year 18, Issue 71 (9-2019)                   J. Med. Plants 2019, 18(71): 67-76 | Back to browse issues page

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Kianbakht S, Ziaee M, Momtaz M, R H. A Toxicological and Phytochemical Study on the Iran’s Ecballium elaterium (L.) A. Rich.. J. Med. Plants 2019; 18 (71) :67-76
1- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran ,
2- Medicinal Plants Research Center, Maragheh University of Medical Sciences, Maragheh, Iran
3- Toxicology and Diseases Group, the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran
4- Medicinal Plants Research Center, Institute of Medicinal Plants, ACECR, Karaj, Iran
Abstract:   (3801 Views)
Background: Ecballium elaterium is endemic to the northwestern Iran and its fruit is traditionally used for therapeutic purposes in Iran. The toxicological and phytochemical characteristics of the Iran’s Ecballium elaterium have not been investigated so far.
Objective: Study on some toxicological and phytochemical features of the Iran’s Ecballium elaterium fruit 90% ethanol extract.
Method: The antioxidant capacity in the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay and total phenol and flavonoid contents were determined by spectrophotometry. The rutin (phytomyelin) content was measured by HPLC. Moreover, oral and intra-peritoneal LD50 (median lethal dose) after 72 hours of the extract administration in rat were determined by the graphical method of Miller and Tainter. The cytotoxicity against several cancer and non-cancer cell lines was determined by the MTT (mitochondrial tetrazolium) method.     
Results: The IC50 (inhibitory concentration 50%) in the DPPH assay was 3.57±0.006 mg/mL. The total phenol in terms of mg Gallic acid/0.05 g extract was 17.84±0.92. The total flavonoid in terms of mg rutin/0.1 g extract was 33.35 ± 1.06. The extract contained 1 mg/g rutin. The oral and intra-peritoneal LD50 of the extract were 472 mg/kg and 425 mg/kg respectively. The extract showed strong cytotoxicity in ACHN and ASPC1 cell lines, which was followed by Caco2 and PC12 cells. Non-neoplastic cells were much less affected by the extract in comparison with the cancerous cells.
Conclusion: The extract has low antioxidant activity. The oral and intra-peritoneal toxicities of the extract in the LD50 test are moderate. The extract has considerable selective toxicity against cancer cells. 
Full-Text [PDF 586 kb]   (1287 Downloads)    
Type of Study: Research | Subject: Pharmacognosy & Pharmaceutics
Received: 2018/10/24 | Accepted: 2019/01/14 | Published: 2019/08/24

1. Mozaffarian V. Identification of Medicinal and Aromatic Plants of Iran. Farhang Moaser. Iran. 2013, pp: 359-60.
2. Vlachos P, Kanitsakis NN and Kokonas N. Fatal cardiac and renal failure due to Ecballium elaterium (squirting cucumber). J. Toxicol. Clin. Toxicol. 1994; 32 (6): 737-8. [DOI:10.3109/15563659409017981]
3. Adwan G, Salameh Y and Adwan K. Effect of ethanolic extract of Ecballium elaterium against Staphylococcus aureus and Candida albicans. Asian Pac. J. Trop. Biomed. 2011; 1 (6): 456-60. [DOI:10.1016/S2221-1691(11)60100-7]
4. Attard E and Cuschieri A. Cytotoxicity of cucurbitacin E extracted from Ecballium elaterium in vitro. J. Nat. Remedies. 2004; 4 (2): 137-44.
5. Bohlooli S, Jafari N and Jahed S. Cytotoxic effect of freeze-dried extract of Ecballium elaterium fruit on gastric adenocarcinoma (AGS) and esophageal squamous cell carcinoma (KYSE30) cell lines. J. Gastrointest. Canc. 2012; 43: 579-83. [DOI:10.1007/s12029-012-9383-4]
6. Karimi N, Bohlooli S and Mazani M. Nanoliposomal formulation of Ecballium elaterium extract: cytotoxic evaluation against human gastric adenocarcinoma (AGS) cell line. Nanomed. Res. J. 2016; 1 (1): 9-14.
7. Agil MH, Risco S, Miro M, Navarro MC, Ocete MA and Jimenez J. Analgesic and antipyretic effects of Ecballium elaterium (L.) A. Richard. extract in rodents. Phytother. Res. 1995; 9: 135-8. [DOI:10.1002/ptr.2650090211]
8. Yesilada E, Tanaka S, Tabata M and Sezik E. Antiinflammatory effects of the fruit juice of Ecballium elaterium on edemas in mice. Phytother. Res. 1989; 3 (2): 75-6. [DOI:10.1002/ptr.2650030210]
9. Khatib SY, Mahmoud II and Hasan ZA. Effects of crude Ecballium elaterium juice on isolated rabbit heart. Int. J. Pharmacog. 1993; 31 (4): 259-68. [DOI:10.3109/13880209309082951]
10. El Naggar el MB, Chalupová M, Pražanová G, Parák T, Švajdlenka E, Žemlička M and Suchý P. Hepatoprotective and proapoptotic effect of Ecballium elaterium on CCl4-induced hepatotoxicity in rats. Asian Pac. J. Trop. Biomed. 2015; 8 (7): 526-31. [DOI:10.1016/j.apjtm.2015.06.012]
11. Elayan H, Gharaibeh M, Zmeili S and Salhab AS. Effects of Ecballium elaterium juice on serum bilirubin concentration in male rats. Pharm. Biol. 1989; 27 (4): 227-34. [DOI:10.3109/13880208909116908]
12. Popov DV, Voinova E, Naidenova EI, Kolarova-Pavlova IK and Dimitrova-Konaklieva SD. Antileukemic P-388 action of aqueous plant extracts. CR Acad. Bulg. 1988; 41: 147-9.
13. Uslu C, Karasen RM, Sahin F, Taysi S and Akcay F. Effect of aqueous extracts of Ecballium elaterium rich, in the rabbit model of rhinosinusitis. Int. J. Pediatr. Otorhinolaryngol. 2006; 70 (3): 515-8. [DOI:10.1016/j.ijporl.2005.07.020]
14. Mazokopakis EE, Karefilakis CM and Starakis IK. The safety and efficacy of the fruit juice of Ecballium elaterium in the treatment of acute rhinosinusitis. J. Altern. Complement. Med. 2009; 15 (12): 1273-4. [DOI:10.1089/acm.2009.0241]
15. Jaradat N, Jodeh S, Rinno T, Kharoof M, Zaid AN and Hannon M. Determination of the presence of phytomelin in Ecballium elaterium to approve its folk uses. Int. J. Pharm. Pharm. Sci. 2012; 4 (2): 233-7.
16. Raikhlin-Eisenkraft B and Bentur Y. Ecballium elaterium (squirting)--remedy or poison? J. Toxicol. Clin. Toxicol. 2000; 38 (3): 305-8. [DOI:10.1081/CLT-100100936]
17. El Sayed ZI and Badr WH. Cucurbitacin glucosides and biological activities of the ethyl acetate fraction from ethanolic extract of Egyptian Ecballium elaterium. J. Appl. Sci. Res. 2012; 8 (2): 1252-8.
18. Obanda M, Owuor PO and Taylor SJ. Flavanol composition and caffeine content of green leaf as quality potential indicators of Kenyan black teas. J. Sci. Food Agric. 1997; 74 (2): 209-15.<209::AID-JSFA789>3.0.CO;2-4 [DOI:10.1002/(SICI)1097-0010(199706)74:23.0.CO;2-4]
19. Marinova D, Ribarova F and Atanassova M. Total phenolics and total flavonoids in Bulgarian fruits and vegetables. J. Univ. Chem. Technol. Metallurgy. 2005; 40 (3): 255-60.
20. Yuan YV, Bone DE and Carrington MF. Antioxidant activity of dulse (Palmaria palmata) extract evaluated in vitro. Food Chem. 2005; 91 (3): 485-94. [DOI:10.1016/j.foodchem.2004.04.039]
21. Marquis JK. A Guide to General Toxicology. 2nd ed. Karger. Switzerland. 1989, pp: 196-8.
22. Ghosh MN. Fundamentals of Experimental Pharmacology. 6th ed. Hilton & Company. India. 2008, pp: 112-4.
23. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods. 1983; 65(1-2):55-63. [DOI:10.1016/0022-1759(83)90303-4]
24. El-Gengaihi S, Abd El-Hamid SR and Kamel AM. Anti-inflammatory effect of some cucurbitaceous plants. Herba Pol. 2009; 55(4): 119-26.
25. Khalil AM and Qaoud KM. Toxicity and partial characterization of Ecballium elaterium fruit juice. Int. J. Pharmacog. 1993; 2: 135-41. [DOI:10.3109/13880209309082930]
26. Shabbar IMS and Maslat A. Genotoxicity of Ecballium elaterium (L) A Rich Cucurbitaceae fruit juice using micronucleus assay and DNA single strand break techniques. Internet J. Health. 2006; 6 (2): 1-12. [DOI:10.5580/1b75]
27. Geran RI, Greenberg NH, McDonald MM, Schumacher A and Abbott BJ. Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemother. Rep. 1972; 3 (2): 17-9.
28. Attard E and Cuschieri A. Cytotoxicity of cucurbitacin E extracted from Ecballium elaterium and anticancer agents in vitro. J. Nat. Remedies. 2004; 4 (2): 137 - 44.
29. Attard E, Cuschieri A and Brincat MP. Morphological effects induced by cucurbitacin E on ovarian cancer cells in vitro. J. Nat. Remedies. 2005; 5 (1): 70 - 4.
30. Chan KT, Li K, Liu SL, Chu KH, Toh M and Xie WD. Cucurbitacin B inhibits STAT3 and the Raf/MEK/ERK pathway in leukemia cell line K562. Cancer Lett. 2010; 289 (1): 46-52. [DOI:10.1016/j.canlet.2009.07.015]
31. Touihri-Barakati I, Kallech-Ziri O, Ayadi W, Kovacic H, Hanchi B, Hosni K and Luis J. Cucurbitacin B purified from Ecballium elaterium (L.) A. Rich from Tunisia inhibits α5β1 integrin-mediated adhesion, migration, proliferation of human glioblastoma cell line and angiogenesis. Eur. J. Pharmacol. 2017; 797: 153-61. [DOI:10.1016/j.ejphar.2017.01.006]
32. Tannin-Spitz T, Grossman S, Dovrat S, Gottlieb HE and Bergman M. Growth inhibitory activity of cucurbitacin glucosides isolated from Citrullus colocynthis on human breast cancer cell lines. Biochem. Pharmacol. 2007; 73 (1): 56-67. [DOI:10.1016/j.bcp.2006.09.012]
33. Takahashi N, Yoshida Y, Sugiura T, Matsuno K, Fujino A and Yamashita U. Cucurbitacin D isolated from Trichosanthes kirilowii induces apoptosis in human hepatocellular carcinoma cells in vitro. Int. Immunopharmacol. 2009; 9 (4): 508-13. [DOI:10.1016/j.intimp.2009.01.006]
34. Escandell JM, Kaler P, Recio MC, Sasazuki T, Shirasawa S, Augenlicht L, Ríos JL and Klampfer L. Activated kRas protects colon cancer cells from cucurbitacin-induced apoptosis: the role of p53 and p21. Biochem. Pharmacol. 2008; 76 (2): 198-207. [DOI:10.1016/j.bcp.2008.05.004]
35. Attard E, Brincat MP and Cuschieri, A. Immunomodulatory activity of cucurbitacin E isolated from Ecballium elaterium. Fitoterapia. 2005; 76 (5): 439-41. [DOI:10.1016/j.fitote.2005.02.007]
36. Rencüzogullari E, Ila HB, Kayraldiz A, Diler SB, Yavuz A, Arslan M, Funda Kaya F and Topaktas M. The mutagenic and anti-mutagenic effects of Ecballium elaterium fruit juice in human peripheral lymphocytes. Genetika. 2006; 42 (6): 768-72. [DOI:10.1134/S1022795406060068]
37. Thoennissen NH, Iwanski GB, Doan NB, Okamoto R, Lin P, Abbassi S, Song JH, Yin D, Toh M, Xie WD, Said JW and Koeffler HP. Cucurbitacin B induces apoptosis by inhibition of the JAK/STAT pathway and potentiates antiproliferative effects of gemcitabine on pancreatic cancer cells. Cancer Res. 2009; 69 (14): 5876-84. [DOI:10.1158/0008-5472.CAN-09-0536]
38. Touihri I, Kallech-Ziri O, Boulila A, Fatnassi S, Marrakchi N, Luis J and Hanchi M. Ecballium elaterium (L.) A. Rich. seed oil: chemical composition and antiproliferative effect on human colonic adenocarcinoma fibrosarcoma cancer cell lines. Arab. J. Chem. 2015; [DOI:10.1016/j.arabjc.2015.02.023]
39. Chen YW, Chen KH, Huang PI, Chen YC, Chiou GY, Lo WL, Tseng LM, Hsu HS, Chang KW and Chiou SH. Cucurbitacin I suppressed stem-like property and enhanced radiation-induced apoptosis in head and neck squamous carcinoma--derived CD44 (+) ALDH1 (+) cells. Mol. Cancer Ther. 2010; 9 (11): 2879-92. [DOI:10.1158/1535-7163.MCT-10-0504]
40. Shi X, Franko B, Frantz C, Amin HM and Lai R. JSI-124 (cucurbitacin I) inhibits Janus kinase-3/signal transducer and activator of transcription-3 signalling, downregulates nucleophosmin-anaplastic lymphoma kinase (ALK), and induces apoptosis in ALK-positive anaplastic large cell lymphoma cells. Br. J. Haematol. 2006; 135 (1): 26-32. [DOI:10.1111/j.1365-2141.2006.06259.x]
41. Lee DH, Iwanski GB and Thoennissen NH. Cucurbitacin: ancient compound shedding new light on cancer treatment. Scientific World J. 2010; 10, 413-8. [DOI:10.1100/tsw.2010.44]

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