.

Maneesai P, Prasarttong P, Bunbupha S, Kukongviriyapan U, Kukongviriyapan V, Tangsucharit P, et al. Synergistic antihypertensive effect of Carthamus tinctorius L. extract and captopril in L-NAME-induced hypertensive rats via restoration of eNOS and AT1R expression. Nutrients. 2016;8(3):122.

Paulis L, Zicha J, Kunes J, Hojna S, Behuliak M, Celec P, et al. Regression of L-NAME-induced hypertension: the role of nitric oxide and endothelium-derived constricting factor. Hypertens Res. 2008;31(4):793-803.

Sonoda K, Ohtake K, Uchida H, Ito J, Uchida M, Natsume H, et al. Dietary nitrite supplementation attenuates cardiac remodeling in l-NAME-induced hypertensive rats. Nitric Oxide. 2017;67:1-9.

Holécyová A, Török J, Bernátová I, Pechánová O. Restriction of nitric oxide rather than elevated blood pressure is responsible for alterations of vascular responses in nitric oxide-deficient hypertension. Physiol Res. 1996;45(4):317-321.

Aekthammarat D, Pannangpetch P, Tangsucharit P. Moringa oleifera leaf extract lowers high blood pressure by alleviating vascular dysfunction and decreasing oxidative stress in L-NAME hypertensive rats. Phytomedicine. 2019;54:9-16.

Hale TM, Robertson SJ, Burns KD, deBlois D. Short-term ACE inhibition confers long-term protection against target organ damage. Hypertens Res. 2012;35(6):604-610.

Ono Y, Ono H, Matsuoka H, Fujimori T, Frohlich ED. Apoptosis, coronary arterial remodeling, and myocardial infarction after nitric oxide inhibition in SHR. J Hypertens. 1999;34(4 Pt 1):609-616.

Tomita H, Egashira K, Kubo-Inoue M, Usui M, Koyanagi M, Shimokawa H, et al. Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels. ATVB. 1998;18(9):1456-1464.

Miguel-Carrasco JL, Mate A, Monserrat MT, Arias JL, Aramburu O, Vázquez CM. The role of inflammatory markers in the cardioprotective effect of L-carnitine in L-NAME-induced hypertension. Am J Hypertens. 2008;21(11):1231-1237.

Koyanagi M, Egashira K, Kitamoto S, Ni W, Shimokawa H, Takeya M, et al. Role of monocyte chemoattractant protein-1 in cardiovascular remodeling induced by chronic blockade of nitric oxide synthesis. Circ. 2000;102(18):2243-2248.

Gross V, Obst M, Kiss E, Janke J, Mazak I, Shagdarsuren E, et al. Cardiac hypertrophy and fibrosis in chronic L-NAME-treated AT2 receptor-deficient mice. J Hypertens. 2004;22(5):997-1005.

Pecháňová O, Bernatova I, Pelouch V, Babal P. L-NAME-induced protein remodeling and fibrosis. Physiol Res. 1999;48:353-362.

Nemtsova V, Vischer AS, Burkard T. Hypertensive heart disease: A narrative review series—Part 1: Pathophysiology and microstructural changes. J Clin Med. 2023;12(7):2606.

Akashiba A, Ono H, Ono Y, Ishimitsu T, Matsuoka H. Valsartan improves L-NAME-exacerbated cardiac fibrosis with TGF-ß inhibition and apoptosis induction in spontaneously hypertensive rats. J Cardiol. 2008;52(3):239-246.

Boonprom P, Boonla O, Chayaburakul K, Welbat JU, Pannangpetch P, Kukongviriyapan U, et al. Garcinia mangostana pericarp extract protects against oxidative stress and cardiovascular remodeling via suppression of p47(phox) and iNOS in nitric oxide deficient rats. Ann Anat. 2017;212:27-36.

Djuricic I, Calder PC. Beneficial outcomes of omega-6 and omega-3 polyunsaturated fatty acids on human health: An update for 2021. Nutrients. 2021;13(7):2421.

Hajizadeh-Sharafabad F, Sharifi Zahabi E. Role of alpha-lipoic acid in vascular function: A systematic review of human intervention studies. Crit Rev Food Sci Nutr. 2022;62(11):2928-2941.

Wang S, Zhu F, Kakuda Y. Sacha inchi (Plukenetia volubilis L.): Nutritional composition, biological activity, and uses. Food Chem. 2018;265:316-328.

Chirinos R, Pedreschi R, Campos D. Enzyme‐assisted hydrolysates from sacha inchi (Plukenetia volubilis) protein with in vitro antioxidant and antihypertensive properties. J Food Process Preserv. 2020;44(12):e14969.

Kodahl N, Sørensen M. Sacha Inchi (Plukenetia volubilis L.) is an underutilized crop with a great potential. Agron. 2021;11(6):1066.

Gonzales GF, Gonzales C. A randomized, double-blind placebo-controlled study on acceptability, safety and efficacy of oral administration of sacha inchi oil (Plukenetia volubilis L.) in adult human subjects. FCT. 2014;65:168-176.