Efficacy of Composite Extract from Leaves and Fruits of Medicinal Plants Used in Traditional Diabetic Therapy against Oxidative Stress in Alloxan-Induced Diabetic Rats
Oxidative stress plays a vital role in diabetic complications. To suppress the oxidative stress mediated damage in diabetic pathophysiology, a special focus has been given on composite extract (CE) and making small dose of naturally occurring antidiabetic plants leaf and fruits. The aim of the present study was to evaluate the beneficial role of CE against alloxan- (ALX-) induced diabetes of Wistar strain rats. A dose-dependent study for CE (25, 50, and 100?mg/kg body weight) was carried out to find the effective dose of the composite compound in ALX-induced diabetic rats. ALX exposure elevated the blood glucose, plasma advanced oxidation product (AOPP), sialic acid demonstrating disturbed antioxidant status.CE at a dose of 100?mg/kg body weight restored/minimised these alterations towards normal values. In conclusion, small dose of CE possesses the capability of ameliorating the oxidative stress in ALX-induced diabetes and thus could be a promising approach in lessening diabetic complications. 1. Introduction Diabetes mellitus is a syndrome characterized by chronic hyperglycemia and associated with absolute or relative deficiency in insulin secretion or insulin action [1]. Herbal medicine has been used as an antidiabetic therapy alone, along with insulin or other synthetic oral hypoglycemic agents. The use of synthetic agents is frequently associated with several undesirable side effects and fails to correct the fundamental biochemical lesion and diabetic complications [2]. The search for a cure for diabetes mellitus continues along with traditional and alternative medicine. Many herbal supplements have been used for the treatment of diabetes, but the scientific evidence to support their effectiveness has only been investigated for a few [3]. To suppress the oxidative stress mediated damage in diabetic pathophysiology, researchers usually look for naturally occurring antioxidants [4, 5]. Diabetes mellitus (DM) is strongly associated with oxidative stress [6]. Chronic hyperglycemia resulting from diabetes brings about a rise in oxidative stress due to overproduction of reactive oxygen species (ROS) as a result of glucose-autoxidation and protein glycosylation. Generation of ROS leads to oxidative damage of the structural components (such as lipids, DNA and proteins) of cells which culminate into complications affecting the eyes, kidney, nerves, and blood vessels [7]. Oxidative insult in cells is also created by the impairment in functioning of endogenous antioxidant enzymes because of nonenzymatic glycosylation and oxidation [8]. Aegle marmelos is a
References
[1]
A. Ramadas, K. F. Quek, C. K. Y. Chan, and B. Oldenburg, “Web-based interventions for the management of type 2 diabetes mellitus: a systematic review of recent evidence,” International Journal of Medical Informatics, vol. 80, no. 6, pp. 389–405, 2011.
[2]
D. K. Patel, S. K. Prasad, R. Kumar, and S. Hemalatha, “An overview on antidiabetic medicinal plants having insulin mimetic property,” Asian Pacific Journal of Tropical Biomedicine, vol. 2, no. 4, pp. 320–330, 2012.
[3]
R. Patil, R. Patil, B. Ahirwar, and D. Ahirwar, “Current status of Indian medicinal plants with antidiabetic potential: a review,” Asian Pacific Journal of Tropical Biomedicine, vol. 1, no. 2, pp. S291–S298, 2011.
[4]
P. Manna, J. Ghosh, J. Das, and P. C. Sil, “Streptozotocin induced activation of oxidative stress responsive splenic cell signaling pathways: protective role of arjunolic acid,” Toxicology and Applied Pharmacology, vol. 244, no. 2, pp. 114–129, 2010.
[5]
P. Manna, J. Das, J. Ghosh, and P. C. Sil, “Contribution of type 1 diabetes to rat liver dysfunction and cellular damage via activation of NOS, PARP, IκBα/NF-κB, MAPKs, and mitochondria-dependent pathways: prophylactic role of arjunolic acid,” Free Radical Biology and Medicine, vol. 48, no. 11, pp. 1465–1484, 2010.
[6]
S. I. Rizvi and N. Srivastava, “Erythrocyte plasma membrane redox system in first degree relatives of type 2 diabetic patients,” International Journal of Diabetes Mellitus, vol. 2, no. 2, pp. 119–121, 2010.
[7]
A. P. Robertson, “Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes,” The Journal of Biological Chemistry, vol. 279, no. 41, pp. 42351–42354, 2004.
[8]
T. J. Lyons, “Oxidized low density lipoproteins: a role in the pathogenesis of atherosclerosis in diabetes?” Diabetic Medicine, vol. 8, no. 5, pp. 411–419, 1991.
[9]
G. R. Gandhi, S. Ignacimuthu, and M. G. Paulraj, “Hypoglycemic and β-cells regenerative effects of Aegle marmelos (L.) Corr. bark extract in streptozotocin-induced diabetic rats,” Food and Chemical Toxicology, vol. 50, no. 5, pp. 1667–1674, 2012.
[10]
Y. Mohammad and I. Mohammad, “Clinical evaluation of antidiabetic activity of Trigonella seeds and Aegle marmelos leaves,” World Applied Sciences Journal, vol. 7, no. 10, pp. 1231–1234, 2009.
[11]
R. Gupta, K. G. Bajpai, S. Johri, and A. M. Saxena, “An overview of Indian novel traditional medicinal plants with anti-diabetic potentials,” African Journal of Traditional, Complementary and Alternative Medicines, vol. 5, no. 1, pp. 1–17, 2008.
[12]
I. J. Atangwho, P. E. Ebong, E. U. Eyong, and G. E. Egbung, “Combined extracts of Vernonia amygdalina and Azadirachta indica may substitute insulin requirement in the management of type I diabetes,” Research Journal of Medicine and Medical Sciences, vol. 5, no. 1, pp. 35–39, 2010.
[13]
H. Yankuzo, Q. U. Ahmed, R. I. Santosa, S. F. U. Akter, and N. A. Talib, “Beneficial effect of the leaves of Murraya koenigii (Linn.) Spreng (Rutaceae) on diabetes-induced renal damage in vivo,” Journal of Ethnopharmacology, vol. 135, no. 1, pp. 88–94, 2011.
[14]
A. N. Kesari, S. Kesari, S. K. Singh, R. K. Gupta, and G. Watal, “Studies on the glycemic and lipidemic effect of Murraya koenigii in experimental animals,” Journal of Ethnopharmacology, vol. 112, no. 2, pp. 305–311, 2007.
[15]
P. Arulselvan, G. P. Senthilkumar, D. S. Kumar, and S. Subramanian, “Anti-diabetic effect of Murraya koenigii leaves on streptozotocin induced diabetic rats,” Pharmazie, vol. 61, no. 10, pp. 874–877, 2006.
[16]
P. K. Mukherjee, K. Maiti, K. Mukherjee, and P. J. Houghton, “Leads from Indian medicinal plants with hypoglycemic potentials,” Journal of Ethnopharmacology, vol. 106, no. 1, pp. 1–28, 2006.
[17]
P. K. Singh, D. Baxi, S. Banerjee, and A. V. Ramachandran, “Therapy with methanolic extract of Pterocarpus marsupium Roxb and Ocimum sanctum Linn reverses dyslipidemia and oxidative stress in alloxan induced type I diabetic rat model,” Experimental and Toxicologic Pathology, vol. 64, no. 5, pp. 441–448, 2012.
[18]
K. B. Burade and B. S. Kuchekar, “Antidiabetic activity of madhunashini (MD-19) in alloxan induced diabetic mellitus,” Journal of Cell and Tissue Research, vol. 11, no. 1, pp. 2515–2520, 2011.
[19]
G. Manonmani, V. Bhavapriya, S. Kalpana, S. Govindasamy, and T. Apparanantham, “Antioxidant activity of Cassia fistula (Linn.) flowers in alloxan induced diabetic rats,” Journal of Ethnopharmacology, vol. 97, no. 1, pp. 39–42, 2005.
[20]
P. S. M. Prince, N. Kamalakkannan, and V. P. Menon, “Antidiabetic and antihyperlipidaemic effect of alcoholic Syzigium cumini seeds in alloxan induced diabetic albino rats,” Journal of Ethnopharmacology, vol. 91, no. 2-3, pp. 209–213, 2004.
[21]
A. C. R. Leite, T. G. Araújo, B. M. Carvalho, N. H. Silva, V. L. M. Lima, and M. B. S. Maia, “Parkinsonia aculeata aqueous extract fraction: biochemical studies in alloxan-induced diabetic rats,” Journal of Ethnopharmacology, vol. 111, no. 3, pp. 547–552, 2007.
[22]
S. Sadeghian, M. A. Boroumand, M. Sotoudeh-Anvari, S. Rabbani, M. Sheikhfathollahi, and A. Abbasi, “Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes,” Endokrynologia Polska, vol. 60, no. 4, pp. 258–262, 2009.
[23]
V. Witko-Sarsat, M. Friedlander, C. Capeillère-Blandin et al., “Advanced oxidation protein products as a novel marker of oxidative stress in uremia,” Kidney International, vol. 49, no. 5, pp. 1304–1313, 1996.
[24]
M.-H. E. Spyridaki and P. A. Siskos, “An improved spectrophotometric method for the determination of free, bound and total N-acetylneuraminic acid in biological fluids,” Analytica Chimica Acta, vol. 327, no. 3, pp. 277–285, 1996.
[25]
W. G. Duncombe, “The colorimetric micro-determination of long-chain fatty acids,” Biochemical Journal, vol. 88, pp. 7–10, 1963.
[26]
D. W. Moss, D. N. Baron, P. G. Walker, and J. H. Wilkinson, “Standardization of clinical enzyme assays,” Journal of Clinical Pathology, vol. 24, no. 8, pp. 740–743, 1971.
[27]
S. Pandey, “Treatment of diabetes and hyperlipidemia with extracts of Eugenia jambolana seed and Aegle marmelos leaf extracts in alloxan induced diabetic rats,” International Journal of Pharma and Bio Sciences, vol. 1, no. 2, article 55, 2010.
[28]
K. B. Pandey, N. Mishra, and S. I. Rizvi, “Protein oxidation biomarkers in plasma of type 2 diabetic patients,” Clinical Biochemistry, vol. 43, no. 4-5, pp. 508–511, 2010.
[29]
J. M. A. Hannan, L. Marenah, L. Ali, B. Rokeya, P. R. Flatt, and Y. H. A. Abdel-Wahab, “Ocimum sanctum leaf extracts stimulate insulin secretion from perfused pancreas, isolated islets and clonal pancreatic β-cells,” Journal of Endocrinology, vol. 189, no. 1, pp. 127–136, 2006.
[30]
S. Gupta, M. Kataria, P. K. Gupta, S. Murganandan, and R. C. Yashroy, “Protective role of extracts of neem seeds in diabetes caused by streptozotocin in rats,” Journal of Ethnopharmacology, vol. 90, no. 2-3, pp. 185–189, 2004.
[31]
S. V. Tembhurne and D. M. Sakarkar, “Protective effect of Murraya koenigii (L) leaves extract in streptozotocin induced diabetics rats involving possible antioxidant mechanism,” Journal of Medicinal Plant Research, vol. 4, no. 22, pp. 2418–2423, 2010.
[32]
H. F. Poon, V. Calabrese, G. Scapagnini, and D. A. Butterfield, “Free radicals and brain aging,” Clinics in Geriatric Medicine, vol. 20, no. 2, pp. 329–359, 2004.
[33]
B. S. Berlett and E. R. Stadtman, “Protein oxidation in aging, disease, and oxidative stress,” The Journal of Biological Chemistry, vol. 272, no. 33, pp. 20313–20316, 1997.
[34]
S. I. Rizvi, R. Jha, and P. K. Maurya, “Erythrocyte plasma membrane redox system in human aging,” Rejuvenation Research, vol. 9, no. 4, pp. 470–474, 2006.
[35]
S. Prasad and A. K. Sinha, “Free radical activity in hypertensive type 2 diabetic patients,” International Journal of Diabetes Mellitus, vol. 2, no. 3, pp. 141–143, 2010.
[36]
M. M. Mehdi, P. Singh, and S. I. Rizvi, “Erythrocyte sialic acid content during aging in humans: correlation with markers of oxidative stress,” Disease Markers, vol. 32, no. 3, pp. 179–186, 2012.
[37]
S. M. Rizk and N. A. Sabri, “Evaluation of clinical activity and safety of Daflon 500?mg in type 2 diabetic female patients,” Saudi Pharmaceutical Journal, vol. 17, no. 3, pp. 199–207, 2009.
[38]
O. C. Ohaeri, “Effect of garlic oil on the levels of various enzymes in the serum and tissue of streptozotocin diabetic rats,” Bioscience Reports, vol. 21, no. 1, pp. 19–24, 2001.
[39]
P. K. Jensen, J. S. Christiansen, K. Steven, and H.-H. Parving, “Renal function in streptozotocin-diabetic rats,” Diabetologia, vol. 21, no. 4, pp. 409–414, 1981.