Isolation and HPLC Quantitative Determination of 5α-Reductase Inhibitors from Tectona grandis L.f. Leaf Extract.

Steroid 5α-reductase plays a crucial role in catalyzing the conversion of testosterone to dihydrotestosterone, which is involved in many androgen-dependent disorders. Leaf-hexane extract from Tectona grandis L.f. has shown promise as a 5α-reductase inhibitor. The objectives of this current study were to isolate and identify 5α-reductase inhibitors from T. grandis leaves and to use them as the bioactive markers for standardization of the extract. Three terpenoid compounds, (+)-eperua-8,13-dien-15-oic acid (1), (+)-eperua-7,13-dien-15-oic acid (2), and lupeol (3), were isolated and evaluated for 5α-reductase inhibitory activity. Compounds 1 and 2 exhibited potent 5α-reductase inhibitory activity, while 3 showed weak inhibitory activity. An HPLC method for the quantitative determination of the two potent inhibitors (1 and 2), applicable for quality control of T. grandis leaf extracts, was also developed. The ethanolic extract showed a significantly higher content of 1 and 2 than found in the hexane extract, suggesting that ethanol is a preferable extraction solvent. This study is the first reported isolation of 5α-reductase inhibitors (1 and 2) from T. grandis leaves. The extraction and quality control methods that are safe and useful for further development of T. grandis leaf extract as an active ingredient for hair loss treatment products are also reported.

Correlation between sensory and instrumental characterization of developed sunscreens containing grape seed extract and a commercial product.

OBJECTIVE: In the development of cosmetic products, sensory evaluation is an important step in determining consumer acceptance before it is released on a market but is often time-consuming and costly. However, correlating sensory characteristics with instrumental parameters using multivariate techniques is a potential way to facilitate the development of cosmetic products. METHODS: Sunscreen formulations varied in the content of grape seed extract (GSE) and ultraviolet (UV) filters, and benchmark products were characterized using sensory descriptive analysis and instrumental analysis. Principal Component Analysis (PCA) was applied to the panel's performance data to study how well the panelists performed compared to each other and to find an association between rheological and textural instrumental parameters of cream samples. Further, applying Partial Least Squares (PLS) regression analysis, the association between sensory attributes and instrumental parameters was analyzed. In addition, a preference for the sensory properties of the studied sunscreen products that are important for consumers living in Southeast Asia was assessed by PLS. RESULTS: In this study, both the sensory and instrumental properties of all tested formulations were described well by PCA. The practicality of PLS was confirmed by an established correlation between sensory attributes from the categories of appearance (glossiness), pick-up (integrity of shape, firmness, glossiness, stringiness), and after-feel (glossiness, spreadability, stickiness) with both rheological and textural parameters. Although the instrumental analysis could not completely replace sensory evaluation, a described method applying PLS can be used as an additional cost-effective and time-saving method during the development of cosmetic products. Moreover, PLS revealed that sunscreens with a light texture and glossy appearance providing smooth skin after-feel are likely to be preferred over the thicker formulations having a residual color appearance in Southeast Asia. CONCLUSION: Until a universal model is created, the cosmetics developers and companies can apply a described method of determining sensory properties from the instrumental parameters of their own products. Future studies will be worth exploiting the applicability of the PLS regression model on instrumental datasets predicting sensory characteristics of other sunscreen products.

OBJECTIF: Dans le développement de produits cosmétiques, l'évaluation sensorielle est une étape importante pour déterminer l'acceptation par le consommateur avant la mise sur le marché, mais elle est souvent longue et coûteuse. Cependant, la corrélation des caractéristiques sensorielles avec les paramètres instrumentaux à l'aide de techniques multivariées est un moyen potentiel afin de faciliter le développement des produits cosmétiques. MÉTHODES: Les formulations d'écrans solaires variants en termes de teneur en extrait de pépins de raisin (EPR) et en filtres ultraviolets (UV), et les produits de référence ont été caractérisés à l'aide d'une analyse sensorielle descriptive et d'une analyse instrumentale. L'analyse en composantes principales (ACP) a été appliquée aux données de performance du panel pour étudier la performance des panélistes les uns par rapport aux autres et pour trouver une association entre les paramètres instrumentaux rhéologiques et texturaux des échantillons de crème. En outre, l'association entre les attributs sensoriels et les paramètres instrumentaux a été analysée au moyen d'une analyse de régression PLS (Partial Least Squares). De plus, une préférence pour les propriétés sensorielles des produits de protection solaire étudiés importantes pour les consommateurs vivant en Asie du Sud-Est a été évaluée par PLS. RÉSULTATS: Dans cette étude, les propriétés sensorielles et instrumentales de toutes les formulations testées ont été bien décrites par l'ACP. L'aspect pratique de l'analyse PLS a été confirmé par une corrélation établie entre les attributs sensoriels des catégories de l'apparence (brillance), de la prise (intégrité de la forme, fermeté, brillance, filant) et de l'impression résiduelle (brillance, capacité d'étalement, adhésivité) avec les paramètres rhéologiques et texturaux. Bien que l'analyse instrumentale ne puisse pas remplacer complètement l'évaluation sensorielle, la méthode décrite appliquant la PLS peut être utilisée comme une méthode supplémentaire rentable et permettant de gagner du temps lors du développement de produits cosmétiques. En outre, l'analyse PLS a révélé que les écrans solaires à la texture légère et à l'aspect brillant, qui procurent une sensation de douceur sur la peau, sont susceptibles d'être préférés aux formulations plus épaisses ayant une couleur résiduelle en Asie du Sud-Est. CONCLUSION: En attendant la création d'un modèle universel, les développeurs et les entreprises de cosmétiques peuvent appliquer une méthode décrite pour déterminer les propriétés sensorielles à partir des paramètres instrumentaux de leurs propres produits. Les études futures devront exploiter l'applicabilité du modèle de régression PLS sur des ensembles de données instrumentales prédisant les caractéristiques sensorielles d'autres produits solaires.

Characterization of Metabolites in Plasma, Urine and Feces of Healthy Participants after Taking Brahmi Essence for Twelve Weeks Using LC-ESI-QTOF-MS Metabolomic Approach.

Brahmi essence, developed from Bacopa monnieri (L.) Wettst. standardized extract and mulberry juice, was proven to improve the memory speed of healthy participants aged 55-80 years old, following a 12-week dietary program. However, the metabolites have not yet been reported. Our objective was to characterize the altered metabolites in the plasma, urine, and feces of healthy volunteers after consumption of Brahmi essence for 12 weeks, using the LC-MS metabolomics approach. The altered metabolites were selected from OPLS-DA S-plots; 15 metabolites in the plasma, 7 in the urine, and 17 in the feces samples were tentatively identified by comparison with an online database and literature. The metabolites in the plasma samples were in the classes of amino acids, acylcarnitine, and phospholipids. Benzeneactamide-4-O-sulphate and 3-hydroxyhippuric acid were found in urine samples. The metabolites in the class of amino acids, together with jujubogenin and pseudojujubogenin, were identified in the fecal samples. The aminoacyl-tRNA, aromatic amino acids, and branched-chain amino acid biosynthetic pathways were mainly related to the identified metabolites in all three samples. It could be implied that those metabolites and their pathways might be linked with the effect of Brahmi essence on memory speed.

The effects of cannabis, cannabinoids, and their administration routes on pain control efficacy and safety: A systematic review and network meta-analysis.

OBJECTIVES: To determine the effects of cannabis, cannabinoids, and their administration routes on pain and adverse euphoria events. DATA SOURCES: A systematic search was performed in PubMed, ScienceDirect, ClincalTrials.gov, Scopus, Cochrane Library, and Embase from inception until June 2017. STUDY SELECTION: Randomized controlled trials investigating the effects of cannabis or cannabinoids on pain reduction. DATA EXTRACTION: Two reviewers extracted and assessed the quality of studies by means of Cochrane risk of bias. Standardized mean difference (SMD) was calculated. Random-effects model was undertaken to pool the treatment effects. RESULTS: A total of 25 studies involving 2270 patients were included. We found that delta-9-tetrahydrocannabinol/cannabidiol (THC/CBD) (oromucosal route), THC (oromucosal route), and standardized dried cannabis (with THC; SCT; inhalation route) could reduce neuropathic pain score (SMD -0.41, 95% CI -0.7 to -0.1; -0.61, 95% CI -1.2 to -0.02; and -0.77, 95% CI -1.4 to -0.2; respectively). For nociceptive pain, only standardized cannabis extract (with THC; SCET) via oral route could reduce pain score (SMD -1.8, 95% C; -2.4 to -1.2). In cancer pain, THC/CBD via oromucosal route and THC via oral or oromucosal route could reduce pain score (SMD -0.7, 95% CI -1.2 to -0.2; and -2.1, 95% CI -2.8 to -1.4; respectively). No study was observed for THC/CBD via oral route or inhalation or THC via inhalation for cancer and nociceptive pain, SCET via oromucosal route or inhalation for neuropathic and cancer pain, THC via oromucosal route for nociceptive pain, and SCT via oromucosal or oral route for neuropathic, cancer, and nociceptive pain. Statistically significant increased risks of euphoria were observed in THC/CBD (oromucosal), THC (oromucosal), and SCT (inhalation). CONCLUSION: The use of cannabis and cannabinoids via certain administration routes could reduce different types of pain. Product developers could consider our findings as part of their product design so that the effective route of cannabis and cannabinoids for pain control can be achieved.

Thermal Degradation Kinetics and pH-Rate Profiles of Iriflophenone 3,5-C-ß-d-diglucoside, Iriflophenone 3-C-ß-d-Glucoside and Mangiferin in Aquilaria crassna Leaf Extract.

The health benefits of the Aquilaria crassna Pierre ex Lecomte leaf extract (AE) make it very useful as an ingredient in food and pharmaceutical products. Iriflophenone 3,5-C-ß-d-diglucoside (1), iriflophenone 3-C-ß-d-glucoside (2) and mangiferin (3) are bioactive compounds of AE. We assessed the stability of AE by investigating the thermal degradation kinetics and shelf-life (t90%) of compounds 1, 2 and 3 using Arrhenius plot models and studied their pH-rate profiles. The results demonstrate that 1 and 2 were degraded, following a first-order kinetic reaction. The degradation of 3 followed first-order reaction kinetics when present in a solution and second-order reaction kinetics in the dried powder form of the extract. According to the first-order kinetic model, the predicted shelf-life (t90%) of the extract at 25 °C in dried form for compound 1 was 989 days with activation energy 129.86 kJ·mol-1, and for 2 it was 248 days with activation energy 110.57 kJ·mol-1, while in the extract solution, the predicted shelf-life of compounds 1-3 was 189, 13 and 75 days with activation energies 86.83, 51.49 and 65.28 kJ·mol-1, respectively. In addition, the pH-rate profiles of 1-3 indicated that they were stable in neutral to acidic environments.

Efficacy and Safety of Centella Asiatica (L.) Urb. on Wrinkles: A Systematic Review of Published Data and Network Meta-Analysis.

Centella asiatica has many applications in cosmetics, including wrinkle treatments, but its effectiveness remains to be clarified. This systematic review study aimed to demonstrate the efficacy and safety of C. asiatica for reducing facial wrinkles. PubMed, Excerpta Medica dataBASE (EMBASE), Cochrane Central Register of clinical trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Thai Library Integrated System, and Thai university database/journals were searched until May 2019. Five double-blinded randomised controlled trials, including 172 Asian females, were included. Endpoints were wrinkling measured by visual score, image analysis, and participant satisfaction. Two placebo-controlled studies applied gel/creams containing C. asiatica or asiaticoside for 12 w to periorbital skin. Two studies applied tretinoin or Pueraria mirifica contralaterally and by network meta-analysis C. asiatica appeared more effective than P. mirifica but possibly less than tretinoin. Asiaticoside applied as a lipstick for 8 w reduced lip wrinkling. Skin hydration was markedly raised by C. asiatica but not tretinoin. One study reported 10 adverse events for C. asiatica and 35 for tretinoin. Cochrane risk of bias was generally low, reporting was weak, and lack of C. asiatica standardization prevents general application. From the reported data, it is possible to conclude that C. asiatica improved lip and periocular wrinkles, and may replace retinoids if its long-term safety is established and C. asiatica is standardized.

Vasodilatory Effects and Mechanisms of Action of Bacopa monnieri Active Compounds on Rat Mesenteric Arteries.

B. monnieri extract (BME) is an abundant source of bioactive compounds, including saponins and flavonoids known to produce vasodilation. However, it is unclear which components are the more effective vasodilators. The aim of this research was to investigate the vasorelaxant effects and mechanisms of action of saponins and flavonoids on rat isolated mesenteric arteries using the organ bath technique. The vasorelaxant mechanisms, including endothelial nitric oxide synthase (eNOS) pathway and calcium flux were examined. Saponins (bacoside A and bacopaside I), and flavonoids (luteolin and apigenin) at 0.1-100 µM caused vasorelaxation in a concentration-dependent manner. Luteolin and apigenin produced vasorelaxation in endothelial intact vessels with more efficacy (Emax 99.4 ± 0.7 and 95.3 ± 2.6%) and potency (EC50 4.35 ± 1.31 and 8.93 ± 3.33 µM) than bacoside A and bacopaside I (Emax 83.6 ± 2.9 and 79.9 ± 8.2%; EC50 10.8 ± 5.9 and 14.6 ± 5.4 µM). Pretreatment of endothelial intact rings, with L-NAME (100 µM); an eNOS inhibitor, or removal of the endothelium reduced the relaxant effects of all compounds. In K+-depolarised vessels suspended in Ca2+-free solution, these active compounds inhibited CaCl2-induced contraction in endothelial denuded arterial rings. Moreover, the active compounds attenuated transient contractions induced by 10 µM phenylephrine in Ca2+-free medium containing EGTA (1 mM). Thus, relaxant effects occurred in both endothelial intact and denuded vessels which signify actions through both endothelium and vascular smooth muscle cells. In conclusion, the flavonoids have about twice the potency of saponins as vasodilators. However, in the BME, there is ~20 × the amount of vaso-reactive saponins and thus are more effective.

Sesquiterpene-Enriched Extract of Curcuma aeruginosa Roxb. Retards Axillary Hair Growth: A Randomised, Placebo-Controlled, Double-Blind Study.

BACKGROUND: Sesquiterpenes in Curcuma aeruginosa Roxb. inhibit steroid 5α-reductase and dihydrotestosterone production, and reverse androgenic alopecia. This study sought to show that a high sesquiterpene C. aeruginosa extract (CA-ext) retards axillary hair growth in women. METHODS: Thirty women (age 20-52 years) were recruited into a 12-week, double-blind, placebo-controlled intervention for CA-ext treatment, where they were randomly allocated to a left or right armpit group. At weekly intervals, axillary hair length was measured videometrically, the hair was shaved, and lotion was applied (to the contralateral axilla) twice daily via roll-on applicators containing either CA-ext or placebo. The primary endpoint of the study was hair growth. RESULTS: Participants showed 22% (range 8-56%, p < 0.0001) reduced axillary hair growth with CA-ext compared to placebo, albeit delayed by 6 weeks. Participants were satisfied with the treatment and no apparent adverse effects were reported. The quantities of lotion used for each axilla were identical between test and placebo throughout the trial for each participant. Participants reported having shorter and finer armpit hair with the test lotion but disliked its smell, even though it was perfumed. The "free of irritation" description gained the highest questionnaire ratings. CONCLUSION: CA-ext in lotion is an efficacious inhibitor of axillary hair growth, the preparation was well accepted and matched the effectiveness of finasteride. Thus, with some refinement, it should provide an alternative pharmacological treatment for unwanted androgenic hair.

Immunoaffinity Knockout of Saponin Glycosides from Asparagus racemosus to Assess Anti-lipid Peroxidation.

INTRODUCTION: Asparagus racemosus Willd (Asparagaceae family), known as Shatavari, is important in Ayurveda and traditional Thai medicines. The saponin glycosides, shatavarin I and IV are major constituents in its roots and may be responsible for their actions including protection against lipid peroxidation and carcinogenesis. OBJECTIVE: To develop an immunoaffinity column for isolating compounds with structures related to shatavarin IV from crude extracts of A. racemosus root. METHODOLOGY: The monoclonal antibody recognising shatavarin IV (mAbShavIV) was coupled to an Affi-Gel Hz gel to isolate compounds with structures related to shatavarin IV from the other components of crude extracts of A. racemosus root. The saponin glycosides in each fraction were analysed by mAbShavIV ELISA and LC-MS/MS. RESULTS: The pooled wash-through fractions contained 3% of loaded mAbShavIV reactive saponin glycosides, while eluted fractions released ~ 90% of shatavarin saponin glycosides in a single step. Using thiobarbiturate (TBARs) to measure lipid-peroxidation, the extract, and the pooled wash-through fractions showed moderate protection against Cu+ -induced oxidation of human low density lipoprotein (LDL) (IC50 11.3 ± 1.4 and 12.6 ± 0.9 µg/mL, respectively). In contrast, the saponin glycosides eluted from the mAbShavIV-column had weaker protectant (IC50 29.7 ± 1.8 µg/mL) suggesting that A. racemosus shatavarins do not inhibit carcinogenesis through preventing lipid peroxidation. CONCLUSION: The strategy described here demonstrates its utility for isolating a group of related compounds from the rest of the extract with selectivity and recovery rate. Pharmacological efficacy and synergistic effects of the components obtained can be further investigated. Copyright © 2017 John Wiley & Sons, Ltd.

Conformational analysis of an anti-androgenic, (E,E)-8-hydroxygermacrene B, using NOESY and dynamic NMR spectroscopy.

(E,E)-8-Hydroxygermacrene B was prepared by ketone reduction of germacrone, a naturally occurring compound from Curcuma aeruginosa Roxb. with NaBH4 at low temperature (4 °C). This compound showed remarkable in vitro anti-androgenic activity (IC50 0.15±0.022 mM) applicable to male baldness treatments. NMR analysis at -50 °C indicated that there were four conformational isomers of (E,E)-8-hydroxygermacrene B in a ratio of 48:40:8:4. The major conformers were assigned by (1)H NMR and 2D-NOESY NMR spectroscopy as having methyl groups at C-10 and C-4 in up-down (UD) orientations (48% predominance) and UU (40%). (1)H NMR spectra implied another two minor conformers with these methyls having DU (8%) and DD (4%) orientations.

Method for screening sunscreen cream formulations by determination of in vitro SPF and PA values using UV transmission spectroscopy and texture profile analysis.

Formulation of sunscreen products to obtain high values of sun protection factor (SPF) and protection from ultraviolet A (PA) is challenging work for cosmetic chemists. This study aimed to study factors affecting SPF and PA values using ultraviolet transmission spectroscopy as well as texture profiles of sunscreen formulations using 23 factorial designs. Results demonstrate that the correlation coefficient between the labeled SPF values of counter-brand sunscreen products and the in vitro SPF values was 0.901. In vitro SPF determination showed that the combination effect of phase volume ratio (PVR) and xanthan gum caused a significant increase to the SPF values of the formulations, whereas the interaction effect between PVR and stearic acid significantly decreased the SPF value. In addition, there was the interaction effect between xanthan gum and stearic acid leading to significant reduction of hardness, compressibility, and pH, but significantly increasing the adhesiveness. All tested factors did not significantly affect the cohesiveness of tested formulations. In conclusion, apart from sunscreen agents, the other ingredients also affected the SPF and PA values. The calculated SPF values range from 21 to 60. However, a selected formulation needs to be confirmed by the standard method of testing. In addition, the physical, chemical, and biological stability; shelf life; and sensory evaluation of all formulations need to be evaluated.

Systematic Review on Transdermal/Topical Cannabidiol Trials: A Reconsidered Way Forward.

Introduction: This systematic review aimed to assess efficacy and safety for skin-applied formulations containing CBD. Methods: Bibliographic and clinical trial registries were searched for interventional human trials using cutaneously administered CBD or reported plasma CBD concentrations (any species). Results: Eight of 544 articles fitted the selection criteria: 3 placebo-controlled randomized and 5 single-arm trials. Eleven more studies were found in clinical trial databases but not accessible. Symptoms targeted were dermatopathologies or safety (two studies), pain (two), and behavior (one). Doses were 50-250 mg or 0.075-1.0% CBD, but coformulated with other ingredients. Risk of bias was high and reporting deficiencies further compromised data reliability. Diverse methodologies and formulations hampered syntheses for CBD dose, efficacy, and safety. Plasma CBD levels in dogs and rodents were 0.01-5 µM translating to <100 nM free, unbound CBD in humans. Adverse events were uncommon and mild, but meaningless without CBD's contribution to efficacy data. Achievable free CBD plasma concentrations ∼100 nM can interact predominantly with high-affinity CBD targets, for example, TRPA1 and TRPM8 membrane channels that are abundantly expressed in pathological conditions. Even if reached, higher CBD concentrations on less susceptible targets risk complex and unsafe CBD therapy. A conceptual framework is proposed where dermal capillary loops create sinking for topical CBD demonstrating parallels between topical and transdermal CBD administration. Conclusions: Users risk generalizing inadequately designed trials to all CBD preparations. New clinical trials are urgently needed: they must demonstrate that outcomes are solely from CBD pharmacology, are reliable, unbiased, safe, and comparable. Measurements of sustained plasma CBD levels are mandatory, irrespective of administration route for successful translation from in vitro systems that express human molecular targets. Placebos must be appropriate. Transcutaneous and topical formulations need preliminary in vitro studies to optimize CBD skin penetration. Then, users can rationally balance efficacy against potential harms and cost-effectiveness of CBD formulations.

Printable-Microencapsulated Ascorbic Acid for Personalized Topical Delivery.

This study presents the successful development of printable-microencapsulated ascorbic acid (AA) for personalized topical delivery using laser printing technology. Rice flour with a 10% AA content was selected as an encapsulation material. Hydrophobic nanosilica was used to create negative electrostatic charges on the microencapsulated surfaces via a high-speed mixture. This process facilitated the microencapsulated AA fabrication using a commercial laser printer and produced a well-patterned design with some minor print defects, such as banding and scattering. The amount of encapsulated AA per area was 0.28 mg/cm2, and the RGB color code was 0,0,0. An emulsion carrier system comprising pentylene glycol (P5G) or diethylene glycol monoethyl ether (DEGEE), Tween 20, oleic acid, and deionized (DI) water at a ratio of 20:30:30:20 was developed to enhance AA transmission into the skin. The Franz diffusion cell technique was used to investigate topical absorption on Strat-M membranes using P5G and DEGEE as enhancers. The steady-state fluxes were 8.40 (±0.64) and 10.04 (±0.58) µg/h/cm2 for P5G and DEGEE, respectively. Cytotoxicity tests conducted on fibroblast cells revealed low cytotoxicity for the encapsulation products and carriers.

Inhibitory efficiency of Andrographis paniculata extract on viral multiplication and nitric oxide production.

Andrographis paniculata (Burm. F.) Nees is a medicinal plant previously reported with broad-spectrum antivirals but the mode of inhibition remains elusive. The objective of this study was to identify the most active fraction from A. paniculata ethanol extract (APE, APE-2A, APE-2B and APE-2C) and dry powder extract (APSP) against influenza A (H3N2), representing RNA viruses, and herpes simplex virus-1 (HSV-1), representing DNA viruses. The results showed that the fractions APSP, APE, APE-2B, and APE-2C directly neutralized the HSV-1 and influenza A (H3N2) when incubated at room temperature for 60 min before infecting the cells. The results also showed that the additional APE-2A fraction also directly neutralized the influenza A (H3N2), but not the HSV-1. The APE, APE-2B and APE-2C inhibited the HSV-1 by more than 0.5 log when the fractions were introduced after infection. Similarly, the APSP and APE inhibited the influenza A (H3N2) more than 0.5 log after infection. Only 50 µg/mL APE-2C inhibited the viruses greater than 0.5 log. In addition, A. paniculata extracts were also evaluated for their interfering capacities against nitric oxide (NO) production in LPS-activated RAW 264.7 macrophages. As well, APE-2C potently inhibited NO production at the IC50 of 6.08 µg/mL. HPLC and LC-MS analysis indicated that the most actively antiviral fractions did not contain any andrographolide derivatives, whereas the andrographolide-rich fractions showed moderate activity.

Polymeric micelles of PEG-PE as carriers of all-trans retinoic acid for stability improvement.

The topical application of all-trans retinoic acid (ATRA) is an effective treatment for several skin disorders, including photo-aging. Unfortunately, ATRA is susceptible to light, heat, and oxidizing agents. Thus, this study aimed to investigate the ability of polymeric micelles prepared from polyethylene glycol conjugated phosphatidylethanolamine (PEG-PE) to stabilize ATRA under various storage conditions. ATRA entrapped in polymeric micelles with various PEG and PE structures was prepared. The critical micelle concentrations were 97-243 µM, depending on the structures of the PEG and PE molecules. All of the micelles had particle diameters of 6-20 nm and neutral charges. The highest entrapment efficiency (82.7%) of the tested micelles was exhibited by ATRA in PEG with a molecular weight of 750 Da conjugated to dipalmitoyl phosphatidylethanolamine (PEG(750)-DPPE) micelles. The PEG(750)-DPPE micelle could significantly retard ATRA oxidation compared to ATRA in 75% methanol/HBS solution. Up to 87% of ATRA remained in the PEG(750)-DPPE micelle solution after storage in ambient air for 28 days. This result suggests that PEG(750)-DPPE micelle can improve ATRA stability. Therefore, ATRA in PEG(750)-DPPE micelle is an interesting alternative structure for the development of cosmeceutical formulations.

Effect of green tea extract loaded chitosan microparticles on facial skin: A split-face, double-blind, randomized placebo-controlled study.

INTRODUCTION: The bioactivities of green tea extract were indicated to promote skin health in vitro. Few clinical studies reported on skin nourishment of topical applying green tea extract due to the limited skin absorption. METHODS: This current study evaluated the clinical effectiveness and safety of green tea extract encapsulated chitosan microparticles (GTP) in emulsion base on a split-face, double-blind, randomized placebo-controlled study. Twenty-nine female volunteers were recruited into the study. They were randomly assigned to apply GTP and placebo creams on each half face for 8 weeks. The facial skin properties on both sides were monitored and evaluated every 2 weeks. RESULTS: The results revealed that skin elasticity (R2) of half face treated with GTP cream (0.748 ± 0.05) was superior to another that received placebo cream (0.722 ± 0.05) at 4th week. In addition, melanin index implying skin dullness of the half face that received GTP cream significantly improved within the 6th week after application (placebo =295.60 ± 58.81, GTP =282.70 ± 59.62). Most importantly, the photographs clearly indicated that the decreasing in facial wrinkles of volunteers applied with GTP cream was more than those applying placebo cream. Signs of skin irritation were not evident in both treatment and placebo cream groups. CONCLUSION: Based on study outcomes, the green tea extract encapsulated chitosan microparticles appear to be the promising active candidate for promoting skin elasticity and improving skin dullness and wrinkles.

Clinical study of Asian skin changes after application of a sunscreen formulation containing grape seed extract.

BACKGROUND: Asian skin undergoing chronological aging, accumulates signs of photoaging mediated by prolonged exposure to ultraviolet (UV) radiation. Although sunscreens are effective in preventing signs of photoaging, polyphenol-rich extracts, for example, grape seed extract (GSE) can provide additional protection through the broad spectrum of biological activities. AIMS: To access the effectiveness of a sunscreen formulation containing GSE as an important cosmetic ingredient for the improvement of age-related changes in Asian skin using noninvasive evaluation techniques. METHODS: Noninvasive methods were used to assess changes in the biophysical properties corresponding to aging signs including melanin and erythema indices, color parameters of the CIE L*a*b* system, elasticity, and hydration of the forearm skin before and after applying the sunscreen with GSE. In addition, to confirm the effectiveness of the tested product, we compared it with benchmark sunscreen, and a cream base containing either GSE or UV filters. RESULTS: Twice-daily application of sunscreen containing 3% GSE significantly reduced the level of melanin and erythema and improved overall skin tone. The hydration was drastically increased after 3 h of wearing formulation and was maintained relatively high for 5 h. Skin elasticity parameters, including Young's modulus, retraction time, and viscoelasticity, improved in participants of all age categories (35-59 years). Moreover, sunscreen with GSE, as acclaimed by participants, improved overall skin appearance. CONCLUSIONS: The balancing potential of GSE on the skin, combined with the photoprotective properties of UV filters demonstrated an added value as an anti-aging agent and proved efficacy for both photo- and chronologically-aged Asian skin.

Chemical and mechanical accelerated and long-term stability evaluation of sunscreen formulation containing grape seed extract.

BACKGROUND: Sunscreens and catechins from grape seed extract (GSE) are sensitive to various environmental factors and undergo certain changes over time that might affect the effectiveness of the final product. To this date, effects of thermal storage conditions have not been sufficiently addressed to guarantee the long-term stability of sunscreen formulations. AIMS: To study the chemical and mechanical accelerated and long-term stability of sunscreen formulation containing GSE at the Climatic Zone IVb conditions. METHODS: Stability studies were performed for 6 months for accelerated stability study at 30°C ± 2 and 50°C ± 2, 75 ± 5% relative humidity; and long-term stability study at 5°C ± 5. The quantification of constituents of three formulations: sunscreen with GSE, cream with UV filters only, and cream with GSE only was performed by high-performance liquid chromatography. In vitro spectrophotometry was used to determine changes in sun protection effectiveness through SPF and UVAPF values. Mechanical stability was evaluated by textural and rheological analyzes. RESULTS: All tested formulations were less stable at high-temperature conditions. The contents of catechin (С) and epicatechin (EC) in sunscreen with GSE were reduced to 37% and 50% at 50°C, respectively, whereas UV filters appeared to be stable. However, despite the significant reduction in catechins over time, polyphenols in GSE remained unchanged at different stored conditions. The SPF values and water resistance of sunscreen with GSE were maintained throughout the study. CONCLUSIONS: A current in vitro study has shown that sunscreen with GSE is a value-added anti-aging ingredient in sunscreen formulation because its polyphenolic composition as well as SPF values and water resistance were maintained under all temperature conditions over time.

Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol: An in vitro study.

OBJECTIVE: To evaluate the anti-inflammatory and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabidiol (CBD). DESIGN: The cellular bioactivities of hemp extract and CBD were determined the inhibition of TNF-α and IL-1ß in LPS-induced murine macrophage (RAW 264.7) cells by using ELISA while wound healing activity in human gingival fibroblast (HGF-1) cells was performed by a scratch test assay. The cytotoxicity was also concerned and evaluated by MTT assay. RESULTS: The hemp extract and CBD significantly decreased TNF-α release by up to 91.05 ± 2.91% and 50.78 ± 7.21% of LPS activity, respectively, in a dose-dependent manner, compared to 10 µg/mL hydrocortisone (61.67 ± 3.79%). The hemp extract and CBD also significantly decreased IL-1ß release, also in dose-dependent response, up to 78.03 ± 3.34% and 85.87 ± 1.11% of LPS activity, respectively, compared to 5 µg/mL hydrocortisone (80.81 ± 3.55%). The mean percentage of closure of the wound area was 27.92 ± 1.21% when exposed to 5 µg/mL hemp extract and 33.49 ± 1.67% when exposed to 0.5 µg/mL CBD, compared to 24.34 ± 2.29% for non-treated control. CONCLUSIONS: Our study demonstrates that both hemp extract and CBD can inhibit TNF-α and IL-1ß production in LPS-induced RAW 264.7 cells and promote wound healing in HGF-1 cells. This is the first to show that short-term exposure to hemp extract and CBD promoted gingival fibroblast wound healing, demonstrating that hemp extract and CBD have potential benefits in the treatment of oral inflammation and ulcers.

The Development of a Physiologically Based Pharmacokinetic (PBPK) Model of Andrographolide in Mice and Scaling it up to Rats, Dogs, and Humans.

BACKGROUND: Andrographolide has a potent antiviral effect in the treatment of coronavirus disease (COVID-19). However, there are no in vivo studies of andrographolide as an anti-COVID-19 treatment. OBJECTIVE: The study aims to develop a physiologically based pharmacokinetic (PBPK) animal model and scale it up to a human model to predict andrographolide concentrations in the lungs. METHODS: ADAPT5 (version 5.0.58) was used to establish the PBPK model based on 24 enrolled pharmacokinetic studies. RESULTS: The perfusion-limited PBPK model was developed in mice and extrapolated to rats, dogs, and humans. The metabolism of andrographolide in humans was described by the Michaelis-Menten equation. The saturation of the metabolism occurred at a high dose (12 g), which could not be used therapeutically. The optimized oral bioavailability in humans was 6.3%. Due to the limit of solubility, the dose-dependent absorption between 20-1000 mg was predicted by GastroPlus®. Using the extrapolated human PBPK model together with the predicted dose-dependent fraction of the dose absorbed that enters the enterocytes by GastroPlus®, the oral dosage of 200 mg q8h of andrographolide would provide a trough level of free andrographolide at a steady state over the reported IC50 value against SARS-CoV-2 in the lungs for the majority of healthy humans. Based on the reported CC50 value, toxicity might not occur at the therapeutic dosage. CONCLUSION: The PBPK model of andrographolide in animals and humans was successfully constructed. Once additional data is available, the model would be needed to recalibrate to gain an understanding of a dose-response relationship and optimization of dosage regimens of andrographolide.