In vitro evaluation of Rheum ribes induced genotoxicity in HepG2 cell lines

Year 2019, Volume: 49 Issue: 3, 132 - 136, 01.12.2019

Mahmoud Abudayyak

Abstract

Rheum ribes is a perennial herbaceous plant belonging to the Polygonaceae family that grows more in rocky and gravelly slopes in high altitude areas of Levant and Turkey. Rheum ribes is consumed as food and widely used in folk medicine against nausea, constipation and for different diseases including diabetesand hypertension. Unfortunately, the researches on Rheum ribes toxicity are insufficient. In our study, human hepatocellular carcinoma (HepG2) cell line was used in cytotoxicity evaluation of Rheum ribes water, methanol and chloroform extracts by MTT and NRU test. Comet assay was used to investigate the genotoxicity potentials of the plant extracts. Our results show that all extracts cause cell death in a concentration dependent manner at 5-50 mg/mL concentrations. The IC50 values are 14.29- 31.94 mg/mL by MTT and 21.15 - 27.66 mg/mL by NRU assay. The highest concentration (25 mg/mL) of methanol extract causes a significant DNA damage (8.7-folds). In conclusion, similar to a lot of plants used in the folk medicine the risk of Rheum ribes is still unknown. The uncontrolled use of this plant could harm to the patients. Our results indicate possible cyto- and gentoxicity effects of Rheum ribes, these results should rise the concerns about the safety of Rheum ribes and other folk herbs.

Cite this article as: Abudayyak M (2019). In vitro evaluation of Rheum ribes induced genotoxicity in HepG2 cell lines. Istanbul J Pharm 10.26650/IstanbulJPharm.2019.19021.

Keywords

Rheum ribes, herbal toxicity, Genotoxicity, Cytotoxicity, HepG2 cells

References

• Abudayyak M, Özdemir Nath E, Özhan G (2015). Toxic potentials of ten herbs commonly used for aphrodisiac effect in Turkey. Turkish J Med Sci 45(3):496-506. Abudayyak M, Jannuzzi AT, Özhan G, Alpertunga B (2015 B). Investigation on the toxic potential of Tribulus terrestris in vitro. Pharm Biol 53(4):469-76. Abudayyak M, Öztaş E, Arici M, Özhan G (2017). Investigation of the toxicity of bismuth oxide nanoparticles in various cell lines. Chemosphere 169:117-123. Abu-Irmaileh BE, Afifi FU (2012). Herbal medicine in Jordan with special emphasis on commonly used herbs. J Ethnopharmacol 89:193-197. Afifi FU, Abu-Irmaileh BE (2000). Herbal medicine in Jordan with emphasis on less commonly used medicinal herbs. J Ethnopharmacol 72:101-110 Alaadin AM, Al-Khateeb EH, Jäger AK (2007). Antibacterial activity of the Iraqi Rheum ribes root. Pharm Biol 45(9):688-690. Amiri N, Shafaghat A, Salimi F (2015). Screening of the essential oil, hexane extract, chemical composition, antioxidant activity, and antimicrobial activity of the flower Rheum ribes L. from Iran. J Essent Oil-Bearing Plants 18(5):1108-1115. Andiç S, Tunçtürk Y, Ocak E, Köse S (2004). Some chemical characteristics of edible wild Rhubarb species (Rheum ribes L ) Res J Agric Biol Sci. 2009;5:973–977. Bonjar S. Evaluation of antibacterial properties of some medicinal plants used in Iran. J Ethnopharmacol 94:301–305. Borenfreund E, and Puerner JA (1985). Toxicity determined in vitro by morphological alterations and neutral red absorption. Toxicol Lett 24, 119-124. Brand RM, Hannah TL, Mueller C, Cetin L, Hamel FG (2000). A novel system to study the impact of epithelial barriers on cellular metabolism. Ann Biomed Eng 28:1210-1217. Cakilcioglu U, Khatun S, Turkoglu I, Hayta S (2011). Ethnopharmacological survey of medicinal plants in Maden (Elazig-Turkey). J Ethnopharmacol 2011;137: 469-486 Cakilcioglu U, Turkoglu I (2010). An ethnobotanical survey of medicinal plants in Sivrice (Elaziğ-Turkey). J Ethnopharmacol 132: 165-175. Çinar I, Eroglu C, Avci E, Çetinkaya S, Dursun HG, Kurar E (2016). Apoptotic effects of Rheum ribes plant extract on MCF-7 cancer cell lines. FEBS J 283:338-338. Chan SM, Khoo KS, Sit NW (2015). Interactions between plant extracts and cell viability indicators during cytotoxicity testing: implications for ethnopharmacological studies. TROP J PHARM RES 14 (11): 1991-1998. Esmaeilbeig M, Kouhpayeh SA, Amirghofran Z (2015). an investigation of the growth inhibitory capacity of several medicinal plants from Iran on tumor cell lines. Iran J Cancer Prev e4032. Farnsworth NR (1990). The role of the ethnopharmacology in drug development. In bioactive compounds from Plants. Chadwick DJ & Marsh J, Bioactive Compounds from Plants, Chichester (CIBA Foundation Symposium), New York, Wiley; Pp.2-21. Fazly-Bazzaz BS, Khajehkaramadin M and Shokooheizadeh HR (2005). In vitro antibacterial activity of Rheum ribes extract obtained from various plant parts against clinical isolates of Gram-negative pathogens. Iranian J Pharm Res 2:87-91. Fotakis G, Timbrell JA (2006). In vitro cytotoxicity assays: Comparison of LDH, neutral red, MTT and protein assay in hepatoma cell lines following exposure to cadmium chloride. Toxicol Lett 160:171-177. Gholamhoseinian A, Moradi MN, Sharifi-far F (2009). Screening the methanol extracts of some Iranian plants for acetylcholinesterase inhibitory activity. Res Pharm Sci 4(2):105-112. Goya L, Martin MA, Ramos S, Raquel M, Laura B (2015). A cell culture model for the assessment of the chemopreventive potential of dietary compounds. Curr Nutr Food Sci 5(1):56-64. Hadjzadeh MAR, Rajaei Z, Keshavarzi Z, Shirazi MG, Toosi V (2013). Effect of aqueous extract of Rheum ribes on cisplatin-induced nephrotoxicity in rat. J Pharm Bioallied Sci 5(4):309–13. Hamzeh S. Farokhi F, Heydari R, Manaffar R (2014). Renoprotective effect of hydroalcoholic extract of Rheum ribes root in diabetic female rats. Avicenna J. Phytomed 4:392-401 Hudson JB, Lee MK, Sener B, Erdemoglu N (2000). Antiviral activities in extracts of Turkish medicinal plants. Pharm Biol 38:171–175. Kasabri V, Afifi FU, Hamdan I (2011). Evaluation of the acute antihyperglycemic effects of four selected indigenous plants from Jordan used in traditional medicine. Pharm Biol 49(7):687-695. Kaval I, Behçet L, Çakılcıoğlu U (2015). Survey of wild food plants for human consumption in Geçitli (Hakkari-Turkey). Indian j. tradit. Knowl 14:183-190. Kirbag S, Zengin F (2006). Antimicrobial activities of some medical plants in Elazığ region. Yyu J Agr Sci 16:77-80 Korkmaz M, Karakus SI (2015). Traditional uses of medicinal plants of üzümlü district, erzincan, Turkey. Pakistan J Bot 47(1):125-134. Krishnaiah D, Sarbatly R, Nithyanandam R (2011). A review of the antioxidant potential of medicinal plant species. FBP 89: 217-233. Martin KR, Failla ML, Smith JC (1997). Differential susceptibility of Caco-2 and HepG2 human cell lines to oxidative stress. J Elisha Mitchell Sci Soc 113(4):149-162. Mojarrab M, Ghanbaria K, Shakeri M, Minoosh Siavash-Haghighi Z, Hosseinzadeh L (2015). Evaluation of acute and 8-week sub-chronic toxicities of aromatic water of Rheum ribes in rats. J Reports Pharm Sci 4(2): 25-134. Mosmann T (1983). Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays. J Immunol Methods 65, 55-63. Munzuroglu O, Karatas F, Gur N (2000). Isgın (Rheum ribes L.) Bitkisindeki A, E ve C vitaminleri ile Selenyum düzeylerinin arastırılması. Turkish J Biol 24:397-404. Nabati F, Mojab f, Habibi-Rezaei M, Bagherzadeh k, Amanlou m, Yousefi B (2012). Large scale screening of commonly used Iranian traditional medicinal plants against urease activity. DARU J Pharm Sci 20 (1):72-81. Naemi F, Asghari G, Yousofi H, Yousefi HA (2014). Chemical composition of essential oil and anti trichomonas activity of leaf , stem , and flower of Rheum ribes L extracts. Avicenna J Phytomedicine 4(3):191-199. Naqishbandi AM, Josefsen K, Pedersen ME, Jger AK (2009). Hypoglycemic activity of Iraqi Rheum ribes root extract. Pharm Biol 47(5):380-383. Nikbakht MR, Esnaashari S, Afshar FH, Ragasa CY (2013). Chemical composition and general toxicity of essential oil extracted from the stalks and flowers of Rheum ribes L. growing in Iran. J Reports Pharm Sci 2(2):165-170. Oktay M, Yildirim A, Bilaloǧlu V, Gülçin I (2007). Antioxidant activity of different parts of isgin (Rheum ribes L.). Asian J Chem 19(4):3047–55. Otoom SA, Alsafis A, Karem ZK, Alkofahi A (2006). The use of medicinal herbs by diabetic Jordanian patients. J Herb Pharmacother 6: 31–41. Özcan MM, Dursun N, Arslan D (2007). Some nutritional properties of Prangos ferulacea (L.) lindl and Rheum ribes L. stems growing wild in Turkey. Int J Food Sci Nutr 58(2):162-167. Öztürk M, Aydoǧmuş-Öztürk F, Duru ME, Topçu G (2007). Antioxidant activity of stem and root extracts of Rhubarb (Rheum ribes): An edible medicinal plant. Food Chem 103(2): 623-630. Polat R, Çakılcıoğlu U, Kaltalıoğlu K, Ulusan MD, Türkmen Z (2015). An ethnobotanical study on medicinal plants in Espiye and its surrounding (Giresun-Turkey). J Ethnopharmacol 163: 1-11 Polat R, Çakılcıoğlu U, Satıl F (2013). Traditional uses of medicinal plants in Solhan (Bingöl-Turkey). J Ethnopharmacol 148:951-963 Polat R, Çakılcıoğlu U, Ulusan MD, Paksoy MY (2015). Survey of wild food plants for human consumption. Sardari S, Shokrgozar MA, Ghavami G (2009). Cheminformatics based selection and cytotoxic effects of herbal extracts. Toxicol Vitr 23(7):1412-1421. Sayyah M, Boostani H, Pakseresht S (2009). Efficacy of hydroalcoholic extract of Rheum ribes L . in treatment of major depressive disorder. J Med Plants 3(8):573-575. Sindhu RK, Kumar P, Kumar J, Kumar A, Arora S (2010). Investigations into the anti-ulcer activity of Rheum ribes linn leaves extracts. Int J Pharm Pharm Sci 2:90-92. Singh NP, McCoy MT, Tice RR, et al., (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res 175, 184–191. Tetik F, Civelek S, Cakilcioglu U (2013). Traditional uses of some medicinal plants in Malatya (Turkey). J Ethnopharmacol 146(1):331–46. Tosun F, Akyüz-Kızılay C (2003). Anthraquinones and flavonoids from Rheum ribes. J Fac Pharm Ankara 32:31-35 Verschaeve L, Kestens V, Taylor JLS (2004). Investigation of the antimutagenenic effects of selected South African medicinal plant extracts. Toxicol in Vitro 18(1):29-35. Wang P, Henning SM, Heber D (2010). Limitations of MTT and MTS-based assays for measurement of antiproliferative activity of green tea polyphenols. PLoS One 16;5(4):e10202. Weyermann J, Lochmann D, Zimmer A (2005). A practical note on the use of cytotoxicity assays. Int J Pharm 288:369-376. Zahedi M, Hojjati MR, Fathpour H, Rabieic Z, Alibabaei Z, Basima A (2015). Effect of Rheum ribes hydro-alcoholic extract on memory impairments in rat model of Alzheimer᾽s disease. Iran J Pharm Res 4(4):1197-1206.