Correlation of antiangiogenic, antioxidant and cytotoxic activities of some Sudanese medicinal plants with phenolic and flavonoid contents

BMC Complementary and Alternative Medicine

Amin MS Abdul Majid⁵  Zeyad D Nassar⁴  Nahdzatul S Muslim⁵  Hussein M Baharetha³  Aman S Abdul Majid¹  Mohamed B Khadeer Ahamed⁵  Loiy Elsir A Hassan² 

[1] Advanced Medical and Dental Institute (IPPT), Universiti Sains Malaysia, Penang, Malaysia;Department of Botany, Faculty of Science& Technology, Omdurman Islamic University, P.O. Box 383, Omdurman, Sudan;Department of Pharmacy, College of medicine and Health Sciences, Hadhramout University, Fuluk, Mukalla, Hadhramout, Republic of Yemen;School of Pharmacy, The University of Queensland, 20 Cornwall Street, Woolloongabba, QLD 4102, Australia;EMAN Research and Testing Laboratory, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia

关键词: Traditional medicine;    Sudanese medicinal plants;    Anticancer;    Antioxidants;    Raorta ring assay;    Antiangiogenesis;   

Others  :  1085916
DOI  :  10.1186/1472-6882-14-406

 received in 2014-07-23, accepted in 2014-10-10,  发布年份 2014

【 摘 要 】

Background

Consumption of medicinal plants to overcome diseases is traditionally belongs to the characteristics of most cultures on this earth. Sudan has been a host and cradle to various ancient civilizations and developed a vast knowledge on traditional medicinal plants. The present study was undertaken to evaluate the antioxidant, antiangiogenic and cytotoxic activities of six Sudanese medicinal plants which have been traditionally used to treat neoplasia. Further the biological activities were correlated with phytochemical contents of the plant extracts.

Methods

Different parts of the plants were subjected to sequential extraction method. Cytotoxicity of the extracts was determined by dimethylthiazol-2-yl)- 2,5diphenyl tetrazolium bromide (MTT) assay on 2 human cancer (colon and breast) and normal (endothelial and colon fibroblast) cells. Anti-angiogenic potential was tested using ex vivo rat aortic ring assay. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was conducted to screen the antioxidant capabilities of the extracts. Finally, total phenolic and flavonoid contents were estimated in the extracts using colorimetric assays.

Results

The results indicated that out of 6 plants tested, 4 plants (Nicotiana glauca, Tephrosia apollinea, Combretum hartmannianum and Tamarix nilotica) exhibited remarkable anti-angiogenic activity by inhibiting the sprouting of microvessels more than 60%. However, the most potent antiangiogenic effect was recorded by ethanol extract of T. apollinea (94.62%). In addition, the plants exhibited significant antiproliferative effects against human breast (MCF-7) and colon (HCT 116) cancer cells while being non-cytotoxic to the tested normal cells. The IC₅₀ values determined for C. hartmannianum, N. gluaca and T. apollinea against MCF-7 cells were 8.48, 10.78 and 29.36 μg/ml, respectively. Whereas, the IC₅₀ values estimated for N. gluaca, T. apollinea and C. hartmannianum against HCT 116 cells were 5.4, 20.2 and 27.2 μg/ml, respectively. These results were more or less equal to the standard reference drugs, tamoxifen (IC₅₀ = 6.67 μg/ml) and 5-fluorouracil (IC₅₀ = 3.9 μg/ml) tested against MCF-7 and HCT 116, respectively. Extracts of C. hartmannianum bark and N. glauca leaves demonstrated potent antioxidant effect with IC_50s range from 9.4–22.4 and 13.4–30 μg/ml, respectively. Extracts of N. glauca leaves and T apollinea aerial parts demonstrated high amount of flavonoids range from 57.6–88.1 and 10.7–78 mg quercetin equivalent/g, respectively.

Conclusions

These results are in good agreement with the ethnobotanical uses of the plants (N. glauca, T. apollinea, C. hartmannianum and T. nilotica) to cure the oxidative stress and paraneoplastic symptoms caused by the cancer. These findings endorse further investigations on these plants to determine the active principles and their mode of action.

【 授权许可】

   
2014 Hassan et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Bray F, Ren JS, Masuyer E, Ferlay J: Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer 2013, 132(5):1133-1145.
• [2]Chorawala MR, Oza PM, Shah GB: Mechanisms of anticancer drugs resistance: an overview. Int J Pharma Sci Drug Res 2012, 1:01-09.
• [3]Cragg GM, Newman DJ: Plants as a source of anti-cancer agents. J Ethnopharmacol 2005, 100(1–2):72-79.
• [4]Jung Park E, Pezzuto J: Botanicals in cancer chemoprevention. Cancer Metastasis Rev 2002, 21(3–4):231-255.
• [5]Shoeb M: Anticancer Agents from Medicinal Plants. Pharmacology: Bangladesh Journal of; 2006:1(2006).
• [6]Newman DJ, Cragg GM: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012, 75(3):311-335.
• [7]Jaspars M, Lawton LA: Cyanobacteria - a novel source of pharmaceuticals. Curr Opin Drug Discov Devel 1998, 1(1):77-84.
• [8]Folkman J: What is the evidence that tumors are angiogenesis dependent? J Natl Cancer Inst 1990, 82(1):4-6.
• [9]Folkman J: Role of angiogenesis in tumor growth and metastasis. Semin Oncol 2002, 29(6, Supplement 16):15-18.
• [10]Scappaticci FA: The therapeutic potential of novel antiangiogenic therapies. Expert Opin Investig Drugs 2003, 12(6):923-932.
• [11]Dell’Eva R, Pfeffer U, Vené R, Anfosso L, Forlani A, Albini A, Efferth T: Inhibition of angiogenesis in vivo and growth of Kaposi’s sarcoma xenograft tumors by the anti-malarial artesunate. Biochem Pharmacol 2004, 68(12):2359-2366.
• [12]Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F: Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer. N Engl J Med 2004, 350(23):2335-2342.
• [13]Al-Suede FSR, Farsi E, Ahamed MKB, Ismail Z, Abdul Majid AS, Abdul Majid AMS: Marked antitumor activity of cat’s whiskers tea (Orthosiphon stamineus) extract in orthotopic model of human colon tumor in nude mice. J Biochem Tech 2012, 5(28 December 2012):S170-S176.
• [14]Dawidowicz AL, Wianowska D, Baraniak B: The antioxidant properties of alcoholic extracts from Sambucus nigra L. (antioxidant properties of extracts). LWT Food Sci Technol 2006, 39(3):308-315.
• [15]Yoysungnoen P, Wirachwong P, Changtam C, Suksamrarn A, Patumraj S: Anti-cancer and anti-angiogenic effects of curcumin and tetrahydrocurcumin on implanted hepatocellular carcinoma in nude mice. World J Gastroenterol 2008, 14(13):2003-2009.
• [16]Munzel T, Gori T, Bruno RM, Taddei S: Is oxidative stress a therapeutic target in cardiovascular disease? Eur Heart J 2010, 31(22):2741-2748.
• [17]Dell’Agli M, Buscialà A, Bosisio E: Vascular effects of wine polyphenols. Cardiovasc Res 2004, 63(4):593-602.
• [18]Galal M, Bashir AK, Salih AM, Adam SL: Activity of water extracts of Albizia Anthelmintica and A. lebek barks against experimenta Hymenolepis diminuta infection in rats. J Ethnopharmacol 1991, 33(1991):333-337.
• [19]Eatock MM, Schatzlein A, Kaye SB: Tumour vasculature as a target for anticancer therapy. Cancer Treat Rev 2000, 26(3):191-204.
• [20]Al-Salahi OSA, Kit-Lam C, Majid AM, Al-Suede FS, Mohammed Saghir SA, Abdullah WZ, Ahamed MB, Yusoff NM: Anti-angiogenic quassinoid-rich fraction from Eurycoma longifolia modulates endothelial cell function. Microvasc Res 2013, 90:30-39.
• [21]Ahamed MB, Aisha AF, Nassar ZD, Siddiqui JM, Ismail Z, Omari SM, Parish CR, Majid AM: Cat’s whiskers tea (Orthosiphon stamineus) extract inhibits growth of colon tumor in nude mice and angiogenesis in endothelial cells via suppressing VEGFR phosphorylation. Nutr Cancer 2012, 64(1):89-99.
• [22]Al-Suede FSR, Khadeer Ahamed MB, Abdul Majid AS, Baharetha HM, Hassan LE, Kadir MOA, Nassar ZD, Abdul Majid AMS: Optimization of cat’s whiskers tea (orthosiphon stamineus) using supercritical carbon dioxide and selective chemotherapeutic potential against prostate cancer cells. Evid Based Complement Alternat Med 2014, 2014:15.
• [23]Baharetha HM, Nassar ZD, Aisha AF, Khadeer AMB, Al-Suede FSR, Abd KMO, Zhari I, Abdul MAMS: Proapoptotic and antimetastatic properties of supercritical CO2 extract of Nigella sativa Linn. against breast cancer cells. J Med Food 2013, 16(12):1121-1130.
• [24]Khadeer Ahamed MB, Krishna V, Dandin CJ: In vitro antioxidant and in vivo prophylactic effects of two gamma-lactones isolated from Grewia tiliaefolia against hepatotoxicity in carbon tetrachloride intoxicated rats. Eur J Pharmacol 2010, 631(1–3):42-52.
• [25]Gibellini L, Pinti M, Nasi M, De Biasi S, Roat E, Bertoncelli L, Cossarizza A: Interfering with ROS metabolism in cancer cells: the potential role of quercetin. Cancer 2010, 2(14 June 2010):1288-1311.
• [26]Coso S, Harrison I, Harrison CB, Vinh A, Sobey CG, Drummond GR, Williams ED, Selemidis S: NADPH oxidases as regulators of tumor angiogenesis: current and emerging concepts. Antioxid Redox Signal 2012, 16(11):1229-1247.
• [27]Ushio-Fukai M, Nakamura Y: Reactive oxygen species and angiogenesis: NADPH oxidase as target for cancer therapy. Cancer Lett 2008, 266(1):37-52.
• [28]Hilmi Y, Abushama MF, Abdalgadir H, Khalid A, Khalid H: A study of antioxidant activity, enzymatic inhibition and in vitro toxicity of selected traditional sudanese plants with anti-diabetic potential. BMC Complement Altern Med 2014, 14(1):1472-6882.
• [29]Balasundram N, Sundram K, Samman S: Phenolic compounds in plants and agri-industrial by-products: antioxidant activity, occurrence, and potential uses. Food Chem 2006, 99(1):191-203.
• [30]Kampa M, Nifli AP, Notas G, Castanas E: Polyphenols and cancer cell growth. Rev Physiol Biochem Pharmacol 2007, 159:79-113.
• [31]Yasuda M, Ohzeki Y, Shimizu S, Naito S, Ohtsuru A, Yamamoto T, Kuroiwa Y: Stimulation of in vitro angiogenesis by hydrogen peroxide and the relation with ETS-1 in endothelial cells. Life Sci 1999, 64(4):249-258.
• [32]Yeldandi AV, Rao MS, Reddy JK: Hydrogen peroxide generation in peroxisome proliferator-induced oncogenesis. Mutat Res 2000, 448(2):159-177.
• [33]Irani K, Xia Y, Zweier JL, Sollott SJ, Der CJ, Fearon ER, Sundaresan M, Finkel T, Goldschmidt-Clermont PJ: Mitogenic signaling mediated by oxidants in Ras-transformed fibroblasts. Science 1997, 275(5306):1649-1652.
• [34]Galati G, O’Brien PJ: Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med 2004, 37(3):287-303.
• [35]Baghel SS, Shrivastava N, RS Baghel PA, Rajput S: A review of quercetin: antioxidant and anticancer properties. World J Pharm Pharmaceutical Sci 2012, 1(1):146-160.
• [36]Harada H, Noro T, Kamei Y: Selective antitumor activity in vitro from marine algae from Japan coasts. Biol Pharm Bull 1997, 20(5):541-546.
• [37]Moghaddam G, Ebrahimi SA, Rahbar-Roshandel N, Foroumadi A: Antiproliferative activity of flavonoids: influence of the sequential methoxylation state of the flavonoid structure. Phytother Res 2012, 26(7):1023-1028.
• [38]Delmulle L, Bellahcène A, Dhooge W, Comhaire F, Roelens F, Huvaere K, Heyerick A, Castronovo V, De Keukeleire D: Anti-proliferative properties of prenylated flavonoids from hops (Humulus lupulus L.) in human prostate cancer cell lines. Phytomedicine 2006, 13(9–10):732-734.
• [39]Chidambara Murthy KN, Kim J, Vikram A, Patil BS: Differential inhibition of human colon cancer cells by structurally similar flavonoids of citrus. Food Chem 2012, 132(1):27-34.
• [40]Batra P, Sharma A: Anti-cancer potential of flavonoids: recent trends and future perspectives. 3 Biotech 2013, 3(6):439-459.
• [41]Clere N, Faure S, Martinez MC, Andriantsitohaina R: Anticancer properties of flavonoids: roles in various stages of carcinogenesis. Cardiovasc Hematol Agents Med Chem 2011, 9(2):62-77.
• [42]Gordon MH: The Mechanism of Antioxidant Action in Vitro. In Food Antioxidants. Edited by Hudson BJF. Netherlands: Springer; 1990:1-18.
• [43]Miliauskas G, Venskutonis PR, van Beek TA: Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem 2004, 85(2):231-237.
• [44]Stoclet J-C, Chataigneau T, Ndiaye M, Oak MH, El Bedoui J, Chataigneau M, Schini-Kerth VB: Vascular protection by dietary polyphenols. Eur J Pharmacol 2004, 500(1–3):299-313.
• [45]Oak MH, El Bedoui J, Schini-Kerth VB: Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem 2005, 16(1):1-8.
• [46]Walter A, Etienne-Selloum N, Brasse D, Schleiffer R, Bekaert V, Vanhoutte PM, Beretz A, Schini-Kerth VB: Red wine polyphenols prevent acceleration of neovascularization by angiotensin II in the ischemic rat hindlimb. J Pharmacol Exp Ther 2009, 329(no. 2):329-699.
• [47]Mariod A, Matthäus B, Hussein IH: Antioxidant activities of extracts from Combretum hartmannianum and Guiera senegalensis on the oxidative stability of sunflower oil. Emir J Food Agric 2006, 18(2006):20-28.
• [48]Ali H, König GM, Khalid SA, Wright AD, Kaminsky R: Evaluation of selected Sudanese medicinal plants for their in vitro activity against hemoflagellates, selected bacteria, HIV-1-RT and tyrosine kinase inhibitory, and for cytotoxicity. J Ethnopharmacol 2002, 83(3):219-228.
• [49]Gotink KJ, Verheul HM: Anti-angiogenic tyrosine kinase inhibitors: what is their mechanism of action? Angiogenesis 2010, 13(1):1-14.
• [50]Faivre S, Demetri G, Sargent W, Raymond E: Molecular basis for sunitinib efficacy and future clinical development. Nat Rev Drug Discov 2007, 6(9):734-745.
• [51]Wilhelm S, Carter C, Lynch M, Lowinger T, Dumas J, Smith RA, Schwartz B, Simantov R, Kelley S: Discovery and development of sorafenib: a multikinase inhibitor for treating cancer. Nat Rev Drug Discov 2006, 5(10):835-844.
• [52]Patel PH, Chaganti RS, Motzer RJ: Targeted therapy for metastatic renal cell carcinoma. Br J Cancer 2006, 94(5):614-619.
• [53]Ibrahim B, Saleh H, A.E.-S: Phytochemical Investigation of Nicotiana glauca and Microbial Degradation of Nicotine as a Water Pollutant of Tobacco. Fairford, GLO, United Kingdom: LAP LAMBERT Academic Publishing; 2012.
• [54]Hassan LEA, Majid ASA, Iqbal MA, Al Suede FSR, Haque RA, Ismail Z, Ein OC, Majid AMSA, M.B.K.A: Crystal structure elucidation and anticancer studies of (-)-pseudosemiglabrin: a flavanone isolated from the aerial parts of tephrosia apollinea. PLoS ONE 2014, 9(3):90806.
• [55]Dai Z-J, Lu WF, Gao J, Kang HF, Ma YG, Zhang SQ, Diao Y, Lin S, Xi-Jing W, Wu WY: Anti-angiogenic effect of the total flavonoids in Scutellaria barbata D. Don. BMC Complement Altern Med 2013, 13(1):1-10. BioMed Central Full Text
• [56]Abou-Douh AM, Toscano RA, Nariman N, El-Khrisy E, I.C: Prenylated flavonoids from the root of Egyptian Tephrosia apollinea–crystal structure analysis. Z Naturforsch 2005, B 60:458-470.
• [57]Abouzid S, Sleem A: Hepatoprotective and antioxidant activities of Tamarix nilotica flowers. Pharm Biol 2011, 49(4):392-395.
• [58]Nawwar MAM, Buddrus J, Bauer H: Dimeric phenolic constituents from the roots of Tamarix nilotica. Phytochemistry 1982, 21(7):1755-1758.
• [59]Barakat HH, Nawwar MA, Buddrus J, Linscheid M: Niloticol, a phenolic glyceride and two phenolic aldehydes from the roots of Tamarix nilotica. Phytochemistry 1987, 26(6):1837-1838.
• [60]Folkman J: Angiogenesis and apoptosis. Semin Cancer Biol 2003, 13(2):159-167.
• [61]Tiwari M: Apoptosis, angiogenesis and cancer therapies. J Cancer Ther Res 2012, 1(1):3.