Topical anti-inflammatory phytomedicine based on Sphagneticola trilobata dried extracts.

CONTEXT: The aerial parts of Sphagneticola trilobata (L.) Pruski (Asteraceae) are popularly used to treat topical inflammation, but have not been fully investigated. OBJECTIVE: To identify polar compounds in S. trilobata extracts and develop a new topical phytomedicine based on the kaurenoic acid (KA) content while monitoring and demonstrating its topical anti-inflammatory activity. MATERIALS AND METHODS: Ethanol spray-dried extract of S. trilobata was analysed by LC-MS while the KA content from semisolid was analysed by LC-UV. The extent of ear edema induced by applying 20 µL of croton oil (2.5%), arachidonic acid (AA; 2 mg/ear) and decanoylphorbol-13-acetate (TPA; 2.5 mg/ear) in mice was used to evaluate the biological activity of the semisolids, which were applied 30 min before the phlogistic agents. RESULTS: Eight phenylpropanoids and four oleanane-type triterpenoid saponins were identified, majority of them reported for the first time in this species, in addition to KA. The semisolid containing 1.0% of dried extract reduced the ear edema induced by croton oil [77.2 ± 4.5%; ID50 = 0.49 (0.28-0.87%)], TPA (81.5 ± 2.4%) and AA (39.1 ± 6.9%), with decreasing effect at higher KA concentrations. This was accompanied by neutrophil migration inhibition as investigated by biochemical and histological assays. DISCUSSION AND CONCLUSION: The anti-inflammatory effects were (at least in part) due to the interference in protein kinase C (PKC) activation, AA-cascade products and neutrophil migration inhibition, demonstrating the efficacy of the folk topical usage of this plant. The results support the development of a novel topical anti-inflammatory phytomedicine properly standardized to treat inflammatory dermatological diseases.

Release of tetracycline from O-carboxymethylchitosan films.

O-carboxymethylchitosan films containing tetracycline were prepared by the casting method. The films were hardened by reaction with glutaraldehyde-induced crosslinking and heat treatment at 90°C, 120°C and 150°C. The effect, on the films, of hardening methods, water uptake, moisture, drug release and antimicrobial activity against Staphylococcus aureus was evaluated. The O-carboxymethylchitosan films were soluble in simulated saliva and after treatment, and the water uptake of the films decreased as the temperature or presence of glutaraldehyde increased. The antimicrobial activity of tetracycline was preserved, and efficiency was dependent on the hardening treatment to which the films were submitted.

Aleurites moluccanus and its main active constituent, the flavonoid 2″-O-rhamnosylswertisin, in experimental model of rheumatoid arthritis.

ETHNOPHARMMACOLOGICAL RELEVANCE: Aleurites moluccana is used in folk medicine to treat pain, fever, asthma, hepatitis, gastric ulcer and inflammatory process in general, and the nut oil had been topically applied to treat arthritis and other joint pain, however the seeds are classified as toxic for oral use. AIM: Faced with the need for new alternative to treat the symptoms and modify rheumatoid arthritis (RA) the aim of this work was to evaluate the effects of A. moluccanus' leaves dried extract in rats and mice submitted to complete Freund adjuvant (CFA)-induced RA. MATERIAL AND METHODS: Wistar Rats and Swiss mice were submitted to CFA-induced RA in the right hindpaw. They received A. moluccanus extract (orally; p.o.), dexamethasone (subcutaneously), 2″-O-rhamnosylswertisin (p.o.) or vehicle (p.o.), from the 14th day after the CFA injection for up to 8 days. The mechanical hypersensitivity was evaluated using the von Frey filaments and the paw-oedema was measured using a plethysmometer. The rats' injected hindpaw was used to perform the histological analysis. RESULTS: A. moluccanus was able to significantly reduce the mechanical hypersensitivity in both ipsi- and contralateral hindpaws of mice injected with CFA, in a dose dependent manner. Furthermore, the paw-oedema was progressively reduced by A. moluccanus. Similar results were obtained for the positive-control drug dexamethasone and the isolated compound 2″-O-rhamnosylswertisin. Besides the effects mentioned above, the extract was also effective to repair the joint damage in CFA-induced RA rats, including reduction of fibrosis, cartilage degradation and bone erosion scores. CONCLUSION: These results together with the literature data reinforce the anti-hypersensitivity and anti-inflammatory activity of A. moluccanus extract. Part of the observed effects is due to the presence of the compound 2″-O-rhamnosylswertisin. The fact that the extract acted as a disease modifier point this herbal product as a promisor and safe tool to treat RA and other associated chronic diseases.

Contribution of α,ß-Amyrenone to the Anti-Inflammatory and Antihypersensitivity Effects of Aleurites moluccana (L.) Willd.

The aim of the study was to analyze the constituents of the dichloromethane fraction obtained from A. moluccana and also to evaluate the anti-inflammatory and antinociceptive properties of α,ß-amyrenone isolated from A. moluccana in mice. The dichloromethane fraction was evaluated by gas chromatography and submitted to purification. The mixture of α,ß-amyrenone was isolated and then evaluated using the carrageenan-induced paw-oedema or pleurisy and CFA-induced arthritis models in mice. Five triterpenes, α,ß-amyrenone, glutinol, and α,ß-amyrin were isolated from dichloromethane fraction of A. moluccana leaf extract. The mixture of α,ß-amyrenone, dosed orally, was able to reduce mechanical hypersensitivity and paw-oedema induced by carrageenan, interfering with neutrophil migration. Similar results were observed in the carrageenan-induced pleurisy model. Repeated administration of the compounds was also effective in reducing the mechanical sensitization and oedema developed in the arthritis model induced by CFA. In conclusion, the results demonstrate that α,ß-amyrenone interferes in both acute and chronic inflammatory processes. We can infer that these effects involve, at least in part, a reduction in the neutrophil migration. Therefore, it seems reasonable to suggest that α,ß-amyrenone could represent a new therapeutic tool for the management of painful and inflammatory diseases, especially those presenting a chronic profile.

Development of an oral suspension containing dry extract of Aleurites moluccanus with anti-inflammatory activity

Abstract Aleurites moluccanus L. (Willd.), Euphorbiaceae, is a tree that is native to Indonesia and India. Various parts of this tree are commonly used in traditional medicine to treat pain, fever, inflammation, hepatitis, gastric ulcer and other ailments. An oral suspension containing dried extract of A. moluccanus was developed and in vivo anti-inflammatory activity was evaluated. Extract 100 and 50 mg/ml loaded oral suspensions were prepared using different suspending agents. The formulations were analysed by their appearance, pH, density, redispersion time, rate of settling, rheological behaviour, distribution of particle size and zeta potential. The dose uniformity was determined by measuring the content of total phenolic compounds expressed in swertisin by a validated HPLC method, as well as the dissolution profile. The stability of oral suspensions was analysed in accelerated studies (40 °C for 6 months). The anti-inflammatory activity was analysed using an in vivo paw oedema model. The taste and odour of the suspensions were shown to be characteristic of the extract. Carmellose sodium (CS; 0.5%) and microcrystalline cellulose and carmellose sodium mixture (MCCS; 1%) showed better physical behaviour. The content of total phenolic compounds was 1.6 mg/ml and approximately 100% of the total phenolic compounds dissolved within 10 min. During the stability study, the formulations were approved by their physical–chemical properties and were shown to lose 12–14% of total phenolic compounds at 40 °C after 6 months. Suspensions containing 50 mg/ml of standardised dried extract inhibited around 35 ± 7.6% of paw oedema. Formulations containing CS showed more anti-inflammatory activity. Suspensions containing dry extract of A. moluccanus were successfully obtained and showed physical and physical–chemistry properties that were appropriate and characteristic of this dosage form, suitable for administration in paediatric and elderly populations, making this an alternative to tablets.

Polissacarídeos biodegradáveis úteis para a preparação de sistemas de liberaçào controlada de fármacos. Parte 1: Quitosana / Biodegradable polysaccharides useful for the preparation of controlled drug delivery systems. Part 1: Chitosan

O interesse crescente por polímeros biodegradáveis tem estímulado, recentemente, a obtenção de um grande número deles. Polímeros produzidos naturalmente, como celulose, amido, quitosana, pectina e alginato, representam materiais biodegradáveis, com baixa toxicidade e de baixo custo. Entre os polissacarídeos, a quitosana vem despertando grande interesse da pesquisa industrial e acadêmica, por suas qualidades especiais de biodegradabilidade e biocompatibilidade e, por outro lado, por sua versatilidade de emprego em diversas formas físicas em diversos produtos. Um crescimento significativo no desenvolvimento de novas formas farmacêuticas capazes de liberar o fármaco de maneira controlada e vetorizada tem sido observado nestes últimos anos. Tais formas farmacêuticas buscam, principalmente, a redução da dose de fármaco administrada e da freqüência da adminstração, a diminuição dos efeitos colaterais e a maior adesão do paciente ao tratamento. O presente artigo descreve a utilização da quitosana em produtos farmacêuticos, especialmente em sistemas de liberação controlada de fármacos.

Sistemas para liberaçäo colônica: uma alternativa para a veiculaçäo de fármacos para efeito local ou sistêmico / Colonic release systems: an alternative to carry drugs for topical or systemic effect

A presença de problemas relacionados com a administraçäo sistêmica de fármacos, como biodistribuiçäo, reduzida seletividade, necessidade de altas doses para obtençäo de níveis adequados do fármaco em locais específicos, toxicidade e efeitos colaterais indesejáveis, tem levado ao desenvolvimento de sistemas capazes de direcionar o fármaco para sítios específicos no organismo. Entre os órgäos-alvo para a vetorizaçäo de fármacos encontra-se o cólon, objetivando-se a aplicaçäo para terapias locais e sistêmicas. No desenvolvimento de sistemas de liberaçäo colônica, algumas estratégias têm sido testadas, como liberaçäo dependente do pH, controlada pela degradaçäo enzimática, pelo tempo e por pressäo. Esta revisäo apresenta uma visäo geral sobre a liberaçäo colônica de fármacos e as estratégias usadas para obtençäo desses sistemas.