Mango-Lime Peel Nanoparticles Improve Diabetic Parameters, Lipid Profiles and Pancreatic Cell Damage in Cigarette Smoke-Exposed Diabetic Rats
Abstract
BACKGROUND: Diabetes mellitus often exacerbated by cigarette smoke, which disrupts glucose homeostasis and lipid metabolism. Mango (Mangifera indica L.) and lime (Citrus amblycarpa) peels contain various phytochemical compounds, including those are reported to have metabolic and cytoprotective properties, but their combined nanoparticle formulation in cigarette smoke-exposed diabetes cases remains unexplored. Therefore, this study was conducted to evaluate the synergistic effect of mango-lime peel nanoparticles (NanoMC) on glycemic control, lipid profiles, and pancreatic cell damage in cigarette smoke-exposed diabetic rats.
METHODS: Mango and lime peel ethanol extract was prepared into nanoparticles using emulsion-solvent evaporation method and followed by sonication and homogenization, and subsequently divided into three concentration groups. Rats were diabetic-induced and smoke-exposed, before being treated with/without Simvastatin + Glibenclamide, 20, 40, or 80 mg/kgBW NanoMC. Parameters including blood glucose, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), homeostatic model assessment of beta-cell function (HOMA-β), hemoglobin A1c (HbA1c), and lipid profiles were then measured. To evaluate pancreatic cell damage, the pancreatic tissue was collected, fixed, and then evaluated by using Hematoxylin and Eosin (H&E) staining.
RESULTS: NanoMC administration significantly reduced blood glucose, HbA1c, triglycerides, cholesterol, and low-density lipoprotein (LDL) levels (p<0.05). NanoMC treatment also increased insulin levels, HOMA-β, and high-density lipoprotein (HDL). After the treatment with NanoMC, particularly with 80 mg/kgBW concentration, fewer degenerative and necrotic cells were found compared to the other groups, showing its ability to attenuate pancreatic cell damage.
CONCLUSION: The combination of NanoMC could improve glycemic status, modulate lipid profiles, and improved pancreatic cell damage in diabetic rats exposed to cigarette smoke.
KEYWORDS: Mangifera indica, Citrus amblycarpa, nanoparticles, diabetes mellitus, cigarette smoke, lipid profiles, pancreatic histopathology
References
Surya ND, Setiawan J, Rensa. The relationship between smoking status and diabetic foot severity. Sriwij Med J. 2020; 3(3): 23-31, CrossRef.
Tangvarasittichai S. Oxidative stress, insulin resistance, dyslipidemia and type 2 diabetes mellitus. World J Diabetes. 2015; 6(3): 456-80, CrossRef.
American Diabetes Association Professional Practice Committee. Pharmacologic approaches to glycemic treatment: Standards of Care in Diabetes-2025. Diabetes Care. 2025; 48(Suppl 1): S181-S206, CrossRef.
Eguchi N, Vaziri ND, Dafoe DC, Ichii H. The role of oxidative stress in pancreatic β cell dysfunction in diabetes. Int J Mol Sci. 2021; 22(4): 1509, CrossRef.
Maddatu J, Anderson-Baucum E, Evans-Molina C. Smoking and the risk of type 2 diabetes. Transl Res. 2017; 184: 101-7, CrossRef.
Campagna D, Alamo A, Di Pino A, Russo C, Calogero AE, Purrello F, et al. Smoking and diabetes: dangerous liaisons and confusing relationships. Diabetol Metab Syndr. 2019; 11: 85, CrossRef.
Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC. Oxidative stress and cardiovascular risk: Obesity, diabetes, smoking, and pollution. J Am Coll Cardiol. 2017; 70(2): 230-51, CrossRef.
Shahwan M, Alhumaydhi F, Ashraf GM, Hasan PMZ, Shamsi A. Role of polyphenols in combating type 2 diabetes and insulin resistance. Int J Biol Macromol. 2022; 206: 567-79, CrossRef.
García-Villegas A, Fernández-Ochoa Á, Rojas-García A, Alañón ME, Arráez-Román D, Cádiz-Gurrea ML, et al. The potential of Mangifera indica L. peel extract to be revalued in cosmetic applications. Antioxidants. 2023; 12(10): 1920, CrossRef.
Gondi M, Basha SA, Bhaskar JJ, Salimath PV, Rao UJS. Anti-diabetic effect of dietary mango (Mangifera indica L.) peel in streptozotocin-induced diabetic rats. J Sci Food Agric. 2015; 95(5): 991-9, CrossRef.
Indriyanti RA, Kharisma Y, Damayanti MM. Mangifera indica Linn. waste peel ethanol extract on inducing Citrus amblycarpa antioxidant activity. Pharmacogn J. 2024 ; 16(5): 1010-4, CrossRef.
Yang B, Dong Y, Wang F, Zhang Y. Nanoformulations to enhance the bioavailability and physiological functions of polyphenols. Molecules. 2020; 25(20): 4613, CrossRef.
Mignet N, Seguin J, Chabot GG. Bioavailability of polyphenol liposomes: a challenge ahead. Pharmaceutics. 2013; 5(3): 457-71, CrossRef.
Mahlani M, Hadi RS, Arifandi F, Mustofa S. The effects of honey fermentation (Apis mellifera) on pancreas histology of cisplatin-induced rats and the review according to Islamic perspective. Junior Medical Journal. 2023; 2(1): 17-29, CrossRef.
Mayyas F, Alzoubi KH. Cardiac effects of cigarette tobacco smoking in rat model of diabetes. Life Sci. 2018; 211: 279-85, CrossRef.
Kumar S, Yadav A. Comparative study of hypoglycemic effect of Holarrhena antidysenterica seeds and glibenclamide in experimentally induced diabetes mellitus in albino rats. Biomed Pharmacol J. 2015; 8(1): 477-83, CrossRef.
Zhang Q, Fan X, Ye R, Hu Y, Zheng T, Shi R, et al. The Effect of simvastatin on gut microbiota and lipid metabolism in hyperlipidemic rats induced by a high-fat diet. Front Pharmacol. 2020; 11: 522, CrossRef.
Parasuraman S, Raveendran R, Kesavan R. Blood sample collection in small laboratory animals. J Pharmacol Pharmacother. 2010; 1(2): 87-93, CrossRef.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985; 28(7): 412-9, CrossRef.
Mayyas F, Alzoubi KH. Impact of cigarette smoking on kidney inflammation and fibrosis in diabetic rats. Inhal Toxicol. 2019; 31(2): 45-51, CrossRef.
Malik F, Iqbal A, Zia S, Ranjha MMAN, Khalid W, Nadeem M, et al. Role and mechanism of fruit waste polyphenols in diabetes management. Open Chem. 2023; 21(1): 20220272, CrossRef.
Błaszczyk N, Rosiak A, Kałużna-Czaplińska J. The potential role of cinnamon in human health. Forests. 2021; 12(5): 648, CrossRef.
Laddha AP, Kulkarni YA. Tannins and vascular complications of diabetes: An update. Phytomedicine. 2019; 56: 229-45, CrossRef.
Rodríguez-González S, Gutiérrez-Ruíz IM, Pérez-Ramírez IF, Mora O, Ramos-Gomez M, Reynoso-Camacho R. Mechanisms related to the anti-diabetic properties of mango (Mangifera indica L.) juice by-product. J Funct Foods. 2017; 37: 190-9, CrossRef.
Sabater AG, Ribot J, Priego T, Vazquez I, Frank S, Palou A, et al. Consumption of a mango fruit powder protects mice from high-fat induced insulin resistance and hepatic fat accumulation. Cell Physiol Biochem. 2017; 42(2): 564-78, CrossRef.
Aligita W, Susilawati E, Sukmawati IK, Holidayanti L, Riswanti J. Antidiabetic activities of Muntingia calabura L. leaves water extract in type 2 diabetes mellitus animal models. Indones Biomed J. 2018; 10(2): 165-70, CrossRef.
Sargowo D, Wihastuti TA, Sukotjo CT, Anjani PM, Handayani O, Adrian LH. The effect of polysaccharides peptides Ganoderma lucidum to aortic foam cell count and lipid profile in type 2 diabetic model Rattus norvegicus strain Wistar. Indones Biomed J. 2017; 9(3): 153-9, CrossRef.
Lin LY, Chuang CH, Chen HC, Yang KM. Lime (Citrus aurantifolia (Christm.) Swingle) essential oils: volatile compounds, antioxidant capacity, and hypolipidemic effect. Foods. 2019; 8(9): 398, CrossRef.
Manuha DM, Paranagama PP, Nageeb DB. Quantitative analysis of vitamin c in lime and lemon in vitro: verification of vitamin c on the impairment of obesity. Int J Adv Sci Res Eng. 2019; 05(10): 157-61, CrossRef.
Kirtaniya AAIK, Lestarini A, Permatananda PANK, Aryastuti AASA. Association of ELMO1 genetic polymorphism (rs741301) with the progression of diabetic kidney disease in Balinese patients with type 2 diabetes mellitus. Mol Cell Biomed Sci. 2023; 7(1): 47-51, CrossRef.
DOI: https://doi.org/10.18585/inabj.v18i4.4220
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