Bacterial rhamnolipids and their 3-hydroxyalkanoate precursors activate Arabidopsis innate immunity through two independent mechanisms.

Plant innate immunity is activated upon perception of invasion pattern molecules by plant cell-surface immune receptors. Several bacteria of the genera Pseudomonas and Burkholderia produce rhamnolipids (RLs) from l-rhamnose and (R)-3-hydroxyalkanoate precursors (HAAs). RL and HAA secretion is required to modulate bacterial surface motility, biofilm development, and thus successful colonization of hosts. Here, we show that the lipidic secretome from the opportunistic pathogen Pseudomonas aeruginosa, mainly comprising RLs and HAAs, stimulates Arabidopsis immunity. We demonstrate that HAAs are sensed by the bulb-type lectin receptor kinase LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION/S-DOMAIN-1-29 (LORE/SD1-29), which also mediates medium-chain 3-hydroxy fatty acid (mc-3-OH-FA) perception, in the plant Arabidopsis thaliana HAA sensing induces canonical immune signaling and local resistance to plant pathogenic Pseudomonas infection. By contrast, RLs trigger an atypical immune response and resistance to Pseudomonas infection independent of LORE. Thus, the glycosyl moieties of RLs, although abolishing sensing by LORE, do not impair their ability to trigger plant defense. Moreover, our results show that the immune response triggered by RLs is affected by the sphingolipid composition of the plasma membrane. In conclusion, RLs and their precursors released by bacteria can both be perceived by plants but through distinct mechanisms.

Production of high molecular-ordered stilbene oligomers for the study of their biological activity: total synthesis, bio-catalyzed synthesis and production by plant systems.

Though the iconic stilbene resveratrol and its related dimers constitute a top storyline in the field of natural product research, resveratrol oligomers (condensation >2) have been left aside despite their higher biological activity compared to that of the monomers. This situation largely results from the difficulty of getting them in sufficient quantities to enable evaluation of their biological properties in vivo. We present here a synthetic and critical analysis of the methods used for the production of high molecular-ordered stilbene oligomers of potential biomedical interest, gathering the most salient data regarding the approaches employed to prepare them by total synthesis, use of biomimetic approaches or through plant systems.

Investigation of Antiparasitic Activity of 10 European Tree Bark Extracts on Toxoplasma gondii and Bioguided Identification of Triterpenes in Alnus glutinosa Barks.

Toxoplasmosis is a worldwide parasitosis that affects one-third of the population. People at risk, such as immunocompromised patients (AIDS, chemotherapy treatment) or fetuses (maternal-fetal transmission) can develop severe forms of the disease. The antiparasitic activity of extracts of different polarities (n-heptane, MeOH, MeOH/H2O) of 10 tree species endemic to temperate regions was investigated against Toxoplasma gondii infection in vitro. Our results showed that the n-heptane extract of the black alder (Alnus glutinosa) exhibited a significant antiparasitic activity without any cytotoxicity at the tested concentrations, with an IC50 of up to 25.08 µg/mL and a selectivity index higher than 3.99. The chemical profiling of this extract revealed triterpenes as major constituents. The ability of commercially available triterpene (betulin, betulinic acid, and betulone) to inhibit the growth of T. gondii was evaluated and showed growth inhibition rates of 44%, 49%, and 99% at 10 µM, respectively.

AMIDE v2: High-Throughput Screening Based on AutoDock-GPU and Improved Workflow Leading to Better Performance and Reliability.

Molecular docking is widely used in computed drug discovery and biological target identification, but getting fast results can be tedious and often requires supercomputing solutions. AMIDE stands for AutoMated Inverse Docking Engine. It was initially developed in 2014 to perform inverse docking on High Performance Computing. AMIDE version 2 brings substantial speed-up improvement by using AutoDock-GPU and by pulling a total revision of programming workflow, leading to better performances, easier use, bug corrections, parallelization improvements and PC/HPC compatibility. In addition to inverse docking, AMIDE is now an optimized tool capable of high throughput inverse screening. For instance, AMIDE version 2 allows acceleration of the docking up to 12.4 times for 100 runs of AutoDock compared to version 1, without significant changes in docking poses. The reverse docking of a ligand on 87 proteins takes only 23 min on 1 GPU (Graphics Processing Unit), while version 1 required 300 cores to reach the same execution time. Moreover, we have shown an exponential acceleration of the computation time as a function of the number of GPUs used, allowing a significant reduction of the duration of the inverse docking process on large datasets.

The Three Pillars of Natural Product Dereplication. Alkaloids from the Bulbs of Urceolina peruviana (C. Presl) J.F. Macbr. as a Preliminary Test Case.

The role and importance of the identification of natural products are discussed in the perspective of the study of secondary metabolites. The rapid identification of already reported compounds, or structural dereplication, is recognized as a key element in natural product chemistry. The biological taxonomy of metabolite producing organisms, the knowledge of metabolite molecular structures, and the availability of metabolite spectroscopic signatures are considered as the three pillars of structural dereplication. The role and the construction of databases is illustrated by references to the KNApSAcK, UNPD, CSEARCH, and COCONUT databases, and by the importance of calculated taxonomic and spectroscopic data as substitutes for missing or lost original ones. Two NMR-based tools, the PNMRNP database that derives from UNPD, and KnapsackSearch, a database generator that provides taxonomically focused libraries of compounds, are proposed to the community of natural product chemists. The study of the alkaloids from Urceolina peruviana, a plant from the Andes used in traditional medicine for antibacterial and anticancer actions, has given the opportunity to test different approaches to dereplication, favoring the use of publicly available data sources.

In Vitro and In Vivo Activity of Anogeissus leiocarpa Bark Extract and Isolated Metabolites against Toxoplasma gondii.

Toxoplasma gondii, belonging to the Apicomplexa phylum, is a cosmopolitan protozoan parasite that affects at least 30% of the world's population. In West Africa, the leaves and bark of the tree species Anogeissus leiocarpa (DC.) Guill. & Perr. are used against zoonosis in traditional medicine and play a key role in controlling diseases induced by Apicomplexans such as malaria. In this study, extracts, fractions, and pure compounds obtained from an ethanol extract of the bark of A. leiocarpa were evaluated against T. gondii infection in vitro and in vivo. The crude bark extract showed significant activity on tachyzoites from the T. gondii RH strain (IC50 = 59.30 µg/mL). The crude bark extract without tannins and pure trachelosperogenin E purified by centrifugal partition chromatography showed the highest activity (IC50s = 12.83 and 26.63 µg/mL, respectively) with satisfying selectivity indexes of 9.61 and 9.75, respectively. The crude bark extract without tannins and pure trachelosperogenin E were able to significantly inhibit host cell invasion by the parasite in vitro, while the crude bark extract without tannins was able to increase mice survival in our murine model of chronic toxoplasmosis. These results provide new biological data for natural compounds that could enhance the current panoply of treatments against toxoplasmosis.

Dereplication of Natural Extracts Diluted in Glycerin: Physical Suppression of Glycerin by Centrifugal Partition Chromatography Combined with Presaturation of Solvent Signals in 13C-Nuclear Magnetic Resonance Spectroscopy.

For scientific, regulatory, and safety reasons, the chemical profile knowledge of natural extracts incorporated in commercial cosmetic formulations is of primary importance. Many extracts are produced or stabilized in glycerin, a practice which hampers their characterization. This article proposes a new methodology for the quick identification of metabolites present in natural extracts when diluted in glycerin. As an extension of a 13C nuclear magnetic resonance (NMR) based dereplication process, two complementary approaches are presented for the chemical profiling of natural extracts diluted in glycerin: A physical suppression by centrifugal partition chromatography (CPC) with the appropriate biphasic solvent system EtOAc/CH3CN/water 3:3:4 (v/v/v) for the crude extract fractionation, and a spectroscopic suppression by presaturation of 13C-NMR signals of glycerin applied to glycerin containing fractions. This innovative workflow was applied to a model mixture containing 23 natural metabolites. Dereplication by 13C-NMR was applied either on the dry model mixture or after dilution at 5% in glycerin, for comparison, resulting in the detection of 20 out of 23 compounds in the two model mixtures. Subsequently, a natural extract of Cedrus atlantica diluted in glycerin was characterized and resulted in the identification of 12 metabolites. The first annotations by 13C-NMR were confirmed by two-dimensional NMR and completed by LC-MS analyses for the annotation of five additional minor compounds. These results demonstrate that the application of physical suppression by CPC and presaturation of 13C-NMR solvent signals highly facilitates the quick chemical profiling of natural extracts diluted in glycerin.

Chemical Profile and Antimicrobial Activity of the Fungus-Growing Termite Strain Macrotermes Bellicosus Used in Traditional Medicine in the Republic of Benin.

The fungus growing termite species Macrotermes bellicosus (M. bellicosus) is used in nutrition and traditional medicine in the Republic of Benin for the treatment of infectious and inflammatory diseases. Previous findings demonstrated evidence of anti-inflammatory and spasmolytic properties of M. bellicosus. The aim of the present study was to evaluate the antimicrobial potential of different extracts of M. bellicosus samples and determine the chemical profile of an ethanolic M. bellicosus extract. Chemical profiling was conducted using centrifugal partition chromatography and 13C-NMR, followed by MALDI-TOF MS. Major identified compounds include hydroquinone (HQ), methylhydroquinone (MHQ), 3,4-dihydroxyphenethyl glycol (DHPG), N-acetyldopamine (NADA) and niacinamide. The fatty acid mixture of the extract was mainly composed of linoleic and oleic acid and highlights the nutritional purpose of M. bellicosus. Using the Kirby-Bauer disc diffusion and broth microdilution assay, an antibacterial activity of M. bellicosus samples was observed against various clinical strains with a highest growth inhibition of S. aureus. In addition, HQ and MHQ as well as fractions containing DHPG, niacinamide and NADA inhibited S. aureus growth. The reported antimicrobial activity of M. bellicosus and identified active substances provide a rationale for the traditional medicinal use of M. bellicosus.

Correction: The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Correction for 'The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research' by James B. McAlpine et al., Nat. Prod. Rep., 2018, DOI: .

The value of universally available raw NMR data for transparency, reproducibility, and integrity in natural product research.

Covering: up to 2018With contributions from the global natural product (NP) research community, and continuing the Raw Data Initiative, this review collects a comprehensive demonstration of the immense scientific value of disseminating raw nuclear magnetic resonance (NMR) data, independently of, and in parallel with, classical publishing outlets. A comprehensive compilation of historic to present-day cases as well as contemporary and future applications show that addressing the urgent need for a repository of publicly accessible raw NMR data has the potential to transform natural products (NPs) and associated fields of chemical and biomedical research. The call for advancing open sharing mechanisms for raw data is intended to enhance the transparency of experimental protocols, augment the reproducibility of reported outcomes, including biological studies, become a regular component of responsible research, and thereby enrich the integrity of NP research and related fields.

Discovery of New Inhibitors of Toxoplasma gondii via the Pathogen Box.

Toxoplasma gondii is a cosmopolitan protozoan parasite which affects approximately 30% of the population worldwide. The drugs currently used against toxoplasmosis are few in number and show several limitations, such as drug intolerance, poor bioavailability, or drug resistance mechanism developed by the parasite. Thus, it is important to find new compounds able to inhibit parasite invasion or proliferation. In this study, the 400 compounds of the open-access Pathogen Box, provided by the Medicines for Malaria Venture (MMV) foundation, were screened for their anti-Toxoplasma gondii activity. A preliminary in vitro screening performed over 72 h by an enzyme-linked immunosorbent assay (ELISA) revealed 15 interesting compounds that were effective against T. gondii at 1 µM. Their cytotoxicity was estimated on Vero cells, and their 50% inhibitory concentrations (IC50) were further calculated. As a result, eight anti-Toxoplasma gondii compounds with an IC50 of less than 2 µM and a selectivity index (SI) value of greater than 4 were identified. The most active was MMV675968, showing an IC50 of 0.02 µM and a selectivity index value equal to 275. Two other compounds, MMV689480 and MMV687807, also showed a good activity against T. gondii, with IC50s of 0.10 µM (SI of 86.6) and 0.15 µM (SI of 11.3), respectively. Structure-activity relationships for the eight selected compounds also were discussed on the basis of fingerprinting similarity measurements using the Tanimoto method. The anti-Toxoplasma gondii compounds highlighted here represent potential candidates for the development of new drugs that could be used against toxoplasmosis.

Reconstruction of HMBC Correlation Networks: A Novel NMR-Based Contribution to Metabolite Mixture Analysis.

A new in silico method is introduced for the dereplication of natural metabolite mixtures based on HMBC and HSQC spectra that inform about short-range and long-range H-C correlations occurring in the carbon skeleton of individual chemical entities. Starting from the HMBC spectrum of a metabolite mixture, an algorithm was developed in order to recover individualized HMBC footprints of the mixture constituents. The collected H-C correlations are represented by a network of NMR peaks connected to each other when sharing either a 1H or 13C chemical shift value. The network obtained is then divided into clusters using a community detection algorithm, and finally each cluster is tentatively assigned to a molecular structure by means of a NMR chemical shift database containing the theoretical HMBC and HSQC correlation data of a range of natural metabolites. The proof of principle of this method is demonstrated on a model mixture of 3 known natural compounds and then on a real-life bark extract obtained from the common spruce (Picea abies L.).

Advanced NMR-Based Structural Investigation of Glucosinolates and Desulfoglucosinolates.

Glucosinolates (GLs) constitute a class of plant secondary metabolites that are characteristic of the order Brassicales. They each contain a common hydrophilic moiety connected to a mostly hydrophobic side chain whose constitution is the most frequent structural variant. Their transformations by myrosinases lead to intensively studied and highly reactive compounds of biological relevancy. In other respects, the enzymatic desulfation of GLs produces derivatives (DS-GLs) that are useful for GL analysis. A collection of 31 compounds, GLs and DS-GLs, representing 17 different side chains was established in order to report accurate descriptions of the molecules' 1H-, 13C-, and 15N-NMR parameters. The descriptions of the 1H-NMR spectra were achieved using the PERCH software, which accurately analyzed the complex coupling patterns that arose from strongly coupled nuclei. The chemical shift assignments were supported by 2D COSY, HSQC, and HMBC spectra. The impact of desulfation and the influence of the nature of the side chains on the chemical shift values are discussed. The results of the spectroscopic analysis and the 3D chemical-structure models of the studied molecules were grouped in structure-and-data-format (SDF) files. The NMR parameters were also collected in a simple text file, a spreadsheet file, and a relational database.

GABA and GABA-Alanine from the Red Microalgae Rhodosorus marinus Exhibit a Significant Neuro-Soothing Activity through Inhibition of Neuro-Inflammation Mediators and Positive Regulation of TRPV1-Related Skin Sensitization.

The aim of the present study was to investigate the neuro-soothing activity of a water-soluble hydrolysate obtained from the red microalgae Rhodosorus marinus Geitler (Stylonemataceae). Transcriptomic analysis performed on ≈100 genes related to skin biological functions firstly revealed that the crude Rhodosorus marinus extract was able to significantly negatively modulate specific genes involved in pro-inflammation (interleukin 1α encoding gene, IL1A) and pain detection related to tissue inflammation (nerve growth factor NGF and its receptor NGFR). An in vitro model of normal human keratinocytes was then used to evaluate the ability of the Rhodosorus marinus extract to control the release of neuro-inflammation mediators under phorbol myristate acetate (PMA)-induced inflammatory conditions. The extract incorporated at 1% and 3% significantly inhibited the release of IL-1α and NGF secretion. These results were confirmed in a co-culture system of reconstructed human epithelium and normal human epidermal keratinocytes on which a cream formulated with the Rhodosorus marinus extract at 1% and 3% was topically applied after systemic induction of neuro-inflammation. Finally, an in vitro model of normal human astrocytes was developed for the evaluation of transient receptor potential vanilloid 1 (TRPV1) receptor modulation, mimicking pain sensing related to neuro-inflammation as observed in sensitive skins. Treatment with the Rhodosorus marinus extract at 1% and 3% significantly decreased PMA-mediated TRPV1 over-expression. In parallel with these biological experiments, the crude Rhodosorus marinus extract was fractionated by centrifugal partition chromatography (CPC) and chemically profiled by a recently developed 13C NMR-based dereplication method. The CPC-generated fractions as well as pure metabolites were tested again in vitro in an attempt to identify the biologically active constituents involved in the neuro-soothing activity of the Rhodosorus marinus extract. Two active molecules, namely, γ-aminobutyric acid (GABA) and its structural derivative GABA-alanine, demonstrated a strong capacity to positively regulate skin sensitization mechanisms related to the TRPV1 receptors under PMA-induced inflammatory conditions, therefore providing interesting perspectives for the treatment of sensitive skins, atopia, dermatitis, or psoriasis.

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.

Anti-Cancer Activity of Resveratrol and Derivatives Produced by Grapevine Cell Suspensions in a 14 L Stirred Bioreactor.

In the present study, resveratrol and various oligomeric derivatives were obtained from a 14 L bioreactor culture of elicited grapevine cell suspensions (Vitis labrusca L.). The crude ethyl acetate stilbene extract obtained from the culture medium was fractionated by centrifugal partition chromatography (CPC) using a gradient elution method and the major stilbenes contained in the fractions were subsequently identified by using a 13C-NMR-based dereplication procedure and further 2D NMR analyses including HSQC, HMBC, and COSY. Beside δ-viniferin (2), leachianol F (4) and G (4'), four stilbenes (resveratrol (1), ε-viniferin (5), pallidol (3) and a newly characterized dimer (6)) were recovered as pure compounds in sufficient amounts to allow assessment of their biological activity on the cell growth of three different cell lines, including two human skin malignant melanoma cancer cell lines (HT-144 and SKMEL-28) and a healthy human dermal fibroblast HDF line. Among the dimers obtained in this study, the newly characterized resveratrol dimer (6) has never been described in nature and its biological potential was evaluated here for the first time. ε-viniferin as well as dimer (6) showed IC50 values on the three tested cell lines lower than the ones exerted by resveratrol and pallidol. However, activities of the first two compounds were significantly decreased in the presence of fetal bovine serum although that of resveratrol and pallidol was not. The differential tumor activity exerted by resveratrol on healthy and cancer lines was also discussed.

Cytotoxicity of Labruscol, a New Resveratrol Dimer Produced by Grapevine Cell Suspensions, on Human Skin Melanoma Cancer Cell Line HT-144.

A new resveratrol dimer (1) called labruscol, has been purified by centrifugal partition chromatography of a crude ethyl acetate stilbene extract obtained from elicited grapevine cell suspensions of Vitis labrusca L. cultured in a 14-liter stirred bioreactor. One dimensional (1D) and two dimensional (2D) nuclear magnetic resonance (NMR) analyses including ¹H, 13C, heteronuclear single-quantum correlation (HSQC), heteronuclear multiple bond correlation (HMBC), and correlation spectroscopy (COSY) as well as high-resolution electrospray ionisation mass spectrometry (HR-ESI-MS) were used to characterize this compound and to unambiguously identify it as a new stilbene dimer, though its relative stereochemistry remained unsolved. Labruscol was recovered as a pure compound (>93%) in sufficient amounts (41 mg) to allow assessment of its biological activity (cell viability, cell invasion and apoptotic activity) on two different cell lines, including one human skin melanoma cancer cell line HT-144 and a healthy human dermal fibroblast (HDF) line. This compound induced almost 100% of cell viability inhibition in the cancer line at a dose of 100 µM within 72 h of treatment. However, at all tested concentrations and treatment times, resveratrol displayed an inhibition of the cancer line viability higher than that of labruscol in the presence of fetal bovine serum. Both compounds also showed differential activities on healthy and cancer cell lines. Finally, labruscol at a concentration of 1.2 µM was shown to reduce cell invasion by 40%, although no similar activity was observed with resveratrol. The cytotoxic activity of this newly-identified dimer is discussed.

13C NMR and LC-MS Profiling of Stilbenes from Elicited Grapevine Hairy Root Cultures.

Resveratrol and related oligostilbenes are defense molecules produced by grapevine in response to stresses including various elicitors or signal molecules. Together with their prominent role in planta, these compounds have been the center of much attention in recent decades due to their pharmacological properties. The cost-effective production of resveratrol derivatives such as viniferins or more structurally complex stilbene oligomers remains a challenging task. In this study, the chemical diversity of stilbenes produced by Vitis vinifera Pinot Noir hairy roots was investigated after elicitation for 4 days with a mixture of methyl jasmonate (100 µM) and cyclodextrins (50 mM). Two crude extracts obtained from the culture medium and from the hairy roots were fractionated by centrifugal partition chromatography. The fractions were chemically investigated by two complementary identification approaches involving a 13C NMR-based dereplication method and liquid chromatography coupled to mass spectrometry (LC-MS). In total, groups of 21 and 18 molecules, including flavonoids and stilbenes, were detected in the culture medium and root extracts, respectively. These included resveratrol monomers, dimers, trimers, and a tetramer, thus highlighting the ability of elicited hairy root culture systems to synthesize a wide diversity of secondary metabolites of pharmaceutical significance. The main compounds were unambiguously identified as trans-resveratrol, ε-viniferin, trans-piceatannol, pallidol, scirpusin A, eriodictyol, naringenin, vitisin B, and maackin.

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.

Bio-Guided Isolation of Methanol-Soluble Metabolites of Common Spruce (Picea abies) Bark by-Products and Investigation of Their Dermo-Cosmetic Properties.

Common spruce (Picea abies L.) is a fast-growing coniferous tree, widely used in several countries for the production of sawn wood, timber and pulp. During this industrial exploitation, large quantities of barks are generated as waste materials. The aim of this study was the bio-guided investigation and the effective recovery of methanol-soluble metabolites of common spruce bark for the development of new dermo-cosmetic agents. The active methanol extract was initially fractionated by Centrifugal Partition Chromatography (CPC) using a triphasic solvent system in a step-gradient elution mode. All resulting fractions were evaluated for their antibacterial activity, antioxidant activity and their capability to inhibit tyrosinase, elastase and collagenase activity. In parallel, the chemical composition of each fraction was established by combining a 13C-NMR dereplication approach and 2D-NMR analyses. As a result, fourteen secondary metabolites corresponding to stilbene, flavonoid and phenolic acid derivatives were directly identified in the CPC fractions. A high amount (0.93 g) of E-astringin was recovered from 3 g of crude extract in a single 125 min run. E-Astringin significantly induced the tyrosinase activity while E-piceid, taxifolin, and taxifolin-3'-O-glucopyranoside exhibited significant anti-tyrosinase activity. The above compounds showed important anti-collagenase and antimicrobial activities, thus providing new perspectives for potential applications as cosmetic ingredients.