Acute, Sub-acute and Cell Toxicity of Allium elburzense Bulb Hydroalcoholic Extract

Document Type: Original paper

Authors

1 Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Office of Research and Development, Vice Chancellery for Food and Drug, Isfahan University of Medical Sciences, Isfahan, Iran.

3 Department of Pharmacognosy, Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran.

Abstract

Background and objectives: Allium elburzense is an endemic plant in north of Iran with some nutritional and medicinal applications; however, there is no data on its safety profile. This study was aimed to investigate cytotoxicity, acute and sub-acute toxicity of hydroalcoholic extract of A. elburzense bulb. Methods: Total phenolic content of the extract was measured using Folin-Ciocalteumethod. For cytotoxicity assay, human umbilical vein endothelial cells (HUVECs) were used. In acute toxicity study, single oral dose of 2000 mg/kg was administered in female and male Wistar rats and they were monitored for two weeks. In sub-acute test, 125, 250 and 500 mg/kg/day of extract were orally administered for four weeks. Results: Total phenolic content was estimated as 32.8 ± 2.5 mg gallic acid equivalent/g of the extract. The extract showed IC50 value of 366.4 µg/mL (95% CI = 246.4-566.1) in HUVECs after 24 h exposure. In acute study, there was no sign of toxicity and no mortality; however, significant increase in relative spleen weight and ALP activity and mild inflammation in kidney tissue were observed. LD50 ˃ 2000 mg/kg was estimated for A. elburzense bulb extract. In sub-acute assay, there were significant elevations in relative spleen weight, blood urea level, AST, ALT, ALP, total WBC, lymphocyte and neutrophil count and significant decrease in blood sugar and triglyceride levels at higher doses of the extract. Conclusion:Allium elburzense bulb extract may be considered as safe at doses lower than 500 mg/kg in rats; however, assessment of liver and kidney functions is recommended during chronic uses.

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Main Subjects


[1] Aschwanden C. Herbs for health, but how safe are they? Bull World Health Organ. 2001; 79(7): 691-692.
[2] Willcox ML, Bodeker G. Traditional herbal medicines for malaria. Br Med J. 2004; 329(7475): 1156-1159.
[3] Sharwan G, Jain P, Pandey R, Shukla SS. Toxicity profile of traditional herbal medicine. J Ayu Herb Med. 2015; 1(3): 81-90.
[4] Christenhusz MJM, Byng JW. The number of known plants species in the world and its annual increase. Phytotoxa. 2016; 261(3): 201-217.
[5] Neshati F, Fritsch RM. Seed characters and testa sculptures of some Iranian Allium L. species (Alliaceae). Feddes Repert. 2009; 120(5-6): 322-332.
[6] Zolfaghari B, Shokoohinia Y, Ramezanlou P, Sadeghi A, Mahmoudzadeh M, Minaiyan M. Effects of methanolic and butanolic fractions of Allium elburzense Wendelbo bulbs on blood glucose level of normal and STZ-induced diabetic rats. Res Pharm Sci. 2012; 7(4): 201-207.
[7] Fritsch RM, Maroofi H. New species and new records of Allium L. (Alliaceae) from Iran. Phyton. 2010; 50(1): 1-26.
[8] Barile E, Capasso R, Izzo A, Lanzotti V, Sajjadi SE, Zolfaghari B. Structure-activity relationships for saponins from Allium hirtifolium and Allium elburzense and their antispasmodic activity. Planta Med. 2005; 71(11): 1010-1018.
[9] Barile E, Zolfaghari B, Sajjadi SE, Lanzotti V. Saponins of Allium elburzense. J Nat Prod. 2004; 67(12): 2037-2042.
[10] Radjabian T, Hosseinpur Yektaei Z, Ghazanfari T, Nasiri Z, Fotovvat M. The immunoregulatory effects of four Allium species on macrophages and lymphocytes viability. Immunoregulation. 2018; 1(3): 143-152.
[11] Safaeian L, Zolfaghari B, Karimi S, Talebi A,  Aghaye Ghazvini M. The effects of hydroalcoholic extract of Allium elburzense Wendelbo bulb on dexamethasone-induced dyslipidemia, hyperglycemia, and oxidative stress in rats. Res Pharm Sci. 2018; 13(1): 22-29.
[12] Yegdaneh A, Ghannadi A, Dayani L. Chemical constituents and biological activities of two Iranian Cystoseira species. Res Pharm Sci. 2016; 11(4): 311-317.
[13] Schleger C, Platz SJ, Deschl U. Development of an in vitro model for vascular injury with human endothelial cells. ALTEX. 2004; 21(3): 12-19.
[14] Bahadoran Z, Mirmiran P, Momenan AA, Azizi F. Allium vegetable intakes and the incidence of cardiovascular disease, hypertension, chronic kidney disease, and type 2 diabetes in adults: a longitudinal follow-up study. J Hypertens. 2017; 35(9): 1909-1916.
[15] Akbari V, Sadeghi HM, Jafarian-Dehkordi A, Abedi D, Chou CP. Improved biological activity of a single chain antibody fragment against human epidermal growth factor receptor 2 (HER2) expressed in the periplasm of Escherichia coli. Protein Expr Purif. 2015; 116: 66-74.
[16] Organization for Economic Co-operation and Development. Test No. 423: acute oral toxicity-acute toxic class method. OECD Publishing [Accessed 2020]. Available from: https://read.oecdilibrary.org/environment/test-no-423-acuteoral-toxicity-acute-toxic-classmethod_9789264071001-en#page1.
[17] Organization for Economic Co-operation and Development. Test No. 407: repeated dose 28-day oral toxicity study in rodents. OECD Publishing [Accessed 2020]. Available from: https://read.oecdilibrary.org/environment/test-no-407-repeated-dose-28-day-oral-toxicity-study-inrodents_9789264070684-en#page1.
[18] Safaeian L, Zolfaghari B,Aghaye-Ghazvini M, Behnampour M. Evaluation of fibrinolytic and antioxidant effects of Allium elburzense bulb extracts. Avicenna J Phytomed. 2017; 7(3): 223-231.
[19] Chen S, Shen X, Cheng S, Li P, Du J, Chang Y, Meng H. Evaluation of garlic cultivars for polyphenolic content and antioxidant properties. PLoS One. 2013; 8(11): 1-12.
[20] United Nations. The globally harmonized system (GHS) of classification and labelling of chemicals. [Accessed 2020]. Available from: http://www.unece.org/trans/danger/publi/ghs/ghs_rev07/07files_e0.html."
[21] Pohjanvirta R, Miettinen H, Sankari S, Hegde N, Lindén J. Unexpected gender difference in sensitivity to the acute toxicity of dioxin in mice. Toxicol Appl Pharmacol. 2012; 262(2): 167-176.
[22] Kuda T, Iwai A, Yano T. Effect of red pepper Capsicum annuum var. conoides and garlic Allium sativum on plasma lipid levels and cecal microflora in mice fed beef tallow. Food Chem Toxicol. 2004; 42(10): 1695-1700.
[23] Odiase DE, Osazee LO. Histological effects aqueous extract of Allium sativum (Alliaceae) bulb on bone and spleen of adult Wistar rats. J Appl Sci Environ Manage. 2017; 21(3): 538-544.
[24] Huzaifa U, Labaran I, Bello AB. Effect of oral administration of aqueous garlic (Allium sativum) extract on liver function on rats. Tech Sci Afr J. 2013; 8(2): 113-115.                     
[25] Abdel Gadir EH, Abdel Gadir WS, Adam SEI. Response of Wistar rats to low levels of dietary Allium cepaAllium sativum and sodium selenite. J Pharmacol Toxicol. 2006; 1(3): 284-288.
[26] Oko MO, Anyim C, Nworie O, Agah MV, Okoli CS. The effects of ethanol extract of Allium sativum leaves on aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in albino rats. J Chem Biol Phy Sci Sec B. 2012; 3(1): 256-263.
[27] Ilyas N, Sadiq M, Jehangir A. Hepatoprotective effect of garlic (Allium sativum) and milk thistle (silymarin) in isoniazid induced hepatotoxicity in rats. Biomedica. 2011; 27(2): 166-170.
[28] Anusuya N, Durgadevi P, Dhinek A, Mythily S. Nephroprotective effect of ethanolic extract of garlic (Allium sativum L.) on cisplatin induced nephrotoxicity in male Wistar rats. Asian J Pharm Clin Res. 2013; 6(8): 97-100.
[29] Zeng Y, Li Y, Yang J, Pu X, Du J, Yang X, Yang T, Yang S. Therapeutic role of functional components in Alliums for preventive chronic disease in human being. Evid-Based Compl Altern Med. 2017; Article ID 9402849. 
[30] Olaniyan OT, Meraiyebu AB, Arogbonlo A, Dare JB, Shekins O, Shafe
MO. Effects of aqueous extract of garlic (Allium sativum) on blood
parameters in adult Wistar rats (Rattus novergicus). Int J Pharm Sci Invent. 2013; 2(3): 42-45.
[31] Mirabeau TY, Samson ES. Effect of Allium cepa and Allium sativum on some immunological cells in rats. Afr J Tradit Complement Altern Med. 2012; 9(3): 374-379.
[32] Banerjee SK, Maulik SK. Effect of garlic on cardiovascular disorders: a review. Nutr J. 2002: 1(1): 1-14.
[33] Aulbach AD, Amuzie CJ. Biomarkers in nonclinical drug development. In: Faqi AS, Ed. A comprehensive guide to toxicology in nonclinical drug development. London: Academic Press, 2017.