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A rapid and efficient high-performance counter-current chromatography ( HPCCC) method was developed to separate five oligostilbenes from the roots of Vitis amurensis. An n-hexane/ethyl acetate/methanol/water system (4:8:4:10, v/v/v/v) was selected as an optimal two-phase solvent system of which the upper phase was used as the stationary phase and the lower phase was used as the mobile one. Partition coefficient values for the target compounds under these optimized conditions were 0.28 ( 1, ampleosin A), 7.12 ( 2, (+)- g-viniferin), 2.26 ( 3, vitisin A), 5.38 ( 4, wilsonol C), and 11.23 ( 5, vitisin B). Flow-rate gradient HPCCC (4 mL/min in 0-70 min, 8 mL/min in 70-250 min) was applied to isolate the target compounds in as high purity as possible within the shortest possible run time. Under these conditions, ampelopsin A (12.1 mg), (+)- g-viniferin (10.4 mg), vitisin A (2.8 mg), wilsonol C (3.2 mg), and vitisin B (37 mg) were isolated with >95% purity from 150 mg of enriched oligostilbene extract. Although the KD of the last eluted compound, vitisin B ( KD = 11.23), was relatively large, it was eluted in 115-145 min using the two-phase solvent system. This study shows that HPCCC is an efficient tool for the isolation and purification of natural products. [ABSTRACT FROM AUTHOR]

Abstract: A simple one-pot synthesis of aryl alkyl sulfides from various bromobenzenes containing a hydroxy, hydroxymethyl, hydroxyethyl, and carboxylic acid group at -o, -m, and -p positions is reported here. The reaction proceeds through, in sequence, in situ protection of the hydroxy or carboxylic acid group by reaction with a Grignard reagent, lithium-halogen exchange, the formation of lithium thiolates, and the nucleophilic attack of lithium thiolates on various electrophiles without isolation of the thiolates, in one vessel. This procedure required a very short reaction time (1–1.5h) and gave the corresponding sulfides in 75–97% yields. [Copyright &y& Elsevier]

Abstract: A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural product libraries. The synthesis of 1 was accomplished starting from vinylmethyl ketone. Ring formation of the α,γ dialkyl γ-lactone was achieved via the stereo-controlled reaction of a ketyl radical anion with a chiral methacrylate. In the PPAR agonistic assay, the most potent of the four stereoisomers had EC50 values of 12μM for mPPARα, 9μM for mPPARδ and >100μM for mPPARγ. [Copyright &y& Elsevier]

Eight kaempferol oligosaccharides were isolated and identified from Camellia japonica seed cake. The chemical structures of the isolates were determined by using chromatographic and spectroscopic techniques, such as high-performance liquid chromatography with a photodiode array detector (HPLC-PDA), one-dimensional (1H and 13C), and two-dimensional nuclear magnetic resonance (1H–1H COSY, HSQC and HMBC), ESI-Q-TOF-MS, and optical rotation. To evaluate the anti-aging efficacy of kaempferol oligosaccharides for cosmetic use, the MMP-1 inhibitory effects of the isolates were studied using human dermal fibroblasts which were cultured in HaCaT cell-conditioned media. The MMP-1 inhibitory assay results revealed that kaempferol-3- O -β- d -xylopyranosyl-(1 → 3)-α- l -rhamnopyranosyl-(1 → 6)- O -β- d -glucopyranosyl-(1 → 2)- O -β- d -glucopyranoside showed the most potent MMP-1 inhibitory activity. The basal level inhibition was 50 ppm, which indicated that C. japonica seed cake is a promising material for the development of anti-aging skin cosmetics. Image 1 • Eight kaempferol oligosaccharides were isolated from Camellia japonica seed cake. • The structures of isolates were elucidated by spectroscopic evidence. • Eight kaempferol oligosaccharides showed MMP-1 inhibitory activities. • Seed cake of C. japonica can be a promising material for anti-aging cosmetics. [ABSTRACT FROM AUTHOR]

Probiotics offer various health benefits. Lactobacillus plantarum has been used for decades to enhance human intestinal mucosal immunity and improve skin barrier integrity. Extracellular vesicles (EVs) derived from eukaryotic or prokaryotic cells have been recognized as efficient carriers for delivery of biomolecules to recipient cells, and to efficiently regulate human pathophysiology. However, the mechanism underlying the beneficial effects of probiotic bacteria-derived EVs on human skin is unclear. Herein, we investigated how L. plantarum-derived EVs (LEVs) exert beneficial effects on human skin by examining the effect of LEVs on cutaneous immunity, particularly on macrophage polarization. LEVs promoted differentiation of human monocytic THP1 cells towards an anti-inflammatory M2 phenotype, especially M2b, by inducing biased expression of cell-surface markers and cytokines associated with M2 macrophages. Pre- or post-treatment with LEVs under inflammatory M1 macrophage-favouring conditions, induced by LPS and interferon-γ, inhibited M1-associated surface marker, HLA-DRα expression. Moreover, LEV treatment significantly induced expression of macrophage-characteristic cytokines, IL-1β, GM-CSF and the representative anti-inflammatory cytokine, IL-10, in human skin organ cultures. Hence, LEVs can trigger M2 macrophage polarization in vitro, and induce an anti-inflammatory phenomenon in the human skin, and may be a potent anti-inflammatory strategy to alleviate hyperinflammatory skin conditions. [ABSTRACT FROM AUTHOR]

Probiotics offer various health benefits. Lactobacillus plantarum has been used for decades to enhance human intestinal mucosal immunity and improve skin barrier integrity. Extracellular vesicles (EVs) derived from eukaryotic or prokaryotic cells have been recognized as efficient carriers for delivery of biomolecules to recipient cells, and to efficiently regulate human pathophysiology. However, the mechanism underlying the beneficial effects of probiotic bacteria‐derived EVs on human skin is unclear. Herein, we investigated how L. plantarum‐derived EVs (LEVs) exert beneficial effects on human skin by examining the effect of LEVs on cutaneous immunity, particularly on macrophage polarization. LEVs promoted differentiation of human monocytic THP1 cells towards an anti‐inflammatory M2 phenotype, especially M2b, by inducing biased expression of cell‐surface markers and cytokines associated with M2 macrophages. Pre‐ or post‐treatment with LEVs under inflammatory M1 macrophage‐favouring conditions, induced by LPS and interferon‐γ, inhibited M1‐associated surface marker, HLA‐DRα expression. Moreover, LEV treatment significantly induced expression of macrophage‐characteristic cytokines, IL‐1β, GM‐CSF and the representative anti‐inflammatory cytokine, IL‐10, in human skin organ cultures. Hence, LEVs can trigger M2 macrophage polarization in vitro, and induce an anti‐inflammatory phenomenon in the human skin, and may be a potent anti‐inflammatory strategy to alleviate hyperinflammatory skin conditions. [ABSTRACT FROM AUTHOR]

Skin aging is a major risk factor for the dermal diseases, and interventions to attenuate cellular senescence are expected to reduce the risk for age-related diseases involving skin atrophy. However, blocking cell death or extending proliferation causally results in side effects and an increased cancer risk. For identification of a safer approach, we focused on PDK1 inhibition, which could revert cellular senescence and reduce senescence factors in skin in vitro, in a human skin equivalent model and in an exploratory, placebo-controlled, interventional trial. Natural phytochemical kaempferol tetrasaccharides resulted in a significant reduction in cellular senescence, and an increase in collagen fiber was observed in the skin cell and human skin equivalent. Clinical enhancement in skin appearance was noted in multiple participants, and an immunohistochemical study revealed improvement in the histological appearance of skin tissue and extracellular matrix. This change was associated with relative improvement in histological markers of senescence and clinical appearance of the aged skin and an increase in collagen fiber, an essential factor for preventing skin atrophy and consistency of the basement membrane. These results indicate that PDK1 inhibition is a potentially effective antiaging intervention, suggesting a diagnostic role and preventive actions of PDK1 in senescence-associated skin atrophy. [Display omitted] • Kaempferol tetrasaccharides (KT1) inhibit PDK1 enzyme activity via direct binding-mediated fashion. • KT1, one of the strong PDK1 inhibitor, attenuates skin atrophy in human skin equivalent model and exhibit anti-wrinkle activity in clinical study. [ABSTRACT FROM AUTHOR]

Two actinomycetes, a member of the rare halophilic genus Streptomonospora and a Nocardiopsis sp. (Nocardiopsaceae), strains CNQ-082 and CNQ-675, respectively, were isolated from marine sediments collected off shore near La Jolla, California. HPLC-UV guided fractionations of the extracts of these strains yielded marinopyrones A–D ( 1 – 4 ), the structures of which were elucidated by interpretation of 1D and 2D NMR and HRMS spectroscopic data. Oxidative ozonation, followed by conversion of the acid product to an α-naphthyl amide, provided the absolute configuration at the chiral center on the side-chain. Marinopyrones A–D were examined for the inhibitory activity on nitric oxide production in LPS-activated mouse macrophage cells (RAW 264.7); marinopyrone D ( 4 ) was inhibitory with an IC 50 value of 13 μM. To our knowledge, marinopyrones A–C are only the second reported natural products from the rare halophilic genus Streptomonospora . [ABSTRACT FROM AUTHOR]

The ethanolic extract of the root of Piper methysticum was found to inhibit melanogenesis in MSH-activated B16 melanoma cells. Flavokawains B and C were isolated from this extract based on their anti-melanogenesis activity and found to inhibit melanogenesis with IC 50 values of 7.7 μM and 6.9 μM, respectively. Flavokawain analogs were synthesized through a Claisen–Schmidt condensation of their corresponding acetophenones and benzaldehydes and were evaluated in terms of their tyrosinase inhibitory and anti-melanogenesis activities. Compound 1b was the most potent of these with an IC 50 value of 2.3 μM in melanogenesis inhibition assays using MSH-activated B16 melanoma cells. [ABSTRACT FROM AUTHOR]

High-performance countercurrent chromatography (HPCCC) with electrospray light-scattering detection was applied for the first time to isolate a spirostanol and a novel furostanol saponin from Liriope platyphylla. Due to the large differences in KD values between the two compounds, a two-step HPCCC method was applied in this study. The primary HPCCC employed methylene chloride/methanol/isopropanol/water (9:6:1:4 v/v, 4 mL/min, normal-phase mode) conditions to yield a spirostanol saponin ( 1). After the primary HPCCC run, the solute retained in the stationary phase (SP extract) in HPCCC column was recovered and subjected to the second HPCCC on the n-hexane/ n-butanol/water system (1:9:10 v/v, 5 mL/min, reversed-phase mode) to yield a novel furostanol saponin ( 2). The isolated spirostanol saponin was determined to be 25( S)-ruscogenin 1- O-β- d-glucopyranosyl (1→2)-[β- d-xylopyranosyl (1→3)]-β- d-fucopyranoside (spicatoside A), and the novel furostanol saponin was elucidated to be 26- O-β- d-glucopyranosyl-25( S)-furost-5(6)-ene-1β-3β-22α-26-tetraol-1- O-β- d-glucopyranosyl (1→2)-[β- d-xylopyranosyl-(1→3)]-β- d-fucopyranoside (spicatoside D). [ABSTRACT FROM AUTHOR]

Abstract: We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 104-fold selectivity over the other two subtypes, namely, hPPARα and hPPARγ. The PPARδ ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy. [Copyright &y& Elsevier]

Abstract: We report the synthesis and in vivo activity of a novel anti-atherogenic agent, isosteric selenium PPARδ-selective ligand. This ligand did not cause significant body or liver weight changes and did not have obvious adverse effects on intestinal polyp formation. Our overall results clearly demonstrate that PPARδ is a viable drug candidate for targeting and treating atherosclerosis. [ABSTRACT FROM AUTHOR]

Summary: Jasmonic acid (JA) plays pivotal roles in diverse plant biological processes, including wound response. Chloroplast lipid hydrolysis is a critical step for JA biosynthesis, but the mechanism of this process remains elusive. We report here that DONGLE (DGL), a homolog of DEFECTIVE IN ANTHER DEHISCENCE1 (DAD1), encodes a chloroplast-targeted lipase with strong galactolipase and weak phospholipase A1 activity. DGL is expressed in the leaves and has a specific role in maintaining basal JA content under normal conditions, and this expression regulates vegetative growth and is required for a rapid JA burst after wounding. During wounding, DGL and DAD1 have partially redundant functions for JA production, but they show different induction kinetics, indicating temporally separated roles: DGL plays a role in the early phase of JA production, and DAD1 plays a role in the late phase of JA production. Whereas DGL and DAD1 are necessary and sufficient for JA production, phospholipase D appears to modulate wound response by stimulating DGL and DAD1 expression. [Copyright &y& Elsevier]

Salicornia europaea L. is a halophyte that grows in salt marshes and muddy seashores, which is widely used both as traditional medicine and as an edible vegetable. This salt-tolerant plant is a source of diverse secondary metabolites with several therapeutic properties, including antioxidant, antidiabetic, cytotoxic, anti-inflammatory, and anti-obesity effects. Therefore, this review summarizes the chemical structure and biological activities of secondary metabolites isolated from Salicornia europaea L. [ABSTRACT FROM AUTHOR]

Ginseng is a traditional herbal medicine in eastern Asian countries. Most active constituents in ginseng are prepared via fermentation or organic acid pretreatment. Extracellular vesicles (EVs) are released by most organisms from prokaryotes to eukaryotes and play central roles in intra- and inter-species communications. Plants produce EVs upon exposure to microbes; however, their direct functions and utility for human health are barely known, except for being proposed as delivery vehicles. In this study, we isolated EVs from ginseng roots (GrEVs) or the culture supernatants of ginseng cells (GcEVs) derived from Panax ginseng C.A. Meyer and investigated their biological effects on human skin cells. GrEV or GcEV treatments improved the replicative senescent or senescence-associated pigmented phenotypes of human dermal fibroblasts or ultraviolet B radiation-treated human melanocytes, respectively, by downregulating senescence-associated molecules and/or melanogenesis-related proteins. Based on comprehensive lipidomic analysis using liquid chromatography mass spectrometry, the lipidomic profile of GrEVs differed from that of the parental root extracts, showing significant increases in 70 of 188 identified lipid species and prominent increases in diacylglycerols, some phospholipids (phosphatidylcholine, phosphatidylethanolamine, lysophosphatidylcholine), and sphingomyelin, revealing their unique vesicular properties. Therefore, our results imply that GEVs represent a novel type of bioactive and sustainable nanomaterials that can be applied to human tissues for improving tissue conditions and targeted delivery of active constituents. [ABSTRACT FROM AUTHOR]

Lactobacillus plantarum is a popular probiotic species due to its safe and beneficial effects on humans; therefore, novel L. plantarum strains have been isolated and identified from various dietary products. Given that bacteria-derived extracellular vesicles (EVs) have been considered as efficient carriers of bioactive materials and shown to evoke cellular responses effectively, L. plantarum-derived EVs are expected to efficiently elicit health benefits. Herein, we identified L. plantarum APsulloc 331261 living in green tea leaves and isolated EVs from the culture medium. We performed quantitative lipidomic analysis of L. plantarum APsulloc 331261 derived EVs (LEVs) using liquid chromatography-mass spectrometry. In comparison to L. plantarum APsulloc 331261, in LEVs, 67 of 320 identified lipid species were significantly increased and 19 species were decreased. In particular, lysophosphatidylserine(18:4) and phosphatidylcholine(32:2) were critically increased, showing over 21-fold enrichment in LEVs. In addition, there was a notable difference between LEVs and the parent cells in the composition of phospholipids. Our results suggest that the lipidomic profile of bacteria-derived EVs is different from that of the parent cells in phospholipid content and composition. Given that lipids are important components of EVs, quantitative and comparative analyses of EV lipids may improve our understanding of vesicle biogenesis and lipid-mediated intercellular communication within or between living organisms. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) irradiation induces detrimental changes in human skin which result in photoaging. UV-induced intracellular changes cause degradation of extracellular matrix (ECM). UV-stimulated cleavage of collagen in ECM occurs via matrix metalloproteinases (MMPs). (±)-syringaresinol (SYR), a phytochemical which belongs to the lignan group of polyphenols, was investigated for its ability to reverse the UVA-induced changes in human HaCaT keratinocytes and dermal fibroblasts (HDFs) in vitro. Effect of SYR on UVA-induced changes was investigated by production and activation of MMPs and its transcriptional upstream effectors; mitogen-activated protein kinases (MAPKs) and pro-inflammatory mediators. Levels of expression were determined using ELISA, RT-PCR and immunoblotting. UVA irradiation stimulated the production of MMP-1 and inhibited collagen production. SYR treatment suppressed MMP-1 and enhanced collagen production in UVA-irradiated HaCaT keratinocytes and HDFs. SYR repressed the UV-induced phosphorylation of p38, ERK and JNK MAPKs in HaCaT keratinocytes while only suppressing JNK phosphorylation in HDFs. In addition, SYR was able to inhibit UVA-induced production of inflammatory cytokines; TNF-α, COX-2, IL-1β and IL-6. Moreover, SYR suppressed the activator protein-1 (AP-1), a heterodimer of phosphorylated transcription factors c-Jun and c-Fos. SYR-treatment decreased nuclear levels of activated c-Fos and c-Jun as a mechanism to inhibit UVA-induced transcriptional activities leading to MMP-1 production. In conclusion, current results demonstrated that SYR could inhibit UVA-induced upregulation of MMP-1 by suppressing MAPK/AP-1 signaling in HaCaT keratinocytes and HDFs. Therefore, SYR was suggested as a potential compound with antiphotoaging properties against UVA-induced skin aging. [ABSTRACT FROM AUTHOR]

Intensive study on the chemical components of a Korean marine sponge, Spongia sp., has led to the isolation of four new scalarane sesterterpenes, scalalactams A–D (1–4). Their chemical structures were elucidated from the analysis of spectroscopic data including 1D-and 2D-NMR as well as MS data. Scalalactams A–D (1–4) possess a scalarane carbon skeleton with a rare structural feature of a γ-lactam moiety within the molecules. Scalalactams A and B (1 and 2) have an extended isopropanyl chain at the lactam ring, and scalalactams C and D (3 and 4) possess a phenethyl group at the lactam ring moiety. Scalalactams A–D (1–4) did not show FXR antagonistic activity nor cytotoxicity up to 100 μM. [ABSTRACT FROM AUTHOR]

Flavokawains B and C (Ia,b) are isolated from the ethanolic extract of the root of Piper methysticum, which is found to inhibit melanogenesis in MSH‐activated B16 melanoma cells. [ABSTRACT FROM AUTHOR]