The potential of Paeonia lactiflora pall seeds oil as a pure natural cosmetics raw material: In Vitro findings.

BACKGROUND: As a traditional Chinese herbal medicine, Paeonia lactiflora Pall is rich in various active ingredients such as polysaccharides and total flavonoids while having ornamental value. It has potential application value in the development of food and cosmetics. OBJECTIVE: To study the in vitro efficacy of Paeonia lactiflora Pall seeds oil. METHODS: Firstly, the levels of linolenic acid and linoleic acid in Paeonia lactiflora Pall seeds oil were quantified using gas chromatography. The impact of Paeonia lactiflora Pall seeds oil on the proliferation rate of B16F10 cells was assessed through the CCK-8 method, while the melanin content of B16F10 cells was determined using the sodium hydroxide lysis method. The inhibitory effects of Paeonia lactiflora Pall seeds oil on elastase, collagenase and hyaluronidase were evaluated by biochemical techniques in vitro. Lastly, the hen's egg chorioallantoic membrane test (HET-CAM) was conducted to confirm the absence of eye irritation caused by Paeonia lactiflora Pall seeds oil. RESULTS: Paeonia lactiflora Pall seeds oil within a certain volume concentration range (0.5%-4%) had no effect on the proliferation of B16F10 cells. Paeonia lactiflora Pall seeds oil showed significant inhibition of elastase, collagenase and hyaluronidase. Notably, the highest concentration tested, 4% Paeonia lactiflora Pall seed oil, yielded the most pronounced outcomes without causing any irritation. CONCLUSION: A certain concentration of Paeonia lactiflora Pall seeds oil has a significant effect on decreasing the melanin content in B16F10 cells and inhibiting the activities of elastase, collagenase, and hyaluronidase, which can provide a reference for the development of pure natural cosmetics raw materials.

Preparation, Characterization, and Antioxidant Activities of Extracts from Amygdalus persica L. Flowers.

A novel water-soluble Amygdalus persica L. flowers polysaccharide (APL) was successfully isolated and purified from Amygdalus persica L. flowers by hot water extraction. Its chemical components and structure were analyzed by IR, GC-MS, and HPLC. APL consisted of rhamnose, arabinose, mannose and glucose in a molar ratio of 0.17:0.034:1.0:0.17 with an average molecular weight of approximately 208.53 kDa and 15.19 kDa. The antioxidant activity of APL was evaluated through radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 3-ethylbenzthiazoline-6-sulfonic acid (ABTS), Hydroxyl radical scavenging, Superoxide radical scavenging, and the reducing power activity was also determined in vitro. Besides, in vivo antioxidant experiment, zebrafish (Danio rerio) embryos were treated with different concentrations of APL and then exposed to LPS to induce oxidative stress. Treatment with APL at 50 or 100 µg/mL significantly reduced LPS-induced oxidative stress in the zebrafish, demonstrating the strong antioxidant activity of APL. Moreover, the effect of APL on zebrafish depigmentation was tested by analyzing the tyrosinase activity and melanin content of zebrafish embryos. APL showed a potential reduction in the total melanin content and tyrosinase activity after treatment. This work provided important information for developing a potential natural antioxidant in the field of cosmetics and food.

Examining Potential Modifiers of Human Skin and Plasma Carotenoid Responses in a Randomized Trial of a Carotenoid-Containing Juice Intervention.

BACKGROUND: Skin carotenoid measurements are emerging as a valid and reliable indicator of fruit and vegetable intake and carotenoid intake. However, little is known about the extent to which skin carotenoid responsivity to dietary changes differs based on demographic and physiologic characteristics. OBJECTIVES: This study examined potential effect modifiers of skin carotenoid and plasma carotenoid responses to a carotenoid-rich juice intervention. METHODS: We leveraged data from 2 arms of a 3-site randomized controlled trial of a carotenoid-containing juice intervention (moderate dose = 6 ounces juice, 4 mg total carotenoids/d, high dose = 12 ounces juice, 8 mg total carotenoids/d) (n = 106) to examine effect modification by age, self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, skin hemoglobin, skin hemoglobin saturation, skin coloration, sun exposure, and baseline intake of carotenoids from foods. Skin carotenoid concentrations were assessed using pressure-mediated reflection spectroscopy (Veggie Meter), and plasma carotenoid concentrations were measured using high-performance liquid chromatography. RESULTS: In bivariate analyses, among the high-dose group (8 mg/d), those of older age had lower skin carotenoid responsiveness than their younger counterparts, and those with greater hemoglobin saturation and lighter skin had higher skin carotenoid score responsiveness. In the moderate-dose group (4 mg/d), participants from one site had greater plasma carotenoid responsiveness than those from other sites. In multivariate analyses, participants with higher baseline skin carotenoids had smaller skin carotenoid responses to both moderate and high doses. CONCLUSIONS: Changes in skin carotenoid scores in response to interventions to increase fruit and vegetable intake should be interpreted in the context of baseline skin carotenoid scores, but other variables (e.g., self-categorized race/ethnicity, biological sex, baseline body fat, body mass index, skin melanin, and sun exposure) do not significantly modify the effect of carotenoid intake on changes in skin carotenoid scores. This trial was registered at clinicaltrials.gov as NCT04056624.

Bioactive molecular network-guided discovery of dihydro-ß-agarofurans from the fruits of Celastrus orbiculatus.

A bioactive molecular networking strategy has been applied to discovery of bioactive constituents from the fruits of Celastrus orbiculatus Thunb., which showed significant inhibitory effects on the α-MSH-induced melanin production in B16F0 melanoma cells. In the obtained molecular network, the nodes with relatively high bioactive scores were prioritized for isolation; as a result, 12 undescribed dihydro-ß-agarofuran sesquiterpenes together with 15 known compounds were isolated from MeOH extracts of the fruits of C. orbiculatus. Their structures were elucidated based on the interpretation of NMR, HRESIMS, ECD data, and single crystal X-ray diffraction. Among the obtained isolates, celastorbin A and (1R,2S,4R,5S,7S,8S,9R,10S)-1,2,8-triacetoxy-9-cinnamoyloxydihydro-ß-agarofuran, which possessed high bioactive scores in the molecular network, exhibited potent inhibitory effects on the α-MSH-induced melanin production in B16F0 cells with IC50 values of 4.1 and 2.0 µM, respectively.

Melanin is a plenteous bioactive phenolic compound in date fruits (Phoenix dactylifera L.).

Date palm fruits (Phoenix dactylifera L.) were found to contain high levels of allomelanin (1.2-5.1%). The melanin is localized in the tanniferous cells between the inner and outer mesocarp tissues of the fruit. The melanin, extracted with 2 M sodium hydroxide, consisted of amorphous graphene-like granular structures of irregular shape and variable size. The date fruit melanin mainly comprises carbon (64.6%) and oxygen (30.6) but no nitrogen, and was thermally stable. It has radical scavenging (63.6-75.1 IC50, µg/mL), antimicrobial (250-1000 µg/mL), hypoglycemic (51.8-58.2%), and angiotensin-converting-enzyme inhibitory (65.8%) effects. The high level of melanin in date fruits highlights the importance of investigating its dietary intake and its impact on nutrition. This study also suggests that date fruit melanin can be a functional ingredient in foods, food packages, pharmaceuticals, and cosmetics.

Chemical constituents of Ruta graveolens L. and their melanogenic effects and action mechanism.

Ruta graveolens L. has been widely used to treat various skin ailments, especially vitiligo. In this study, we isolated a new furanocoumarin named Rutagrarin (1) along with 14 known compounds (2-15) from the aerial parts of R. graveolens and elucidated their chemical structures via various spectroscopy. We found that compound 5 promoted melanogenesis and tyrosinase activity in B16 cells. Further investigation on underlying mechanisms revealed that compound 5 activated the transcription of microtia-related transcription factors and promoted the production of melanin in B16 cells via the Akt/GSK-3ß/ß-catenin pathway. Therefore, we confirmed the traditional efficacy of R. graveolens and speculated that compound 5 could be used as a natural drug to treat vitiligo.

Projections from the dorsomedial division of the bed nucleus of the stria terminalis to hypothalamic nuclei in the mouse.

As stressful environment is a potent modulator of feeding, we seek in the present work to decipher the neuroanatomical basis for an interplay between stress and feeding behaviors. For this, we combined anterograde and retrograde tracing with immunohistochemical approaches to investigate the patterns of projections between the dorsomedial division of the bed nucleus of the stria terminalis (BNST), well connected to the amygdala, and hypothalamic structures such as the paraventricular (PVH) and dorsomedial (DMH), the arcuate (ARH) nuclei and the lateral hypothalamic areas (LHA) known to control feeding and motivated behaviors. We particularly focused our study on afferences to proopiomelanocortin (POMC), agouti-related peptide (AgRP), melanin-concentrating-hormone (MCH) and orexin (ORX) neurons characteristics of the ARH and the LHA, respectively. We found light to intense innervation of all these hypothalamic nuclei. We particularly showed an innervation of POMC, AgRP, MCH and ORX neurons by the dorsomedial and dorsolateral divisions of the BNST. Therefore, these results lay the foundation for a better understanding of the neuroanatomical basis of the stress-related feeding behaviors.

Borage Oil Treated with Immobilized Lipase Inhibits Melanogenesis.

In the present study, we demonstrated that borage (Borago officinalis L.) seed oil subjected to immobilized lipase pretreatment are enriched with linoleic acid (LNA, 18:2n-6), γ-linolenic acid (GLA, 18:3n-6), and oleic acid (OLA, 18:1n-9). We further showed that lipase-treated borage oil (LT-BOL) regulates the activity and degradation of tyrosinase, an important enzyme implicated in the synthesis of melanin in murine melanocytes, B16F10. LT-BOL and its free fatty acid components reduced the levels of melanin and tyrosinase in melanocytes with GLA exerting similar or stronger effects compared with LNA and OLA. The brightening efficacy of LT-BOL on melanin metabolism in humans was tested by an 8-week, double-blind, randomized clinical trial, which enrolled 21 Korean female adults (mean age 48.57 ± 3.28). Visual evaluation showed that cream containing 1% LT-BOL significantly decreased (p < 0.05) melasma on the treated skin area after 6 and 8 weeks. The analysis of the skin brightness using Chromameter CR-400 confirmed that the brightness of the treated area was significantly increased (p < 0.01) after 4, 6, and 8 weeks. Together, our results suggest that LT-BOL may be suitable as a natural skin whitening cosmeceutical product.

Non-contact imaging of peripheral hemodynamics during cognitive and psychological stressors.

Peripheral hemodynamics, measured via the blood volume pulse and vasomotion, provide a valuable way of monitoring physiological state. Camera imaging-based systems can be used to measure these peripheral signals without contact with the body, at distances of multiple meters. While researchers have paid attention to non-contact imaging photoplethysmography, the study of peripheral hemodynamics and the effect of autonomic nervous system activity on these signals has received less attention. Using a method, based on a tissue-like model of the skin, we extract melanin [Formula: see text] and hemoglobin [Formula: see text] concentrations from videos of the hand and face and show that significant decreases in peripheral pulse signal power (by 36% ± 29%) and vasomotion signal power (by 50% ± 26%) occur during periods of cognitive and psychological stress. Via three experiments we show that similar results are achieved across different stimuli and regions of skin (face and hand). While changes in peripheral pulse and vasomotion power were significant the changes in pulse rate variability were less consistent across subjects and tasks.

The Antimelanogenic Effect of Inularin Isolated from Flowers of Inula britannica on B16F10 Melanoma Cells and Zebrafish Embryos.

In the search for novel, natural melanogenesis inhibitors, a new sesquiterpene, inularin, was isolated from the flowers of Inula britannica, and the structure was determined using spectroscopic and chemical methods. The antimelanogenic effects of inularin on B16F10 melanoma cells and zebrafish embryos were evaluated. Inularin dose-dependently reduced melanocyte-stimulating hormone-induced melanin production and L-DOPA oxidation in B16F10 cells. Zebrafish embryos were used to confirm the antimelanogenic activity. Inularin significantly decreased the pigmentation of embryos compared with untreated controls.

Diterpenes with potential treatment of vitiligo from the aerials parts of Euphorbia antiquorum L.

Six new diterpenes Euphonoids A-F including one ingenol (1), three lathyrane (2-5), one ent-abietane (6) and fifteen known derivatives (7-21) were isolated from the aerial parts of Euphorbia antiquorum L. Their structures were elucidated by physical data analysis. Compounds 1, 12, and 16 improve the melanogenesis in B16 cells in vitro.

Soluble melanins of the Randia echinocarpa fruit - Structural characteristics and toxicity.

The water-soluble melanins (SM) of Randia echinocarpa fruit possess interesting biological activities and have been scarcely characterized. In this study, SM were obtained at boiling (SMBT) and room (SMRT) temperatures and characterized by UV-Vis, IR, thermogravimetric analysis, and GC-MS of the hydrolysis products of the SM; besides, the solid-state 13 C NMR, elemental analysis, and acute and sub-acute toxicity of the SMBT were determined. SMBT and SMRT contain organic acids and carbohydrates and their spectroscopic signals and thermograms were similar, but the SMBT yield was higher. The SMBT were characterized by their elemental composition (C 48.260 ± 0.011%, N 3.693 ± 0.009% and H 6.093 ± 0.076%) consistent with the presence of aromatic rings and eumelanins, degradation temperature at 300°C, 13 C NMR signals supporting melanin-bonding with carbohydrates and organic acids, and innocuity in Balb/C mice (acute assay, LD50  > 5 g/kg b.w.; sub-acute assay, no lethality at 500 mg/kg b.w. for 30 days). PRACTICAL APPLICATIONS: The consumption of melanins has been associated with health benefits because of their biological activities (e.g., antioxidant, immunostimulatory, UV- and radiation-protective). Randia echinocarpa is employed in Mexican traditional medicine against chronic degenerative diseases (e.g., cancer and diabetes) and ailments of organs (e.g., kidney and lung) and systems (e.g., circulatory and gastrointestinal). The R. echinocarpa fruit contains water-soluble melanins (SM) that inhibit carbohydrate-digestive enzymes and show high antioxidant activity; thus, SM could be useful for the prevention and treatment of diabetes. This study showed that the SM structure contains melanin-bonding organic acids and carbohydrates, which could be associated with the SM solubility and higher yield, and that SMBT were innocuous in the acute and sub-acute assays in mice. Thus, the R. echinocarpa SMBT could be used as safe potential ingredients to develop functional products.

Melanin-concentrating hormone peptidergic system: Comparative morphology between muroid species.

Melanin-concentrating hormone (MCH) is a conserved neuropeptide, predominantly located in the diencephalon of vertebrates, and associated with a wide range of functions. While functional studies have focused on the use of the traditional mouse laboratory model, critical gaps exist in our understanding of the morphology of the MCH system in this species. Even less is known about the nontraditional animal model Neotomodon alstoni (Mexican volcano mouse). A comparative morphological study among these rodents may, therefore, contribute to a better understanding of the evolution of the MCH peptidergic system. To this end, we employed diverse immunohistochemical protocols to identify key aspects of the MCH system, including its spatial relationship to another neurochemical population of the tuberal hypothalamus, the orexins. Three-dimensional (3D) reconstructions were also employed to convey a better sense of spatial distribution to these neurons. Our results show that the distribution of MCH neurons in all rodents studied follows a basic plan, but individual characteristics are found for each species, such as the preeminence of a periventricular group only in the rat, the lack of posterior groups in the mouse, and the extensive presence of MCH neurons in the anterior hypothalamic area of Neotomodon. Taken together, these data suggest a strong anatomical substrate for previously described functions of the MCH system, and that particular neurochemical and morphological features may have been determinant to species-specific phenotypes in rodent evolution.

An In-Vitro Assay Estimating Changes in Melanin Content of Melanoma Cells due to Ultra-Dilute, Potentized Preparations.

INTRODUCTION: The authors had previously conducted an in-vitro study to observe the effect of homeopathic medicines on melanogenesis, demonstrating anti-vitiligo potential by increasing the melanin content in murine B16F10 melanoma cells. A similar experiment was performed using further homeopathic preparations sourced from kojic acid (KA), hydrogen peroxide (H2O2; HP), 6-biopterin (BP), and [Nle4, D-Phe7]-α-melanocyte-stimulating hormone (NLE), some of which are known to induce vitiligo or melano-destruction at physiological dose. MATERIALS AND METHODS: The homeopathic preparations of BP, KA, NLE, and HP were used in 30c potency. Alcohol and potentized alcohol were used as vehicle controls. Prior to starting the main experiment, the viability of B16F10 melanoma cells after treatment with study preparations was assayed. Melanin content (at 48 h and 96 h) and tyrosinase activity in melanocytes were determined. RESULTS: At the end of 48 hours, NLE and HP in 30c potency had a significantly greater melanin content (p = 0.015 and p = 0.039, respectively) compared with controls; BP and KA in 30c potency had no significant effects. No significant changes were seen at the end of 96 hours. KA, NLE, HP, and vehicle controls showed an inhibition of tyrosinase activity. CONCLUSION: The study demonstrated melanogenic effects of two homeopathic preparations. Further research to evaluate the therapeutic efficacy of these medicines is warranted.

The clinical effect of glutathione on skin color and other related skin conditions: A systematic review.

BACKGROUND: Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione on skin color. However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability. AIM: To determine the clinical effects of glutathione on skin color and related skin conditions. PATIENTS/METHODS: A systematic review was conducted using PubMed, CINAHL, Scopus, EMBASE and Cochrane library were searched from inceptions to October 2017. All clinical studies evaluating the effect of glutathione on any skin effects in healthy volunteer were included. RESULTS: A total of four studies were included. Three studies were RCTs with placebo control, while one was a single-arm trial. One study used topical form, while others used oral form of glutathione with 250 to 500 mg/day. We found that both oral glutathione with the dosage of 500 mg/day and topical 2.0% oxidized glutathione could brighten skin color in sun-exposed area measured by skin melanin index. No significant differences in the reduction in skin melanin index were observed in sun-protected area for any products. In addition, glutathione also has a trend to improve skin wrinkle, skin elasticity, and UV spots. Some adverse events but nonserious were reported. CONCLUSIONS: Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings. However, there is a trend that glutathione might brighten skin color at skin-exposed area.

Skin Tolerance of Three Types of Dead Sea Mud on Healthy Skin: A Short-Term Study.

Dead Sea mud (DSM) is commonly used by patients with various skin conditions because of its contents of healing elements. No study was published to show whether DSM application weakens or strengthens skin barrier function. In this study, we investigated the impact of 30-minute single application of various types of DSM ("As Is" mud, mud with extra Dead Sea salt, and over-the-shelf mud) on the barrier function of normal skin. The influence of 30-minute application of various types of DSM was investigated noninvasively on skin barrier properties of healthy female adult volunteers (n = 75) on predetermined circular areas. Skin hydration, transepidermal water loss (TEWL), erythema and melanin levels, and skin pH were measured directly, 30 minutes, and 60 minutes after mud removal. Thirty-minute single application of DSM was well tolerated with short-lived moisturizing effects, which was enhanced by the presence of humectant ingredients, and with no negative impact on barrier integrity, pH, and erythema and melanin levels.

Feeding state and age dependent changes in melanin-concentrating hormone expression in the hypothalamus of broiler chickens.

We aimed to quantify the gene expression changes of the potent orexigenic melanin-concentrating hormone (MCH) in chicken (Gallus gallus) hypothalamus with quantitative real-time polymerase chain reaction (qPCR), and for the first time determine peptide concentrations with a novel radioimmunoassay (RIA) under different feeding status. Three different experimental conditions, namely ad libitum feeding; fasting for 24 h; fasting for 24 h and then refeeding for 2 h, were applied to study changes of the aforementioned target and its receptor (MCHR4) gene expression under different nutritional status. The relative changes of MCH and MCHR4 were also studied from 7 to 35 days of age. Expression of PMCH and MCHR4 along the gastrointestinal tract (GIT) was also investigated. We found that expression of both targets was significant in the hypothalamus, while only weak expression was detected along the GIT. Different nutritional states did not affect the PMCH and MCHR4 mRNA levels. However, fasting for 24 h had significantly increased the MCH-like immunoreactivity by 25.65%. Fasting for 24 h and then refeeding for 2 h had further significantly increased the MCH peptide concentration by 32.51%, as compared to the ad libitum state. A decreasing trend with age was observable for both, the PMCH and MCHR4 mRNA levels, and also for the MCH-like immunoreactivity. Correlation analysis did not result in a significant correlation between MCH peptide concentration and abdominal fat mass in ad libitum fed birds. In conclusion, MCH peptide concentration altered in response to 24 h fasting, which indicated that this peptide may take part in feed intake regulation of broiler chickens.

Antimetastatic pectic polysaccharide from Decalepis hamiltonii; galectin-3 inhibition and immune-modulation.

Melanoma is a malignant neoplasm of major concern because of its high mortality rate and failure of chemotherapy. Previously we have shown that galectin-3, a galactose specific lectin, plays a pivotal role in the initiation of metastasis. It was hypothesized that blocking galectin-3 with galactose rich dietary pectic polymer would inhibit metastasis. The current study analyzes the preventive effect and mode of action of a pectic polymer from Swallow Root (Decalepis hamiltonii) in a preventative study of B16F10 cells lung colonization. Matrix metalloproteinase (MMPs) activity was assayed by zymography. Apoptotic/proliferative markers and cytokines were analyzed by immunoassay. Results indicated ~88% inhibition of lung colonization by SRPP as compared to 60% by CPP and only 7% by GRPP. Further molecular analysis revealed that galectin-3 blockade was associated with down regulation of MMPs and NFκB. Activation of caspases supported the apoptotic effect of SRPP. Infiltration of inflammatory cells into the lung was evidenced by presence of CD11b+ cells and release of the pro-inflammatory cytokine-IL-17, indicating inflammation during the cancer cell colonization process. SRPP enhanced the release of IL-12 that enables the reduction of inflammation. Our data for the first time indicate the effective anti-metastatic effect of SRPP due to both galectin-3 blockade and immunomodulation.

A pilot study for triple combination therapy with a low-fluence 1064 nm Q-switched Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl's Melanosis.

BACKGROUND: Riehl's melanosis presents as a diffuse gray-brown to black hyperpigmentation around face. The treatment of this disease is challenging and quite limited despite patients' excessive psychological stresses. OBJECTIVE: In this prospective pilot study, we evaluated the efficacy and safety for a novel combination therapy based on low-fluence Q-switched 1064 nm Nd:YAG laser, hydroquinone cream and oral tranexamic acid for recalcitrant Riehl's melanosis. METHODS: Totally eight patients with Riehl's melanosis who had failed improvements previously received multiple sessions (10-18 times) of combination treatment regimen. The primary endpoint was clinical score by the physician and the secondary endpoints were clinical score by the patients, instrumental analysis using melanin and erythema values, and histopathological score. RESULTS: Among eight patients, three received "Almost clear" grade, the other five patients received "Marked improvement" grade at final visits. No serious adverse events and post-treatment downtime was observed. Mean Melanin and Erythema Indexes also showed significant decreases compared with baseline. Histopathologic examination confirmed a significantly greater reduction of melanin content in melanophages. CONCLUSION: This combination method can be a viable option for Asian patients having Riehl's melanosis with high risk of post-inflammatory hyperpigmentation, maintaining low-dose laser irradiation.

Two new compounds from the seeds of Vernonia anthelmintica.

Two new compounds, named benzoyl-vernovan (1) and 2-(4'-hydroxyphenyl)-6-methyl-4H-pyran-4-one (2), together with one biflavonoid (3), one aurone (4) and six flavonoids were isolated from the seeds of Vernonia anthelmintica. Their structures were elucidated by extensive spectroscopic analyses and comparison with published data, and their influence on melanin content in B16 melanoma cells were tested. 5 and 9 increased melanin content by 2.2% and 30.9% higher than positive control 8-methoxypsoralen.