Therapeutic Potential of Ginger Ethanolic Extract, Ginger-Loaded Chitosan ‎Nanoparticles, and Chitosan Nanoparticles in Induced Type 2 Diabetes Mellitus in Dogss in Induced Type 2 Diabetes Mellitus in Dogs

Main Article Content

Rasema M Hameed
Alaa K Mahmood

Abstract





Type 2 diabetes mellitus (T2DM) in dogs is a complex, multifactorial disease that is characterized by chronic hyperglycemia and insulin resistance. Current therapeutic options are often limited by side effects and variable efficacy, highlighting the need for more effective and safer treatments. This study assessed the therapeutic potential of ginger ethanolic extract (GEE), GEE-loaded chitosan nanoparticles (GEE-CNPs), and chitosan nanoparticles (CNPs) against T2DM in dogs. Twenty adult local breed mongrel dogs of both sexes, aged 7 to 13 months, with an average body weight of 10.4±0.76 kg, were included. The dogs were allocated into five groups (n=4 each): a non-diabetic, untreated Negative Control group, and four diabetic treatment groups, following T2DM induction via a single intravenous alloxan-nicotinamide injection. Each treatment group received daily oral administrations of either saline (Positive Control), GEE, GEE-CNPs, or CNPs at a dosage of 81.7 mg/kg BW over 45 days. Serum glycemic status (fasting serum glucose, insulin, and insulin resistance) was ‎recorded at baseline and on days 7, 14, 21, 28, 35, 42, and 45 post-treatments. ‎Additionally, on day 45, serum lipid profiles, liver function indicators (alanine aminotransferase [ALT], gamma-glutamyl transferase [GGT], and bilirubin), and ‎markers of antioxidant status (glutathione [GSH] and malondialdehyde [MDA]) were assessed.‎ The results showed that dogs in the diabetic Positive Control group ‎exhibited ‎hyperglycemia, dyslipidemia‎, liver ‎dysfunction, and elevated ‎oxidative stress markers, ‎‎underscoring the severe impact of T2DM. Compared to the diabetic Positive Control, oral GEE, GEE-CNPs, and CNPs ‎treatments significantly (P<0.05) improved ‎fasting glucose levels, insulin sensitivity, lipid profiles (reduced total cholesterol, ‎triglycerides, and LDL-C), liver function markers, and antioxidant status, indicating ‎enhanced metabolic health and reduced oxidative stress. The findings suggest that GEE, GEE-CNPs, and CNPs offer potential as therapeutic agents for T2DM in dogs, demonstrating ‎significant benefits in glycemic control, lipid normalization, liver function, and oxidative ‎stress reduction. Further investigations with larger cohorts and longer durations are ‎recommended to confirm these results and ascertain the clinical applicability and safety of ‎these natural remedies in managing canine diabetes‎‎‎.


 


 


 





Downloads

Download data is not yet available.

Article Details

How to Cite
Therapeutic Potential of Ginger Ethanolic Extract, Ginger-Loaded Chitosan ‎Nanoparticles, and Chitosan Nanoparticles in Induced Type 2 Diabetes Mellitus in Dogss in Induced Type 2 Diabetes Mellitus in Dogs. (2024). The Iraqi Journal of Veterinary Medicine, 48(2), 15-25. https://doi.org/10.30539/fae5kc34
Section
Articles

How to Cite

Therapeutic Potential of Ginger Ethanolic Extract, Ginger-Loaded Chitosan ‎Nanoparticles, and Chitosan Nanoparticles in Induced Type 2 Diabetes Mellitus in Dogss in Induced Type 2 Diabetes Mellitus in Dogs. (2024). The Iraqi Journal of Veterinary Medicine, 48(2), 15-25. https://doi.org/10.30539/fae5kc34

References

O'Kell AL, Davison LJ. Etiology and Pathophysiology of ‎Diabetes ‎‎Mellitus ‎in Dogs. Vet Clin North Am Small Anim Pract. 2023;‎‎‎53(3):493–‎‎510. https://doi.org/10.1016/j.cvsm.2023.01.004

‎Fracassi F. Diabetes Mellitus in Dogs. In: Côté E, Ettinger SJ, Feldman EC, editors. Ettinger's Textbook of Veterinary Internal Medicine. 9th ed. Philadelphia, PA: Elsevier; 2024. p. 1678-1703.

Behrend E, Holford A, Lathan P, Rucinsky R, Schulman R. ‎‎2018 ‎AAHA ‎‎Diabetes ‎Management Guidelines for Dogs and Cats. J Am ‎Anim Hosp ‎Assoc. 2018;54:1–‎‎19. https://doi.org/10.5326/JAAHA-MS-6822

Niessen SJ, Powney S, Guitian J, Niessen AP, Pion PD, Shaw JA, et al. Evaluation of quality-of-life tool for ‎dogs with ‎‎diabetes mellitus, J Vet Intern Med. 2012;26(4):953-961‎. https://doi.org/10.1111/j.1939-1676.2012.00947.x

Aptekmann KP, Armstrong J, Coradini M, Rand J. Owner experiences in treating dogs and cats diagnosed with diabetes mellitus in the United States. J Am Anim Hosp Assoc. 2014 ;50(4):247-53. https://doi.org/10.5326/JAAHA-MS-6101

Reinhart JM, Graves TK. The Future of Diabetes Therapies: New Insulins and Insulin ‎Delivery Systems, Glucagon-Like Peptide 1 Analogs, Sodium-Glucose Cotransporter ‎Type 2 Inhibitors, and Beta Cell Replacement Therapy. Vet Clin North Am Small Anim ‎Pract. 2023;53(3):675-690. https://doi.org/10.1016/j.cvsm.2023.01.003

Vaitaitis G, Webb T, Webb C, Sharkey C, Sharkey S, Waid D, et al. Canine ‎diabetes mellitus demonstrates multiple markers of chronic inflammation including ‎Th40 cell increases and elevated systemic-immune inflammation index, consistent with ‎autoimmune dysregulation. Front Immunol. 2024;14:1319947. https://doi.org/10.3389/fimmu.2023.1319947

Chapman S. Canine diabetes mellitus. Vet Nur. 2019;10(7):360-363. 10.12968/vetn.2019.10.7.360

Suemanotham N, Phochantachinda S, Chatchaisak D, Sakcamduang W, ‎Chansawhang ‎A, Pitchakarn P et al. Antidiabetic ‎effects of Andrographis ‎paniculata supplementation on biochemical ‎parameters, inflammatory responses, and ‎oxidative stress in canine ‎diabetes. Front. Pharmacol. 2023;14:1077228. https://doi.org/10.3389/fphar.2023.1077228

Suemanotham N, Photcharatinnakorn P, Chantong B, Buranasinsup S, ‎‎Phochantachinda S, Sakcamduang W, et al. Curcuminoid supplementation in canine diabetic ‎mellitus and ‎its complications using proteomic analysis. Front Vet Sci. 2022;9:1057972.‎ https://doi.org/10.3389/fvets.2022.1057972

Hassan H, Zaghawa A, Aly M, Kamr A, Nayel M, Mohamed M A-E-G, ‎Abdelazeim A and Hassan B (2019). The effects of some medicinal plants ‎with insulin on the inflammatory and metabolic responses in dogs with ‎induced diabetes mellitus. Online J. Anim. Feed Res., 9(6): 212-224‎. https://doi.org/10.36380/scil.2019.ojafr30

Ogbu SO, Agwu KK, Asuzu IU. Gongronema latifolium ‎delays ‎gastric ‎emptying of semi-solid meals in diabetic dogs. Afr. J. Tradit. ‎Complement. ‎Altern. Med. 2013;‎‎10(5):325–331. https://doi.org/10.4314/ajtcam.v10i5.17

Russell KR, Omoruyi FO, Pascoe KO, Morrison EY. ‎Hypoglycaemic ‎activity of Bixa orellana extract in the dog. Methods Find. ‎Exp. Clin. Pharmacol.2008;30(4):‎‎301–305. https://doi.org/10.1358/mf.2008.30.4.1186073

Akash MSH, Rehman K, Chen S. Role of inflammatory mechanisms in ‎pathogenesis of ‎‎type ‎‎2 diabetes ‎mellitus. J Cell Biochem. ‎‎2013;114(3):525–531‎. https://doi.org/10.1002/jcb.24402

Garza-Cadena C, Ortega-Rivera DM, Machorro-García G, Gonzalez-Zermeño ‎EM, ‎‎Homma-‎Dueñas D, Plata-Gryl M, et al. A ‎comprehensive ‎review on ‎Ginger ‎‎(Zingiber officinale) as a potential source ‎of nutraceuticals for ‎food ‎formulations: ‎Towards the polishing of gingerol ‎and other present ‎biomolecules. Food ‎Chem. 2023;‎‎413:135629. https://doi.org/10.1016/j.foodchem.2023.135629

Zhang M, Zhao R, Wang D, Wang L, Zhang Q, Wei S, et al. Ginger ‎‎‎(Zingiber officinale‎ Rosc.) and its bioactive components are ‎potential resources for ‎‎health beneficial agents. Phytother Res. 2021;35(2):711-‎‎742. https://doi.org/10.1002/ptr.6858

Sonia TA, Sharma CP. An overview of natural polymers for oral insulin delivery. Drug ‎Discov Today. 2012;17(13-14):784-792. https://doi.org/10.1016/j.drudis.2012.03.019

‎Priyanka DN, Prashanth KH, Tharanathan, RN. A review on potential anti-‎diabetic ‎‎‎‎mechanisms of chitosan and its derivatives. Carbohydr Polym Technolo ‎‎‎‎Appl. 2022;3:100188. https://doi.org/10.1016/j.carpta.2022.100188

Nie X, Chen Z, Pang L, Wang L, Jiang H, Chen Y, et al. Oral Nano Drug Delivery Systems for the Treatment of Type 2 Diabetes Mellitus: ‎An Available Administration Strategy for Antidiabetic Phytocompounds. Int.J.Nanomed.2020;15:10215–10240. https://doi.org/10.2147/IJN.S285134

‎‎Salih SI, Al-Mutheffer EA, Mahdi AK, Al-Naimi RAS. Role of chitosan application in ‎‎‎postoperative abdominal adhesions in rabbits. Iraqi J VetMed.2015;‎‎39(1):105–111. https://doi.org/10.30539/iraqijvm.v39i1.206

Majeed R, Mahmood AK. Protective effects of ginger ethanolic extract, chitosan ‎nanoparticles, ‎and ginger ethanolic extract-loaded chitosan nanoparticles on pancreatic ‎DNA damage and ‎histological changes in dogs with alloxan-nicotinamide induced type ‎‎2 diabetes. Adv. ‎Anim. Vet.Sci.2024;12(1):32-43. https://doi.org/10.17582/journal.aavs/2024/12.1.32.43

‎Buishand F. Diabetes Mellitus in Dogs and Cats. MSD Veterinary Manual. Updated May 2024. Available from

Abbas AB, Abbas DA. Evaluation of lipid profile and inflammatory parameters in female ‎‎diabetes type 2 induced rabbits treated with glimepride, bromocriptine and fluoxtein. ‎Iraqi ‎J. Vet. Med. 2019;42(2):97-104. https://doi.org/10.30539/iraqijvm.v42i2.305

Vattam KK, Raghavendran H, Murali MR, Savatey H, Kamarul T. Coadministration of ‎‎alloxan and nicotinamide in rats produces biochemical changes in blood and ‎pathological ‎alterations comparable to the changes in type II diabetes mellitus. Hum. ‎Expert. Toxicol.2016;‎‎35(8):893-901. https://doi.org/10.1177/0960327115608246

Sari DR, Ahmad FF, Djabir YY, Yulianty R. Breadfruit leaves extract (Artocarpus ‎altilis) ‎effect on pancreatic damage in diabetic type II animal model induced by alloxan– ‎‎nicotinamide. Med. Clín. Práct. 2020;3(1):100099. https://doi.org/10.1016/j.mcpsp.2020.100099

Uchigata Y, Yamamoto H, Nagai H, Okamoto H. Effect of poly (ADP-ribose) synthetase ‎‎inhibitor administration to rats before and after injection of alloxan and streptozotocin ‎on ‎islet proinsulin synthesis. Diabetes.1983;32(4):316-318. https://doi.org/10.2337/diab.32.4.316

Lenzen S. The mechanisms of alloxan- and streptozotocin-induced diabetes. Diabetologia.‎‎2008;51(2):216-226. https://doi.org/10.1007/s00125-007-0886-7

Akhani SP, Vishwakarma SL, Goyal RK. Anti-diabetic activity of Zingiber officinale in ‎‎‎streptozotocin-induced type I diabetic rats. J PharmPharmacol.2004;56:101-105‎.‎ https://doi.org/10.1211/0022357022403

Al-Amin ZM, Thomson M, Al-Qattan KK, Peltonen-Shalaby R, Ali M. Antidiabetic and hypolipidaemic ‎‎properties ‎of ginger (zingiber officinale) in streptozotocin-induced diabetic ‎rats. ‎Br J Nut. ‎‎2006;96(4):660–666.‎ https://doi.org/10.1079/BJN20061849

Son MJ, Miura Y, Yagasaki K. Mechanisms for antidiabetic effect of gingerol in ‎cultured ‎cells and obese diabetic model mice. Cytotechnology. ‎‎2015;67:641‎.‎ https://doi.org/10.1007/s10616-014-9730-3

Arzati MM, Honarvar NM, Saedisomeolia A, Anvari S, Effatpanah M, Arzati RM, et al. ‎The ‎‎effects of ginger on fasting blood sugar, hemoglobin A1c, and lipid profiles in ‎patients ‎with ‎type 2 diabetes. Int J Endocrinol Metabol. 2017;15(4):e57927‎. 10.5812%2Fijem.57927

Khandouzi N, Farzad S, Asadollah R, Tayebeh R, Payam H, Mohsen MT. The ‎effects ‎of ‎ginger on fasting blood sugar, hemoglobin A1c, apolipoprotein ‎B, ‎apolipoprotein AI and ‎malondialdehyde in type 2 diabetic patients. ‎Iran J Pharm Res. 2015;14(1):131‎-140.

Li Y, Tran VH, Duke CC, Roufogalis BD. Gingerols of Zingiber officinale ‎enhance ‎‎glucose ‎uptake by increasing cell surface GLUT4 in cultured L6 ‎myotubes. Planta ‎Med ‎‎2012;78(14):1549-1555.‎ https://doi.org/10.1055/s-0032-1315041

Li Y, Tran VH, Duke CC, Roufogalis BD. Preventive and protective properties ‎of ‎‎Zingiber ‎‎officinale (ginger) in diabetes mellitus, diabetic ‎complications, and ‎‎associated ‎lipid ‎and other metabolic disorders: A ‎brief review. Evid Based ‎‎Complement ‎Alternat Med. ‎‎2012;2012:516870. https://doi.org/10.1155/2012/516870

Van B, Abdalla AN, Algarni AS, Khalid A, Zengin G, Aumeeruddy MZ, et al. ‎‎Zingiber officinale Roscoe (Ginger) and its bioactive compounds in diabetes: A ‎‎systematic review of clinical studies and insight of mechanism of action. Curr Med ‎‎Chem. 2023;31(7):887-903. https://doi.org/10.2174/0929867330666230524122318

Mashhadi N, Moshref M, Tangey B, Gilor C, Papas KK, ‎Williamson P, et al. ‎Concise review: Canine diabetes mellitus as ‎a translational model for ‎innovative regenerative medicine approaches. Stem Cells ‎Trans ‎Med. 2019;8(5):450–455. https://doi.org/10.1002/sctm.18-0163

Young HY, Liao JC, Chang YS, Luo YL, Lu ML, Peng WH. ‎Synergistic effect of ginger and nifedipine on human platelet ‎aggregation: a study in ‎hypertensive patients and normal volunteers. Am. J. ‎Chin. Med. 2006;34:545–551‎. https://doi.org/10.1142/S0192415X06004089

Samad MB, Mohsin MNAB, Razu BA, Hossain MT, Mahzabeen S, Unnoor N, et al. [6]-‎Gingerol, from Zingiber officinale, potentiates GLP-1 mediated glucose-stimulated ‎insulin secretion pathway in pancreatic β-cells and increases RAB8/RAB10-regulated ‎membrane presentation of GLUT4 transporters in skeletal muscle to improve ‎hyperglycemia in Leprdb/db type 2 diabetic mice. BMC Complement Altern Med. ‎‎2017;17(1):395. https://doi.org/10.1186/s12906-017-1903-0

Guo W, Yi L, Zhou B, Li M. Chitosan modifies glycemic levels in people with metabolic ‎syndrome and related disorders: meta-analysis with trial sequential analysis. Nutr J. ‎‎2020;19(1):130. https://doi.org/10.1186/s12937-020-00647-4

Othman SI, Alturki AM, Abu-Taweel GM, Altoom NG, Allam AA, Abdelmonem R. ‎Chitosan for biomedical applications, promising antidiabetic drug delivery system, and ‎new diabetes mellitus treatment based on stem cell. Int J Biol Macromol. 2021;190:417-‎‎432. https://doi.org/10.1016/j.ijbiomac.2021.08.154

Sarkar S, Das D, Dutta P, Kalita J, Wann SB, Manna P. Chitosan: A promising therapeutic ‎agent and effective drug delivery system in managing diabetes mellitus. Carbohydr ‎Polym. 2020;247:116594. https://doi.org/10.1016/j.carbpol.2020.116594‎

‎ Ojewole JAO. Analgesic, antiinflammatory and hypoglycaemic effects of ethanol ‎extract of ‎Zingiber officinale (Roscoe) rhizomes (Zingiberaceae) in mice and rats. ‎Phytother Res. ‎‎2006;20(9):764-772.‎ https://doi.org/10.1002/ptr.1952

Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber ‎‎‎officinale ‎on dyslipidaemia in diabetic rats. J Ethnopharmacology. 2005;97(2):227–230. https://doi.org/10.1016/j.jep.2004.11.011

Al-Noory AS, Amreen AN, Hymoor S. Antihyperlipidemic effects of ginger extracts in ‎‎alloxan-‎induced diabetes and propylthiouracil-induced hypothyroidism in (rats). ‎‎Pharmacognosy ‎Res. 2013;5:157-161‎.‎ https://doi.org/10.4103/0974-8490.112419

Arablou T, Aryaeian N, Valizadeh M, Sharifi F, Hosseini A, Djalali M. The effect of ginger ‎‎consumption on glycemic status, lipid profile and some inflammatory markers in ‎patients with ‎Type 2 diabetes mellitus. Int J Food Sci Nutr. 2014;65(4):515-520‎. https://doi.org/10.3109/09637486.2014.880671

Hsieh YL, Yao HT, Cheng RS, Chiang MT. Chitosan reduces plasma adipocytokines and ‎lipid accumulation in liver and adipose tissues and ameliorates insulin resistance in ‎diabetic rats. J Med Food. 2012;15(5):453-60. https://doi.org/10.1089/jmf.2011.1882

Kong S, Ding C, Huang L, Bai Y, Xiao T, Guo J, et al. The effects of COST on the ‎differentiation of 3T3-L1 preadipocytes and the mechanism of action. Saudi J Biol Sci. ‎‎2017;24(2):251-255. https://doi.org/10.1016/j.sjbs.2016.09.008

Madkor HR, Mansour SW, Ramadan G. Modulatory effects of garlic, ginger, turmeric and their ‎mixture on hyperglycemia, dyslipidemia and oxidative stress in streptozotocin-nicotinamide ‎diabetic rats. Br. J.Nutr.2011;105(8):1210–1217‎. https://doi.org/10.1017/S0007114510004927

Maritim AC, Sanders RA, Watkins JB 3rd. Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol. 2003;17(1):24-38. https://doi.org/10.1002/jbt.10058

Shanmugam KR, Mallikarjuna K, Nishanth K, Kuo CH, Reddy KS. Protective effect of dietary ginger on antioxidant enzymes and oxidative damage in experimental diabetic rat tissues. Food Chem. 2011;124(4):1436-1442. https://doi.org/10.1016/j.foodchem.2010.07.104

Similar Articles

You may also start an advanced similarity search for this article.