Granule Nanoparticle Citrus sinensis (L.) Osbeck Peel Lowers Blood Glucose Levels and HbA1C in Alloxan-induced Diabetes Rats

Maya Sari Mutia, Yelvreza Rastiani Sipayung, Dwi Elmiam, Widya Yanti Sihotang, Juliana Lina

Abstract


BACKGROUND: The peel of Citrus sinensis (L.) Osbeck (sunkist orange) peels, which are often seen as waste, actually contains valuable properties such as antioxidants, hypoglycemic, nephroprotective, and anti-inflammatories. The potential effects of C. sinensis peel on diabetes have been discussed but not clear yet. Therefore, this study was performed to evaluate the effects of Granule Nanoparticle Sunkist Peel (GNSP) extracts as an antidiabetic agent in alloxan-induced diabetic rats.

METHODS: The nanoparticle suspension was prepared by mixing a formulation of 0.2% chitosan and 0.1% sodium tripolyphosphate. The characteristics of nanoparticles were measured by flow time, tap index and angle of repose. Rats were induced with alloxan injection to create diabetes rat models. Rats were divided into five groups; normal control group, diabetic controls, and diabetic rats receiving either 50, 100, or 200 mg/kg/day GNSP. After 28 days of diabetes induction, rats were euthanized, and blood as well as tissue samples were collected. Blood glucose levels, HbA1c, and histopathology of the liver, kidneys, and pancreas were then assessed.

RESULTS: The particle size of the synthesized material was 92.3 nm, which confirmed the nature of nanoparticle. The characteristics of the granule nanoparticle were also in accordance with the standards for drugs suitable for consumption. The administration of GNSP in dose dependent manner significantly decrease blood glucose levels and HbA1C to normal levels compared to control group (p<0.05). Histopathological analysis indicated recovery in pancreas, liver, and kidney tissues following GNSP administration.

CONCLUSION: GNSP administration lowers blood glucose levels and HbA1C, as well as improved histopathological condition of pancreas, liver, and kidney in diabetic rats. These findings suggest the potential of utilizing GNSP as a potent antidiabetic agent.

KEYWORDS: Citrus Sinensis (L.) Osbeck, histopathology, hyperglycemia, nano medicine, and type 2 diabetes mellitus


Full Text:

PDF

References


Agarwal C, Jahan T, Parveen N, Yousuf Y. Diabetes: The silent killer. 2018; 5(8): 444-6, article.

Bhatti JS, Sehrawat A, Mishra J, Sidhu IS, Navik U, Khullar N, et al. Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radic Biol Med. 2022; 184: 114-34, CrossRef.

Haq FU, Siraj A, Ameer MA, Hamid T, Rahman M, Khan S, et al. Comparative review of drugs used in diabetes mellitus-New and Old. J Diabetes Mellit. 2021; 11(4): 115-31, CrossRef.

Wang J, Zhang Y, Li B, Zhao Z, Huang C, Zhang X, et al. Asthma and allergic rhinitis among young parents in China in relation to outdoor air pollution, climate and home environment. Sci Total Environ. 2021; 751: 141734, CrossRef.

Salehi S, Mehrpour S, Koohmanaee S, Maleknejad S, Esfandiari MA, Maroufizadeh S, et al. Is there any need for the early detection of non-alcoholic fatty liver disease in children with type 1 diabetes mellitus? Hepat Mon. 2023; 23(1): e135941, CrossRef.

Lautié E, Russo O, Ducrot P, Boutin JA. Unraveling plant natural chemical diversity for drug discovery purposes. Front Pharmacol. 2020; 11: 1-37, CrossRef.

Dey P, Sowmya A, Jain AM, Sreenath A, Saji GS. Advances and prospects of medicinal herbs and their natural bioactive components for effective control of diabetics. Res J Chem Environ. 2022; 26(6): 142-9, CrossRef.

Rosenzweig T, Sampson SR. Activation of insulin signaling by botanical products. Int J Mol Sci. 2021; 22(8): 4193, CrossRef.

Patel D, Prasad S, Kumar R, Hemalatha S. An overview on antidiabetic medicinal plants having insulin mimetic property. Asian Pac J Trop Biomed. 2012; 2(4): 320-30, CrossRef.

Sun C, Zhao C, Guven EC, Paoli P, Simal‐Gandara J, Ramkumar KM, et al. Dietary polyphenols as antidiabetic agents: Advances and opportunities. Food Front. 2020; 1(1): 18-44, CrossRef.

Mutia MS, Damayanti EWH, Suyono T, Sihotang WY. The antiacne activity of sunkist peels methanol extract in Propionibacterium acne-induced acne vulgaris. AVERROUS J Kedokt dan Kesehat Malikussaleh. 2023; 9(2): 10-22, CrossRef.

Sihotang WY, Putri IJD, Henny H, Suandy S, Mutia MS. Effect of sunkist orange peel nanoparticle granules on cardiac and aorta histopathology in diabetic rats. J Prima Med Sains. 2023; 5(2): 94-9, CrossRef.

Mutia MS. Ekstrak Kulit Jeruk Sunkist: Kajian Antioksidan Bagi Kesehatan Hepar. Medan: UNPRI Press; 2021, article.

Pallavi M, Ramesh CK, Siddesha JM, Krishna V, Kavitha GC, Nethravathi AM, et al. Anti-hyperlipidemic effects of citrus fruit peel extracts against high fat diet-induced hyperlipidemia in rats. Int J Res Pharm Sci. 2021; 12(3): 2226-32, CrossRef.

Ghaffari M, Dolatabadi JEN. Nanotechnology for pharmaceuticals. In: Industrial Applications of Nanomaterials. Amsterdam: Elsevier; 2019. p. 475-502, CrossRef.

Kadian R. Nanoparticles: A promising drug deliverry approach. Asian J Pharm Clin Res. 2018; 11(1): 30-5, CrossRef.

Adepu S, Ramakrishna S. Controlled drug delivery systems: Current status and future directions. Molecules. 2021; 26(19): 5905, CrossRef.

Beaven E, Kumar R, An JM, Mendoza H, Sutradhar SC, Choi W, et al. Potentials of ionic liquids to overcome physical and biological barriers. Adv Drug Deliv Rev. 2024; 204: 115157, CrossRef.

Sari M, Ginting CN, Yulizal O. Sunkist peel ethanol extract ameliorates diabetic nephropathy in streptozotocin-induced diabetic wistar rats. Open Access Maced J Med Sci. 2021; 9: 1086-91, CrossRef.

Alghazeer R, El-Saltani H, Saleh N, Al-Najjar A, Hebail F. Antioxidant and antimicrobial properties of five medicinal Libyan plants extracts. Nat Sci. 2012; 4(5): 324-35, CrossRef.

Souto EB, Souto SB, Campos JR, Severino P, Pashirova TN, Zakharova LY, et al. Nanoparticle delivery systems in the treatment of diabetes complications. Molecules. 2019; 24(23): 4209, CrossRef.

Liu Y, Yang G, Jin S, Xu L, Zhao CX. Development of high-drug-loading nanoparticles. Chempluschem. 2020; 85(9): 2143-57, CrossRef.

Nagaraja S, Ahmed SS, D R B, Goudanavar P, M RK, Fattepur S, et al. Green synthesis and characterization of silver nanoparticles of Psidium guajava leaf extract and evaluation for its antidiabetic activity. Molecules. 2022; 27(14): 4336, CrossRef.

Mutia MS, Harahap S, Nurhady FZ, Gunawan R, Dewani Y, Chairul M, et al. Effect of sunkist orange peel extract nanoparticle granules on the lipid profile levels in diabetic wistar rat. J Prima Med Sains. 2023; 5(2): 135-8, CrossRef.

Beheshtipour J. Comment on "Anion gap toxicity in alloxan induced type 2 diabetic rats treated with antidiabetic noncytotoxic bioactive compounds of ethanolic extract of Moringa oleifera." J Toxicol. 2019; 2019: 3930587, CrossRef.

Rohilla A, Ali S. Alloxan induced diabetes: Mechanisms and effects. Int J Res Pharm Biomed Sci. 2012; 3(2): 819-23, article.

Shehadeh MB, Suaifan GARY, Abu-Odeh AM. Plants secondary metabolites as blood glucose-lowering molecules. Molecules. 2021; 26(14): 4333, CrossRef.

Mojo T, Sutrisno, Marfuah S. Chemical content and pharmacology of sweet orange (Citrus sinensis) fruit peel: A review. E3S Web Conf. 2024; 481: 06002, CrossRef.

Grajang IB, Wahyuningsih I. Formulation of Sechium edule extract effervescent granule with the variation of citric acid, tartrate acid and sodium bicarbonate. In: Proceedings of the 1st Muhammadiyah International Conference on Health and Pharmaceutical Development. Yogyakarta: SCITEPRESS - Science and Technology Publications; 2018. p. 54-60, CrossRef.

Maysarah H, Sari I, Faradilla M, Kwok K. Formulation of effervescent granule from robusta green coffee bean ethanolic extract (Coffea canephora). J Pharm Bioallied Sci. 2020; 12(Suppl 2): S743-6, CrossRef.

Da R, Simamora S, Tedi. Potential granule effervescent from a mixture of beetroot extract (Beta vulgaris L), Malang apple (Malus sylvestris L.) and Carrot (Daucus carota L.) as preparation for lowering blood cholesterol Levels. Int J Innov Sci Res Technol. 2022; 7(2): 934-8, article.

(yg penulisnya kurang cuman 1)

Orefice L, Remmelgas J, Neveu A, Francqui F, Khinast JG. A novel methodology for data analysis of dynamic angle of repose tests and powder flow classification. Powder Technol. 2024; 435: 119425, CrossRef.

Bereda G. Brief overview of diabetes mellitus. Diabetes Manag. 2021; S1: 21-7, article.

Miller BR, Nguyen H, Hu CJH, Lin C, Nguyen QT. New and emerging drugs and targets for type 2 diabetes: Reviewing the evidence. Am Heal Drug Benefits. 2014; 7(8): 452-61, PMID.

Bai L, Li X, He L, Zheng Y, Lu H, Li J, et al. Antidiabetic potential of flavonoids from traditional Chinese medicine: A review. Am J Chin Med. 2019; 47(5): 933-57, CrossRef.

Widowati W, Wargasetia TL, Afifah E, Mozef T, Kusuma HSW, Nufus H, et al. Antioxidant and antidiabetic potential of Curcuma longa and its compounds. Asian J Agri Biol. 2018; 6(2): 149-61, article.

Deshmukh D. A review: On herbal medicine used in the treatment of diabetes mellitus. J Emerg Technol Innov Res. 2021; 8(8): 312-22, article.

González P, Lozano P, Ros G, Solano F. Hyperglycemia and oxidative stress: An integral, updated and critical overview of their metabolic interconnections. Int J Mol Sci. 2023; 24(11): 9352, CrossRef.

Alotaibi MR, Fatani AJ, Almnaizel AT, Ahmed MM, Abuohashish HM, Al-Rejaie SS. In vivo assessment of combined effects of glibenclamide and losartan in diabetic rats. Med Princ Pract. 2019; 28(2): 178-85, CrossRef.

Anjajo EA, Workie SB, Tema ZG, Woldegeorgis BZ, Bogino EA. Determinants of hypertension among diabetic patients in southern Ethiopia: a case-control study. BMC Cardiovasc Disord. 2023; 23(1): 233, CrossRef.




DOI: https://doi.org/10.18585/inabj.v17i1.3334

Copyright (c) 2025 The Prodia Education and Research Institute

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

 

Indexed by:

                  

               

                

 

 

The Prodia Education and Research Institute