Pterocarpus santalinus ameliorates streptozotocin-induced diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function

Document Type: Original Article

Authors

1 Medical lab specialist, Cleopatra hospital, Cairo

2 Mammalian Toxicology Department, Central Agriculture Pesticides Lab, Agriculture Research Center, Dokki, Giza, 12618, Egypt

3 University of Ain Shams, Faculty of Science, Department of Biochemistry

4 University of Ain Shams, Faculty of Science, Department of Zoology, Abbassia 11566, Cairo, Egypt

Abstract

Objective(s): Morbidity and mortality due to diabetes mellitus (DM) result in exorbitant psycho-economical costs, so there is a strong need to create new strategies and drugs for controlling DM. The aim of the current study was to investigate the anti-diabetic effect of the aqueous extract of Pterocarpus santalinus on streptozotocin (STZ)-induced DM as compared to glustin.
Materials and Methods: Thirty male rats were divided into five groups of six rats each as follows: control; the second group, received the aqueous plant extract (250 mg/kg) orally and daily for three weeks; the third group, was intraperitoneally injected with a single dose of 65 mg/kg of STZ and sacrificed after four weeks; the fourth and fifth groups, were injected with STZ, then after one week these were treated orally with either plant extract or with 3 mg/kg of glustin for three weeks, then sacrificed.
Results: HPLC analysis of the plant aqueous extract showed that it contains many polyphenols and flavonoids. Treatment with STZ resulted in significant reductions in body weight, insulin level, and the expression of Fetuin-A and IRS-1. It also caused significant elevations in glucose, HOMA-IR, glycated hemoglobin, urea, and the expression of JNK and SIRT-1. STZ also caused an extensive β-cell degranulation and decreased cellular density. The aqueous extract of red sandalwood was able to abrogate the deleterious effects caused by STZ and improved the histological architecture of pancreas
Conclusion: The aqueous extract of P. santalinus ameliorates diabetes mellitus via anti-inflammatory pathways and enhancement of insulin function.

Keywords

Main Subjects


1. Albalawi Y, Amin H S, Alharbi K. Comparison of diabetes control among type 2 diabetes mellitus patients treated in the primary health care clinics and diabetes center in King Saud University Hospitals. Am J Res Commun 2014; 2: 1-27.
2. Keskin M, Çulha C, Gülçelik NE, Ademoğlu E, Keskin A, Yalçın AY. Fetuin-A levels determine cardiovascular risk in young diabetic patients. Biomed Res 2017; 28: 6767-6772.
3. Geidl-Flueck B, Gerber PA. Insights into the hexose liver metabolism glucose versus fructose. Nutrients 2017; 9: 1026-1047.
4. Harris VK, Bell L, Langan R, Tuddenham J, Landy M, Sadiq SA. Fetuin-A deficiency protects mice from experimental autoimmune encephalomyelitis (EAE) and correlates with altered innate immune response. Pub Library Sci 2017; 12: e0175575. https://doi.org/10.1371/journal.pone.0175575.
5. Wang H, Zhang M, Bianchi M, Sherry B, Sama A, Kevin J. Fetuin (a2-HS-glycoprotein) opsonizes cationic macrophage deactivating molecules. PNAS 1998; 95: 14429–14434.
6. Pal D, Dasgupta S, Kundu R, Maitra S, Das G. Fetuin-A acts as an endogenous ligand of TLR4 to promote lipid-induced insulin resistance. Nature Med 2012; 18 : 1279-1285.
7. Sag S, Kamanl A, Altındis M, Sag S, Harman H, Tekeoglu I, et al. The relationship of pentraxin-3 levels with IL-17, fetuin-A, insulin in patients with Behçet’s disease. Dermatologica Sinica 2017; 35: 195-200.
8. Farahnak S, Sheikhpour R, Iranmanesh F. Evaluation of Immunoglobulin A in Diabetic Patients and its Relation with Oral Complications. Iranian J Diabetes Obes 2015; 7: 182-186.
9. Taylor DM, Maxwell MM, Luthi-Carter R, Kazantsev AG. Biological and potential therapeutic roles of sirtuin deacetylases. Cell Mol Life Sci 2008; 65: 4000-4018.
10. de Kreutzenberg SV, Ceolotto G, Papparella I. Down regulation of the longevity-associated protein sirtuin 1 in insulin resistance and metabolic syndrome: potential biochemical mechanisms. Diabetes 2010; 59: 1006-1015.
11. Henstridge DC, Bruce CR, Pang CP, Lancaster GI, Allen TL, Estevez E, et al. Skeletal muscle-specific overproduction of constitutively activated c-Jun N-terminal kinase (JNK) induces insulin resistance in mice. Diabetologia 2012; 55: 2769–2778.
12. Ghodsi R, Hamayeli-Meharbani H, Avand A, Bordbar A, Ahmadzadeh S. A study on the prevalence of diabetic complications in fasa diabetes clinic. Asian J Med Pharmaceut Res 2014; 4: 68-72.
13. Bhagour K, Arya D, Gupta RS. A review: Antihyperglycemic plant medicines in management of diabetes. Acupuncture Related Ther 2016; 4: 7-16
14. Howes MJ, Simmonds MS. The role of phytochemicals as micronutrients in health and disease. Curr Opin Clin Nutr Metab Care 2014; 17:558-566.
15. Bulle S,  Reddyvari H, Nallanchakravarthula V, Vaddi DR. Therapeutic Potential of Pterocarpus santalinus L.: An Update. Pharmacogn Rev 2016; 10: 43-49.
16. Halim ME, Misra A. The effects of the aqueous extract of Pterocarpus santalinus heartwood and vitamin E supplementation in streptozotocin-induced diabetic rats. J Med Plants Res 2011; 5: 398-409.
17. Kondeti VK, Badri KR, Maddirala DR, Thur SKM, Sameena FS, Kasetti RB, et al. Effect of Pterocarpus santalinus bark, on blood glucose, serum lipids, plasma insulin and hepatic carbohydrate metabolic enzymes in streptozotocin-induced diabetic rats. Food Chem Toxicol 2010; 48: 1281-1287.
18. Kameswara RB, Giri R, Kesavulu MM, Apparao C. Effect of oral administration of bark extracts of Pterocarpus santalinus L. on blood glucose level in experimental animals. J Ethnopharmacol 2001; 74:69-74.
19. Al-Hariri MT. Comparison the rate of diabetes mellitus induction using streptozotocin dissolved in different solvents in male rats. J Comp Clin Pathol Res 2012; 1/3: 96-99.
20. Bhuvaneswari P, Krishnakumari S. Nephro protective effects of ethanolic extract of Sesamum indicum seeds (Linn.) in streptozotocin induced diabetic male albino rats. Int J Green Pharm 2012; 2012:330-335.
21. Peng J, Li Q, Li K, Zhu L, Lin X, Lin X, et al. Quercetin improves glucose and lipid metabolism of diabetic rats: Involvement of Akt signaling and SIRT1. J Diabetes Res 2017; 2017: 1-10.
22. García-Lafuente A, Guillamón E, Villares A, Rostagno MA, Martínez JA. Flavonoids as anti-inflammatory agents: implications in cancer and cardiovascular disease. Inflamm Res 2009; 58: 537-552.
23. Lenzen S. Oxidative stress: The vulnerable beta-cell. Biochem Soc Transact 2008; 36: 343-347.
24. Mahajan RD, Mishra B. Using Glycated Hemoglobin HbA1C for diagnosis of Diabetes mellitus: An Indian perspective. Int J Biol Med Res 2011; 2: 508-512.
25. Grzesik M, Naparło K , Bartosz G, Sadowska-Bartosz I. Antioxidant properties of catechins: Comparison with other antioxidants. Food Chem 2018; 241: 480–492.
26. Ghorbani A. Mechanisms of antidiabetic effects of flavonoid rutin. Biomed Pharmacother 2017; 96:305-312.
27. Salih ND, Kumar GH, Noah RM, Muslih RK. The effect of  streptozotocin induced diabetes mellitus on liver activity in mice. Glob J Adv Pure Appl Sci 2014; 3: 67-75.
28. Voss C, Brachmann K, Hartmann K. Effect of streptozotocin on transaminases, creatinine and urea in serum of rats. Exp Clin Endocrinol 1988; 92: 37-42.
29. El-Hadidy EM, Refat OG, Halaby MS, Elmetwaly EM, Omar AA. Effect of lion’s foot (Alchemilla vulgaris) on liver and renal functions in rats induced by CCl4. Food Nutr Sci 2018; 2018: 46-62.
30. Kishore L, Kaur N, Singh R. Nephroprotective effect of Paeonia emodi via inhibition of advanced glycation end products and oxidative stress in streptozotocine nicotinamide induced diabetic nephropathy. J Food Drug Anal 2016; 25: 576 -588.
31. Parvizi MR, Parviz M, Tavangar SM, Soltani N, Kadkhodaee M, Seifi B, et al. Protective effect of magnesium on renal function in STZ-induced diabetic rats. J Diabetes Metabol Disorders 2014; 13: 84-93.
32. Fernandes AAH, Novelli ELB, Junior AF, Galhardi CM. Effect of naringerin on biochemical parameters in the streptozotocin-induced diabetic rats. Brazilian Arch Biol Technol 2009; 52: 51-59.
33. Abtahi-Evari S, Shokoohi M, Abbasi A, Rajabzade A, Shoorei H, Kalarestaghi H. Protective Effect of Galega officinalis extract on streptozotocin-induced kidney damage and biochemical factor in diabetic rats.  Crescent J Med Biol Sci 2017; 4: 108-114.
34. Ghelani H, Razmovski-Naumovski V, Nammi S. Chronic treatment of (R)-a-lipoic acid reduces blood glucose and lipid levels in high-fat diet and low-dose streptozotocin-induced metabolic syndrome and type 2 diabetes in Sprague-Dawley rats. Pharmacol Res Perspectives 2017; 5: 1-12.
35. Abdel-Rahman MM, Mahmoud AM, Bastawy NA, Eissa HM.  Anti-hyperlipidemic and myocardial enhancing effects of berberine in high fat diet/streptozotocin-induced diabetic rats; possible role of adiponectin. Nutr Food Sci Int J 2017; 2 : 1-7.
36. Xia C, Rao X, Zhong J. Role of T-Lymphocytes in type 2 diabetes and diabetes-associated inflammation. J Diabetes Res 2017; 2017: 1-6.
37. Jensen MK,  Bartz TM, Djousse L,  Kizer JR, Zieman SJ, Rimm EB, et al. Genetically elevated fetuin-A levels, fasting glucose levels, and risk of type 2 diabetes. Diabetes Care 2013; 36: 3121-3127.
38. Sindhu S, Nadeem A, Rasheed A. Fetuin a (AHSG) in Metabolic and Inflammatory Diseases: A Foe or A Friend. Diabetes Obes Int J 2016; 1: 1-5.
39. Rodgers JT, Puigserver P. Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1. PNAS 2007; 104: 12861–1286.
40. Ali AHK, Mahmoud AA, NourEldin E. Sirtuin 1 gene rs2273773 C > T single nucleotide polymorphism and protein oxidation markers in asthmatic patients. Egyptian J Med Hum Genetics 2016; 17: 191-196.
41. Zhang W, Huang Q, Zeng Z, Wu J, Yaoyuan Zhang Y, Chen Z. Sirt1 inhibits oxidative stress in vascular endothelial cells. Oxidative Med Cell Longev 2017; 2017: 1-8.
42. Werner H, LeRoith D. Insulin and insulin-like growth factor receptors in the brain: Physiological and pathological aspects. Euro Neuropsycho-pharmacol 2014; 24: 1947-1953.
43. Elmadhun MD, Nassrene Y, Antonio D, Lassaletta MD, Louis M, Chu MD, et al. Metformin alters the insulin signaling pathway in ischemic cardiac tissue in a swine model of metabolic syndrome. Cardiovascular Surg 2013; 145: 258-266.
44. Unger EK,  Piper ML, Olofsson LE,  Xu AW. Functional role of c-Jun-N-terminal kinase in feeding regulation. Endocrinology 2010; 151: 671-682.
45. Zhu L, Yuan C, Huang L, Ding X, Wang J, Zhang D, et al.The activation of p38MAPK and JNK pathways in bovine herpes virus 1 infected MDBK cells. Veterinary Res 2016; 47: 91-98.
46. Sharma V, Kalim S, Srivastava MK, Nanda S,  Mishra S. Oxidative stress and coxsackie virus infections as mediators of beta cell damage: A review. Scientific Res Essays 2009; 4: 42-58.
47. Hosseini A, Shafiee-Nick R, Ghorbani A. Pancreatic beta cell protection/regeneration with phytotherapy. Pharmaceutical Sci 2015; 51:1-16.