Effects of Limonin on Vascular Function and Morphology in a Rat Model of Obesity

Main Article Content

Banyaphon Chanao
Thanapat Sararat
Petcharat Chiangsaen
Sophida Phuthong
Poungrat Pakdeechote
Putcharawipa Maneesai


Background and Objectives: Obesity has been reported to be associated with vascular dysfunction and morphology changes. This study aimed to evaluate the effect of limonin on vascular function and morphology in high fat (HF) diet-induced obesity in rats.

Methods: Male Sprague-Dawley rats were divided into 3 groups; control group fed with normal diet and tap water; obese group fed with a HF-diet and 15% fructose solution for 16 weeks and obese+LM100 group fed with a HF-diet plus 15% fructose solution, and limonin (100 mg/kg/day) for the last 4 weeks. At the end of the study, body weight (BW), retroperitoneal fat weight (RFW), vascular function, vascular morphology and oxidative stress markers were determined.

Results: Obese rats had increases in BW and RFW while treatment with limonin can attenuate the high BW and RFW (p<0.05).  Limonin improved vascular function by reducing the enhancement of contractile response to electrical filed stimulation in the mesenteric vascular beds and attenuated the impairment of vasorelaxation response to acetylcholine in aortic rings isolated from obese rats (p<0.05).  Aortic hypertrophy, indicated by increases in cross-sectional area, aortic wall thickness and wall/lumen ratio, was normalized in obese rats after limonin treatment. Moreover, increased vascular superoxide production, and decreased plasma nitric oxide metabolites were also observed in obese rats and these were restored by limonin treatment (p<0.05).

Conclusion: Limonin alleviated vascular dysfunction and hypertrophy in obese rats. The possible mechanism might associate with its anti-obesity and antioxidant properties.


Download data is not yet available.

Article Details

How to Cite
Chanao B, Sararat T, Chiangsaen P, Phuthong S, Pakdeechote P, Maneesai P. Effects of Limonin on Vascular Function and Morphology in a Rat Model of Obesity . SRIMEDJ [Internet]. 2022 Apr. 28 [cited 2023 Feb. 7];37(2):173-8. Available from: https://li01.tci-thaijo.org/index.php/SRIMEDJ/article/view/253741
Original Articles


Mechanick JI, Garber AJ, Handelsman Y, Garvey WT, Beir DM, Bohannon NJV, et al. American Association of Clinical Endocrinologists’ Position Statement on Obesity and Obesity Medicine. Endocr Pract 2012;18:642–8.

Ansari S, Haboubi H, Haboubi N. Adult obesity complications: challenges and clinical impact. Ther Adv Endocrinol Metab 2020;11:204201882093495.

Lee S, Lee HJ, Kim SC, Joo JK. Association between nutrients and metabolic syndrome in middle-aged Korean women. Arch Endocrinol Metab 2020;64:298–305.

Bhandarkar NS, Brown L, Panchal SK. Chlorogenic acid attenuates high-carbohydrate, high-fat diet–induced cardiovascular, liver, and metabolic changes in rats. Nutr Res 2019; 62:78–88.

Lee GH, Hoang TH, Jung ES, Jung SJ, Chae SW, Chae HJ. Mulberry Extract Attenuates Endothelial Dysfunction through the Regulation of Uncoupling Endothelial Nitric Oxide Synthase in High Fat Diet Rats. Nutrients 2019;11:978.

Lobato NS, Filgueira FP, Hagihara GN, Akamine EH, Pariz JR, Tostes RC, et al. Improvement of metabolic parameters and vascular function by metformin in obese non-diabetic rats. Life Sci 2012;90:228–35.

Maneesai P, Bunbupha S, Kukongviriyapan U, Prachaney P, Tangsucharit P, Kukongviriyapan V, et al. Asiatic acid attenuates renin-angiotensin system activation and improves vascular function in high-carbohydrate, high-fat diet fed rats. BMC Complement Altern Med 2016;16:123.

Panchal SK, Poudyal H, Arumugam TV, Brown L. Rutin Attenuates Metabolic Changes, Nonalcoholic Steatohepatitis, and Cardiovascular Remodeling in High-Carbohydrate, High-Fat Diet-Fed Rats. J Nutr 2011;141:1062–9.

Bunbupha S, Prasarttong P, Poasakate A, Maneesai P, Pakdeechote P. Imperatorin alleviates metabolic and vascular alterations in high-fat/high-fructose diet-fed rats by modulating adiponectin receptor 1, eNOS, and p47phox expression. Eur J Pharmacol 2021; 899:174010.

Qin S, Lv C, Wang Q, Zheng Z, Sun X, Tang M, et al. Extraction, identification, and antioxidant property evaluation of limonin from pummelo seeds. Anim Nutr 2018;4:281-7.

Li Y, Yang M, Lin H, Yan W, Deng G, Ye H, et al. Limonin Alleviates Non-alcoholic Fatty Liver Disease by Reducing Lipid Accumulation, Suppressing Inflammation and Oxidative Stress. Front Pharmacol 2022;12:801730.

Deng J, Huang M, Wu H. Protective effect of limonin against doxorubicin-induced cardiotoxicity via activating nuclear factor - like 2 and Sirtuin 2 signaling pathways. Bioengineered 2021;12:7975–84.

Lu FJ, Lin JT, Wang HP, Huang WC. A simple, sensitive, non-stimulated photon counting system for detection of superoxide anion in whole blood. Experientia 1996;52:141–4.

Verdon CP, Burton BA, Prior RL. Sample Pretreatment with Nitrate Reductase and Glucose-6-Phosphate Dehydrogenase Quantitatively Reduces Nitrate While Avoiding Interference by NADP+ When the Griess Reaction Is Used to Assay for Nitrite. Anal Biochem 1995;224: 502–8.

Luangaram S, Kukongviriyapan U, Pakdeechote P, Kukongviriyapan V, Pannangpetch P. Protective effects of quercetin against phenylhydrazine-induced vascular dysfunction and oxidative stress in rats. Food Chem Toxicol 2007;45:448–55.

Nakmareong S, Kukongviriyapan U, Pakdeechote P, Donpunha W, Kukongviriyapan V, Kongyingyoes B, et al. Antioxidant and vascular protective effects of curcumin and tetrahydrocurcumin in rats with l-NAME-induced hypertension. Naunyn Schmiedebergs Arch Pharmacol 2011;383:519–29.

Bastías-Pérez M, Serra D, Herrero L. Dietary Options for Rodents in the Study of Obesity. Nutrients 2020;12:3234.

Hariri N, Thibault L. High-fat diet-induced obesity in animal models. Nutr Res Rev 2010; 23:270–99.

Senaphan K, Kukongviriyapan U, Sangartit W, Pakdeechote P, Pannangpetch P, Prachaney P, et al. Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet. Nutrients 2015;7:6446–64.

Manna P, Jain SK. Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies. Metab Syndr Relat Disord 2015;13:423–44.

Jiang F, Lim HK, Morris MJ, Prior L, Velkoska E, Wu X, et al. Systemic upregulation of NADPH oxidase in diet-induced obesity in rats. Redox Rep 2011;16:223–9.

Fortuño A, José GS, Moreno MU, Díez J, Zalba G. Oxidative stress and vascular remodelling: Oxidative stress and vascular remodelling. Exp Physiol 2005;90:457–62.

Lang P, Hasselwander S, Li H, Xia N. Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice. Sci Rep 2019;9:19556.

Mokbel MS, Hashinaga F. Evaluation of the antioxidant activity of extracts from buntan (Citrus grandis Osbeck) fruit tissues. Food Chem 2006;94:529–34.

Yu J, Wang L, Walzem RL, Miller EG, Pike LM, Patil BS. Antioxidant Activity of Citrus Limonoids, Flavonoids, and Coumarins. J Agric Food Chem 2005;53:2009–14.