Leontopodium Alpinum Research Articles

Effects of Plant Meristem-Cell-Based Cosmetics on Menopausal Skin: Clinical Data and Mechanisms.

A randomised open clinical/laboratory study was performed to evaluate the safety and cosmetic efficacy of facial cosmetics for females during the menopausal period. The cosmetics contain active ingredients of meristem cells derived from the medicinal plants Leontopodium alpinum, Buddeleja davidii, Centella asiatica, and Echinacea angustifolia. Recently, the major bioactive molecules of these medicinal plants (leontopodic acid, verbascoside, asiaticoside, and echinacoside, respectively) have been thoroughly evaluated in vitro for molecular pathways and cellular mechanisms and their preventive/curative effects on human skin cells exposed to factors promoting premature skin ageing and cellular senescence. Nevertheless, clinical data on their safety/efficacy to ageing human skin are scarce. This clinical study enrolled 104 Caucasian females in pre-menopause, menopause, or post-menopause periods. They applied cosmetic serums daily for 1 month. Questionnaires and instrumental and biochemical methods were used to assess dermatological/ophthalmological safety and cosmetic efficacy through changes of the skin physiology markers characteristic of ageing/menopause (elasticity, barrier functions, moisture, sebum, ultrasonic properties, and collagen content and structure). Quantitative microbiological tests were carried out for skin microbiota fluctuations. Data showed that the cosmetics were safe, and they shifted the skin physiology parameters to a younger biological age, enhanced collagen synthesis, inhibited lipid peroxidation, and favoured normal microbiota.

Farmers’ knowledge in the Swiss canton Valais: cultural heritage with future significance for European veterinary medicine?

BackgroundThe demand for natural product-based treatment options for livestock is increasing by animals’ owners, veterinarians and policy makers. But at the same time, the traditional knowledge about it is at risk of falling into oblivion in Europe. The present study recorded this knowledge for the linguistically and geographically interesting Swiss canton of Valais.MethodOpen, semi-structured interviews were used to collect detailed information on formulations and applications, including plant species and natural substances, origin of material, extraction and preparation of herbal products, indication and type of application, dosage, sources of knowledge, frequency of usage and self-assessment of the treatment.Results and discussionIn the course of 43 interviews, 173 homemade single species herbal remedy report (HSHR) were recorded. They included 53 plant species from 30 botanical families. Plant species from the botanical families of Asteraceae, Rubiaceae and Cupressaceae were mentioned the most, while the most frequently documented plant species were Coffea arabica L., Juniperus sabina L., Arnica montana L. and Matricaria chamomilla L. For the 173 HSHR, a total of 215 uses were mentioned, most of which were for the treatment of gastrointestinal and metabolic disorders, followed by skin lesions and genito-urinary tract problems. Regional peculiarities emerged, such as the use of Leontopodium alpinum Cass. for diarrhea in the French-speaking Valais, while Matricaria chamomilla and Camellia sinensis L. were used in the German-speaking part instead. In comparison with other regions of Switzerland, 10 plants were reported for the first time, including Juniperus sabina with 18 use reports.ConclusionThe daily use on farms and the high satisfaction of farmers with homemade herbal remedies demonstrate their high practical relevance. In conclusion, the traditional regional knowledge about the use of medicinal plants is not only a cultural heritage worth protecting, but also an essential resource for the further development of European veterinary medicine.

Genomes and secondary metabolomes of Streptomyces spp. isolated from Leontopodium nivale ssp. alpinum.

Bacterial endophytes dwelling in medicinal plants represent an as yet underexplored source of bioactive natural products with the potential to be developed into drugs against various human diseases. For the first time, several Streptomyces spp. were isolated from the rare and endangered traditional medicinal plant Leontopodium nivale ssp. alpinum, also known as Edelweiss. In the search for novel natural products, nine endophytic Streptomyces spp. from Edelweiss were investigated via genome sequencing and analysis, followed by fermentation in different media and investigation of secondary metabolomes. A total of 214 secondary metabolite biosynthetic gene clusters (BGCs), of which 35 are presumably unique, were identified by the bioinformatics tool antiSMASH in the genomes of these isolates. LC-MS analyses of the secondary metabolomes of these isolates revealed their potential to produce both known and presumably novel secondary metabolites, whereby most of the identified molecules could be linked to their cognate BGCs. This work sets the stage for further investigation of endophytic streptomycetes from Edelweiss aimed at the discovery and characterization of novel bioactive natural products.

Active Components of Leontopodium alpinum Callus Culture Extract for Blue Light Damage in Human Foreskin Fibroblasts.

Leontopodium alpinum is a source of raw material for food additives and skin health. The purpose of this study was to investigate the application of Leontopodium alpinum callus culture extract (LACCE) to prevent blue light damage to the skin. We screened and identified the blue light-damage-protecting activities and mechanisms of ten components of LACCE, including chlorogenic acid (A), isoquercitrin (B), isochlorogenic acid A (C), cynaroside (D), syringin (E), isochlorogenic acid (F), cynarin (G), rutin (H), leontopodic acid A (I), and leontopodic acid B (J), using a novel blue light-induced human foreskin fibroblast (HFF-1) cell injury model. The study examined the cytotoxicity of ten ingredients using the cell counting kit-8 (CCK-8) assay, and selecting concentrations of 5, 10, and 20 μM for experiments with a cell viability above 65%. We explored the effects and mechanisms of action of these LACCE components in response to blue light injury using Western blotting and an enzyme-linked immunosorbent assay. We also measured ROS secretion and Ca2+ influx. Our study revealed that leontopodic acid A effectively boosted COI-1 expression, hindered MMP-1 expression, curbed ROS and Ca2+ endocytosis, and reduced OPN3 expression. These results provide theoretical support for the development of new raw materials for the pharmaceutical and skincare industries.

Is acute low-dose gamma irradiation an effective elicitor for secondary metabolism in Leontopodium alpinum (Cass.) callus culture?

Leontopodium alpinum Cass. (Edelweiss) is a protected species in some European countries and has become of growing interest for exploitation by the food supplements and cosmetics industry, due to its valuable composition in bioactive and biocompatible compounds. Small scale field cultivation and in vitro biotechnological approaches are economically viable alternatives to the production via chemical synthesis. In this study, we aimed to compare two performant L. alpinum callus culture lines and to investigate the effect of acute low dose gamma irradiation on biomass accumulation (Gi), total phenolic content (TPC), total flavonoid content (TFC), antioxidant activity (DPPH) and secondary metabolites’ profile. A purple, pigmented line (PC) was obtained under lightning conditions and in the absence of light, an unpigmented greenish line (GC) was established. Both lines displayed impressive proliferative capacity after 14 days of culture, with an 18.31 ( ± 1.83) fold mass increase for PC and a 13.27 ( ± 2.42) for GC. In respect to Gi, TPC, TFC and DPPH, the purple callus line significantly outperformed the unpigmented line. According to the UPLC-HRMS analysis of the methanolic extracts, both callus lines displayed similar metabolic profiles, having similar quantities of 3,5-dicaffeoylquinic acid, leontopodic acids A and B, but 60% higher concentration of chlorogenic acid in the GC line. In the methanolic callus extracts, 9 economically important phenylpropanoid derivatives were identified. The two callus lines responded differently to low dose gamma irradiation. Although the control values measured for Gi, TPC, TFC and DPPH were significantly higher in the PC line, this line was generally negatively impacted by the gamma treatments. On the contrary, higher, but not significant, values were registered in some GC variants post irradiation with 25, 30 and 40 Gy. UPLC-HRMS investigations emphasized the overproduction of 7 compounds, post irradiation with all doses, for the PC line, while for the unpigmented line only one compound was stimulated by all irradiation treatments. The highest stimulative effect was obtained for the 35 and 40 Gy experimental variants, in the GC line, where dihydroxybenzoic acid glucoside accumulation was increased by 160%. The results of this study showed, for the first time, the different responses of two distinct L. alpinum callus lines using gamma irradiation elicitation method, which can be successfully applied to stimulate the production of certain industrially important compounds as chlorogenic acid, dicaffeoylquinic acid isomers or characteristic glucaric acids.

Effects and Mechanism of the Leontopodium alpinum Callus Culture Extract on Blue Light Damage in Human Foreskin Fibroblasts

Leontopodium alpinum is an important source of raw material for food, medicine, and modern cosmetics. The purpose of this study was to develop a new application for protection against blue light damage. To investigate the effects and mechanism of action of Leontopodium alpinum callus culture extract (LACCE) on blue light damage, a blue-light-induced human foreskin fibroblast damage model was established. The contents of collagen (COL-I), matrix metalloproteinase 1 (MMP-1), and opsin 3 (OPN3) were detected using enzyme-linked immunosorbent assays and Western blotting. The calcium influx and reactive oxygen species (ROS) levels were measured via flow cytometry and the results showed that the LACCE (10-15 mg/mL) promoted the production of COL-I, inhibited the secretion of MMP-1, OPN3, ROS and calcium influx, and may play a role in inhibiting the activation of blue light on the OPN3-calcium pathway. Thereafter, high-performance liquid chromatography and ultra-performance liquid chromatography-tandem mass spectrometry were used to quantitatively analyze the contents of nine active ingredients in the LACCE. The results indicated that LACCE has an anti-blue-light-damage effect and provides theoretical support for the development of new raw materials in the natural food, medicine, and skin care industries.

Pengelolaan dan Konservasi Vegetasi Tanaman Gumi Banten di Desa Besakih, Kecamatan Rendang, Karangasem

Taman Gumi Banten is an area that is utilized as a habitat for plant growth. An important background that supports Taman Gumi Banten is the preservation of rare plants classified as ceremonial plants, usada, and puspa dewata. This research aims to manage and conserve vegetation in the Taman Gumi Banten Besakih, as an effort to preserve ceremonial plants, usada, and puspa dewata. This research was conducted in Taman Gumi Banten Besakih with an area of 2 hectares, conducted for 3 months (May-July 2021). Sampling method with plot method. Primary data, both vegetation data and soil data were taken at the observation site, while secondary data were taken from the Karangasem BMKG office. Data analysis was carried out with vegetation analysis, namely the importance value index, diversity index and species distribution pattern, and vegetation rarity status based on PERMENLHK No. 20 of 2018. While soil data will be analyzed at the Soil Science Laboratory, Faculty of Agriculture, UNUD. The results concluded that the number of species found was 101 species, consisting of 2297 individuals, with low diversity and uniform distribution patterns. There are 2 species classified as rare, namely the kasna kasna (Anaphalis javanica) and gegirang tree (Leontopodium alpinum), soil conditions especially high levels of organic carbon and soil texture all sandy loam are very supportive of vegetation development, and the number of plants in Taman Gumi Banten has only been fulfilled 2297 individuals while the shortage of 2703 individuals (being pursued).

Classification of Edelweiss Flowers Using Data Augmentation and Linear Discriminant Analysis Methods

Edelweiss is a plant that grows at a height, and is known as a perennial flower because it has beautiful petals and does not wilt easily. Although edelweiss in Indonesia is still in the same family as Leontopodium Alpinum, it turns out that the type of edelweiss found in the mountains of Indonesia is different from edelweiss found abroad. Therefore, in this study, an image processing system was developed that can classify the types of edelweiss flowers based on their image using Linear Discriminant Analysis to classify data into several classes based on the boundary line (straight line) obtained from linear equations. In this study, the types of edelweiss flowers used in this study were Anaphalis Javanica and Leontopodium Alpinum, the two types of edelweiss flowers were distinguished based on their color characteristics using hue and saturation values. The images used are 1500 images for training data and 450 test data images with a training and test data ratio of 70:30, so that the accuracy produced in the testing process is 99.77% in the Linear Discriminant Analysis method.

An extract of Leontopodium alpinum inhibits catagen development ex vivo and increases hair density in vivo.

ObjectivesHair loss and reduction in hair volume are hallmarks of hair disorders, such as telogen effluvium, or male or female pattern hair loss, and hair ageing, which can cause severe distress in both men and women. Common anti‐hair loss drugs carry some side effects; therefore, novel, safer approaches targeting milder phenotypes are highly advocated. In this context, we investigated an extract of the alpine plant Edelweiss, Leontopodium alpinum var. Helvetia, for its ability to modulate hair follicle (HF) growth ex vivo and inhibit hair loss while increasing hair regeneration in vivo.MethodsHuman amputated HFs were microdissected from three donors, two women and one man, and cultured ex vivo for 6 days. After treatment with 0.001% Edelweiss extract (EWDE), we investigated hair shaft production and anagen/catagen conversion, and measured known parameters associated with hair growth, that is hair matrix keratinocyte proliferation and apoptosis, dermal papilla inductivity, and growth factors, by quantitative (immuno)histomorphometry. To assess the anti‐hair loss potential of the alpine plant compound, we performed a randomized, placebo‐controlled human study enrolling Caucasian women and men, aged 18 to 65 years, with normal hair loss. After 5 months’ daily use of an extract containing leave‐on serum, we analysed hair density and anagen‐to‐catagen/telogen ratio by the Trichogram analysis.ResultsOur results revealed a significant prolongation in the anagen phase in HFs treated with 0.001% Edelweiss, as indicated by an increase in HFs remaining in anagen and a significant decrease in hair cycle score. In line with this effect, EWDE significantly stimulated hair matrix (HM) keratinocyte proliferation, and dermal papilla inductivity, as shown by a significant up‐regulation of versican expression and alkaline phosphatase activity, and a tendential increase in FGF7 immunoreactivity in the dermal papilla of all HFs or only anagen VI HFs. Corroborating the ex vivo results, we observed a significant increase in growing hair shaft numbers (hair density) after treatment with Edelweiss extract formulation, and a tendential up‐regulation in the anagen‐to‐catagen/telogen ratio.ConclusionsWe show here, through several lines of evidence, that the selected extract of the alpine plant Leontopodium alpinum var Helvetia (Edelweiss) inhibits premature catagen induction, possibly by stimulating dermal papilla inductivity. It is therefore worth exploiting this extract clinically as an anti‐hair loss agent, both for preventing ageing‐associated hair shedding and as an adjuvant therapy for hair loss disorders.

Profiling of Polyphenolic Compounds of Leontopodium alpinum Cass Callus Cultures Using UPLC/IM-HRMS and Screening of In Vitro Effects.

Leontopodium alpinum Cass. (edelweiss) is recognized as a frequent constituent of anti-aging skin care products, providing increased antioxidant and anti-inflammatory defense. Considering the growing demand and the protected status of edelweiss in many countries, alternative methods of production have been developed, one of them being callus culturing. This study reports the phytochemical composition of a methanolic extract of L. alpinum callus cultures, characterized by liquid chromatography coupled to ion-mobility high resolution mass spectrometry (UPLC/IM-HRMS). The methanolic extract exhibited strong free radical scavenging activity (122.19 ± 7.28 mg AAE/g dw), while the quantitative evaluation revealed that four major constituents (phenylpropanoid derivatives) represent 57.13% (m/m) of the extract. Consequently, a screening of antiproliferative effects was performed on ten cancer cell lines, representative of prostate, colon, lung and breast cancer, showing inhibition of colony formation in all cases. These results provide a comprehensive phytochemical characterization of L. alpinum callus cultures using advanced IM-HRMS, while the in vitro explorations confirmed the potent antioxidant properties of edelweiss which are worth exploring further in cancer prevention.

330 A novel cosmetic anti-hair loss approach: An extract of Leontopodium alpinum inhibits catagen development

Hair loss disorders, such as telogen effluvium or androgenetic alopecia, as well as reduction of hair volume during aging result mainly from the shortening of the phase during which the hair follicles (HFs) are producing the hair shaft (anagen). Therefore, novel anti hair loss strategies should aim at efficiently inhibiting the development of the regression phase (catagen). Here, we investigated the potential of a novel cosmetically applicable extract deriving from Leontopodium alpinum (Edelweiss), first ex vivo, in human microdissected anagen VI scalp hair follicles (HFs) from three individuals (two females, one male). After 5 days of treatment with the 0.001% edelweiss extract, significantly more HFs remained in anagen and showed increased hair matrix keratinocyte proliferation. Given that higher activity of alkaline phosphatase, and up-regulated expression of versican, and FGF7 was observed in the dermal papilla of female treated HFs, the anagen prolonging effect of the extract may be possibly mediated by stimulation of dermal papilla fibroblasts inductivity. To independently confirm these results, a 5 months double-blind, placebo controlled clinical study on Caucasian volunteers (both male and female, age 18-65, 30 volunteers per group) was conducted. Treatment with the edelweiss extract lead to a significant increase in hair density (Trichoscan) over time, as well as anagen to catagen/telogen ratio (Trichogram) compared to placebo. Therefore, our results provide evidence for a beneficial effect of the Leontopodium alpinum extract as an adjuvant anti-hair loss agent.

Integrating demography and distribution modeling for the iconic Leontopodium alpinum Colm. in the Romanian Carpathians.

Both climate change and human exploitation are major threats to plant life in mountain environments. One species that may be particularly sensitive to both of these stressors is the iconic alpine flower edelweiss (Leontopodium alpinum Colm.). Its populations have declined across Europe due to over‐collection for its highly prized flowers. Edelweiss is still subject to harvesting across the Romanian Carpathians, but no study has measured to what extent populations are vulnerable to anthropogenic change.Here, we estimated the effects of climate and human disturbance on the fitness of edelweiss. We combined demographic measurements with predictions of future range distribution under climate change to assess the viability of populations across Romania.We found that per capita and per‐area seed number and seed mass were similarly promoted by both favorable environmental conditions, represented by rugged landscapes with relatively cold winters and wet summers, and reduced exposure to harvesting, represented by the distance of plants from hiking trails. Modeling these responses under future climate scenarios suggested a slight increase in per‐area fitness. However, we found plant ranges contracted by between 14% and 35% by 2050, with plants pushed into high elevation sites.Synthesis. Both total seed number and seed mass are expected to decline across Romania despite individual edelweiss fitness benefiting from a warmer and wetter climate. More generally, our approach of coupling species distribution models with demographic measurements may better inform conservation strategies of ways to protect alpine life in a changing world.

Залежність між темпами розвитку і життєвістю особин у популяціях раритетних видів рослин високогір’я Українських Карпат

The article presents an overview of long-term research and numerous publications on the relationship between developmental rate and individual vitality in populations of rare and endemic plant species in the high-mountain zone of the Ukrainian Carpathians: a case study on Ranunculus thora, Primula halleri, Leontopodium alpinum, Gentiana acaulis, Doronicum clusii, Saussurea alpina, Oreochloa disticha, Pulsatilla alba, Rhododendron myrtifolium, Senecio сarpathicus, Festuca carpatica, Heracleum carpaticum, Phyteuma vagneri etc. Stationary in-situ research was conducted at the study sites founded 5–30 years ago. The greatest impact on the individual and population vitality is caused by the position changes in coenosis of the species of different life forms and strategies. Increasing of the shrub positions accelerates the decreasing of vitality of low shrubs and grasses especially, and vice versa, increasing of the coenotic position of high-growing shrubs and grasses cau­ses the vitality decrease of short-growing heliophytes, including most of the rare species. The individual vitality and population viability determines some influence on the dynamics of their seasonal development. The individual development is faster at higher vitality level. It results in the relatively earlier beginning of phenophases. In the coenoses where the value of population as ecosystem engineer is higher, the accelerated dynamics of pre-flowering phases and longer flowering period is observed. The individual vitality and relative age of vegetatively active species increase significantly under the developmental conditions without vegetative reproduction. The vitality of vegetative diaspores significantly change due to the effect of autonomous development of shoots and ramets in comparison to the original vitality of maternal individuals. The effect of inertia of individual and population vitality consists in the gradual change of their vitality under the changeable conditions of their existence. Only drastic adverse exogenous effects can cause a sudden decrease of their vitality. Processes of the transition of low vitality individuals to the high rank are the slowest ones.

601 Hair growth properties of Cinchona succirubra Extract, Leontopodium alpinum Extract and Manganese PCA in human hair follicle dermal papilla cells

601 Hair growth properties of Cinchona succirubra Extract, Leontopodium alpinum Extract and Manganese PCA in human hair follicle dermal papilla cells

575 An extract of Leontopodium alpinum prolongs anagen phase in human hair follicles ex vivo

Aging and hair follicle disorders, such as telogen effluvium or androgenetic alopecia, lead to premature catagen induction and decreased hair density. Hair loss is an aesthetic problem that may cause major psychological distress in affected individuals. While severe types of hair loss are targeted by the pharmaceutical industry, with drugs exhibiting unwanted side effects, the cosmetic industry is looking for milder, and natural treatment options. Bearing this in mind, we focused on an extract of Leontopodium alpinum (Edelweiss) and investigated its effects on hair growth ex vivo. We treated microdissected anagen VI scalp hair follicles (HFs) from three individuals (two female, one male) with 0.001% edelweiss extract and evaluated hair growth-associated parameters. After 5 days of treatment, we observed significantly more HFs remaining in anagen, and increased hair matrix keratinocyte proliferation. On a molecular level, higher activity of alkaline phosphatase, and up-regulated expression of versican was observed in the dermal papilla of female treated HFs, suggesting improvement of dermal papilla inductivity. In addition, the expression of hair growth-associated growth factors, i.e. IGF-1 or FGF7, was found to be up-regulated in the outer root sheath, and/or dermal papilla of female hair follicles. Our ex vivo results provide preliminary evidence for a beneficial effect of the Leontopodium alpinum extract in limiting hair shedding in vivo.

Dereplication of Natural Extracts Diluted in Propylene Glycol, 1,3-Propanediol and Glycerin. Comparison of Leontopodium alpinum Cass. (Edelweiss) Extracts as a Case Study

Many natural extracts used as cosmetic ingredients are available as solutions prepared in high-boiling-point solvents, called carrier solvents, such as propylene glycol (1,2-propanediol), propanediol (1,3-propanediol) and glycerin. The upstream chemical profiling of these extracts represents a major asset for the cosmetic industry, because it accelerates product development. A new workflow for the rapid characterization of the main metabolites present in natural extracts diluted in propylene glycol and 1,3-propanediol is presented here as an extension of previous works on glycerin-containing extracts. This method is an optimized version of a well-established dereplication procedure and consists of a fractionation by centrifugal partition chromatography followed by 13C nuclear magnetic resonance analysis and dedicated data processing. The concentration by evaporation under reduced pressure was considered as a pertinent preliminary step, particularly adapted to the analysis of highly diluted extracts. A dried hydro-ethanolic extract of Leontopodium alpinum Cass. was prepared at laboratory scale and used for method validation. Three solutions at 5% wt. of dry extract were prepared with propylene glycol/water (1:1), 1,3-propanediol/water (1:1) and glycerin/water (1:1) as carrier solvents. The dereplication workflow was applied to the three resulting L. alpinum extracts. Each study led to the quick identification of 26 metabolites including five flavonoids (luteolin and its derivatives), five hydroxycinnamic acids (among which are leontopodic acids), sugars and organic acids.

Endophytic Akanthomyces sp. LN303 from Edelweiss Produces Emestrin and Two New 2-Hydroxy-4 Pyridone Alkaloids.

In the search for new antibiotics, several fungal endophytes were isolated from the medicinal plant Leontopodium nivale subsp. alpinum (Edelweiss). The extract from one of these fungi classified as Akanthomyces sp. displayed broad-spectrum antibiotic activity against gram-negative bacteria and fungi. Further investigation into the composition of this extract using bioactivity-guided fractionation, HRMS, and nuclear magnetic resonance revealed two new 4-hydroxy-2-pyridone alkaloids (1, 2) and emestrin (3), an epidithiodioxopiperazine not previously known to be produced by a member of Cordycipitaceae. Further testing of purified compounds 1 and 2 proved that they are devoid of antibiotic activity, and all the activities observed in the crude extract could be assigned to emestrin (3), whose configuration was confirmed by crystallographic data. This study demonstrates, for the first time, that endophytic fungi from Edelweiss can produce new compounds, prompting further investigation into them for drug discovery.

Characterization of a Structural Leoligin Analog as Farnesoid X Receptor Agonist and Modulator of Cholesterol Transport.

The ligand-activated farnesoid X receptor is an emerging therapeutic target for the development of drugs against metabolic syndrome-related diseases. In this context, selective bile acid receptor modulators represent a novel concept for drug development. Selective bile acid receptor modulators act in a target gene- or tissue-specific way and are therefore considered less likely to elicit unwanted side effects. Based on leoligin, a lignan-type secondary plant metabolite from the alpine plant Leontopodium nivale ssp. alpinum, 168 synthesized structural analogs were screened in a farnesoid X receptor in silico pharmacophore-model. Fifty-six virtual hits were generated. These hits were tested in a cell-based farnesoid X receptor transactivation assay and yielded 7 farnesoid X receptor-activating compounds. The most active one being LT-141A, with an EC50 of 6 µM and an Emax of 4.1-fold. This analog did not activate the G protein-coupled bile acid receptor, TGR5, and the metabolic nuclear receptors retinoid X receptor α, liver X receptors α/β, and peroxisome proliferator-activated receptors β/γ. Investigation of different farnesoid X receptor target genes characterized LT-141A as selective bile acid receptor modulators. Functional studies revealed that LT-141A increased cholesterol efflux from THP-1-derived macrophages via enhanced ATP-binding cassette transporter 1 expression. Moreover, cholesterol uptake in differentiated Caco-2 cells was significantly decreased upon LT-141A treatment. In conclusion, the leoligin analog LT-141A selectively activates the nuclear receptor farnesoid X receptor and has an influence on cholesterol transport in 2 model systems.

Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract Through Transcriptome Profiling.

Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.

Design and Synthesis of a Compound Library Exploiting 5-Methoxyleoligin as Potential Cholesterol Efflux Promoter.

5-Methoxyleoligin and leoligin are natural occurring lignans derived from Edelweiss (Leontopodium nivale ssp. alpinum), displaying potent pro-angiogenic and pro-arteriogenic activity. Cholesterol efflux from macrophages is associated with reverse cholesterol transport which inhibits the development of cardiovascular disease. Within this study, we developed a modular and stereoselective total synthesis of 5-methoxyleoligin which can be readily used to prepare a novel compound library of related analogs. The target 5-methoxyleoligin was synthesized exploiting a recently disclosed modular route, which allows also rapid synthesis of analogous compounds. All obtained products were tested towards macrophage cholesterol efflux enhancement and the performance was compared to the parent compound leoligin. It was found that variation on the aryl moiety in 2-position of the furan ring allows optimization of the activity profile, whereas the ester-functionality does not tolerate significant alterations.