A pharmacotoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse…

A pharmacotoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse…

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Article_Title: A pharmacotoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse experimental nevi and skin lesions
Authors: Sorina A. Ciurlea1, Corina Tiulea1, Erzsébet Csanyi2, Szilvia Berko2, Claudia-Crina Toma3, Cristina A. Dehelean1*, Felicia Loghin4
Affiliation: 1 University of Medicine and Pharmacy “Victor Babes” Timisoara, Faculty of Pharmacy, Eftimie Murgu Square no.2, 300041, Timisoara, Romania
2 University of Szeged, Faculty of Pharmacy, Department of Pharmaceutical Technology,
Eotvos u.no.6, Szeged, Hungary
3 “Vasile Goldis” Western University of Arad, Romania
4 University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Faculty of Pharmacy, Romania
Abstract: Betulin is an important triterpenic compound obtained from natural sources such as birch bark. It has antiinflammatory and antitumor activity. The birch bark ointment and betulin added in specific topical formulations are very active in actinic keratosis, pathology with damaged keratinocytes correlated from the histological point of view a squamos carcinoma. The aim of present study was to test the biological activity of a topical formulation with 5% betulin on chemical damaged mouse skin. Materials and methods used betulin, a composed cream with the next active agents: 2-propanol, transcutol, isopropyl myristate, labrasol and PEG 4000 and C57BL/6J type mice. The tumoral applied substances were DMBA (7,12-dimethylbenz[α]anthracene) and croton oil. The mexametric measurements were performed using a mexameter MX18 (Courage&Khazaka Electronics, Cologne, Germany). The protocol followed the observations on melanin evolution and haemoglobin status (pigmentation and erythema). Results and discussions indicated that the substances applied as carcinogens determined the apparition of skin pigmentation and lesions as it is mentioned in literature protocol. The cream applied on the skin had adequate rheological properties and a composition that determined a good delivery of active substance. Our investigations confirm the activity on betulin in reducing skin lesions and irritation by significantly decreasing erythema (haemoglobin) indices. The main conclusion of present study is that betulin could be applied as prophylactic and therapeutic compound in skin pathology more important in skin lesions.
Keywords: betulin, topical, skin, melanin, erythema
References: Dehelean CA, Soica CM, Toma CC, Feflea S, Gruia AT, Kasa P jr., Antitumoral activity of betulin, a compound present in birch tree, in formulations with cyclodextrin, Studia Universitatis Vasile Goldis din Arad, Seria Stiintele Vietii, 20(1), 55-58, 2010;
Drag M, Surowiak P, Drag-Zalesinska M, Dietel M, Lage H, Oleksyszyn J, Comparision of the cytotoxic effects of birch bark extract, betulin and betulinic acid towards human gastric carcinoma and pancreatic carcinoma drug-sensitive and drug-resistant cell lines, Molecules, 14, 1639-1651, 2009;
Dwivedi C, Maydew ER, Hora JJ, Ramaeker DM, Guan X, Chemopreventive effects of various concentrations of α-santolol on skin cancer development in CD-1 mice, European Journal of Cancer Prevention, 14, 473-476, 2005.
Fulda S, Betulinic acid for cancer treatment and prevention, Int.J.Mol.Sci., 9, 1096-1107, 2008;
Guidoin MF, Yang J, Pichette A, Roy C, Betulin isolation from birch bark by vacuum and atmospheric sublimation. A termogravimetric study, Thermochimica Acta, 153-166, 2003;
Huyke C, Laszczyk M, Scheffler A, Ernst R, Schempp CM, Treatment of actinic keratoses with birch bark extract, a pilot study, JDDG, 4, 132-137, 2006;
Huyke C, Reuter J, Rodig M, Kersten A, Laszczyk M, Scheffler A, Nashan D, Schempp C, Treatment of actinic keratoses with anovel betulin-based oleogel. A prospective, randomized, comparative pilot study, JDDG, 7, 128-133, 2009;
Mullauer BF, Kessler JH, Medema JP, Betulin is a potent anti-tumor agent that is enhanced by cholesterol, Plosone, 4(4), e5361, 2009;
Nguyen T, Novak EK, Kermani M, Fluhr J, Peters LL, Swank RT, Wei ML, Melanosome morphologies in murine models of Hermansky-Pudlak syndrome reflect blocks in organelle development, The Journal of Investigative Dermatology, 119(5), 1156-1164, 2002;
Patocka J, Biologically active pentacyclic triterpenes and their current medicine signification, Journal of Applied Biomedicine, 1, 7-12, 2003;
Tormo D, Ferrer A, Gaffal E et al., Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation, The American Journal of Pathology, 169(2), 665-672, 2006.
Read_full_article: pdf/20-2010/20-4-2010/SU20-4-10Ciurlea.pdf
Correspondence: Cristina A. Dehelean, University of Medicine and Pharmacy “Victor Babes” Timisoara, Faculty of Pharmacy, Eftimie Murgu Square no.2, 300041, +40723604614, email:cadehelean@umft.ro

Read full article
Article Title: A pharmacotoxicological evaluation of a betulin topical formulation tested on C57BL/6J mouse experimental nevi and skin lesions
Authors: Sorina A. Ciurlea1, Corina Tiulea1, Erzsébet Csanyi2, Szilvia Berko2, Claudia-Crina Toma3, Cristina A. Dehelean1*, Felicia Loghin4
Affiliation: 1 University of Medicine and Pharmacy “Victor Babes” Timisoara, Faculty of Pharmacy, Eftimie Murgu Square no.2, 300041, Timisoara, Romania
2 University of Szeged, Faculty of Pharmacy, Department of Pharmaceutical Technology,
Eotvos u.no.6, Szeged, Hungary
3 “Vasile Goldis” Western University of Arad, Romania
4 University of Medicine and Pharmacy “Iuliu Hatieganu” Cluj-Napoca, Faculty of Pharmacy, Romania
Abstract: Betulin is an important triterpenic compound obtained from natural sources such as birch bark. It has antiinflammatory and antitumor activity. The birch bark ointment and betulin added in specific topical formulations are very active in actinic keratosis, pathology with damaged keratinocytes correlated from the histological point of view a squamos carcinoma. The aim of present study was to test the biological activity of a topical formulation with 5% betulin on chemical damaged mouse skin. Materials and methods used betulin, a composed cream with the next active agents: 2-propanol, transcutol, isopropyl myristate, labrasol and PEG 4000 and C57BL/6J type mice. The tumoral applied substances were DMBA (7,12-dimethylbenz[α]anthracene) and croton oil. The mexametric measurements were performed using a mexameter MX18 (Courage&Khazaka Electronics, Cologne, Germany). The protocol followed the observations on melanin evolution and haemoglobin status (pigmentation and erythema). Results and discussions indicated that the substances applied as carcinogens determined the apparition of skin pigmentation and lesions as it is mentioned in literature protocol. The cream applied on the skin had adequate rheological properties and a composition that determined a good delivery of active substance. Our investigations confirm the activity on betulin in reducing skin lesions and irritation by significantly decreasing erythema (haemoglobin) indices. The main conclusion of present study is that betulin could be applied as prophylactic and therapeutic compound in skin pathology more important in skin lesions.
Keywords: betulin, topical, skin, melanin, erythema
References: Dehelean CA, Soica CM, Toma CC, Feflea S, Gruia AT, Kasa P jr., Antitumoral activity of betulin, a compound present in birch tree, in formulations with cyclodextrin, Studia Universitatis Vasile Goldis din Arad, Seria Stiintele Vietii, 20(1), 55-58, 2010;
Drag M, Surowiak P, Drag-Zalesinska M, Dietel M, Lage H, Oleksyszyn J, Comparision of the cytotoxic effects of birch bark extract, betulin and betulinic acid towards human gastric carcinoma and pancreatic carcinoma drug-sensitive and drug-resistant cell lines, Molecules, 14, 1639-1651, 2009;
Dwivedi C, Maydew ER, Hora JJ, Ramaeker DM, Guan X, Chemopreventive effects of various concentrations of α-santolol on skin cancer development in CD-1 mice, European Journal of Cancer Prevention, 14, 473-476, 2005.
Fulda S, Betulinic acid for cancer treatment and prevention, Int.J.Mol.Sci., 9, 1096-1107, 2008;
Guidoin MF, Yang J, Pichette A, Roy C, Betulin isolation from birch bark by vacuum and atmospheric sublimation. A termogravimetric study, Thermochimica Acta, 153-166, 2003;
Huyke C, Laszczyk M, Scheffler A, Ernst R, Schempp CM, Treatment of actinic keratoses with birch bark extract, a pilot study, JDDG, 4, 132-137, 2006;
Huyke C, Reuter J, Rodig M, Kersten A, Laszczyk M, Scheffler A, Nashan D, Schempp C, Treatment of actinic keratoses with anovel betulin-based oleogel. A prospective, randomized, comparative pilot study, JDDG, 7, 128-133, 2009;
Mullauer BF, Kessler JH, Medema JP, Betulin is a potent anti-tumor agent that is enhanced by cholesterol, Plosone, 4(4), e5361, 2009;
Nguyen T, Novak EK, Kermani M, Fluhr J, Peters LL, Swank RT, Wei ML, Melanosome morphologies in murine models of Hermansky-Pudlak syndrome reflect blocks in organelle development, The Journal of Investigative Dermatology, 119(5), 1156-1164, 2002;
Patocka J, Biologically active pentacyclic triterpenes and their current medicine signification, Journal of Applied Biomedicine, 1, 7-12, 2003;
Tormo D, Ferrer A, Gaffal E et al., Rapid growth of invasive metastatic melanoma in carcinogen-treated hepatocyte growth factor/scatter factor-transgenic mice carrying an oncogenic CDK4 mutation, The American Journal of Pathology, 169(2), 665-672, 2006.
*Correspondence: Cristina A. Dehelean, University of Medicine and Pharmacy “Victor Babes” Timisoara, Faculty of Pharmacy, Eftimie Murgu Square no.2, 300041, +40723604614, email:cadehelean@umft.ro