Bioactive Molecules from Myrianthus arboreus, Acer rubrum, and Picea mariana Forest Resources.

Forest trees are the world's most important renewable natural resources in terms of their dominance among other biomasses and the diversity of molecules that they produce. Forest tree extractives include terpenes and polyphenols, widely recognized for their biological activity. These molecules are found in forest by-products, such as bark, buds, leaves, and knots, commonly ignored in forestry decisions. The present literature review focuses on in vitro experimental bioactivity from the phytochemicals of Myrianthus arboreus, Acer rubrum, and Picea mariana forest resources and by-products with potential for further nutraceutical, cosmeceutical, and pharmaceutical development. Although these forest extracts function as antioxidants in vitro and may act on signaling pathways involved in diabetes, psoriasis, inflammation, and skin aging, much still remains to be investigated before using them as therapeutic candidates, cosmetics, or functional foods. Traditional forest management systems focused on wood must evolve towards a holistic approach, allowing the use of these extractives for developing new value-added products.

Updated view of tars for psoriasis: what have we learned over the last decade?

Tars are one of the most effective, unknown, and oldest therapies for psoriasis. They include coal tar (CT) and biomass-derived products. These treatments, particularly the CT, have proven to be cost-effective with long remission times compared to other systemic or topical treatments. However, they have hardly evolved in recent years, as they are not well-embraced by clinicians or patients because of concerns regarding cosmesis and safety. This review summarizes current knowledge about the chemical characterization, mechanism of action, toxicity, and clinical studies supporting the use of tars for psoriasis over the last decade. Trends within these above aspects are reviewed, and avenues of research are identified. CT is rich in polycyclic aromatic hydrocarbons, whereas biomass-derived tars are rich in phenols. While the activation of the aryl hydrocarbon receptor is involved in the antipsoriatic effect of CT, the mechanism of action of biomass-derived products remains to be elucidated. No conclusive evidence exists about the risk of cancer in psoriasis patients under CT treatment. Large, randomized, double-blind, controlled clinical trials are necessary to promote the inclusion of tars as part of modern therapies for psoriasis.

Gallic, ellagic acids and their oral combined administration induce kidney, lung, and heart injury after acute exposure in Wistar rats.

Gallic (GA) and ellagic (EA) acids are present in foods, medicinal plants, teas, and dietary supplements. An acute toxicological study was conducted by oral administration of both compounds alone (200, 1000, and 2000 mg/kg) and combined (2000 mg/kg) and their effects on the electron transport chain (ETC) and the ROS production in kidney mitochondria further evaluated. All treatments induced a dose-dependent heart, lung, and kidney injury. However, the intensity of these effects varied according to the substance, with greater cardiac and renal toxicity for EA and pulmonary injury for GA, while the combination attenuated the toxicity of the isolated molecules. All substances inhibited the activity of complexes II, III, and IV of the ETC from renal mitochondria. However, no changes were observed regarding mitochondrial ROS production. These compounds have a non-negligible inherent deleterious potential, so their uncontrolled use at high doses (≥200 mg/kg) could cause undesirable effects.

Prediction of the impact induced by Cd in binary interactions with other divalent metals on wild-type and Cd-resistant strains of Dictyosphaerium chlorelloides.

The metals present in freshwater have a toxic profile with bioaccumulation and are biomagnified along the aquatic food chain. The metals induce high sensitivity in most aquatic organisms, while others, such as some microalgae species, evolve towards resistance. Therefore, this research predicted through the Combination Index method the binary interaction exposed to divalent metals by inhibiting population growth in a Cd-resistant strain (DcRCd100) compared to the wild-type strain (Dc1Mwt) of Dictyosphaerium chlorelloides and evaluate the specific resistance level obtained by DcRCd100 to Cd relative to other divalent metals.The results showed that DcRCd100 presents resistance compared to Dc1Mwt in individual exposure in the order of Fe2+ > Ni2+ > Cd2+ > Co2+ > Zn2+ > Cu2+ > Hg2+ with 50% inhibitory concentration at 72 h of exposure (IC50(72)) values 1253, 644.4, 423, 162.7, 141.3, 35.1, and 9.9 µM, respectively. It induces cross-resistance with high antagonistic rates (Combination Index (CI); CI > > 1) in the Cd/Zn and Cd/Cu. Cd/Ni, its initial response, is antagonistic, and it ends in an additive (CI = 1). DcRCd100 showed a lower resistance in Co, and Cd/Fe resistance was reduced individually. The interaction with Hg increased its resistance ten times more than individually.This research highlights the use of the CI as a highly efficient prediction method of the binary metal interactions in wild-type and Cd-resistant strains of D. chlorelloides. It may have the potential for metal accumulation, allowing the development of new methods of bioremediation of metals in effluents, and to monitor the concentration of metals in wastewater, its relative availability, transport, and mechanisms on resistant strains of microalgae.

The 5-HT1A receptor agonist, 8-OH-DPAT, attenuates long-lasting pain in imiquimod-induced psoriasis in mice.

Psoriasis pain is a common symptom underestimated and rarely evaluated in psoriasis clinical trials. This work aimed to investigate whether the development of secondary chronic allodynia and hyperalgesia in the imiquimod (IMQ)-induced psoriasis mice model could be modulated by anti-inflammatory agents and compound 48/80 (C48/80) and to determine whether the activation of 5-HT1A receptor modulates these nociceptive behaviours. C57BL/6 male mice were treated with 5% IMQ for 7 days. The paw withdrawal responses to von Frey filaments (10 and 250 mN) were used to assess the allodynia and hyperalgesia. Nociceptive behaviours were also evaluated using ketorolac 15 mg/kg s.c., adalimumab 10 mg/kg s.c. and C48/80 10 mg/kg i.p. Then, the serum serotonin and the impact of 8-OH-DPAT (1 mg/kg s.c), a 5-HT1A receptor agonist, on long-lasting pain were examined. Mice receiving IMQ showed enhanced nociception, which decreased with all tested compounds. The serum serotonin in the IMQ group showed a significant decrease (947.042 ng/ml) regarding the control group (1143.68 ng/ml). The pretreatment with 8-OH-DPAT alleviated pain-related behaviours. These results suggest that the long-lasting pain resulting from psoriasis inflammation is also associated with the serotonergic system. The 5-HT1A receptor should be further explored as a potential therapeutic target for psoriasis pain modulation.

Design and validation of quality indicators for drug dispensing in a pediatric hospital.

OBJECTIVES: This article presents a methodological strategy to design and validate quality indicators for drug dispensing in a pediatric hospital. SETTING: The literature evaluation, design, and validation of indicators by experts were carried out from September 2017 to March 2018 in the pharmaceutical services of a pediatric hospital at the Autonomous University of the State of Hidalgo, Mexico. PRACTICE DESCRIPTION: The design and validation of quality indicators for dispensing allow the evaluation, planning, and follow-up of this activity. PRACTICE INNOVATION: The development of the indicators follows a holistic vision considering the relationship between the structure on which the pediatric dispensation is based, the involved processes, and the outcomes and provide a simple tool to improve the quality of the dispensing service. EVALUATION: A methodological investigation for the development of systems and health services in drug dispensing was performed. For the indicator's design, the Mexican standards for establishments dedicated to the sale and supply of drugs, the Good Dispensation Practices, and the Donabedian model were considered. The validation of such indicators was carried out using the Delphi method and the Torgerson mathematical model. RESULTS: Indicators of structure, process, and results were designed; of the 16 indicators designed, 15 reached the average score of greater than 3.5, and the percentage of experts who qualified each indicator in the highest categories was greater than 50%. CONCLUSION: The design of indicators guarantees the quality of the dispensing service and can be extrapolated to the pharmaceutical services of any pediatric hospital.

Funcionamiento familiar y uso de terapias complementarias en pacientes con psoriasis / Family functioning and the use of complementary therapies in patients with psoriasis

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Investigation of the Antibacterial Activity and Subacute Toxicity of a Quercus crassifolia Polyphenolic Bark Extract for its Potential Use in Functional Foods.

Oak wood is used in barrels for wine aging. During aging, polyphenols are transferred from the barrels to the liquid. Although the bioactivity of oak polyphenols in wines has been extensively studied, no investigation exists on their toxicological properties, which limits their use as functional safe ingredients for other products. In this work, the chemical composition of a polyphenolic extract of Quercus crassifolia bark (QCBe) was studied by GC-MS. Its antibacterial properties on probiotic and pathogenic bacteria and its subacute-oral toxicity were determined as a way to understand the potential impact from its addition to fermented food as a functional ingredient. QCBe shows a selective inhibition of Escherichia coli compared with Lactobacillus bulgaricus and Streptococcus thermophylus. According to the toxicity evaluation, the subacute no-observed-adverse-effect-level was achieved at 11 mg/kg bw/day, whereas the subacute lowest-observed-adverse-effect-level for kidney damage was at 33 mg/kg bw/day. These results suggest that, given the fact an adverse effect was observed after subacute administration of this extract, further longer term toxicological studies are needed to provide sufficient safety evidence for its use in humans. PRACTICAL APPLICATION: Mexico's yogurt market is growing which creates opportunities for the development of some yogurt products as functional foods. As a first step to evaluate its potential use in yogurt formulation, the antibacterial effect of a Quercus crassifolia polyphenolic extract (QCBe) on probiotic bacteria and its subacute-oral toxicity in rats were studied. A low inhibition on probiotic bacteria growth was observed after QCBe addition to Lactobacillus bulgaricus and Streptococcus thermophylus cultures. Exposure to QCBe for a subacute duration resulted in renal injury in rats at dosages greater than or equal to 33 mg/kg/bw/day. This adverse effect indicates the importance of performing further long-term toxicological assessments prior to the addition of QCBe to a food like yogurt, which is regularly eaten by consumers.

Antioxidantes en asma: polifenoles / Antioxidants in asthma: polyphenols

Resumen EL asma es una enfermedad relacionada con estrés oxidativo. Los practicantes de la medicina alternativa han usado plantas que tienen altas concentraciones de polifenoles en el tratamiento de pacientes con asma. Este artículo revisa la administración de antioxidantes no vitamínicos en pacientes con asma, con insistencia en los polifenoles. Se realizó una búsqueda en Google Scholar y en la base de datos de RIMA de Astra Zeneca con las palabras clave y frases "asthma and flavonoids", "antioxidant therapy in asthma" "resveratrol and asthma" y "polyphenols and asthma". Se priorizó la búsqueda de estudios experimentales en modelos animales y de estudios en humanos. Existe tendencia a aceptar los efectos favorables de los polifenoles en pacientes con asma. La mayor parte de la información es más consistente en trabajos experimentales realizados en animales que cuando se comparan entre sí los pocos estudios clínicos en humanos. La interpretación de los estudios a partir de experiencias con la dieta tiene el inconveniente que el tipo y concentración de polifenoles cambia entre poblaciones y depende de regiones geográficas. Es recomendable diseñar estudios con gran cantidad de personas para evaluar la contribución de la terapia con polifenoles en sujetos con asma en profilaxis y en manejo de crisis y en terapias para el control de la enfermedad a largo plazo.

Abstract Asthma is a disease related to oxidative stress. Practitioners of alternative medicine have used plants that have high concentrations of polyphenols in the treatment of patients with asthma. This paper reviews the use of non-vitamin antioxidants in asthma, with emphasis in polyphenols. A search was made in Google Scholar and in the RIMA database of Astra Zeneca with the keywords and phrases "asthma and flavonoids", "antioxidant therapy in asthma", "resveratrol and asthma" and "polyphenols and asthma". We prioritized the search for experimental studies in animal models and studies with humans. There is a tendency to accept the favorable effects of polyphenols in asthma. Most of the information is more consistent in experimental work on animals than when comparing experiences among the few clinical studies in humans. The interpretation of studies from dietary experiences has the drawback that the type and concentration of polyphenols changes between populations and depends on geographical regions. It is advisable to design studies with a large number of people to evaluate the contribution of polyphenols in subjects with asthma in prophylaxis, crisis management and long-term disease control therapies.

La psoriasis: de la investigación básica y clínica al desarrollo de nuevos tratamientos.

La psoriasis es una enfermedad cutánea incurable que afecta a 2.9 % de la población mexicana, por lo que es trascendente analizar el impacto de la medicina traslacional en el desarrollo de medicamentos antipsoriásicos. En esta revisión se discuten conceptos etiopatogénicos de la enfermedad y se analizan artículos publicados entre 2005 y 2017 en torno a medicamentos en desarrollo, además, se presenta un análisis crítico sobre las perspectivas futuras en el desarrollo de nuevos tratamientos. El uso de estrategias bidireccionales de la medicina traslacional ha permitido incrementar significativamente el número de tratamientos antipsoriásicos disponibles. Se encontraron 18 nuevos fármacos en exploración. La caracterización de antígenos responsables de la activación inmunológica, la identificación de biomarcadores predictivos de eficacia farmacológica, el desarrollo de modelos más representativos de la enfermedad, así como la integración de aspectos farmacogenómicos a estrategias de medicina traslacional fueron identificados como elementos relevantes que deben ser incorporados en el desarrollo de nuevas opciones terapéuticas.Psoriasis is an incurable cutaneous disease that affects 2.9% of the Mexican population, and it is therefore important for the impact of translational medicine on the development of anti-psoriatic drugs to be analyzed. In this review, current etiopathogenic concepts of the disease are discussed, and articles on drugs under development published between 2005 and 2017 are reviewed; in addition, a critical analysis on future perspectives for the development new treatments is presented. The use of translational medicine bi-directional strategies of has allowed to significantly increase the number of available anti-psoriatic therapies. Eighteen new investigational drugs were found. Characterization of antigens responsible for immune activation, identification of predictive biomarkers with pharmacologic efficacy, and the development of more representative disease models, as well as the integration of pharmacogenomic aspects to translational medicine strategies were identified as relevant aspects that should be incorporated in the development of new therapeutic options.

Antioxidant Properties of Polyphenolic Extracts from Quercus Laurina, Quercus Crassifolia, and Quercus Scytophylla Bark.

The objective of this work was to determine the concentration of total phenols, total flavonoids, hydroxycinnamic acids, and proanthocyanidins present in crude extracts of Quercus laurina, Q. crassifolia, and Q. scytophylla bark. They were extracted by ethanol (90%) maceration and hot water. The antioxidant capacity was determined by the ability to capture OH•, O2•−, ROO•, H2O2, NO•, and HClO. The hot water crude extract of Q. crassifolia was chosen to be concentrated and purified due to its higher extraction yield (20.04%), concentration of phenol compounds (747 mg gallic acid equivalent (GAE)/g, 25.4 mg quercetin equivalent (QE)/g, 235 mg ChAE/g, 25.7 mg chlorogenic acid equivalents (ChAE)/g), and antioxidant capacity (expressed as half maximal effective concentration (EC50, µg/mL): OH• = 918, O2•− = 80.5, ROO• = 577, H2O2 = 597, NO• ≥ 4000, HClO = 740). In a second stage, Q. crassifolia extracted with hot water was treated with ethyl acetate, concentrating the phenol compounds (860 mg GAE/g, 43.6 mg QE/g, 362 ChAE/g, 9.4 cyanidin chloride equivalents (CChE)/g) and improving the scavenging capacity (OH• = 467, O2•− = 58.1, ROO• = 716, H2O2 = 22.0, NO• ≥ 4000, HClO = 108). Q. crassifolia had the highest polyphenolic concentration and the better capacity for scavenging reactive species, being a favorable candidate to be considered in the development of new products.

[Antioxidant vitamins in asthma]. / Vitaminas antioxidantes en asma.

Asthma is a condition of unknown etiology characterized by chronic airway inflammation. Cells that mediate the inflammatory response generate reactive oxygen species that, together with other respiratory tract naturally-occurring oxidant species, produce a rupture of the redox balance, generating oxidative stress. It has been proposed that oxidative stress can be reverted by supplemental or dietary intake of antioxidant vitamins such as vitamin A, C, D and E, and this way relieve, improve or protect people with asthma. In this research, observational and placebo-controlled trials with regard to the role of antioxidant vitamins in the course of asthma, published between 1979 and 2016, were reviewed. The search engines were Google and Google Scholar, whereas consulted databases were PubMed and The Cochrane Library. There were 75 articles relevant to the subject that were found and reviewed, and it was concluded that it is not clear if the intake of supplements of these vitamins has any beneficial clinical effect on asthma control. Further controlled, longer trials are needed to elucidate the role of these nutrients in the course of asthma.

El asma es una enfermedad de etiología desconocida que cursa con inflamación crónica de las vías respiratorias. Las células que median la respuesta inflamatoria generan especies reactivas de oxígeno, que en conjunto con otras especies oxidantes presentes de manera natural en las vías aéreas ocasionan la ruptura del equilibrio redox, generando estrés oxidativo. Se ha propuesto que este puede revertirse mediante la administración de vitaminas antioxidantes como A, C, E y D y de esta forma aliviar, mejorar o proteger a las personas con asma. En esta investigación se revisaron los ensayos observacionales y controlados con placebo relativos al papel de las vitaminas antioxidantes en el curso del asma, publicados entre 1979 y 2016. Los motores de búsqueda fueron Google y Google Scholar; las bases de datos consultadas fueron PubMed y The Cochrane Library. Se encontraron y revisaron 75 artículos relevantes para el tema, de los cuales se concluyó que no está claro si la ingesta de suplementos de estas vitaminas tiene algún efecto clínico benéfico en el control del asma. Son necesarios más ensayos controlados y de mayor duración para elucidar el papel de estos nutrientes en el curso del asma.

Toxicological evaluation of an aqueous suspension from leaves and stems of Petiveria alliacea L. (Phytolaccaceae).

ETHNOPHARMACOLOGICAL RELEVANCE: Petiveria alliacea L. (Phytolaccaceae) is used in folk medicine due to its antispasmodic, diuretic, hypoglycemic, abortive, anti-inflammatory and anticancerogenic properties. Although P. alliacea is considered toxic by people, its toxicity remains a concern since it is strongly dependent on the extraction method and the part of the plant used during tests. Even if some healers prefer to use the aerial parts in a liquefied form or by chewing them, instead of decoctions or infusions, no toxicological studies exist using whole dried stems and leaves. MATERIALS AND METHODS: The toxicity of a suspension of the powder from the leaves and stems of P. alliacea was assessed in Sprague Dawley rats by oral administration using two tests: 1) the acute toxic class method, which allows classification of substances according to their intrinsic toxicity and 2) the repeated dose 28-day method, following the guidelines 423 and 407 respectively from the Organization for the Economic Cooperation and Development. Chemical characterization of this powder was performed by GC-MS, UV-fluorescence, proximate and elemental analysis. RESULTS AND CONCLUSIONS: P. alliacea powder from stems and leaves was classed in the hazard category 5 (LD50 > 2000mg/kg) according to the acute toxicology study. There were no toxicity signs at 1000mg/kg in the repeated dose study, although higher values of total leukocytes were found in the satellite and males of the experimental group, which were attributed to the immunomodulatory properties of this plant. According to GC-MS, the prevailing compounds identified were phytol, (R)-(-)-(Z)-14-methyl-8-hexadecen-1-ol, 1-(2-hydrohyethyl)-1,2,4-triazole and methyl ß-dimethylaminoisobutyrate. In conclusion, the oral administration of the P. alliacea powder to Sprague Dawley rats did not result in deaths and was not associated with adverse effects reflected in the general condition, body weights or histopathological abnormalities.

Influence of polyvinylpyrrolidone, microcrystalline cellulose and colloidal silicon dioxide on technological characteristics of a high-dose Petiveria alliacea tablet.

PURPOSE: Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub used by its immunomodulatory, anticancerogenic and anti-inflammatory properties. This study determined the influence of polyvinylpyrrolidone (PVP), colloidal silicon dioxide (CSD) and microcrystalline cellulose (MC) on the technological characteristic of a high-dose P. alliacea tablet prepared by the wet granulation method. METHODOLOGY: The botanical and pharmacognostic analysis of the plant material was firstly performed, followed by a 23 factorial design considering three factors at two levels: (a) the binder (PVP) incorporated in formulation at 10% and 15% (w/w); (b) the compacting agent (CSD) added at 10% and 15% (w/w) and; (c) the diluent (MC) included at 7.33% and 12.46% (w/w). The analysis of pharmaceutical performance and the accelerated and long-term stability of the best prototype were also completed. RESULT AND DISCUSSION: The binder, compacting agent and the interaction binder/diluent had a significant impact on breaking force of high-dose P. alliacea tablet. The optimum formula was found to contain 15% (w/w) of CSD, 7.33% (w/w) of MC and 10% (w/w) of PVP. At these conditions, the tablet shows a breaking force of 77.96 N, a friability of 0.39%, a total phenol content of 1.30 mg/tablet and a maximum disintegration time of 6 min. CONCLUSIONS: The use of adequate amounts of PVP, MC and CSD as per the factorial design allowed the preparation of a tablet suitable for administration, despite the inappropriate flow and compressibility properties of the P. alliacea powder.

Picea mariana polyphenolic extract inhibits phlogogenic mediators produced by TNF-α-activated psoriatic keratinocytes: Impact on NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Picea mariana ((Miller) Britton, Sterns, and Poggenburg; Pinaceae) bark has been traditionally used by North American natives for treating topical inflammations. It has been also suggested to improve various inflammatory skin disorders like Psoriasis vulgaris. Extracts from this bark storage protein contain polyphenolic compounds which have well-known antiinflammatory activities. Based on the capacity of polyphenolic compounds to modulate functions of normal human keratinocytes, this study was set up to decipher the mechanisms of action of a chemically characterized polyphenolic extract from Picea mariana bark (BS-EAcf) on lesional keratinocytes of skin with psoriasis vulgaris, a disease driven by the immune system in which TNF-α plays a significant role. MATERIALS AND METHODS: BS-EAcf corresponds to the ethyl acetate soluble fraction from the hot water extract of Picea mariana bark. BS-EAcf effects were evaluated in normal human (NHK) and psoriatic (PK) keratinocytes stimulated by TNF-α. Cell viability was assessed by lactate deshydrogenase release and propidium iodide (PI) staining. The mechanisms of action of BS-EAcf in keratinocytes were investigated by flow cytometry, ELISAs, RT-PCR and western blot analyses. RESULTS: PK exhibited a higher response to TNF-α than NHK regarding the ICAM-1 expression and the production of NO, IL-6, IL-8, fractalkine and PGE2, whereas BS-EAcf significantly inhibited this TNF-α-induced increase at concentrations without causing keratinocyte toxicity. Additionally, this extract significantly inhibited the TNF-α-induced release of elafin and VEGF by PK and NHK. Since TNF-α activation of most of these factors is dependent on the NF-κB pathway, this latter was studied in TNF-α-activated PK. BS-EAcf inhibited the TNF-α-induced phosphorylation and degradation of total IκBα as well as phosphorylation of NF-κB p65. CONCLUSIONS: The ethyl acetate fraction from Picea mariana bark extract showed inhibitory effects of cytokines, chemokines, adhesion molecules, nitric oxide and prostaglandins produced by keratinocytes under TNF-α activation through down-regulating the NF-κB pathway. This study demontrated that this extract could be a potential antiinflammatory agent capable of improving psoriatic skin.

New therapies under development for psoriasis treatment.

PURPOSE OF REVIEW: An improved understanding of the psoriasis pathogenesis has provided new insights into potential new therapeutic targets, which has positively influenced the development of novel therapies. This monograph reviews recent clinical trials concerning new small molecules and biotech products under investigation for plaque psoriasis treatment. Emphasis is placed on mechanism of action, efficacy and adverse effects of these new agents. RECENT FINDINGS: Recent literature has shown that there are several new drugs under development for psoriasis treatment including new A3 adenosine receptor agonists, biologics like anti-tumor necrosis factor, anti-interleukin-17, anti-interleukin-12/23 and anti-interleukin-17 receptor agents, as well as Janus kinase and phosphodiesterase 4 inhibitors, among others. Although clinical trials were too short for predicting the real long-term safety of these treatments, other studies longer than those presently available are expected in the future. SUMMARY: On the basis of novel advances in psoriasis therapy, treatment paradigms could change in the following years. However, the real contribution of these new drugs to the antipsoriatic therapeutic armamentarium still needs to be established.

Picea mariana bark: a new source of trans-resveratrol and other bioactive polyphenols.

The ethyl acetate soluble fraction obtained from the hot water extract of Picea mariana bark (BS-EAc(f)) has been demonstrated to have anti-inflammatory and antioxidant properties. Thus, in the current study, we isolated and characterised major compounds of this fraction by HPLC, NMR and MS analyses. On the whole, 28 compounds were identified, among which were five neolignans, seven lignans, trans-resveratrol, three phenolic acids and four flavonoids. To the best of our knowledge, 2,3-dihydro-3-(4-hydroxy-3-methoxyphenyl)-2-(hydroxymethyl)-(2S,3S)-1,4-benzodioxin-6-propanol, threo and erythro 3-methoxy-8,4'-oxyneolignan-3',4,7,9,9'-pentol, pallasiin, (±) epi-taxifolin, homovanillyl alcohol, orcinol and 2-[4-(3-hydroxypropyl)-2-methoxyphenoxy]-1,3-propanediol are reported for the first time in the Picea genus. P. mariana dry bark contains at least 104µgg(-1)dw of trans-resveratrol and it could be therefore considered as a new accessible source of this molecule. This study provides novel information about the identity of major compounds present in BS-EAc(f), which is essential for the understanding of the anti-inflammatory and nutraceutical potential of this extract.

Antipsoriatic drug development: challenges and new emerging therapies.

Psoriasis is a chronic recurring skin disorder affecting up to 2% of the world's population. Psoriatic lesions are generally visible, leading to significant emotional and social disabilities for patients. In the context of psoriasis, the orchestrated interplay between activated T cells, antigen-presenting cells and keratinocytes leads to the release of proinflammatory cytokines, chemokines and chemical mediators responsible for the perpetuation of this disease. Even though some therapies are available for psoriasis treatment, there is still no cure for this skin disorder and psoriatic patients are significantly unsatisfied, as demonstrated by recent worldwide surveys. Unlike other diseases, psoriasis does not have a generally accepted animal model, which complicates the successful introduction of new antipsoriatic drugs into clinical phases of development. Moreover, psoriasis affects infants, children and elderly patients which require long-term therapies. Thus, the development of new therapeutic approaches should consider multiple factors such as efficacy, dosing frequency, route of administration, toxicity as well as co-morbidities of patients. This article analyzes current challenges for the antipsoriatic drug development and reviews recent patent applications gathered from 2000 to 2011 for psoriasis treatment. Additionally, future perspectives for antipsoriatic drug development are summarized.

Antioxidant, toxicological and antiproliferative properties of Canadian polyphenolic extracts on normal and psoriatic keratinocytes.

AIMS OF THE STUDY: In a first attempt for establishing the possible utilization of polyphenolic extracts from barks of Canadian wood species in psoriasis treatment, we aimed to study (a) their antioxidant capacity, (b) their toxicological properties on normal human keratinocytes (NHK), and (c) their effect on the growth of normal and psoriatic keratinocytes (PK). MATERIALS AND METHODS: Polyphenolic extracts were obtained by 90% ethanolic maceration and hot water extraction (HWE). Scavenging capacity was evaluated towards hydrogen peroxide, hydroxyl, superoxide, nitric oxide and peroxyl radicals. MTT assay and Trypan blue dye exclusion (TBDE) method were used for evaluating the initial toxicity of the most antioxidant extracts on NHK during 24 and 48 h. The effects of extracts on the growth of NHK and PK at non-toxic concentrations were determined after exposure for 48 h. RESULTS: Yellow birch extract obtained by maceration (YB(Mac)) and black spruce extract obtained by HWE (BS(HWE)) were determined to have the highest antioxidant capacity, but BS(HWE) was less toxic on NHK. Toxicity of extracts on keratinocyte plasma membrane and mitochondria after 24 h was attributed to their content of hydroxycinnamic acids and proanthocyanidins. BS(HWE) inhibited the growth of NHK and non-lesional PK, but was not selective for lesional PK. CONCLUSION: Given that BS(HWE) presented elevated content of total phenols and flavonoids and showed a low toxicity on NHK as well as an adequate chemical reactivity towards different radicals and some antiproliferative properties, it was considered as the most valuable extract obtained from barks of Canadian wood species.