In vitro diffusion of plant phenolics through the skin: A review update.

OBJECTIVE: Excessive skin exposure to deleterious environmental variables results in inflammation as well as molecular and cellular impairments that compromise its functionality, aesthetic qualities, and overall well-being. The implementation of topical administration of antioxidants and other compounds as a method for preventing or reversing damage is a rational approach. Numerous phenolic compounds derived from plants have demonstrated capabilities such as scavenging free radicals and promoting tissue healing. However, the primary obstacle lies in effectively delivering these compounds to the specific place on the skin, and accurately forecasting their diffusion through the skin can assist in determining the most effective tactics. Hence, this article provides a comprehensive analysis of recent literature pertaining to the in vitro skin diffusion characteristics of plant phenolics. The aim is to gain a deeper understanding of their behaviour when present in various forms such as solutions, suspensions, and formulations. METHOD: The data on plant extracts and isolated plant phenolic compounds in vitro skin diffusion assays published over the last six years were compiled and discussed. RESULTS: Even though the gold standard Franz diffusion cell is the most commonly used in the assessment of in vitro plant phenolic skin diffusion profiles, a plethora of skin models and assay conditions are reported for a variety of compounds and extracts in different vehicles. CONCLUSION: The presence of numerous models and vehicles poses a challenge in creating correlations among the existing data on plant phenolic compounds. However, it is possible to draw some general conclusions regarding molecular, vehicle, and skin characteristics based on the gathered information.

OBJECTIF: Une exposition excessive de la peau a des variables environnementales délétères entraîne une inflammation ainsi que des déficiences moléculaires et cellulaires qui compromettent sa fonctionnalité, ses qualités esthétiques et son bien­être général. La mise en œuvre de l'administration topique d'antioxydants et d'autres composés comme méthode de prévention ou d'inversion des dommages est une approche rationnelle. De nombreux composés phénoliques dérivés de plantes ont démontré des capacités telles que l'élimination des radicaux libres et la promotion de la cicatrisation des tissus. Cependant, le principal obstacle réside dans l'administration efficace de ces composés à un endroit spécifique de la peau, et une prévision précise de leur diffusion a travers la peau peut aider à déterminer les tactiques les plus efficaces. Par conséquent, cet article fournit une analyse complète de la littérature récente concernant les caractéristiques de diffusion cutanée in vitro des composés phénoliques végétaux. L'objectif est de mieux comprendre leur comportement lorsqu'ils sont présents sous diverses formes telles que solutions, suspensions et formulations. MÉTHODES: Les données sur les extraits de plantes et les composés phénoliques végétaux isolés in vitro par diffusion cutanée, publiées au cours des six dernières années, ont été compilées et discutées. RÉSULTATS: Même si la cellule de diffusion Franz de référence est la plus couramment utilisée dans l'évaluation des profils de diffusion cutanée phénoliques végétales in vitro, une pléthore de modelés de peau et de conditions d'analyse sont rapportées pour une variété de composés et d'extraits dans différents véhicules. CONCLUSION: La présence de nombreux modèles et véhicules pose un défi dans la création de corrélations entre les données existantes sur les composés phénoliques végétaux. Cependant, il est possible de tirer des conclusions générales concernant les caractéristiques moléculaires du véhicule et de la peau sur la base des informations recueillies.

Production of rice bran oil (Oryza sativa L.) microparticles by spray drying taking advantage of the technological properties of cereal co-products.

Microparticles loaded with rice bran oil were produced by spray drying. Rice flour (RF) and rice protein (RP), considered as co-products of the cereal production chain, were tested as stabilizers in the encapsulation process to improve emulsion stability and the properties of the particles. Rice bran oil presented 1.75% É£-oryzanol, a powerful antioxidant with health benefits. AG/RP treatment (10% of rice protein): no phase separation after 24 h, higher zeta potential (-29.09 mV ± 0.67), encapsulation efficiency (73.90% ± 0.22), real density (1.27 g/cm-3), and smaller particle size (8.27 µm ± 0.13). Microparticles containing co-products were the most appropriate to slow down the autooxidation (at 60°C for 8 weeks), especially associated with the use of rice flour. The co-products improve the emulsion characteristics, particle properties and stability of the encapsulated oil. This study presented the technological effects of the use of rice chain co-products, which is in line with the current scenario of sustainability.

Improving the performance of transglutaminase-crosslinked microparticles for enteric delivery.

Various agents for cross-linking have been investigated for stabilizing and controlling the barrier properties of microparticles for enteric applications. Transglutaminase, in addition to being commercially available for human consumption, presents inferior cross-linking action compared to glutaraldehyde. In this study, the intensity of this enzymatic cross-linking was investigated in microparticles obtained by complex coacervation between gelatin and gum Arabic. The effectiveness of cross-linking in these microparticles was evaluated based on swelling, release of a model substance (parika oleoresin: colored and hydrophobic) and gastrointestinal assays. The cross-linked microparticles remained intact under gastric conditions, whereas the uncross-linked microparticles have been dissolved. However, all of the microparticles have been dissolved under intestinal conditions. The amount of oily core that was released decreased as the amount of transglutaminase increased. For the most efficient microparticles (50U/g of protein), the performance was improved by increasing the pH of cross-linking from 4.0 to 6.0, resulting in a release of 17.1% rather than 32.3% of the core material. These results were considerably closer to the 10.3% of core material released by glutaraldehyde-cross-linked microparticles (1mM/g of protein).

Anthelmintic activity of Artemisia annua L. extracts in vitro and the effect of an aqueous extract and artemisinin in sheep naturally infected with gastrointestinal nematodes.

There is no effective natural alternative control for gastrointestinal nematodes (GIN) of small ruminants, with Haemonchus contortus being the most economically important GIN. Despite frequent reports of multidrug-resistant GIN, there is no new commercial anthelmintic to substitute failing ones. Although trematocidal activity of artemisinin analogs has been reported in sheep, neither artemisinin nor its plant source (Artemisia annua) has been evaluated for anthelmintic activity in ruminants. This study evaluated the anthelmintic activity of A. annua crude extracts in vitro and compared the most effective extract with artemisinin in sheep naturally infected with H. contortus. A. annua leaves extracted with water, aqueous 0.1% sodium bicarbonate, dichloromethane, and ethanol were evaluated in vitro by the egg hatch test (EHT) and with the bicarbonate extract only for the larval development test (LDT) using H. contortus. The A. annua water, sodium bicarbonate (SBE), ethanol, and dichloromethane extracts tested in vitro contained 0.3, 0.6, 4.4, and 9.8% of artemisinin, respectively. The sodium bicarbonate extract resulted in the lowest LC99 in the EHT (1.27 µg/mL) and in a LC99 of 23.8 µg/mL in the LDT. Following in vitro results, the SBE (2 g/kg body weight (BW)) and artemisinin (100 mg/kg BW) were evaluated as a single oral dose in naturally infected Santa Inês sheep. Speciation from stool cultures established that 84-91% of GIN were H. contortus, 8.4-15.6 % were Trichostrongylus sp., and 0.3-0.7% were Oesophagostomum sp. Packed-cell volume and eggs per gram (EPG) of feces were used to test treatment efficacy. The SBE tested in vivo contained no artemisinin, but had a high antioxidant capacity of 2,295 µmol of Trolox equivalents/g. Sheep dosed with artemisinin had maximum feces concentrations 24 h after treatment (126.5 µg/g artemisinin), which sharply decreased at 36 h. By day 15, only levamisole-treated sheep had a significant decrease of 97% in EPG. Artemisinin-treated and SBE-treated sheep had nonsignificant EPG reductions of 28 and 19%, respectively, while sheep in infected/untreated group had an average EPG increase of 95%. Sheep treated with artemisinin and A. annua SBE maintained blood hematocrits throughout the experiment, while untreated/infected controls had a significant reduction in hematocrit. This is the first time oral dose of artemisinin and an aqueous extract of A. annua are evaluated as anthelmintic in sheep. Although oral dose of artemisinin and SBE, at single doses, were ineffective natural anthelmintics, artemisinin analogs with better bioavailability than artemisinin should be tested in vivo, through different routes and in multiple doses. The maintenance of hematocrit provided by artemisinin and A. annua extract and the high antioxidant capacity of the latter suggest that they could be combined with commercial anthelmintics to improve the well-being of infected animals and to evaluate potential synergism.

Geranylgeraniol and 6α,7ß-dihydroxyvouacapan-17ß-oate methyl ester isolated from Pterodon pubescens Benth.: Further investigation on the antinociceptive mechanisms of action.

The crude alcoholic extracts obtained from Pterodon pubescens Benth. seeds are widely used in Brazilian folk medicine as anti-inflammatory, analgesic, anti-rheumatic tonics and depurative preparations. We previously demonstrated the antinociceptive activity on writhing capsaicin, glutamate, and hot-plate tests of two compounds isolated from P. pubescens: geranylgeraniol (C1) and 6α,7ß-dihydroxyvouacapan-17ß-oate methyl ester (C2). This work is a continuation of the previous study investigating the possible mechanisms of action for compounds C1 and C2, and the differences between them. The present study demonstrated that when administered intraperitoneally (i.p.): i), compounds C1 and C2 produced significant anti-allodynic activity during the acute phase of the Complete Freund's Adjuvant (CFA)-induced persistent pain model; ii) compound C1 produced significant anti-hypernociception activity in the carrageenan-induced pain model; iii) compound C2 presented a significant loss of activity after p-chlorophenylalanine methyl ester hydrochloride (PCPA) [5-HT synthesis inhibitor] treatment, suggesting that the mechanisms of action could be related to either the synthesis or release of serotonin; iv) compound C1 presented a significant loss of activity after ondansetron (5-HT(3) receptor antagonist) treatment suggesting activity upon 5-HT(3) serotonin receptors; v) compound C1 presented a significant loss of activity after efaroxan (mixed I(1) imidazoline/α(2)-adrenoceptor antagonist) treatment suggesting the participation of this compound upon imidazoline I(1) receptors; and vi) both compounds C1 and C2 did not appear to exert their activity via 5-HT(1A), 5-HT(2A), imidazoline I(2), α(2)-adrenoceptor, nitric oxide, GABA(A), acetylcholine muscarinic, and nicotinic receptors when evaluated in acetic acid-induced nociception.

Antinociceptive effect of geranylgeraniol and 6alpha,7beta-dihydroxyvouacapan-17beta-oate methyl ester isolated from Pterodon pubescens Benth.

BACKGROUND: Pterodon pubescens Benth seeds are commercially available in the Brazilian medicinal plant street market. The crude alcoholic extracts of this plant are used in folk medicine as anti-inflammatory, analgesic, and anti-rheumatic preparations. The aim of this study was to evaluate the contribution of geranylgeraniol (C1) and 6alpha, 7beta-dihydroxyvouacapan-17beta-oate methyl ester (C2) isolated from Pterodon pubescens Benth. to the antinociceptive activity of the crude extract. RESULTS: Compounds C1 and C2 demonstrated activity against writhing with intraperitoneal (i.p.) and oral (p.o.) routes, capsaicin (i.p. and p.o.), glutamate (i.p.), and in the hot-plate (p.o.) tests, demonstrating their contribution to the antinociceptive activity of crude Pterodon pubescens Benth extracts. The observed activity of compounds C1 and C2 may be related to vanilloid receptors VR1, and/or glutamate peripheral receptors. In hot-plate model, the antinociceptive activity was maintained when naloxone chloride (opioid antagonist) was administered prior to treatment with compounds suggesting that C1 and C2 (p.o.) do not exert their antinociceptive effects in the hot-plate test via opioid receptors. The findings presented herein also suggest that compounds within the crude Pterodon pubescens Benth. extract may exert a synergistic interactive effect, since the crude extract (300 mg x kg-1) containing lower concentrations of compounds C1 (11.5%- 34.6 mg x kg-1) and C2 (1.5% - 4.7 mg x kg-1) gave statistically the same effect to the pure compounds when tested separately (C1 = C2 = 300 mg.kg-1) in writhing experimental model with p.o. administration. Further studies will be undertaken to establish more specifically the mechanisms of action for compounds C1 and C2. Possible synergistic interactions will be evaluated employing the Isobole method. CONCLUSION: These results allowed us to establish a relationship between the popular use of Pterodon pubescens seeds for pain relief and the activity of two major compounds isolated from this species which demonstrated antinociceptive activity. Various "in vivo" experimental models corroborate the folk use of this species for different pain and inflammation disorders.