Dr. Weeks’ Comment: We have seen the power of black cumin seed for myriad chronic degenerative diseases – including diabetes. Here is another powerful article. Thanks to the great Dr. Richard Kunin for sending me this article so that I might share it with you!
“…These results showed that hydroalcholic extract of NS at low doses has hypoglycemic effect and ameliorative effect on regeneration of pancreatic islets and may be used as a therapeutic agent in the management of diabetes mellitus. The hypoglycemic effect observed could be due to amelioration of Î²-cell, thus leading to increased insulin levels. Consequently, N. sativa may prove clinically useful in the treatment of diabetics and in the protection of Î²-cells against streptozotocin…”
Protective and antidiabetic effects of
extract from Nigella sativa on blood
glucose concentrations against
streptozotocin (STZ)-induced diabetic in
rats: an experimental study with
BackgroundDiabetes in humans induces chronic complications such as cardiovascular damage, cataracts and retinopathy, nephropathy and polyneuropathy. The most common animal model of human diabetes is streptozotocin (STZ)-induced diabetes in the rat. The present study investigated the effects of Nigella sativa hydroalcholic extract on glucose concentrations in streptozotocin (STZ) diabetic rats.
MethodsIn this study Twenty-five Wister-Albino rats (aged 8-9 weeks and weighing 200-250 g) were tested. Rats were divided into five experimental groups (control, untreated STZ-diabetic (60 mg/kg B.W., IP), treated STZ-diabetic with hydroalcholic extract of Nigella Sativa (NS) (5 mg/kg B.W, IP), treated STZ-diabetic with hydroalcholic extract of NS (10 mg/kg B.W., IP) and treated STZ-diabetic with hydroalcholic extract of NS (20 mg/kg B.W., IP and 32 days were evaluated to assess its effect on fasting blood glucose (FBG), and in different groups fasting blood glucose (FBG) and body weight (BW) were measured in the particular days (1, 16 and 32). At the end of the study, the animals were fasted overnight, anaesthetized with an intraperitoneal injection of sodium pentobarbital (60 mg/kg), and sacrificed for obtaining tissues samples (liver, pancreases). The number of islets and cells were counted and the islet diameters were determined by calibrated micrometer. The glycogen content in the liver was examined by Periodic Acid-Schiff (PAS) staining.
ResultsTreatment with NS (5 mg/kg b.w.) markedly increased BW gain and the FBG level was significantly (p<0.001) reduced when compared to the control. Histopathological examination showed that the NS (5 mg/kg b.w.) partially recovered hepatic glycogen content and protected the great deal of the pancreatic islet cells. The number of islets, cells and islets diameter were found statistically significant when compared to the control (p<0.01, p<0.05).
ConclusionsHigher doses of NS did not exhibit any therapeutic effect. These results showed that hydroalcholic extract of NS at low doses has hypoglycemic effect and ameliorative effect on regeneration of pancreatic islets and may be used as a therapeutic agent in the management of diabetes mellitus. The hypoglycemic effect observed could be due to amelioration of Î²-cell, thus leading to increased insulin levels. Consequently, N. sativa may prove clinically useful in the treatment of diabetics and in the protection of Î²-cells against streptozotocin.
Virtual slideThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1845133011104231(for the entire article, see this link to the complete article )
DiscussionDiabetes mellitus is a chronic, systemic, metabolic disease defined by hyperglycemia and characterized by alterations in the metabolism of carbohydrate, protein and lipid. Oxidative stress thought to be increased in a system where the rate of free radical production is increased and/or the antioxidant mechanisms are impaired. In recent years, the oxidative stress-induced free radicals have been implicated in the pathology of insulin dependent diabetes mellitus [3,5,8–10].In our study, a significant weight loss was observed in the diabetic group while NS treated (5 mg/kg b.w.) rats exhibited significant increase in the BW in comparison to diabetic group (Group 2) but was lower than in the normal controls. This effect on the BW was not observed at higher doses of extract. This finding is in agreement with Kanter et al., 2004 reported that NS markedly improved BW gain in STZ-induced diabetic rats. A possible explanation for this might be that NS reduces hyperglycemia, and therefore protein wasting due to inaccessibility of carbohydrate does not occur .In present study, the hydroalcholic extract of NS at dose of 5 mg/kg b.w. revealed a significant hypoglycemic effect in STZ-induced diabetic rats by diminishing the FBG levels. The FBG lowering effect of that was further increased after 32 day treatment. In addition, results showed that the anti-hyperglycemic effect of the NS extract is time dependent. This finding is in agreement with Fararh et al., 2002 .In present study, the lowering effects of black seed oil on blood glucose were correspondent with the previous trials. Some studies have been conducted on the characterization of the bioactives and mechanisms mediating its anti-hyperglycemic action. In an experimental study, Alsaif  reported that blood glucose lowering effect of black seed oil was due to improved insulin insensitivity in diabetic rats. Another study proposed its hypoglycemic effect is due to improved extrapancreatic actions of insulin rather than by stimulated insulin release . Furthermore, Abdelmeguid et al.  reported that the anti-hyperglycemic effect of black seed oil and its active component thymoquinone could be due to reduction of oxidative stress, thus preserving pancreatic Î² -cell integrity lead to insulin levels increase. Furthermore, the black seed oil contains many bioactive constituents such as thymoquinone, p-cymene, pinene, dithymoquinone and thymohydroquinone .The increase in glycogen levels could be due to the antidiabetic activity of NS, streptozotocin induces degeneration of the pancreas with a lobular atrophy and a decline in size and number of Langerhans islets [23,24]. In this study, the damage of pancreas in STZ treated diabetic rats and regeneration of Langerhans islets by NS extract was observed. Furthermore, the number of islets, islet cells and islets diameter significantly increased in NS (5 mg/kg b.w.) treated group compared to STZ-induced diabetic group. However, there have been no morphometric studies to date examining the pancreatic structure in STZ-diabetic rats treated with NS extract. Histopathlogically, treatment with the hydroalcholic extract of NS (5 mg/kg b.w.) revealed partial regeneration of the islet cells with light hydropic degeneration and necrosis in the remaining cells. These findings are in accordance with the results reported by Kanter et al. .Measurement of the effect of N. sativa on gluconeogenesis and liver glucose production helps to clarify part of the hypoglycemic mechanism since hepatic glucose production through gluconeogenesis is known to contribute to hyperglycemia in diabetic patients. Research on isolated hepatic cells showed a significant decrease in glucose production from gluconeogenic elements like glycerol, alanine and lactate in Nigella sativa oil-treated animals as compared to the untreated animals [3–5]. This significant decrease in liver glucose output and ameliorative effect on regeneration of pancreatic islets suggests that the observed antidiabetic action of N. sativa is at least partially mediated through an effect on hepatic gluconeogenesis.
ConclusionsIn conclusion, based on the experimental findings, it was suggested that administration of N. sativa, at a safe dose level, suppresses STZ-induced diabetic in the rat. We believe that further preclinical research into the utility of N. sativa treatment may indicate its usefulness as a potential treatment in diabetic patients, our results suggested that hydroalcholic extract of NS at low doses has beneficial effect on FBG level and ameliorative effect on regeneration of pancreatic islets and may be used as a therapeutic agent in the management of diabetes mellitus.
Competing interestsThe authors declare that they have no competing interests.
Authors’ contributionsSA and RH participated in the histopathological evaluation, performed the literature review, acquired photomicrographs and drafted the manuscript and gave the final histopathological diagnosis and designed and carried out all the experiments. JJ is the principal investigator of the laboratory in which the research was performed and contributed to the interpretation of the data and writing of the manuscript. DKH, RM, FKH, MT and HA edited the manuscript and made required changes and wrote the manuscript. All authors have read and approved the final manuscript.
AcknowledgmentsThe authors are deeply grateful to Department of Pathology, Urmia University, Urmia, Iran, for their excellent technical assistance in preparing the histological specimen.
- Swamy SMK, Tan BKH. Cytotoxic and immunopotentiating effects of ethanolic extract of Nigella sativa L. seeds. J Ethnopharmacol. 2000;70:1-7. doi: 10.1016/S0378-8741(98)00241-4. [PubMed][Cross Ref]
- Boulos L. Medicinal plants of North Africa. Algonac, MI: Reference Publications; 1983. p. 103.
- Houghton PJ, Zakara R, Heras B, Hoult JR. Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation. Planta Med. 1995;61:33-36. doi: 10.1055/s-2006-957994. [PubMed][Cross Ref]
- Agarwal R, Kharya MD, Shrivastava R. Antimicrobial and anti-helminthic activities of the essential oil of Nigella sativa Linn. Ind J Exp Biol. 1979;17:1264-1265. [PubMed]
- Al-Hader A, Aqel M, Hasan Z. Hypoglycemic effect of the volatile oil of Nigella sativa seeds. Int J Pharmacog. 1993;31:96-100. doi: 10.3109/13880209309082925.[Cross Ref]
- Haq A, Lobo PI, Al-Tufail M, Rama N, Al-Sedairy S. Immunomodulatory effect of Nigella sativa proteins fractionated by ion exchange chromatography. Int J Immunopharmacol. 1999;21:283-295. doi: 10.1016/S0192-0561(99)00010-7.[PubMed][Cross Ref]
- Javanbakht J, Hobbenaghi R, Hosseini E, Bahrami AM, Khadivar F, Fathi S, Hassan MA. Histopathological investigation of neuroprotective effects of Nigella sativa on motor neurons anterior horn spinal cord after sciatic nerve crush in rats. Pathol Biol (Paris) 2013. [PubMed] [Cross Ref]
- Van Bremen T, DrÃ¶mann D, Luitjens K, Dodt C, Dalhoff K, Goldmann T, Schaaf B. Triggering receptor expressed on myeloid cells-1 (Trem-1) on blood neutrophils is associated with cytokine inducibility in human E. coli sepsis. Diagn Pathol. 2013;8:24. doi: 10.1186/1746-1596-8-24. [PMC free article] [PubMed] [Cross Ref]
- Ramakrishna V, Jailkhani R. Evaluation of oxidative stress in Insulin Dependent Diabetes Mellitus (IDDM) patients. Diagn Pathol. 2007;2:22. doi: 10.1186/1746-1596-2-22. [PMC free article] [PubMed] [Cross Ref]
- Otani N, Akimoto T, Yumura W, Matsubara D, Iwazu Y, Numata A, Miki T, Takemoto F, Fukushima N, Muto S, Kusano E. Is there a link between diabetic glomerular injury and crescent formation? A case report and literature review. Diagn Pathol. 2012;7:46. doi: 10.1186/1746-1596-7-46. [PMC free article][PubMed] [Cross Ref]
- Baurakiades E, Martins AP, Victor Moreschi N, Souza CD, Abujamra K, Saito AO, Mecatti MC, Santos MG, Pimentel CR, Silva LL, Cruz CR, de Noronha L. Histomorphometric and immunohistochemical analysis of infectious agents, T-cell subpopulations and inflammatory adhesion molecules in placentas from HIV-seropositive pregnant women. Diagn Pathol. 2011;6:101. doi: 10.1186/1746-1596-6-101.[PMC free article] [PubMed] [Cross Ref]
- Baynes JW, Thorpe SR. The role of oxidative stress in diabetic complications. Curr Opin Endocrinol. 1996;3:277-84. doi: 10.1097/00060793-199608000-00001.[Cross Ref]
- Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405-12. doi: 10.2337/diabetes.40.4.405. [PubMed] [Cross Ref]
- Gillery P, Monboisse JC, Maquart FX, Borel JP. Does oxygen free radical increased formation explain longterm complications of Diabetes mellitus? Med Hypotheses. 1989;29:47-50. doi: 10.1016/0306-9877(89)90167-9. [PubMed] [Cross Ref]
- Seven A, Guzel S, Seymen O, Civelek S, Bolayirli M, Yigit G. Nitric oxide synthase inhibition by L-NAME in streptozotocin induced diabetic rats: impacts on oxidative stress. Tohoku J Exp Med. 2003;99:205-10. [PubMed]
- Matkovics B, Kotorman M, Varga IS, Hai DQ, Varga C. xidative stress in experimental diabetes induced by streptozotocin. Acta Physiol Hung. 1997-1998;85:29-38. [PubMed]
- Kanter M, Coskun O, Korkmaz A. Effects of Nigella sativa on oxidative stress and Î²-cell damage in streptozotocin-induced diabetic rats. Anat Rec A Discov Mol Cell Evol Biol. 2004;279A(1):685-691. doi: 10.1002/ar.a.20056. [PubMed] [Cross Ref]
- Fararh KM, Atoji Y, Shimizu Y. Isulinotropic properties of Nigella sativa oil in streptozotocin plus nicotinamide diabetic hamster. Research Veterinary Science. 2002;73:279-282. doi: 10.1016/S0034-5288(02)00108-X. [PubMed] [Cross Ref]
- Alsaif MA. Effect of Nigella sativa oil on impaired glucose tolerance and insulin insensitivity induced by high-fat-diet and turpentine-induced trauma. Pak J Biol Sci. 2008;11(8):1093-9. [PubMed]
- El-Dakhakhny M, Mady N, Lembert N, Ammon HP. The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic actions. Plant Med. 2002;68(5):465-6. doi: 10.1055/s-2002-32084. [PubMed] [Cross Ref]
- Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativaand thymoquinone on biochemical and subcellular changes in pancreatic Î²-cells of streptozotocin-induced diabetic rats. Diabetes. 2010;2(4):256-66. doi: 10.1111/j.1753-0407.2010.00091.x. [PubMed] [Cross Ref]
- Geng D, Zhang S, Lan J. Analysis on chemical components of volatile oil and determination of thymoquinone from seed of Nigella glandulifera. Zhongguo Zhong Yao Za Zhi. 2009;34(22):2887-90. [PubMed]
- Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats. Life Sci. 2009;85(23-26):830-834. [PubMed]
- Grover J, Vats V, Yadav S. Effect of feeding aqueous extract of Pterocarpus marsupium on glycogen content of tissues and the key enzymes of carbohydrate metabolism. Mol Cell Biochem. 2002;241:53-59. doi: 10.1023/A:1020870526014.[PubMed][Cross Ref]
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