Citrus leaf extract reduces blood pressure and vascular damage in repeatedly heated palm oil diet-Induced hypertensive rats
Graphical abstract
Introduction
Fresh vegetable oils, which are rich in unsaturated fatty acids and antioxidants, are beneficial in reducing risk of cardiovascular disease [1]. The oils are commonly used for frying in food preparation and repeatedly used to save cost [2]. This habit is practiced not only in developing countries but also in developed countries [3], [4]. However, the quality of the oils deteriorates after repeated heating, which includes increased viscosity and darkening in color, due to altered fatty acid composition of the oil [5].
Heated vegetable oil undergoes thermal oxidation and a series of chemical reactions which generate polar compounds and reactive oxygen species (ROS), namely hydroxyl, alkoxy and peroxyl radicals, leading to increased oxidative stress [6]. Oxidative stress promotes vascular inflammation, endothelial dysfunction, and imbalance between vasodilation and vasoconstriction agents which eventually lead to the development of hypertension [7], [8], [9], [10], [11], [12], [13]. Previous studies in rats showed that prolonged intake of repeatedly heated palm and soy oil increased lipid peroxidation [12], [13] and blood pressure [8], [9], [10], [11], [12] as well as causing the imbalance between vasodilator and vasoconstrictor mediators in favor of vasoconstriction [11], [15]. Furthermore, studies by Ng et al. [9] reported the involvement of adverse vascular remodeling in the heated vegetable oil-induced hypertension in rat model.
The extract (CLE) is derived from Citrus spp. leaves (Rutaceae family) consisting of combinations of C. hystrix, C. aurantifolia, C. microcarpa and C. sinensis [16–18], developed and patented (patent number: US8425969B2) by Universiti Putra Malaysia researchers. It is used to reduce vegetable oil thermal oxidation. [19]. The established extraction methods for acquiring CLE was designed to effectively isolate and extract polyphenols in particular the flavonoids, such as diosmin, lutein, obacunone, isoquercitrin, hesperidin, didymin, eriocitrin, neocriocitrin, narirutin, naringin, neohesperidin and 7-OH flavonone [19]. Flavonoids are the most abundant polyphenols subgroup detected in citrus plants in Malaysia [16], [17], [18]. Previously, Sukalingam et al. [20] shown that CLE which was also named as ADD-X (patent no: US 8425969B2), reduced blood pressure and improved oxidative stress status in atherosclerotic rat model. Citrus species generally have antihypertensive effect attributed to their flavonoid-rich composition except for citrus aurantium [21], [22], [23], [24], [25]. We postulated that CLE may prevent blood pressure-raising effect of heated oil by regulating the vasoactive mediators and vascular remodeling apart from antioxidant effect. Therefore, this study was undertaken to evaluate the effects of CLE extract on blood pressure, blood pressure-regulating enzymes and mediators including angiotensin converting enzyme (ACE), heme oxygenase-1 (HO-1), thromboxane (TXA2) and prostacyclin (PGI2), lipid peroxidation (TBARS) as well as vascular histomorphometry in rats fed with heated oil.
Section snippets
Materials
CLE was obtained from Institute of Bioscience, Universiti Putra Malaysia, Selangor. Palm oil was purchased from Lam Soon Edible Oils, Selangor, Malaysia. TBARS, thromboxane B2 and 6-keto-PGF1α kits were purchased from Cayman Chemical, Ann Arbor, MI, USA. Heme oxygenase-1 and ACE kits were purchased from Cloud-Clone Corp, Houston, TX, USA. Other chemicals were obtained from Sigma-Aldrich Chemical Co. (St. Louis, MO, USA). The chemical characteristics of CLE determined by HPLC, LC–MS and FTIR are
Blood pressure
Fig. 2 shows systolic blood pressure at week 0 (pre-treatment) and week 16 (post-treatment) of all experimental groups. There was no difference in blood pressure at 0 week among all groups. At week 16, the blood pressure was significantly increased in 5HPO and 10HPO group compared to control and FPO groups, as well as their respective values at week 0 (p < 0.05). The blood pressure in 5HPO + CLE group was significantly lower compared to 5HPO group at week 16 (p < 0.05). However, blood pressure in
Discussion
Five and ten times heated palm oil increase blood pressure after 16 weeks. This finding was consistent with previous studies which reported that consumption of repeatedly heated vegetable oil increase blood pressure [8], [9], [10], [11], [12], [28]. Thermally oxidized vegetable oil contains polar compounds and reactive oxygen species (ROS) that cause increased oxidative stress upon prolonged consumption [6]. Oxidative stress promotes vascular inflammation and endothelial dysfunction which
Conclusions
CLE supplementation was able to attenuate the blood pressure raising effect of 5HPO but not in 10HPO. The reductions of blood pressure in heated vegetable oil-induced hypertension were paralleled with improvement in aortic histomorphometry. CLE supplementation also reduced TBARS, thromboxane and ACE activity while increased HO-1 activity. It is therefore suggested that CLE reduces blood pressure and vascular damage in heated palm oil diet-induced hypertension.
Conflict of interest
The authors declare that there is no conflict of interest.
Acknowledgments
This study was funded by grant GUP-2013-059. The authors would like to express the appreciation to Mr. Fadhlullah Zuhair Japar Sidek and Mrs. Juliana Abd Hamid for their excellent technical assistance.
References (62)
- et al.
Heated vegetable oils and cardiovascular disease risk factors
Vascul. Pharmacol.
(2014) - et al.
The role of oxidative stress, antioxidants and vascular inflammation in cardiovascular disease (a review)
Vascul. Pharmacol.
(2015) - et al.
Antihypertensive effect of sweetie fruit in patients with stage I hypertension
Am. J. Hypertens.
(2005) - et al.
Protein measurement with the Folin phenol reagent
J. Biol. Chem.
(1951) - et al.
Effect of the flavonoid fraction of Lithocarpus polystachyus Rehd on spontaneously hypertensive and normotensive rats
J. Ethnopharmacol.
(2012) - et al.
Additive or synergetic effects of phenolic compounds on human low density lipoprotein oxidation
Food Chem. Toxicol.
(2006) - et al.
Effects of deep frying oil on blood pressure and oxidative stress in spontaneously hypertensive and normotensive rats
Nutrition
(2010) - et al.
Antioxidation, angiotensin converting enzyme inhibition activity, nattokinase, and antihypertension of Bacillus subtilis (natto)-fermented pigeon pea
J. Food Drug Anal.
(2015) - et al.
Heme oxygenase-1 protein localizes to the nucleus and activates transcription factors important in oxidative stress
J. Biol. Chem.
(2007) - et al.
Antiplatelet activity of hesperetin, a bioflavonoid, is mainly mediated by inhibition of PLC-gamma2 phosphorylation and cyclooxygenase-1 activity
Atherosclerosis
(2007)
Effect of flavonoids and Vitamin E on cyclooxygenase-2 (COX-2) transcription
Mutat. Res.
Adaptation and remodelling of vascular wall; biomechanical response to hypertension
J. Mech. Behav. Biomed. Mater.
Frying performance of high oleic oil enriched in biophenols during discontinuous and prolonged thermal treatment
Food Nutr. Sci.
Level of knowledge, attitude and practice of night market outlet operator in Kuala Lumpur regarding the usage of repeatedly heated cooking oil
Med. J. Malaysia
The quality of cooking oil used in informal food processing in Malawi: a preliminary study
Int. J. Consumer Stud.
Is the frying oil in deep-fried foods safe?
J. Oleo. Sci.
Quality changes in trans and trans free fats/oils and products during frying
Eur. Food Res. Technol.
The role of repeatedly heated soybean oil in the development of hypertension in rats: association with vascular inflammation
Int. J. Exp. Pathol.
Involvement of inflammation and adverse vascular remodelling in the blood pressure raising effect of repeatedly heated palm oil in rats
Int. J. Vasc. Med.
Association of elevated blood pressure and impaired vasorelaxation in experimental Sprague-Dawley rats fed with heated vegetable oil
Lipid Health Dis.
Intake of repeatedly heated palm oil causes elevation in blood pressure with impaired vasorelaxation in rats, Tohoku
J. Exp. Med.
Effect of repeatedly heated palm olein on blood pressure-regulating enzymes activity and lipid peroxidation in rats
Malays. J. Med. Sci.
Effects of repeatedly heated palm oil on serum lipid profile, lipid peroxidation and homocystein levels in a post-menopausal rat model
Mcgill J. Med.
Heating reduces vitamin E content in palm and soy oils
Malays. J. Biochem. Mol. Biol.
Virgin coconut oil prevents blood pressure elevation and improves endothelial functions in rats fed with repeatedly heated palm oil
Evid. Based Complement. Alternat. Med.
Flavonoid hesperidine, total phenolic contents and antioxidant activities from Citrus species
Afr. J. Biotechnol.
Antioxidant activity, phenol and flavonoid contents of 13 citrus species peels and tissues
Pak. J. Pharm. Sci.
Antioxidative activity of Malaysian herb extracts in refined, bleached and deodorized palm olein
J. Oil Palm Res.
Consumption of ADD-X and repeatedly heated palm oil on the blood pressure and oxidative stress markers in ovarectomized rats
Int. J. Pharmacol.
Effects of p-synephrine alone and in combination with selected bioflavonoids on resting metabolism, blood pressure, heart rate and self-reported mood changes
Int. J. Med. Sci.
Cited by (24)
Enrichment of Beverages With Health Beneficial Ingredients
2019, Value-Added Ingredients and Enrichments of Beverages: Volume 14: The Science of BeveragesImpact of consumption and cooking manners of vegetable oils on cardiovascular diseases- A critical review
2018, Trends in Food Science and TechnologyOxidized palm oil impairs reproductive functions and architectures in female rats
2023, Asian Pacific Journal of ReproductionIranian traditional medicinal plants for management of chronic heart failure: A review
2023, Medicine (United States)Beneficial effects of citrus leaf extract supplementation on renal vasoactive substances in rats fed with repeatedly heated palm oil diet
2022, Pakistan Journal of Pharmaceutical Sciences