Study of the betulin enriched birch bark extracts effects on human carcinoma cells and ear inflammation

Chemistry Central Journal

Melania Munteanu¹  Simona Cinta-Pinzaru⁴  Atena Gǎluşcan⁵  Istvan Zupko²  Mihaela Aluaş⁴  Ionuţ Ledeţi³  Codruţa Şoica³  Cristina A Dehelean³ 

[1]Department of Clinical Laboratory and Sanitary Chemistry, “Vasile Goldis” University, 1 Feleacului Str, Arad, 310396, Romania

[2]Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary

[3]Faculty of Pharmacy, Victor Babeş University of Medicine and Pharmacy, Eftimie Murgu Square 2, Timişoara, RO- 300041, România

[4]Faculty of Physics, Babes-Bolyai University, Kogalniceanu 1, Cluj-Napoca, 400084, Romania

[5]Faculty of Dentistry, Victor Babes University of Medicine and Pharmacy Timisoara, 9th Revolutiei din 1989 Blvd, Timisoara, 300041, Romania

关键词: 13C NMR;    SERS;    Raman;    Anticancer;    Birch extract;    Betulin;   

Others  :  788033
DOI  :  10.1186/1752-153X-6-137

 received in 2012-08-28, accepted in 2012-11-12,  发布年份 2012

【 摘 要 】

Background

Pentacyclic triterpenes, mainly betulin and betulinic acid, are valuable anticancer agents found in the bark of birch tree. This study evaluates birch bark extracts for the active principles composition.

Results

New improved extraction methods were applied on the bark of Betula pendula in order to reach the maximum content in active principles. Extracts were analyzed by HPLC-MS, Raman, SERS and ¹³C NMR spectroscopy which revealed a very high yield of betulin (over 90%). Growth inhibiting effects were measured in vitro on four malignant human cell lines: A431 (skin epidermoid carcinoma), A2780 (ovarian carcinoma), HeLa (cervix adenocarcinoma) and MCF7 (breast adenocarcinoma), by means of MTT assay. All of the prepared bark extracts exerted a pronounced antiproliferative effect against human cancer cell lines. In vivo studies involved the anti-inflammatory effect of birch extracts on TPA-induced model of inflammation in mice.

Conclusions

The research revealed the efficacy of the extraction procedures as well as the antiproliferative and anti-inflammatory effects of birch extracts.

【 授权许可】

   
2012 Dehelean et al.; licensee Chemistry Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Mullauer FB, Kessler JH, Medema JP: Betulin is a potent anti-tumor agent that is enhanced by cholesterol. PLoS ONE 2009, 4(4):e1.
• [2]Şoica C, Dehelean C, Ordodi V, Antal D, Vlaia V: Complexation with hydroxipropilgamma cyclodextrin of birch tree extract. Physico-chemical characterisation of their binary products. Rev Chim 2008, 59:678-681.
• [3]Rajendran P, Jaggy M, Singh MK, Mukherjee R, Burman AC: Pharmacological evaluation of C-3 modified betulinic acid derivates with potent anticancer activity. Invest New Drugs 2008, 26:25-34.
• [4]Hänsel R, Keller K, Rimpler H, Schneider G: Drogen A-D: Betula. Berlin: Springer Verlag; 1992.
• [5]Yogeeswari P, Sriram D: Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem 2005, 12:657-666.
• [6]Nosik NN, Deriabin PG, Isaeva EI, Kondrashina NG, Lavrukhina LA, Inozemtsev AN, Presnova GA, Topoleva TV: Interferon-inducing properties of dry birch bark extract and its effect on experimental infection caused by hepatitis C virus. Vopr Virusol 2005, 50:29-32.
• [7]Alakurtti S, Taru M, Salme K, Jari YK: Pharmacological properties of the ubiquitous natural product betulin. Eur J Pharm Sci 2006, 29:1-13.
• [8]Chichewicz RH, Kouzi SA: Chemistry, biological activity and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med Res Rev 2004, 24:90-114.
• [9]Flekhter OB, Medvedeva NI, Karachurina LT, Baltina LA, Galin FZ, Zarudii FS, Tolstikov GA: Synthesis and pharmacological activity of betulin, betulinic acid and allobetulin esters. Pharm Chem J 2005, 39:401-404.
• [10]Kovalenko LP, Shipaeva EV, Balakshin VV, Presnova GA, Chistyakov AN, Klodt PM, Kudrin VS, Durnev AD: Antiallergic activity of birch bark dry extract with at least 70% betulin content. Pharm Chem J 2009, 43:110-114.
• [11]Guidoin MF, Yang J, Pichette A, Roy C: Betulin isolation from birch bark by vacuum and atmospheric sublimation. A thermogravimetric study. Thermochimica Acta 2003, 398:153-166.
• [12]Soica CM, Dehelean CA, Peev CI, Aluas M, Zupko I, Kasa P, Alexa E: Physico-chemical comparison study of betulinic acid, betulin and birch bark extract and in vitro investigation of their cytotoxic effects towards skin epidermoid carcinoma (A431), breast carcinoma (MCF7) and cervix adenocarcinoma (HeLa) cell-lines. Nat Prod Res 2012, 26:968-974.
• [13]De Oliveira BH, Santos AM, Espindola DM: Determination of the triterpenoid, betulinic acid, in Doliocarpus schottianus by HPLC. Phytochem Anal 2002, 13:95-98.
• [14]Tolstikova TG, Sorokina IV, Tolstikova TA, Tolstikova AG: Biological activity and pharmacological prospects of lupine terpenoids: natural lupane derivatives. Bioorg Khim 2006, 32:42-55.
• [15]Chen QH, Fu ML, Liu J, Zhang HF, He GQ, Ruan H: Optimization of ultrasonic-assisted extraction (UAE) of betulin from white birch bark using response surface methodology. Ultrason Sonochem 2009, 16:599-604.
• [16]Zhang Y-H, Yu T, Wang Y: Extraction of betulin from bark of Betula platyphylla by supercritical carbon dioxide extraction. Journal of Forestry Research 2003, 14:202-204.
• [17]Diouf PN, Stefanovic T, Boutin Y: The effect of extraction process on polyphenol content, triterpene composition and bioactivity of yellow birch (Betula alleghaniensis Britton) extracts. Industrial Crops and Products 2009, 30:297-303.
• [18]Jager S, Laszczyk MN, Scheffler A: A preliminary pharmacokinetic study of betulin, the main pentacyclic triterpene from extract of outer bark of birch (Betula alba cortex). Molecules 2008, 13:3224-3235.
• [19]Eckerman C, Ekman R: Comparison of solvents for extraction and crystallization of betulinol from birch bark waste. Paperi ja Puu 1985, 67:100-106.
• [20]Dehelean CA, Cîntă Pînzaru S, Peev CI, Soica C, Antal DS: Characterization of birch tree leaves, buds and bark dry extracts with antitumor activity. J Optoelectr Adv Mat 2007, 9:783-787.
• [21]Falamas A, Cînta Pinzaru S, Dehelean CA, Peev CI, Soica C: Betulin and its natural resource as potential anticancer drug candidate seen by FT-Raman and FT-IR spectroscopy. J Raman Spectrosc 2011, 42:97-107.
• [22]Abyshev AZ, Agaev EM, Guseinov AB: Studies of the chemical composition of birch bark extracts (Cortex betula) from the Betulaceae family. Pharm Chem J 2007, 41:22-26.
• [23]Huyke C, Laszczyk M, Scheffler A, Ernst R, Schempp CM: Treatment of actinic keratoses with birch bark extract, a pilot study. JDDG 2006, 4:132-137.
• [24]Durvanei AM, Ribeiro OG, Pizzocaro KF, De Franco M, Cabrera WK, Starobinas N, Gallois V, Siqueira M, Seman M, Ibañez OM: Resistance to melanoma metastases in mice selected for high acute inflammatory response. Carcinogenesis 2001, 22:337-342.
• [25]Bralley EE, Greenspan P, Hargrove JL, Wicker L, Hartle DK: Topical anti-inflammatory activity of Polygonum cuspidatum extract in the TPA model of mouse ear inflammation. J Inflamm 2008, 5:1-8. BioMed Central Full Text
• [26]Al-Reza SM, Yoon JI, Kim HJ, Kim JS, Kang SC: Anti-inflammatory activity of seed essential oil from Zizyphus jujuba. Food Chem Toxicol 2010, 48:639-643.
• [27]Patocka J: Biologically active pentacyclic triterpenes and their current medicine signification. J Appl Biomed 2003, 1:7-12.
• [28]Andrew ER: Magic angle spinning. Intern Rev Phys Chem 1981, 1:195-224.
• [29]Benett AE, Rienstra CM, Auger M, Lakshmi KV, Griffin RG: Heteronuclear decoupling in rotating solids. J Chem Phys 1995, 103:6951-6957.
• [30]Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65:55-63.
• [31]Yasukawa K, Takido M, Matsumoto T, Takeuchi M, Nakagawa S: Sterol and triterpene derivatives from plants inhibit the effects of a tumor promoter, and sitosterol and betulinic acid inhibit tumor formation in mouse skin two-stage carcinogenesis. Oncology 1991, 48:72-76.