سال 19، شماره 74 - ( 4-1399 )                   سال 19 شماره 74 صفحات 177-191 | برگشت به فهرست نسخه ها


XML English Abstract Print


Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:

Sharifiyan F, Mirjalili S A, Fazilati M, Poorazizi E, Habibollahi S. Cytotoxic effect of hydro-alcoholic extract of pomegranate (Punica granatum L.) flowers and isolated ursolic acid on B16f10 melanoma cells. J. Med. Plants. 2020; 19 (74) :177-191
URL: http://jmp.ir/article-1-2248-fa.html
شریفیان فاطمه، میرجلیلی عباس، فضیلتی محمد، پورعزیزی الهه، حبیب اللهی سعید. بررسی اثر سمیت سلولی عصاره هیدروالکلی گل‌های انار (Punica granatum L.) و اسید اورسولیک خالص ‌شده از آن بر روی سلول‌های ملانوما B16f10. فصلنامه گياهان دارویی. 1399; 19 (74) :177-191

URL: http://jmp.ir/article-1-2248-fa.html


1- گروه زیست‌شناسی، دانشگاه پیام‌نور، ایران
2- مرکز آموزش عالی امام خمینی (ره)، سازمان تحقیقات، آموزش و ترویج کشاورزی، تهران، ایران ، abmirjalili@gmail.com
3- مرکز آموزش عالی امام خمینی (ره)، سازمان تحقیقات، آموزش و ترویج کشاورزی، تهران، ایران
4- گروه بیوشیمی، واحد نجف‌آباد، دانشگاه آزاد اسلامی، نجف‌آباد، ایران
5- دانشکده شیمی، دانشگاه پیام‌نور، ایران
چکیده:   (139 مشاهده)
مقدمه: ملانوما خطرناک‌ترین نوع سرطان پوست است و بیشترین سرعت رشد را در میان انواع سرطان‌ها داراست. اسید اورسولیک یکی از تری‌ترپنوئیدهای پنتاسیکلیک شناخته ‌شده است که به ‌طور گسترده در گیاهان دارویی از جمله گل انار وجود دارد. هدف: مطالعه حاضر به بررسی اثر سایتوتوکسیک عصاره اتانولی گل‌های انار و همچنین اسید اورسولیک خالص‌شده از آن بر سلول‌های ملانوما موشی B16f10 می‌پردازد. روش بررسی: خالص‌سازی اسید اورسولیک از گل‌های انار، با استفاده از عصاره‌گیری با کمک اولتراسوند و به دنبال آن فلش کروماتوگرافی فاز نرمال انجام شد. ساختار شیمیایی اسید اورسولیک خالص‌شده به‌وسیله کروماتوگرافی گازی جفت شده با اسپکتروسکوپی جرمی (GC-MS)، طیف‌سنجی مادون‌قرمز (IR) و 1H-NMR تأیید شد. سپس اثر عصاره اتانولی گل‌های انار و همچنین اسید اورسولیک خالص ‌شده از آن در مهار تکثیر سلول‌های ملانوما موشی B16f10 با استفاده از روش MTT انجام شد. نتایج: نتایج این مطالعه استخراج و خالص‌سازی موفق و پربازده اسید اورسولیک از گل‌های انار را توسط این روش فلش نشان داد. بعد از یک ‌بار فلش کروماتوگرافی، درصد خلوص اسید اورسولیک بیش از 97 درصد و مقدار محصول 1/0 درصد پودر خشک گل انار بود. تیمار سلول‌های B16f10 با عصاره‌ اتانولی گل‌های انار و اسید اورسولیک خالص‌شده از آن، فعالیت ضد‌تکثیری معنی‌داری را بعد از 48 و 72 ساعت نشان داد. این فعالیت مهاری از ‌عصاره گل‌های انار به‌صورت وابسته به غلظت و زمان مشاهده شد. نتیجه‌گیری: نتایج این تحقیق حاکی از ارزشمند بودن عصاره‌ گل‌های انار و اسید اورسولیک خالص‌شده از آن در پیشگیری و درمان ملانوما می‌باشد.
متن کامل [PDF 1178 kb]   (42 دریافت)    
نوع مطالعه: پژوهشی | موضوع مقاله: گياهان دارویی
دریافت: 1397/6/7 | پذیرش: 1398/1/17 | انتشار: 1399/4/31

فهرست منابع
1. Giblin AV and Thomas JM. Incidence, mortality and survival in cutaneous melanoma. J. Plast. Reconstr. Aesthet. Surg. 2007; 60: 32-40. [DOI:10.1016/j.bjps.2006.05.008]
2. Miller AJ and Mihm MC. Melanoma. NEJM. 2006; 355: 51-65. [DOI:10.1056/NEJMra052166]
3. Pinon A, Limami Y, Micallef L, Cook-Moreau J, Liagre B, Delage C, Emmanuel Duval R and Simon A. A novel form of melanoma apoptosis resistance: Melanogenesis up-regulation in apoptotic B16-F0 cells delays ursolic acid-triggered cell death. Exp. Cell Res. 2011; 317: 1669-76. [DOI:10.1016/j.yexcr.2011.04.014]
4. Harmand PO, Duval R, Liagre B, Jayat-Vignoles C, Beneytout JL, Delage C and Simon A. Ursolic acid induces apoptosis through caspase-3 activation and cell cycle arrest in HaCat cells. Int. J. Oncol. 2003; 23: 105-12. [DOI:10.3892/ijo.23.1.105]
5. Jhappan C, Noonan FP and Merlino G. Ultraviolet radiation and cutaneous malignant melanoma. Oncogene. 2003; 22: 3099-112. [DOI:10.1038/sj.onc.1206450]
6. Ivry GB, Ogle CA and Shim EK. Role of sun exposure in melanoma. Dermatol. Surg. 2006; 32: 481-92. [DOI:10.1111/j.1524-4725.2006.32101.x]
7. Kumar RS, Rajkapoor B and Peruma P. In vitro and in vivo anticancer activity of Indigofera cassioides Rottl. Ex. DC. Asian Pac. J. Trop. Med. 2011; 4: 379-85. [DOI:10.1016/S1995-7645(11)60108-9]
8. Dadashi S, Mousazadeh M, Emam-Djomeh Z and Mousavi SM. Pomegranate (Punica granatum L.) seed: A comparative study on biochemical composition and oil physicochemical characteristics. Int. J. Adv. Biol. Biomed. Res. 2013; 1(4): 351-63.
9. Tehranifar A, Zarei M, Nemati Z, Esfandiyari B and Vazifeshenas MR. Investigation of physico-chemical properties and antioxidant activity of twenty Iranian pomegranate (Punica granatum L.) cultivars. Sci. Hortic. 2010; 126: 180-5. [DOI:10.1016/j.scienta.2010.07.001]
10. Kaur G, Jabbar Z, Athar M and Alam MS. Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem. Toxico. 2006; 44: 984-93. [DOI:10.1016/j.fct.2005.12.001]
11. Zhang L, Yang X, Zhang Y, Wang L and Zhang R. In vitro antioxidant properties of different parts of pomegranate flowers. Food Bioprod. Process. 2011; 8(9): 234-40. [DOI:10.1016/j.fbp.2010.04.007]
12. Amjad L and Shafighi M. Evaluation of Antioxidant Activity, Phenolic and Flavonoid Content in Punica granatum var. Isfahan Malas Flowers. Int. J. Agri. Crop Sci. 2013; 5: 1133-9.
13. Fu Q, Zhang L, Cheng N, Jia M and Zhang Y. Extraction optimization of oleanolic and ursolic acids from pomegranate (Punica granatum L.) flowers. Food Bioprod. Process 2014; 9(2): 321-3. [DOI:10.1016/j.fbp.2012.12.006]
14. Zhang L, Fu Q and Zhang Y. Composition of anthocyanins in pomegranate flowers and their antioxidant activity. Food Chem. 2011; 127: 1444-9. [DOI:10.1016/j.foodchem.2011.01.077]
15. Rao VS, de Melo CL, Queiroz MGR, Lemos TLG, Menezes DB, Melo TS and Santos FA. Ursolic Acid, a Pentacyclic Triterpene from Sambucus australis, Prevents Abdominal Adiposity in Mice Fed a High-Fat Diet. J. Med. Food. 2011; 14: 1375-82. [DOI:10.1089/jmf.2010.0267]
16. Chen H, Gao Y, Wang A, Zhou X, Zheng Y and Zhou J. Evolution in medicinal Chemistry of ursolic acid derivatives as anticancer agents. Eur. J. Med. Che. 2015; 92: 648-55. [DOI:10.1016/j.ejmech.2015.01.031]
17. Novotny L, Vachalkova A and Biggs D. Ursolic acid: an anti-tumorigenic and chemopreventive activity. Minireview. Neo-plasma. 2001; 48: 241-6.
18. Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H, Ukiya M, Watanabe K, Kimura Y, Hasegawa J and Nishino H. Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci. Biotechnol. Biochem. 2004; 68: 85-90. [DOI:10.1271/bbb.68.85]
19. Senthil S, Chandramohan G and Pugalendi KV. Isomers (oleanolic and ursolic acids) differ in their protective effect against isoproterenol-induced myocardial ischemia in rats. Int. J. Cardiol. 2007; 119: 131-33. [DOI:10.1016/j.ijcard.2006.07.108]
20. Cunha WR, deMatos GX, Souza MG, Tozatti MG, Andrade e Silva ML, Martins CH, da Silva R and Da Silva Filho AA. Evaluation of the antibacterial activity of the methylene chloride extract of Miconia ligustroides, isolated triterpene acids, and ursolic acid derivatives. Pharm. Biol. 2010; 48: 166-9. [DOI:10.3109/13880200903062648]
21. Ngouela S, Ndjakou BL, Tchamo DN, Zelefack F, Tsamo E and Connolly JD. A prenylated xanthone with antimicrobial activity from the seeds of Symphonia globulifera. Nat. Prod. Res. 2005; 19: 23-7. [DOI:10.1080/14786410310001643876]
22. Shishodia S, Majumdar S, Banerjee S and Aggarwal BB. Ursolic acid inhibits nuclear factor-kappaB activation induced by carcinogenic agents through suppression of IkappaBalpha kinase and p65 phosphorylation: correlation with down-regulation of cyclooxygenase2, matrix metallo proteinase 9, and cyclin D1. Cancer Res. 2003; 63: 4375-83.
23. Ovesna Z, Vachalkova A, Horvathova K and Tَthova D. Pentacyclic triterpenoic acids: New chemoprotective compounds minireview. Neoplasma 2004; 51: 327-33.
24. Ishikawa T, Donatini Rdos S, Diaz IE, Yoshida M, Bacchi EM and Kato ET. Evaluation of gastroprotective activity of Plinia edulis (Vell.) Sobral (Myrtaceae) leaves in rats. J. Ethnopharmacol. 2008; 118: 527-9. [DOI:10.1016/j.jep.2008.05.007]
25. Ikeda Y, Murakami A and Ohigashi H. Ursolic acid: An anti- and pro-inflammatory Triterpenoid. Mol. Nutr. Food Res. 2008; 52: 26-42. [DOI:10.1002/mnfr.200700389]
26. Yang YC, Wei MC, Hong SJ, Huang TC and Lee SZ. Development/optimization of a green procedure with ultrasound-assisted improved supercritical carbon dioxide to produce extracts enriched in oleanolic acid and ursolic acid from Scutellaria barbata D. Don. Ind. Crop. Prod. 2013; 49: 542-53. [DOI:10.1016/j.indcrop.2013.05.013]
27. Shanmugam MK, Nguyen AH, Kumar AP, Tan BK and Sethi G. Targeted inhibition of tumor proliferation, survival, and metastasis by pentacyclic triterpenoids: potential role in prevention and therapy of cancer. Cancer Lett. 2012; 320: 158-70. [DOI:10.1016/j.canlet.2012.02.037]
28. Shao JW, Dai YC, Xue JP, Wang JC, Lin FP and Guo YH. In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives. Eur. J. Med. Chem. 2011; 46: 2652-61. [DOI:10.1016/j.ejmech.2011.03.050]
29. Still WC, Kahn M and Mitra A. Rapid chromatographic technique for preparative separations with moderate resolution. J. Org. Chem. 1978; 43: 2923-5. [DOI:10.1021/jo00408a041]
30. Fair JD and Kormos CM. Flash column chromatograms estimated from thin-layer chromatography data. J. Chromatogr. A. 2008; 1211: 49-54. [DOI:10.1016/j.chroma.2008.09.085]
31. Wu JW, Lee MH, Ho CT and Chang SS. Elucidation of the chemical structures of natural antioxidants isolated from rosemary. J. Am. Oil Chem. Soc. 1982; 59: 339-45. [DOI:10.1007/BF02541016]
32. Gnoattoa SCB, Dassonville-Klimpt A, Da Nascimento S, Galéra P, Boumediene K, Gosmann G, Sonnet P and Moslemi S. Evaluation of ursolic acid isolated from Ilex paraguariensis and derivatives on aromatase inhibition. Eur. J. Med. Chem. 2008; 43: 1865-77. [DOI:10.1016/j.ejmech.2007.11.021]
33. Suhagia BN, Rathod IS, Ezhava SB and Patel JA Simple Method for the Isolation and Estimation of Ursolic acid in Alstonia Scholaris R. BR. Int. J. Pharmaceut. Sci. Res. 2013; 4: 2807-11.
34. Li Y, Yang F, Zheng W, Hu M, Wang J, Ma S, Deng Y, Luo Y, Ye T and Yin W. Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro. Biomed. Pharmacother. 2016; 80: 227-35. [DOI:10.1016/j.biopha.2016.03.023]
35. Cardoso CAL, Vilegas W and Honda NK. Qualitative determination of indole alkaloids, triterpenoids and steroids of Tabernaemontana hilariana. J. Chromatogr. A. 1998; 808: 264-268. [DOI:10.1016/S0021-9673(98)00084-3]
36. Campos Ziegenbein F, Anisen HP and Konig WA. Secondary metabolites from Ganoderma lucidum and Spongiporus leucomallellus. Phytochem. 2006; 67: 202-11. [DOI:10.1016/j.phytochem.2005.10.025]
37. Janicsak G, Veres K, Kakasy AZ and Mathe I. Study of the oleanolic and ursolic acid contents of some species of the Lamiaceae. Biochem. Syst. Ecol. 2006; 34: 392-6. [DOI:10.1016/j.bse.2005.12.004]
38. Kalola J and Rajan M. Extraction and TLC Desitometric Determination of Triterpenoid Acids (Arjungenin, Arjunolic Acid) from Terminalia arjuna Stem Bark Without Interference of Tannins. Chromatographia 2006; 63: 475-81. [DOI:10.1365/s10337-006-0772-3]
39. Luque de Castro MD and Luque-Garc JL. Acceleration and Automation of Solid Sample Treatment, Elsevier, Amsterdam, 2002. [DOI:10.1016/S0166-526X(03)41022-2]
40. Henry MC, Yonker CR. Supercritical fluid chromatography, pressurized liquid extraction, and supercritical fluid extraction. Anal. Chem. 2006; 78: 3909-16. [DOI:10.1021/ac0605703]
41. Zhao J, Zhang XQ, Li SP, Yang FQ, Wang YT and Ye WC. Quality evaluation of Ganoderma through simultaneous determination of nine triterpenes and sterols using pressurized liquid extraction and high performance liquid chromatography. J. Sep. Sci. 2009; 29: 2609-15. [DOI:10.1002/jssc.200600178]
42. Bernatoniene J, Cizauskaite U, Ivanauskas L, Jakstas V, Kalveniene Z and Kopustinskiene DM. Novel approaches to optimize extraction processes of ursolic, oleanolic and rosmarinic acids from Rosmarinus officinalis leaves. Ind. Crop. Prod. 2016; 84: 72-9. [DOI:10.1016/j.indcrop.2016.01.031]
43. Fan JP, Kong T, Zhang XH, Zhang L, Tong SH, Tian ZY and Zhu JH. Solubilities of oleanolic acid and ursolic acid in (ethanol + water) mixed solvents from T = (292.2 to 328.2) K. J. Chem. Thermodyn. 2012; 47: 372-5. [DOI:10.1016/j.jct.2011.11.017]
44. Mandal V and Mandal SC. Design and performance evaluation of a microwave based low carbon yielding extraction technique for naturally occurring bioactive triterpenoid: oleanolic acid. Biochem. Eng. J. 2010; 5: 63-70. [DOI:10.1016/j.bej.2010.03.005]
45. Mazumder K, Siwu ERO, Nozaki S, Watanabe Y, Tanaka K and Fukase K. Ursolic acid derivatives from Bangladeshi medicinal plant, Saurauja roxburghii: Isolation and cytotoxic activity against A431 and C6 glioma cell lines. Phytochem. Lett. 2011; 4(3): 287-91. [DOI:10.1016/j.phytol.2011.04.019]
46. Machado DG, Neis VB, Balen GO, Colla A, Cunha MP, Dalmarco JB, Pizzolatti MG, Prediger RD and Rodrigues ALS. Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: Evidence for the involvement of the dopaminergic system. Pharmacol. Biochem. Behav. 2012; 103: 204-11. [DOI:10.1016/j.pbb.2012.08.016]
47. Frighettoa RTS, Welendorf RM, Nigro EN, Frighetto N and Siani AC. Isolation of ursolic acid from apple peels by high speed counter-current chromatography. Food Chem. 2008; 106: 767-71. [DOI:10.1016/j.foodchem.2007.06.003]
48. Yu XX, Wang QW, Xu XJ, Lv WJ, Zhao MQ and Liang ZK. Preparative isolation of Heteroclitin D from Kadsurae Caulis using normal-phase flash chromatography. J. Pharm. Anal. 2013; 3: 456-459. [DOI:10.1016/j.jpha.2013.07.004]
49. Wu YJ, Shi QY, Lei HL, Jin Y, Liu XS and Luan LJ. Simple and efficient preparation of 3, 6′-disinapoylsucrose from Polygalae Radix via column chromatographic extraction and reversed-phase flash chromatography. Sep. Purif. Technol. 2014; 135: 7-13. [DOI:10.1016/j.seppur.2014.07.052]
50. Huang YY, Liu XF, Liu JZ, Li L, Cui Q, Wang LT, Fu YJ and Luo M. Separation and purification of indigotin and indirubin from Folium isatidis extracts using a fast and efficient macroporous resin column followed reversed phase flash chromatography. J. Taiwan. Inst. Chem. E. 2016; 67: 61-8. [DOI:10.1016/j.jtice.2016.07.030]
51. Orgil O, Schwartz E, Baruch L, Matityahu I, Mahajna J and Amir R. The antioxidative and anti-proliferative potential of non-edible organs of the pomegranate fruit and tree. LWT-Food Sci. Technol. 2014; 58: 571-7. [DOI:10.1016/j.lwt.2014.03.030]
52. Es-saady D, Simon A, Ollier M, Maurizis JC, Chulia AJ and Delage C. Inhibitory effect of ursolic acid on B16 proliferation through cell cycle arrest. Cancer Lett. 1996; 106: 193-7. [DOI:10.1016/0304-3835(96)04312-1]
53. Ye Y, Chou GX, Wang H, Chu JH and Yu ZL. Flavonoids, apigenin and icariin exert potent melanogenic activities in murine B16 melanoma cells. Phytomedicine 2010; 18: 32-5. [DOI:10.1016/j.phymed.2010.06.004]
54. Manu KA and Kuttan G. Ursolic acid induces apoptosis by activating p53 and caspase-3 gene expressions and suppressing NF-κB mediated activation of bcl-2 in B16F-10 melanoma cells. Int. Immunopharmacol. 2008; 8: 974-81. [DOI:10.1016/j.intimp.2008.02.013]
55. Harmand PO, Duval R, Delage C and Simon A. Ursolic acid induces apoptosis through mitochondrial intrinsic pathway and caspase-3 activation in M4Beu melanoma cells. Int. J. Cancer. 2005; 114: 1-11. [DOI:10.1002/ijc.20588]
56. Kowalczyk MC, Walaszek Z, Kowalczyk P, Kinjo T, Hanausek M and Slaga TJ. Differential effects of several phytochemicals and their derivatives on murine keratinocytes in vitro and in vivo: implications for skin cancer prevention. Carcinogenesis 2009; 30: 1008-15. [DOI:10.1093/carcin/bgp069]
57. Tokuda H, Ohigashi H, Koshimizu K and Ito Y. Inhibitory effects of Ursolic acid on skin tumor promotion by 12O-Tetradecaniylphorbol-13-Acetate. Cancer Let. 1986; 33: 279-85. [DOI:10.1016/0304-3835(86)90067-4]
58. Zaker F. Anti tumoral and differentiation effects of alkaloids of harmine and harmaline on leukaemic cells treated with atra and g-csf. Razi Journal of Medical Sciences 2004; 10 (38): 869-75.

ارسال نظر درباره این مقاله : نام کاربری یا پست الکترونیک شما:
CAPTCHA

ارسال پیام به نویسنده مسئول


کلیه حقوق این وب سایت متعلق به فصلنامه علمی پژوهشی گیاهان دارویی می باشد.

طراحی و برنامه نویسی : یکتاوب افزار شرق

© 2020 All Rights Reserved | Journal of Medicinal Plants

Designed & Developed by : Yektaweb