Enkephalin related peptides are released from jejunum wall by orally ingested bromelain.

Stem bromelain [EC 3.4.22.32] is a thiol-endopeptidase and orally recommended in traditional medicine due to its analgesic activity, but the mechanisms are not known. Proenkephalin is expressed in the nervous system, but also in the gastrointestinal tract, where it can be assessed by ingested stem bromelain. Here we demonstrated that stem bromelain hydrolyses synthetic proenkephalin fragments after basic amino acid residues flanking the enkephalin sequences. We also observed with in vivo studies that oral administration of bromelain reduced jejunum proenkephalin levels and increased the serum enkephalin in mice. Effective anti-nociceptive effects in mice were observed 3 h after oral administration of 3 mg/kg stem bromelain by the acetic acid-induced writhing test. However, with higher doses this effect is reduced due to hydrolysis of enkephalin that possibly occurs by the presence of ananain in commercial pineapple stem bromelain preparations, that is also a thiol-protease with broad specificity. The analgesic effects were also evaluated by hot-plate and formalin tests and the obtained results indicated that enkephalin generated in intestine acts in periphery where it also can have anti-inflammatory activity.

Lafoensia pacari A. St.-Hil.: Wound healing activity and mechanism of action of standardized hydroethanolic leaves extract.

ETHNOPHARMACOLOGICAL IMPORTANCE: Lafoensia pacari A. St.-Hil., (Lythraceae) is a native tree of Brazilian Cerrado and commonly known in Brazil as "mangava-brava". Its leaves are used in Brazilian folk medicine in wound healing, cutaneous mycoses, and in the treatment of gastritis and ulcers. AIM OF THE STUDY: The present study was designed to evaluate the wound healing activity and mechanism of action of the hydroethanolic extract of Lafoensia pacari A. St.-Hil. leaves (HELp), and to advance in its chemical profiling. MATERIALS AND METHODS: HELp was prepared by maceration in 70% hydroethanolic solution (1:10, w/v). The phytochemical analyses were investigated using colorimetry and electrospray ionization/mass spectrometric detection (ESI-MSn). Its in vitro cytotoxicity was evaluated in CHO-K1 and L929 cells, while the in vivo acute toxicity was performed in mice. The potential in vivo wound healing activity was assessed using excision and incision rat models and histopathology of the wounded skin (excision model) was carried out. The in vitro wound healing activity of HELp was demonstrated by scratch assay in L-929 cells, by measuring proliferation/migration rate and p-ERK 1/2 protein expression using western blot analysis. HELp's in vivo anti-inflammatory activity was evaluated by lipopolysaccharide (LPS) induced peritonitis in mice, along with the determination of nitric oxide (NO) and cytokines (TNF-α and IL-10) in the peritoneal lavages. Its potential in vitro antibacterial activity was performed using microbroth dilution assay, while in vitro antioxidant activities was by 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical, and ferric reducing antioxidant power (FRAP) assays. RESULTS: The phytochemical analysis of HELp revealed the presence of polyphenols with ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside being the most prominent. HELp showed no toxicity on CHO-k1 and L929 cell lines. Topical treatment with HELp (10 and 30 mg/g of gel) presented increased rates of wound contraction at all the days evaluated with complete wound re-epithelialization at 22.0 ±â€¯1.5 (p < 0.05) and 21.7 ±â€¯1.6 (p < 0.01) days, respectively. Topical application of HELp (10, 30 or 100 mg/g of gel) in incised wounds caused an increase in tensile break strength at all concentrations resulting in moderate re-epithelialization and neovascularization, increased cell proliferation an accelerated remodeling phase of the wound, in a manner comparable to standard drug (Madecassol®, 10 mg/g). In the scratch assay with L929 cells, HELp (0.1 and 0.03 mg/mL) and PDGF (5 ng/mL) resulted in the increased proliferation/migration rate of fibroblasts and higher expression of p-ERK 1/2 protein. In LPS-induced peritonitis, HELp (100 and 200 mg/kg p.o.) decreased total leukocyte migration, comparable to the dexamethasone (0.5 mg/kg p.o.). In RAW 264.7 macrophages activated by LPS, HELp produced anti-inflammatory activity dependent on increased concentrations of IL-10, reduction in NO production, without altering the TNF-α levels. HELp also presented potent antioxidant activity in the DPPH and FRAP, but lacks in vitro antibacterial activity. CONCLUSION: The present study results support the popular use of the leaves of L. pacari in the treatment of wounds. Its wound healing activity is multi-targeted and involves inhibition of the proliferative and anti-inflammatory phases, antioxidant and positive modulation of the remodeling phase that might be involved different secondary metabolites, with emphasis on the ellagic acid, punicalagin, punicalin, kaempferol, quercetin-3-O-xylopyranoside and quercetin-3-O-rhamnopyranoside.

Cannabis Sativa L(Maconha): Medicamento que renasce? / Cannabis saiva ll (marijuana): medicine on the rvvival?

Objetivo. Demonstrar que a Cannabis sativa L (maconha) é um medicamento que está renascendo, apesar de oponentes ao seu uso médico afirmarem que a maconha não tem efeitos terapêuticos bem comprovados. Método. Revisão da literatura científica de 2004 a 2010 e comparação com declarações publicadas na mídia no exterior de 2005 a 2010 e no Brasil em 2010. Resultados e discussão. Ocorre atualmente uma discussão emocional sobre o uso medicinal da maconha,mas há anos seus princípios ativos são utilizados para o tratamento de morbidades e seus sinais e sintomas ou para minimizar as reações adversas de outros medicamentos. Esses usos estão documentados tanto na literatura científica quanto na mídia e já têm aprovação oficial pelos órgãos governamentais de saúde e por sociedades científicasde vários países. Atualmente os seguintes medicamentos à base de princípios da maconha estão sendo comercializados em vários países, os quais são ? Marinol®, comercializado por Abbott Laboratories; Cesamet®, comercializado por Meda Pharmaceuticals Inc.; Bedrocan®, Bedrobinol®, Bediol® e Bedica®, comercializados por Bedrocan BV; Sativex®, comercializado por Bayer HealthCare AG, Novartis Pharma AG, Otsuka Pharmaceutical Co. Ltd, Almirall S.A. e Neopharm Group. Conclusão. Devido ao renascimento do uso medicinal da Cannabis sativa e às exigências da Organização das Nações Unidas, faz-se necessário oficializar a Agência Brasileira da Canabis Medicinal para regular e controlar o cultivo medicinal da Cannabis sativa, esclarecer a população sobre os benefícios e riscos que advêm do tratamento ezelar pela abordagem racional do uso medicinal da maconha.

Objective. To demonstrate that Cannabis sativa L (marijuana) is a medical drug on the revival, even though the opponents to its medical use declare in the media that it has no well established therapeutic effects. Method. Review of the medical literature and its comparison with declarations in the media.Results and discussion. Although there is now an emotional discussion on the medical use of marijuana, its ingredients have long been clinically used in the treatment of diseases or to minimize the side effects of other medications. Those uses are well documented in the literature and in the media, and are approved by Health Authorities ofseveral countries. Currently the following medications based on principles of marijuana are being marketed in several countries, which are, Marinol®, marketed by Abbott Laboratories; Cesamet®, marketed by Meda Pharmaceuticals Inc.;Bedrocan®, Bedrobinol®, Bediol® and Bedica® marketed by Bedrocan BV; Sativex®, marketed by Bayer HealthCareAG, Novartis Pharma AG, Otsuka Pharmaceutical Co. Ltd, Almirall SA and Neopharm Group.Conclusion. Due to the revival of the medical use of cannabis and the demands of the United Nations, it is necessaryto formalize the Agência Brasileira da Canabis Medicinal (Brazilian Agency of Medical Cannabis) in order to regulate the cultivation of Cannabis sativa and its derivatives; enlighten the population as regards the benefits and risks that might result from its medical use, and make sure there is a rational and scientific approach to the medical use ofmarijuana.