Abstract
Aims
Diabetes mellitus is a major manifestation of metabolic disorder which presents with hyperglycemia (high levels of serum blood sugar). In the present study, we aimed to investigate the effects of celery seed extract on different biochemical factors and histopathological changes in normal and streptozotocin (STZ)-induced diabetic rats.
Methods
A total of 35 male Wistar rats were divided into five groups (one normal and four diabetic groups). STZ was injected intraperitoneally to induce diabetes. The effects of hexane extract of celery seed and glibenclamide (as a positive control) were compared. Blood samples were analyzed on days 0, 18, and 33, and histopathological evaluations were performed at the end of the study.
Results
Glucose, triglycerides, and cholesterol levels significantly decreased, whereas insulin and high-density lipoprotein (HDL) levels increased in the extract-administered groups, as compared to the negative diabetic control group (P < 0.0001). The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of the extract-administered groups were significantly less than the negative control group (P < 0.0001). Histopathological reports revealed significantly less atrophy, necrosis, and inflammation in the rats receiving celery seed extract compared to the negative control group.
Conclusions
The results indicated that celery seed extract can be effective in controlling hyperglycemia and hyperlipidemia in diabetic rats, and demonstrated its protective effects against pancreatic toxicity resulting from STZ-induction.
Similar content being viewed by others
References
Jensen TM et al (2015) Impact of intensive treatment on serum methylglyoxal levels among individuals with screen-detected type 2 diabetes: the ADDITION-Denmark study. Acta Diabetol 52(5):929–936
Bergis D et al (2014) Coronary artery disease as an independent predictor of survival in patients with type 2 diabetes and Charcot neuro-osteoarthropathy. Acta Diabetol 51(6):1041–1048
Bjornstad P et al (2014) Serum uric acid predicts vascular complications in adults with type 1 diabetes: the coronary artery calcification in type 1 diabetes study. Acta Diabetol 51(5):783–791
Hull RL et al (2004) Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab 89(8):3629–3643
Iyer A, Chan V, Brown L (2010) The DOCA-salt hypertensive rat as a model of cardiovascular oxidative and inflammatory stress. Curr Cardiol Rev 6(4):291–297
Anjana RM et al (2014) Regularity of follow-up, glycemic burden, and risk of microvascular complications in patients with type 2 diabetes: a 9-year follow-up study. Acta Diabetol 52(3):601–609
Wild S et al (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27(5):1047–1053
Hasani-Ranjbar S, Larijani B (2014) Medicinal plants as potential new target drugs in endocrine disorders-review article. Iranian J Public Health 43(1):24–34
Heather LC, Clarke K (2011) Metabolism, hypoxia and the diabetic heart. J Mol Cell Cardiol 50(4):598–605
Kamal M, Jawaid T (2010) Pharmacological activities of Lawsonia inermis Linn.: a review. Int J Biomed Res 1(2):37–43
Palsamy P, Subramanian S (2009) Modulatory effects of resveratrol on attenuating the key enzymes activities of carbohydrate metabolism in streptozotocin–nicotinamide-induced diabetic rats. Chem Biol Interact 179(2):356–362
Larijani B (2007) The clinical investigation of Securigera securidaca (l.) Degen & doerfler seeds in treatment of type II diabetic patients: a randomized, double-blind, placebo-controlled study. Diabetes 56:A562
Mahmoodabadi NA et al (2006) Preventive effect of hydroalcoholic Cynara scolymus extract on appearance of type 1 diabetes mellitus in male rats. J Diabetes Metab Disord 6(1):175
Kim JD et al (2007) Ameliorative anti-diabetic activity of dangnyosoko, a Chinese herbal medicine, in diabetic rats. Biosci Biotechnol Biochem 71(6):1527–1534
Jurikova T et al (2012) Polyphenolic profile and biological activity of Chinese hawthorn (Crataegus pinnatifida BUNGE) fruits. Molecules 17(12):14490–14509
Soleymanifard S et al (2014) An investigation of the effects of raw garlic on radiation-induced bystander effects in MCF7 cells. Iranian J Med Phys 11(4):350–357
Moghadam MH, Imenshahidi M, Mohajeri SA (2013) Antihypertensive effect of celery seed on rat blood pressure in chronic administration. J Med Food 16(6):558–563
Renault S et al (2003) CAY-I, a novel antifungal compound from cayenne pepper. Med Mycol 41(1):75–82
Broadhurst CL, Polansky MM, Anderson RA (2000) Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro. J Agric Food Chem 48(3):849–852
Powanda M, Rainsford K (2011) A toxicological investigation of a celery seed extract having anti-inflammatory activity. Inflammopharmacology 19(4):227–233
Powanda MC, Whitehouse MW, Rainsford KD (2015) Celery seed and related extracts with antiarthritic, antiulcer, and antimicrobial activities, in novel natural products: therapeutic effects in pain, arthritis and gastro-intestinal diseases. Springer, Berlin, pp 133–153
Domagała-Świątkiewicz I, Gąstoł M (2012) Comparative study on mineral content of organic and conventional carrot, celery and red beet juices. Acta Sci Pol Hortorum Cultus 11(2):173–183
Zhou K et al (2009) Triterpenoids and flavonoids from celery (Apium graveolens). J Nat Prod 72(9):1563–1567
Houston MC (2005) Nutraceuticals, vitamins, antioxidants, and minerals in the prevention and treatment of hypertension. Prog Cardiovasc Dis 47(6):396–449
Zhu J, Zhang Y, Yang C (2015) Protective effect of 3-n-butylphthalide against hypertensive nephropathy in spontaneously hypertensive rats. Mol Med Rep 11(2):1448–1454
Dimo T et al (2003) Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized rats. Phytother Res 17(10):1135–1139
Popović M et al (2006) Effect of celery (Apium graveolens) extracts on some biochemical parameters of oxidative stress in mice treated with carbon tetrachloride. Phytother Res 20(7):531–537
Singh A, Handa S (1995) Hepatoprotective activity of Apium graveolens and Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats. J Ethnopharmacol 49(3):119–126
Peng Y et al (2012) L-3-n-butylphthalide reduces tau phosphorylation and improves cognitive deficits in AβPP/PS1-Alzheimer’s transgenic mice. J Alzheimers Dis 29(2):379–391
Momin RA, Nair MG (2002) Antioxidant, cyclooxygenase and topoisomerase inhibitory compounds from Apium graveolens Linn. seeds. Phytomedicine 9(4):312–318
Zimmet P, Alberti KG, Shaw J (2001) Global and societal implications of the diabetes epidemic. Nature 414(6865):782–787
Alimohammadi S et al (2013) Protective and antidiabetic effects of extract from Nigella sativa on blood glucose concentrations against streptozotocin (STZ)-induced diabetic in rats: an experimental study with histopathological evaluation. Diagn Pathol 8:137
Eddouks M, Chattopadhyay D, Zeggwagh NA (2012) Animal models as tools to investigate antidiabetic and anti-inflammatory plants. Evid Based Complement Altern Med 2012:142087. doi:10.1155/2012/142087
Battu G et al (2007) Hypoglycemic and anti-hyperglycemic effect of alcoholic extract of Benincasa hispida in normal and in alloxan induced diabetic rats. Pharmacogn Mag 3(10):101
Pari L, Saravanan G (2002) Antidiabetic effect of Cogent db, a herbal drug in alloxan-induced diabetes mellitus. Comp Biochem Physiol C: Toxicol Pharmacol 131(1):19–25
Pushparaj PN, Tan BKH, Tan CH (2001) The mechanism of hypoglycemic action of the semi-purified fractions of Averrhoa bilimbi in streptozotocin-diabetic rats. Life Sci 70(5):535–547
Chatterjea M, Shinde R (2012) Textbook of medical biochemistry. Jaypee Brothers Medical Publishers, New Delhi, India
Fazal SS, Singla RK (2012) Review on the pharmacognostical and pharmacological characterization of Apium graveolens Linn. Indo Glob J Pharm Sci 2(1):36–42
Abbaskhan A et al (2012) Biological activities of Indian Celery, Seseli diffusum (Roxb. ex Sm.) Sant. & Wagh. Phytother Res 26(5):783–786
Al-Sa’aidi JA, Alrodhan MN, Ismael AK (2012) Antioxidant activity of n-butanol extract of celery (Apium graveolens) seed in streptozotocin-induced diabetic male rats. Res Pharm Biotechnol 4(2):24–29
Veeramani C, Pushpavalli G, Pugalendi KV (2008) Antihyperglycaemic effect of Cardiospermum halicacabum Linn. leaf extract on STZ-induced diabetic rats. J Appl Biomed 6:19–26
Akram E, Maryam E (2009) Antidiabetic effects of sage (Salvia officinalis L.) leaves in normal and streptozotocin-induced diabetic rats. Diabetes Metab Syndr: Clin Res Rev 39:40–44
Kanter M et al (2004) Effects of Nigella sativa on oxidative stress and β-cell damage in streptozotocin-induced diabetic rats. Anat Rec A: Discov Mol Cell Evol Biol 279(1):685–691
Ramakrishna V, Jailkhani R (2007) Evaluation of oxidative stress in Insulin Dependent Diabetes Mellitus (IDDM) patients. Diagn Pathol 2(1):22–30
Sokeng S et al (2005) Antihyperglycemic effect of Bridelia ndellensis ethanol extract and fractions in streptozotocin-induced diabetic rats. Afr J Trad CAM 2(2):94–102
Das M et al (2011) Antihyperglycemic and antihyperlipidemic activity of Urtica dioica on type 2 diabetic model rats. J Diabetol 2(2):1–6
Lin L-Z, Lu S, Harnly JM (2007) Detection and quantification of glycosylated flavonoid malonates in celery, Chinese celery, and celery seed by LC-DAD-ESI/MS. J Agric Food Chem 55(4):1321–1326
Forbes JM, Coughlan MT, Cooper ME (2008) Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes 57(6):1446–1454
Miura K, Kikuzaki H, Nakatani N (2002) Antioxidant activity of chemical components from sage (Salvia officinalis L.) and thyme (Thymus vulgaris L.) measured by the oil stability index method. J Agric Food Chem 50(7):1845–1851
Golalipour MJ et al (2011) Protective effect of Urtica dioica L. (Urticaceae) on morphometric and morphologic alterations of seminiferous tubules in STZ diabetic rats. Iranian J Basic Med Sci 14(5):472
Nencu I et al (2012) Preliminary research regarding the therapeutic uses of Urtica dioica L. Note I. The polyphenols evaluation. Farmacia 60(4):493–500
Lansky EP, Newman RA (2007) Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol 109(2):177–206
Jang S, Kelley KW, Johnson RW (2008) Luteolin reduces IL-6 production in microglia by inhibiting JNK phosphorylation and activation of AP-1. Proc Natl Acad Sci USA 105(21):7534–7539
Joseph B, Jini D (2011) Insight into the hypoglycaemic effect of traditional Indian herbs used in the treatment of diabetes. Res J Med Plant 5(4):352–376
Taskinen MR (1987) Lipoprotein lipase in diabetes. Diabetes/Metab Rev 3(2):551–570
Association AD (2008) Diagnosis and classification of diabetes mellitus. Diabetes Care 31(Supplement 1):S55–S60
Tan BK, Tan CH, Pushparaj PN (2005) Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats. Life Sci 76(24):2827–2839
Winocour P et al (1986) Lipoprotein abnormalities in insulin-dependent diabetes mellitus. The Lancet 327(8491):1176–1178
Cheng M-C et al (2010) Chemical synthesis of 9 (Z)-octadecenamide and its hypolipidemic effect: a bioactive agent found in the essential oil of mountain celery seeds. J Agric Food Chem 58(3):1502–1508
Mansi K et al (2009) Hypolipidemic effects of seed extract of celery (Apium graveolens) in rats. Pharmacogn Mag 5(20):301
Iyer D, Patil U (2011) Effect of chloroform and aqueous basic fraction of ethanolic extract from Apium graveolens L. in experimentally-induced hyperlipidemia in rats. J Complement Integr Med 8(1). doi:10.2202/1553-3840.1529
Concepción NM et al (1993) Free radical scavenger and antihepatotoxic activity of Rosmarinus tomentosus. Planta Med 59(4):312–314
Sultana S et al (2005) Inhibitory effect of celery seeds extract on chemically induced hepatocarcinogenesis: modulation of cell proliferation, metabolism and altered hepatic foci development. Cancer Lett 221(1):11–20
Peng Y et al (2007) l-3-n-Butylphthalide improves cognitive impairment induced by chronic cerebral hypoperfusion in rats. J Pharmacol Exp Ther 321(3):902–910
Liu K et al (2012) Protection against neurotoxicity by an autophagic mechanism. Braz J Med Biol Res 45(5):401–407
Li L et al (2009) DL-3-n-butylphthalide protects endothelial cells against oxidative/nitrosative stress, mitochondrial damage and subsequent cell death after oxygen glucose deprivation in vitro. Brain Res 1290:91–101
Zhang T, Jia W, Sun X (2010) 3-n-Butylphthalide (NBP) reduces apoptosis and enhances vascular endothelial growth factor (VEGF) up-regulation in diabetic rats. Neurol Res 32(4):390–396
Acknowledgments
We gratefully thank the vice chancellor of research, Mashhad University of Medical Sciences, for financial and logistic support of this Project through Grant Number 910889. This result was obtained from a Pharm. D. thesis (Dr. Masoud Ramezani).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical standard
This article does not contain any study with human participants. All procedures performed in this study involving animals were in accordance with the ethical standards of “Ethics Committee Acts” of Mashhad University of Medical Sciences.
Human and animal rights
This article does not contain any studies with human performed by the any of the authors. The experimental procedures for all animals were in accordance with the Ethics Committee Acts of Mashhad University of Medical Sciences.
Informed consent
For this type of study formal consent is not required.
Additional information
Managed by Antonio Secchi.
Rights and permissions
About this article
Cite this article
Tashakori-Sabzevar, F., Ramezani, M., Hosseinzadeh, H. et al. Protective and hypoglycemic effects of celery seed on streptozotocin-induced diabetic rats: experimental and histopathological evaluation. Acta Diabetol 53, 609–619 (2016). https://doi.org/10.1007/s00592-016-0842-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-016-0842-4