ß-caryophyllene Delivery Systems: Enhancing the Oral Pharmacokinetic and Stability.

BACKGROUND: The ß-caryophyllene (BCP), a phytocannabinoid present in various essential oils, demonstrated selective action on the CB2 endocannabinoid receptor and attracted considerable attention because of its several pharmacological activities. Despite this recognized potential, this hydrophobic compound is a volatile and acid-sensitive sesquiterpene that readily oxidizes when exposed to air, and has low bioavailability in oral formulations. Thus, the development of formulations that guarantee its stability and increase its bioavailability is a challenge for its use in the pharmaceutical field. METHODS: The present review brings for the first time a comprehensive overview of the controlled and vectorized release formulations tested for BCP administration. Among these, we have addressed nanoemulsions, inclusion complexes with cyclodextrins, liposomes, wound dressings, nanocomposites and nanoparticles. A literature search was performed on Pubmed, Web of Science and Science direct, and patents documents were also searched on European Patent Office, World Intellectual Property Organization and Brazilian National Institute of Industrial Property. RESULTS: The systems presented here may represent an interesting approach to overcome the limitations already mentioned for this terpene. These systems proved to be promising for improving solubility, stability and controlled release of this pharmacological relevant sesquiterpene. In the industrial field, some companies have filed patent applications for the commercial use of the BCP, however, the use of pharmaceutical formulations still appeared moderate. CONCLUSION: This prospective study evidenced the new perspectives related to BCP vectorization systems in the pharmaceutical and industrial marketing field and may serve as a basis for further research and pharmaceutical use of this powerful cannabinoid.

Methyl-ß-cyclodextrin Inclusion Complex with ß-Caryophyllene: Preparation, Characterization, and Improvement of Pharmacological Activities.

ß-Caryophyllene (BCP) is a sesquiterpene that shows high potential in pharmacological applications. However, these have been drastically limited by the respective volatility and poor water solubility. The present study investigates the formation of inclusion complexes between BCP and methyl-ß-cyclodextrin (MßCD) and shows that these complexes promote a significant improvement of the anti-inflammatory, gastric protection, and antioxidant activities relative to neat BCP. It is shown that the solubility of BCP is significantly increased through complexation in phase solubility studies. Inclusion complexes with MßCD in solid state were prepared by three different methods, kneading, rotary evaporation, and lyophilization, with the latter confirmed by differential scanning calorimetry, Fourier transformed infrared spectroscopy, scanning electron microscopy, 1H NMR spectroscopy, and molecular dynamics studies. This study provides for the first time a full characterization of inclusion complexes between BCP and MßCD and highlights the impact of complex formation upon pharmacological activity.

Evaluation of Antioxidant Activity of Phytol Using Non- and Pre-Clinical Models.

BACKGROUND: Phytol (3,7,11,15-tetramethylhexadec-2-en-1-ol; PHY), the alcoholic diterpenoid is particularly interesting due to its diverse activities found in literature. This study evaluated in vitro and in vivo antioxidant capacity of PHY. METHODS: We conducted DPPH• (2,2-diphenyl-1-picrylhydrazyl) and ABTS•+ (2,2'-azino-bis(3- ethylbenzthiazoline-6-sulphonic acid)) radical scavenging tests as in vitro, while Saccharomyces cerevisiae test as in vivo. For in vitro tests, trolox and for in vivo test hydrogen peroxide (H2O2) were taken as standard and stressor, respectively. Additionally, we measured the superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), lipid peroxidation (LP) and nitrite (NO2 -) contents in mouse hippocampus taking 0.05% Tween 80 dissolved in 0.9% saline (0.25 ml) and ascorbic acid (250 mg/kg; AA) as vehicle and standard, respectively. PHY was administered at doses 25, 50 and 75 mg/kg. In the latter case, all the treatments were administered via intraperitoneal (i.p.) route. RESULTS: PHY at 7.2 µg/ml exhibited 59.89 ± 0.73% and 62.79 ± 1.99% scavenging capacity of DPPH• and ABTS•+, respectively. In S. cerevisiae strains, PHY showed prominent protective effects. Moreover, in Swiss mouse hippocampus; PHY reduced the LP and NO2 - contents, while increased in GSH, SOD and CAT activities. CONCLUSION: PHY exerted antioxidant potential in our current non- and preclinical test systems and can be a good candidate for the development of treatments of oxidative stress mediated diseases.

Estudos agronômicos, genéticos, morfoanatômicos, fitoquímicos, toxicológicos e farmacológicos de Bellis perennis L. (margarida) / Estudios agronómicos, genéticos, morfoanatómicos, fitoquímicos, toxicológicos y farmacológicos de Bellis perennis L. (margarita) / Agronomic, genetic, morphoanatomic, phytochemical, toxicological and pharmacological studies of Bellis perennis L. (daisy)

Introdução: Bellis perennis L. (Asteraceae) é conhecida popularmente como margarida, margarita, margarida-vulgar, margarida-menor ou margarida-comum. É uma herbácea perene, amplamente distribuída em toda a Europa e Norte da África. Objetivo: realizar um levantamento bibliográfico sobre aspectos agronômicos, genéticos, morfoanatômicos, químicos, toxicológicos e farmacológicos desta espécie. Métodos: realizada uma revisão dos artigos completos originais e de revisão disponíveis na literatura, por meio de busca de artigos nos idiomas português, inglês ou espanhol, compreendidos entre os anos de 1962 e 2011 nas seguintes bases de dados: Literatura Latino-Americana e do Caribe em Ciências da Saúde, Science Direct, Scielo e Medical Literature Analysis and Retrieval Sistem on-line. Foram utilizados, para busca dos artigos, os seguintes descritores: Bellis perennis, B. perennis, Asteraceae, estudos botânicos, estudos químicos, estudos toxicológicos e atividades farmacológicas. Além disso, foram incluídos os resultados experimentais dos estudos de toxicidade aguda em camundongos tratados com extrato etanólico das flores de B. perennis. Resultados: sua ampla utilização como planta medicinal e devido à ausência de informações sistematizadas sobre sua toxicidade e ações farmacológicas justificam a importância dessa revisão, uma vez que já foram isolados vários constituintes químicos. Em virtude dessas propriedades terapêuticas ainda não serem bem compreendidas, e devido à sua importância na fitoterapia, novos estudos fitoquímicos e farmacológicos devem ser conduzidos. Conclusão: apesar do seu amplo uso, a literatura não fornece detalhes sobre as suas propriedades toxicológicas e farmacológicas, demonstrando a uma necessidade de novas pesquisas científicas.

Introducción: Bellis perennis L. (Asteraceae) es popularmente conocida como margarita. Es una hierba perenne, de amplia distribución en toda Europa y el norte de África. Objetivos: realizar una revisión de la literatura sobre los aspectos agronómicos, genéticos, morfológicos y anatómicos, químicos, toxicológicos y farmacológicos de esta especie. Métodos: se llevó a cabo una revisión de los artículos completos originales, así como de la literatura disponible en portugués, inglés o español, entre 1962 y 2011, en las bases de datos siguientes: LILACS, Science Direct, Scielo y Medical Literature Analysis and Retrieval Sistem on-line. Se utilizó para buscar artículos, los descriptores siguientes: Bellis perennis, Bellis perennis, Asteraceae, estudios botánicos, químicos, estudios toxicológicos y actividades farmacológicas. Adicionalmente, se incluyeron los resultados de los estudios experimentales de toxicidad aguda en ratones, tratados con el extracto de etanol de flores de Bellis perennis. Resultados: su amplio uso como planta medicinal y por causa de la falta de información sistemática sobre su toxicidad y acciones farmacológicas, se justifica la importancia de esta opinión, porque ya se han aislado varios componentes químicos. Como estas propiedades terapéuticas aún no se comprenden bien, y por su importancia en fitoterapia, nuevos estudios fitoquímicos y farmacológicos deben realizarse. Conclusión: a pesar de su uso generalizado, la literatura no proporciona detalles acerca de sus propiedades toxicológicas y farmacológicas, lo que demuestra la necesidad de la investigación científica.

Introduction: Bellis perennis L. (Asteraceae), commonly known as daisy, is a perennial herb of wide distribution throughout Europe and the north of Africa. Objectives: conduct a bibliographic review about the agronomic, genetic, morphological and anatomic, chemical, toxicological and pharmacological characteristics of this species. Methods: a review was carried out of full-text original papers, as well as materials published in Portuguese, English and Spanish between 1962 and 2011 in the following databases: LILACS, Science Direct, Scielo and Medical Literature Analysis and Retrieval System on-line. The search terms used were Bellis perennis, B. perennis, Asteraceae, botanical studies, chemical studies, toxicological studies and pharmacological activities. We also included the results of experimental studies on acute toxicity in mice treated with ethanolic extract of flowers of Bellis perennis. Results: its wide use as a medicinal plant and the scarcity of systematic information about its toxicity and pharmacological actions, justify the relevance of this review, since several chemical components have already been isolated. Given the fact that these therapeutic properties are still not well understood, and in view of their importance for phytotherapy, it is recommended that further phytochemical and pharmacological studies be carried out. Conclusion: despite the widespread use of this plant, the bibliography on the topic does not offer details about its toxicological and pharmacological properties. Hence the need for further scientific research.