Action of Mangifera indica Leaf Extract on Acne-Prone Skin through Sebum Harmonization and Targeting C. acnes.

(1) Background: Preclinical studies report that the ethanolic fraction from Mangifera indica leaves is a potential anti-acne agent. Nevertheless, the biological activity of Mangifera indica leaves has scarcely been investigated, and additional data are needed, especially in a clinical setting, for establishing the actual effectiveness of Mangifera indica extract as an active component of anti-acne therapy. (2) Methods: The evaluation of the biological activity of Mangifera indica extract was carried out through different experimental phases, which comprised in silico, in vitro, ex vivo and clinical evaluations. (3) Results: In silico and in vitro studies allowed us to identify the phytomarkers carrying the activity of seboregulation and acne management. Results showed that Mangifera indica extract reduced lipid production by 40% in sebocytes, and an improvement of the sebum quality was reported after the treatment in analyses performed on sebaceous glands from skin explants. The evaluation of the sebum quantity and quality using triglyceride/free fatty acid analysis conducted on Caucasian volunteers evidenced a strong improvement and a reduction of porphyrins expression. The C. acnes lipase activity from a severe acne phylotype was evaluated in the presence of Mangifera indica, and a reduction by 29% was reported. In addition, the analysis of the skin microbiota documented that Mangifera indica protected the microbiota equilibrium while the placebo induced dysbiosis. (4) Conclusions: Our results showed that Mangifera indica is microbiota friendly and efficient against lipase activity of C. acnes and supports a role for Mangifera indica in the therapeutic strategy for prevention and treatment of acne.

Well-aging: A new strategy for skin homeostasis under multi-stressed conditions.

BACKGROUND: Several studies evidenced significant increase of cortisol is the consequence of UV or emotional stress and leads to various deleterious effects in the skin. AIM: The well-aging, a new concept of lifestyle, procures an alternative to the anti-aging strategy. We demonstrated that Tephrosia purpurea extract is able to stimulate well-being hormones while reducing cortisol release. Furthermore, we hypothesized that the extract could positively influence the global skin homeostasis. METHOD: We evaluated the impact of the extract on cortisol, ß-endorphin, and dopamine, released by normal human epidermal keratinocytes (NHEKs). A gene expression study was realized on NHEKs and NHDFs. The protein over-expression of HMOX1 and NQO1 was evidenced at cellular and tissue level. Finally, we conducted a clinical study on 21 women living in a polluted environment in order to observe the impact of the active on global skin improvement. RESULTS: The extract is able to reduce significantly the cortisol release while inducing the production of ß-endorphin and dopamine. The gene expression study revealed that Tephrosia purpurea extract up-regulated the genes involved in antioxidant response and skin renewal. Moreover, the induction of HMOX and NQO1 expression was confirmed on NHDFs, NHEKs and in RHE. We clinically demonstrated that the extract improved significantly the skin by reducing dark circles, represented by an improvement of L*, a*, and ITA parameters. CONCLUSION: Tephrosia purpurea extract has beneficial effects on skin homeostasis through control of the well-being state and antioxidant defenses leading to an improvement of dark circles, a clinical features particularly impacted by emotional and environmental stress.

From stem cells protection to skin microbiota balance: Orobanche rapum extract, a new natural strategy.

BACKGROUND: Healthy skin is a delicate balance between skin renewal and microbiota homeostasis, and its imbalance promotes premature aging and dermatological disorders. Skin stem cells are key actors in this process but their sensitivity to aging and external stressors such as UV reduces the skin renewal power. The skin microbiota has been recently described as active in the healthy skin, and its imbalance could trigger some disorders. AIMS: We hypothesized that reactivation of stem cells and maintenance of microbiota could be a disruptive strategy for younger and healthier skin. We thus developed a new plant extract that restores the entire skin renewal process by sequential activation from stem cells stimulation to microbiota protection. METHODS: We studied stem cells comportment in the presence of Orobanche rapum extract by survivin immunocytochemistry and caspases 3 and 9 dosages. We also analyzed epidermal differentiation markers by immunohistochemistry and lipids organization by GC/MS At the clinical level, we investigated the impact of O. rapum extract on microbiota and on skin aspect. RESULTS: We demonstrated an active protection of skin stem cells through the maintenance of their clone-forming capacity and resistance to UV through the overexpression of survivin coupled to caspases inhibition. Furthermore, we showed the restoration of epidermal differentiation markers and ceramide biosynthesis favorable to orthorhombic organization. Clinical studies, including microbiota analysis, showed an active skin surface renewal coupled with microbiota protection. CONCLUSION: We evidenced that our active ingredient is able to stimulate skin rejuvenation while protecting the cutaneous microbiota, creating healthier skin and thereby beauty.

Computer-Aided 13C NMR Chemical Profiling of Crude Natural Extracts without Fractionation.

A computer-aided, 13C NMR-based dereplication method is presented for the chemical profiling of natural extracts without any fractionation. An algorithm was developed in order to compare the 13C NMR chemical shifts obtained from a single routine spectrum with a set of predicted NMR data stored in a natural metabolite database. The algorithm evaluates the quality of the matching between experimental and predicted data by calculating a score function and returns the list of metabolites that are most likely to be present in the studied extract. The proof of principle of the method is demonstrated on a crude alkaloid extract obtained from the leaves of Peumus boldus, resulting in the identification of eight alkaloids, including isocorydine, rogersine, boldine, reticuline, coclaurine, laurotetanine, N-methylcoclaurine, and norisocorydine, as well as three monoterpenes, namely, p-cymene, eucalyptol, and α-terpinene. The results were compared to those obtained with other methods, either involving a fractionation step before the chemical profiling process or using mass spectrometry detection in the infusion mode or coupled to gas chromatography.

Computer-aided Dereplication and Structure Elucidation of Natural Products at the University of Reims.

Natural product chemistry began in Reims, France, in a pharmacognosy research laboratory whose main emphasis was the isolation and identification of bioactive molecules, following the guidelines of chemotaxonomy. The structure elucidation of new compounds of steadily increasing complexity favored the emergence of methodological work in nuclear magnetic resonance. As a result, our group was the first to report the use of proton-detected heteronuclear chemical shift correlation spectra for the computer-assisted structure elucidation of small organic molecules driven by atom proximity relationships and without relying on databases. The early detection of known compounds appeared as a necessity in order to deal more efficiently with complex plant extracts. This goal was reached by an original combination of mixture fractionation by centrifugal partition chromatography, analysis by 13 C NMR, digital data reduction and alignment, hierarchical data clustering, and computer database search.

In Vitro Dermo-Cosmetic Evaluation of Bark Extracts from Common Temperate Trees.

Wood residues produced from forestry activities represent an interesting source of biologically active, high value-added secondary metabolites. In this study, 30 extracts from 10 barks of deciduous and coniferous tree species were investigated for their potential dermo-cosmetic use. The extracts were obtained from Fagus sylvatica, Quercus robur, Alnus glutinosa, Prunus avium, Acer pseudoplatanus, Fraxinus excelsior, Populus robusta, Larix decidua, Picea abies, and Populus tremula after three successive solid/liquid extractions of the barks with n-heptane, methanol, and methanol/water. All extracts were evaluated for their radical scavenging capacity, for their elastase, collagenase, and tyrosinase inhibitory activities, as well as for their antibacterial activity against gram-positive Staphylococcus aureus. In parallel, the global metabolite profiles of all extracts were established by 1D and 2D NMR and related to their biological activity. The results showed that the methanol extracts of Q. robur, A. glutinosa, L. decidua, and P. abies barks exhibit particularly high activities on most bioassays, suggesting their promising use as active ingredients in the dermo-cosmetic industry.

Exploiting the Complementarity between Dereplication and Computer-Assisted Structure Elucidation for the Chemical Profiling of Natural Cosmetic Ingredients: Tephrosia purpurea as a Case Study.

The aqueous-ethanolic extract of Tephrosia purpurea seeds is currently exploited in the cosmetic industry as a natural ingredient of skin lotions. The aim of this study was to chemically characterize this ingredient by combining centrifugal partition extraction (CPE) as a fractionation tool with two complementary identification approaches involving dereplication and computer-assisted structure elucidation. Following two rapid fractionations of the crude extract (2 g), seven major compounds namely, caffeic acid, quercetin-3-O-rutinoside, ethyl galactoside, ciceritol, stachyose, saccharose, and citric acid, were unambiguously identified within the CPE-generated simplified mixtures by a recently developed (13)C NMR-based dereplication method. The structures of four additional compounds, patuletin-3-O-rutinoside, kaempferol-3-O-rutinoside, guaiacylglycerol 8-vanillic acid ether, and 2-methyl-2-glucopyranosyloxypropanoic acid, were automatically elucidated by using the Logic for Structure Determination program based on the interpretation of 2D NMR (HSQC, HMBC, and COSY) connectivity data. As more than 80% of the crude extract mass was characterized without need for tedious and labor-intensive multistep purification procedures, the identification tools involved in this work constitute a promising strategy for an efficient and time-saving chemical profiling of natural extracts.

Centrifugal partition extraction in the pH-zone-refining displacement mode: an efficient strategy for the screening and isolation of biologically active phenolic compounds.

Centrifugal partition extraction (CPE) was developed for the first time in the pH-zone-refining mode to fractionate a crude bark extract of the African tree Anogeissus leiocarpus Guill. & Perr. (Combretaceae). The fractionation process was performed at a flow rate of 20mL/min using a biphasic solvent system composed of methyl tert-butyl ether/acetonitrile/water (4:1:5, v/v/v) in the ascending mode. Sodium hydroxide (40mM) and trifluoroacetic acid (30mM) were used as retainer and displacer agents, respectively. In a single run of 67min, 3g of the initial crude extract were successfully separated into fractions selectively enriched in ionizable triterpenes, ellagic acid derivatives and flavonoids. The antioxidant potential of the initial crude extract, isolated compounds and fraction pools was also evaluated by using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) stable free radical scavenging assay, providing an interesting view about the effect of the degree of substitution of ellagic acid derivatives on their radical scavenging activity. This study will demonstrate that centrifugal partition extraction used in the pH-zone-refining mode can be proposed as an efficient strategy for the rapid screening of natural phenolic compounds.

Stepwise elution of a three-phase solvent system in centrifugal partition extraction: a new strategy for the fractionation and phytochemical screening of a crude bark extract.

INTRODUCTION: Tree bark represents an interesting source of bioactive molecules for the discovery of new pharmaceutical agents. However, the detailed screening of secondary metabolites in crude bark extracts is often hampered by the presence of tannins, which are difficult to separate from other plant constituents. OBJECTIVE: In the present study, a new centrifugal partition extraction (CPE) method was developed in order to fractionate a crude bark extract of Anogeissus leiocarpus Guill. & Perr. (Combretaceae). METHODS: A three-phase solvent system composed of n-heptane, methyl tert-butyl ether, acetonitrile and water was optimised for the stepwise elution at 20 mL/min of different phytochemical classes according to their hydrophobicity. Onedimensional and two-dimensional NMR analyses of the simplified fractions were then performed in order to characterise potentially interesting metabolites. RESULTS: In one step, 5 g of the initial crude extract were efficiently fractionated to yield highly simplified fractions that contained triterpenes, ellagic acid derivatives, flavonoids and phenolic compounds. All undesired compounds, that is, the highly abundant water-soluble tannins (78.8%), were totally removed and each run was rapidly achieved in 90 min on a the multi-gram scale and with low solvent volumes. CONCLUSION: Centrifugal partition extraction in the elution mode using a three-phase solvent system can thus be proposed as an efficient and cost-effective alternative for a rapid fractionation of crude bark extracts and for an effective screening of potentially active secondary metabolites.