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1.
Forsch Komplementmed ; 17(5): 271-3, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20980767

RESUMEN

Betulin, a pentacyclic triterpene, is the main constituent of the outer bark of birches (Betula alba). In recent years, anti-microbial, anti-inflammatory and differentiation-promoting effects of betulin have been described. A betulin-based emulsion without preservatives and detergent emulsifiers can be prepared from birch bark extract. We report the successful treatment with betulin emulsion of a severe necrotising herpes zoster in an immunosuppressed patient who had not responded to a conventional topical treatment. The betulin emulsion was directly applied to the wounds without causing any side effects. The presented case report demonstrates impressive skin tolerance and wound-healing properties of the betulin emulsion. These should be further evaluated.


Asunto(s)
Betula , Herpes Zóster/tratamiento farmacológico , Triterpenos/uso terapéutico , Herpes Zóster/patología , Humanos , Masculino , Persona de Mediana Edad , Corteza de la Planta/química , Enfermedades de la Piel/tratamiento farmacológico , Enfermedades de la Piel/patología , Resultado del Tratamiento , Triterpenos/aislamiento & purificación , Cicatrización de Heridas
2.
J Invest Dermatol ; 130(1): 113-23, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19675576

RESUMEN

It has been shown recently that triterpenes inhibit cancer cell growth of various cell types in vitro. In this work, the effect of highly purified triterpenes (TE) with betulin as the major compound (>80% w/w) on cell proliferation, apoptosis, and differentiation of human keratinocytes was analyzed in vitro, ex vivo, and in vivo. In vitro, TE increased calcium influx into primary keratinocytes and upregulated various differentiation markers including keratin 10. TE also specifically increased the expression of the non-selective transient receptor potential canonical (subtype) 6 (TRPC6) in keratinocytes, and knocking down TRPC6 inhibited keratin 10 upregulation. Ex vivo, in human skin explants TE induced the expression of TRPC6 in the epidermis and increased DNA fragmentation of terminally differentiating keratinocytes. Topical treatment with TE of actinic keratoses, that represent in situ squamous cell carcinomas with disturbed epithelial differentiation, resulted in downgrading of aberrant Ki67 expression and upregulation of keratin 10 in vivo. Our data indicate that TE promotes keratinocyte differentiation in vitro and in vivo. This effect seems to be mediated at least in part by TRPC6.


Asunto(s)
Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Queratosis Actínica/tratamiento farmacológico , Queratosis Actínica/patología , Canales Catiónicos TRPC/genética , Triterpenos/farmacología , Adulto , Apoptosis/efectos de los fármacos , Biopsia , Calcio/metabolismo , Carcinoma de Células Escamosas/tratamiento farmacológico , Diferenciación Celular/efectos de los fármacos , Células Cultivadas , Fragmentación del ADN/efectos de los fármacos , Células Epidérmicas , Epidermis/fisiología , Expresión Génica/fisiología , Humanos , Técnicas In Vitro , Queratina-10/genética , Queratina-10/metabolismo , Queratinocitos/fisiología , Queratosis Actínica/fisiopatología , ARN Interferente Pequeño , Neoplasias Cutáneas/tratamiento farmacológico , Canales Catiónicos TRPC/metabolismo , Canal Catiónico TRPC6
3.
Planta Med ; 75(15): 1549-60, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19742422

RESUMEN

Today cancer treatment is not only a question of eliminating cancer cells by induction of cell death. New therapeutic strategies also include targeting the tumour microenvironment, avoiding angiogenesis, modulating the immune response or the chronic inflammation that is often associated with cancer. Furthermore, the induction of redifferentiation of dedifferentiated cancer cells is an interesting aspect in developing new therapy strategies. Plants provide a broad spectrum of potential drug substances for cancer therapy with multifaceted effects and targets. Pentacyclic triterpenes are one group of promising secondary plant metabolites. This review summarizes the potential of triterpenes belonging to the lupane, oleanane or ursane group, to treat cancer by different modes of action. Since Pisha et al. reported in 1995 that betulinic acid is a highly promising anticancer drug after inducing apoptosis in melanoma cell lines in vitro and in vivo, experimental work focused on the apoptosis inducing mechanisms of betulinic acid and other triterpenes. The antitumour effects were subsequently confirmed in a series of cancer cell lines from other origins, for example breast, colon, lung and neuroblastoma. In addition, in the last decade many studies have shown further effects that justify the expectation that triterpenes are useful to treat cancer by several modes of action. Thus, triterpene acids are known mainly for their antiangiogenic effects as well as their differentiation inducing effects. In particular, lupane-type triterpenes, such as betulin, betulinic acid and lupeol, display anti-inflammatory activities which often accompany immune modulation. Triterpene acids as well as triterpene monoalcohols and diols also show an antioxidative potential. The pharmacological potential of triterpenes of the lupane, oleanane or ursane type for cancer treatment seems high; although up to now no clinical trial has been published using these triterpenes in cancer therapy. They provide a multitarget potential for coping with new cancer strategies. Whether this is an effective approach for cancer treatment has to be proven. Because various triterpenes are an increasingly promising group of plant metabolites, the utilisation of different plants as their sources is of interest. Parts of plants, for example birch bark, rosemary leaves, apple peel and mistletoe shoots are rich in triterpenes and provide different triterpene compositions.


Asunto(s)
Antineoplásicos Fitogénicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Triterpenos Pentacíclicos/uso terapéutico , Fitoterapia , Extractos Vegetales/uso terapéutico , Antineoplásicos Fitogénicos/farmacología , Humanos , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/farmacología , Ácido Oleanólico/uso terapéutico , Triterpenos Pentacíclicos/farmacología , Extractos Vegetales/farmacología , Triterpenos/farmacología , Triterpenos/uso terapéutico
4.
Molecules ; 14(6): 2016-31, 2009 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-19513002

RESUMEN

Pentacyclic triterpenes are secondary plant metabolites widespread in fruit peel, leaves and stem bark. In particular the lupane-, oleanane-, and ursane triterpenes display various pharmacological effects while being devoid of prominent toxicity. Therefore, these triterpenes are promising leading compounds for the development of new multi-targeting bioactive agents. Screening of 39 plant materials identified triterpene rich (> 0.1% dry matter) plant parts. Plant materials with high triterpene concentrations were then used to obtain dry extracts by accelerated solvent extraction resulting in a triterpene content of 50 - 90%. Depending on the plant material, betulin (birch bark), betulinic acid (plane bark), oleanolic acid (olive leaves, olive pomace, mistletoe sprouts, clove flowers), ursolic acid (apple pomace) or an equal mixture of the three triterpene acids (rosemary leaves) are the main components of these dry extracts. They are quantitatively characterised plant extracts supplying a high concentration of actives and therefore can be used for development of phytopharmaceutical formulations.


Asunto(s)
Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/aislamiento & purificación , Extractos Vegetales/química , Cromatografía de Gases , Cromatografía Líquida de Alta Presión , Estructura Molecular , Ácido Oleanólico/química , Ácido Oleanólico/aislamiento & purificación , Triterpenos/química , Triterpenos/aislamiento & purificación , Ácido Betulínico , Ácido Ursólico
5.
Molecules ; 13(12): 3224-35, 2008 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-19104487

RESUMEN

During the last two decades triterpenes have attracted attention because of their pharmacological potential. Triterpene extract (TE) from outer bark of birch consisting mainly of betulin is able to form an oleogel which was successfully tested in the treatment of actinic keratosis. Some aspects of TE in vitro pharmacology are already known. Now we show preliminary pharmacokinetics of betulin and results of a subchronic toxicity study of TE in rats and dogs. Because of poor aqueous solubility of the TE-triterpenes (< 0.1 microg/mL respectively), for pharmacokinetic studies it was suspended in sesame oil (rats, i.p.) and PEG 400 / 0.9 % NaCl (dogs, s.c.). I.p. administered, betulin, the main component of TE, shows time dependency over a period of 4 h and reaches a dose-independent serum level of 0.13 microg/mL. Dose dependency was observed with s.c. administration. At 300 mg/kg a maximum plasma concentration of 0.33 microg/mL betulin was detected after 28 daily applications. The subchronic toxicity study showed no toxicity of TE in rats (i.p.) and dogs (s.c.). In conclusion, triterpene extract from birch bark is safe, its betulin is bioavailable and in addition to published triterpene biological activities TE provides high potential for further pharmaceutical and pharmacological research.


Asunto(s)
Betula/química , Corteza de la Planta/química , Extractos Vegetales/farmacocinética , Triterpenos/farmacocinética , Animales , Perros , Femenino , Inyecciones Intraperitoneales , Inyecciones Subcutáneas , Masculino , Extractos Vegetales/administración & dosificación , Extractos Vegetales/sangre , Extractos Vegetales/toxicidad , Ratas , Ratas Sprague-Dawley , Reproducibilidad de los Resultados , Solubilidad , Solventes , Triterpenos/administración & dosificación , Triterpenos/sangre , Triterpenos/toxicidad
6.
Inflamm Allergy Drug Targets ; 6(4): 236-44, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18220958

RESUMEN

Allergic contact dermatitis is induced by chemicals or metal ions. A hallmark of this T cell mediated skin disease is the activation of the innate immune system by contact allergens. This immune response results in inflammation and is a prerequisite for the activation of the adaptive immune system with tissue-specific migration of effector and regulatory T cells. Recent studies have begun to address in detail the innate immune cells as well as the innate receptors on these cells and the associated signaling pathways which lead to skin inflammation. We review here recent findings regarding innate and adaptive immune responses and immune regulation of contact dermatitis and other skin diseases as well as recent developments towards an in vitro assessment of the allergenic potential of chemicals. The elucidation of the innate inflammatory pathways, cellular components and mediators will help to identify new drug targets for more efficient treatment of allergic contact dermatitis and hopefully also for its prevention.


Asunto(s)
Enfermedades Autoinmunes/inmunología , Dermatitis Alérgica por Contacto/inmunología , Inmunidad Activa/inmunología , Inmunidad Innata/inmunología , Alérgenos/inmunología , Animales , Enfermedades Autoinmunes/genética , Dermatitis Alérgica por Contacto/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Inmunidad Activa/genética , Inmunidad Innata/genética , Factores de Riesgo
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