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.

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.

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.

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.

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.