Sulfur-containing spiroketals from and evaluations of their anti-inflammatory effect.

spp. are a key source of sulfur-containing spiroketal glycosides with potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals - breynin J (), epibreynin J (), and probreynogenin () - along with four known compounds - probreynin I (), phyllaemblic acid (), breynin B (), and epibreynin B () - were isolated from the roots of .

Regulation of adipogenesis through retinoid X receptor and/or peroxisome proliferator-activated receptor by designed lignans based on natural products in 3T3-L1 cells.

We previously synthesized two retinoid X receptor (RXR) agonists, 4'-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid ethyl ester (4'OHE) and 6-hydroxy-3'-propyl-[1,1'-biphenyl]-3-propanoic acid ethyl ester (6OHE), based on the structure of magnaldehyde B, a natural product obtained from Magnolia obovata. 4'OHE and 6OHE exhibited different selectivities for peroxisome proliferator-activated receptor (PPAR)/RXR heterodimers. To examine the regulatory effects of these compounds in adipogenesis, 3T3-L1 mouse preadipocytes were treated with a differentiation cocktail with or without test compounds to induce differentiation, and subsequently treated with test compounds in insulin-containing medium every alternate day.

Two new ɑ-pyrone derivatives from the endophytic Diaporthe sp. ECN371.

Diaportholides A (1) and B (2), two polyketides with ɑ-pyrone moieties, were isolated from the cultures of an endophytic Diaporthe sp. ECN371 isolated from Orixa japonica, together with four known polyketides, phomopsolide B (3), phomopsolidones A (4) and B (5), and 5-[(1R)-1-hydroxyethyl]-γ-oxo-2-furanbutanoic acid (6). The structures of 1 and 2 were determined by extensive analysis of NMR and MS spectroscopic data.

Transmembrane G protein-coupled receptor 5 signaling stimulates fibroblast growth factor 21 expression concomitant with up-regulation of the transcription factor nuclear receptor Nr4a1.

Fibroblast growth factor 21 (FGF21) acts as an endocrine factor, playing important roles in the regulation of energy homeostasis, glucose and lipid metabolism. It is induced by diverse metabolic and cellular stresses, such as starvation and cold challenge, which in turn facilitate adaptation to the stress environment. The pharmacological action of FGF21 has received much attention, because the administration of FGF21 or its analogs has been shown to have an anti-obesity effect in rodent models.

Muyocopronones A and B: azaphilones from the endophytic fungus .

Two new azaphilones, namely muyocopronones A () and B (), were isolated from the cultures of an endophytic fungus ECN279. Their structures were elucidated by extensive spectroscopic analysis. Their absolute configurations were determined using the modified Mosher's method and through comparisons of experimental and calculated electronic circular dichroism data.

Discovery and SAR of Natural-Product-Inspired RXR Agonists with Heterodimer Selectivity to PPARδ-RXR.

A known natural product, magnaldehyde B, was identified as an agonist of retinoid X receptor (RXR) α. Magnaldehyde B was isolated from (Magnoliaceae) and synthesized along with more potent analogs for screening of their RXRα agonistic activities. Structural optimization of magnaldehyde B resulted in the development of a candidate molecule that displayed a 440-fold increase in potency.

Correction to: Sesquiterpenes with new carbon skeletons from the basidiomycete Phlebia tremellosa.

The article Sesquiterpenes with new carbon skeletons from the basidiomycete Phlebia tremellosa, written by Ken ichi Nakashima, Junko Tomida, Takao Hirai, Yoshiaki Kawamura and Makoto Inoue was originally published Online First without Open Access.

Absolute configurations of talaromycones A and B, α-diversonolic ester, and aspergillusone B from endophytic sp. ECN211.

Talaromycones A () and B (), new xanthenediones, were isolated from the cultures of sp. ECN211, an endophytic fungus, along with α-diversonolic ester (), aspergillusone B (), glauconic acid (), and rosellisin (). The planar structures of and were elucidated by extensive spectroscopic analyses.

Paraconiothins A-J: Sesquiterpenoids from the Endophytic Fungus ECN258.

Paraconiothins A-J (-), 10 new sesquiterpenoids, as well as five known sesquiterpenoids, were isolated from the cultures of the endophytic fungus ECN-258. The structures of the sesquiterpenoids were elucidated by extensive spectroscopic analysis. Furthermore, the absolute structures of and were determined by comparing their experimental and computed electronic circular dichroism data.

Kurarinone from Roots Triggers ATF4 Activation and Cytostatic Effects Through PERK Phosphorylation.

In response to cellular stresses, activating transcriptional factor 4 (ATF4) regulates the expression of both stress-relieving genes and apoptosis-inducing genes, eliciting cell fate determination. Since pharmacological activation of ATF4 exerts potent anti-tumor effects, modulators of ATF4 activation may have potential in cancer therapy. We herein attempted to identify small molecules that activate ATF4.

[Evaluation of Naturally Occurring Compounds Regulating Brown/Beige Adipocyte Differentiation].

Brown adipose tissue is a critical regulator of metabolic health, and contributes to thermogenesis by uncoupling oxidative phosphorylation through the action of mitochondrial uncoupling protein 1 (Ucp1). Recent studies have shown that cold exposure and the stimulation of β3-adrenergic receptors induce the development of brown cell-like "beige" adipocytes in white adipose tissue. Brown and/or beige adipocyte-mediated thermogenesis suppresses high-fat diet-associated obesity.

Berberine stimulates fibroblast growth factor 21 by modulating the molecular clock component brain and muscle Arnt-like 1 in brown adipose tissue.

Fibroblast growth factor 21 (FGF21), a member of the FGF subfamily that acts through the FGF receptor 1 with the co-receptor β-Klotho, functions as an important metabolic regulator of peripheral glucose tolerance and lipid homeostasis in an endocrine or autocrine and/or paracrine manner. Previous studies showed that FGF21 ameliorated and prevented the development of metabolic disorders, such as obesity and diabetes mellitus. In the present study, we demonstrated that berberine, a naturally occurring compound, stimulated FGF21 expression in brown adipose tissue (BAT).

Correction to: Neuroprotective effect of naturally occurring RXR agonists isolated from Sophora tonkinensis Gagnep. on amyloid-β-induced cytotoxicity in PC12 cells.

In the original publication of the article, Table 1 and Fig. 1 were incorrectly published.

Sesquiterpenes with new carbon skeletons from the basidiomycete Phlebia tremellosa.

Three new sesquiterpenes, phlebidiol, phlebioic acid, and phlebiolide, as well as the known compound tremetriol, were isolated from cultures of the basidiomycete Phlebia tremellosa. The structures of all isolated compounds were established by extensive spectroscopic analyses, including those involving extensive two-dimensional nuclear magnetic resonance. The absolute configurations of phlebidiol, phlebioic acid, and phlebiolide were determined by comparisons of experimental and calculated electronic circular dichroism spectra.

Anti-inflammatory effects of naturally occurring retinoid X receptor agonists isolated from Sophora tonkinensis Gagnep. via retinoid X receptor/liver X receptor heterodimers.

Retinoid X receptor (RXR) ligands have a wide range of beneficial effects in mouse models of Alzheimer's disease (AD). Recently accumulated evidence suggests that early neuroinflammation may be a therapeutic target for AD treatment. We therefore investigated the anti-inflammatory effects of the prenylated flavanoids SPF1 and SPF2, which were previously isolated from root of Sophora tonkinensis and identified as potent ligands for RXR, and potential mechanisms involved.

Baicalein stimulates fibroblast growth factor 21 expression by up-regulating retinoic acid receptor-related orphan receptor α in C2C12 myotubes.

Retinoic acid receptor-related orphan receptor (ROR) α has been implicated in various physiological functions, including the immune system, inflammation, and circadian rhythms. In the present study, the synthetic RORα/γ agonist SR1078 stimulated the production and gene expression of fibroblast growth factor 21 (FGF21) in C2C12 myotubes. FGF21, a member of the FGF family, plays important roles in the regulation of peripheral glucose tolerance and lipid metabolism and improves metabolic health.

Neuroprotective effect of naturally occurring RXR agonists isolated from Sophora tonkinensis Gagnep. on amyloid-β-induced cytotoxicity in PC12 cells.

Neuronal cell death induced by amyloid-β (Aβ) oligomers is implicated in neuronal degeneration and is a leading cause of Alzheimer's disease (AD). Therefore, to identify effective therapeutic agents for AD, we investigated the neuroprotective effects of two naturally occurring retinoid X receptor (RXR) agonists (SPF1 and SPF2), isolated from the root of Sophora tonkinensis Gagnep., on the Aβ-induced cytotoxicity against nerve growth factor-differentiated rat pheochromocytoma (PC12) cells.

Induction of beige adipocytes by naturally occurring β3-adrenoceptor agonist p-synephrine.

The prevalence of obesity and its associated diseases is increasing worldwide, and the therapeutic potential of increasing energy expenditure through differentiation or activation of beige adipocytes has attracted much interest. Therefore, we explored naturally occurring compounds that induce beige adipocytes by screening for activity to induce mRNA expression of uncoupling protein 1 (UCP1) in stromal vascular fraction (SVF) cells cultured in beige adipocyte differentiation medium. Through screening, p-synephrine, a compound isolated from Citrus unshiu Marcov.

Brazilian propolis ethanol extract and its component kaempferol induce myeloid-derived suppressor cells from macrophages of mice in vivo and in vitro.

Background: Brazilian green propolis is produced by mixing secretions from Africanized honey bees with exudate, mainly from Baccharis dracunculifolia. Brazilian propolis is especially rich in flavonoids and cinammic acid derivatives, and it has been widely used in folk medicine owing to its anti-inflammatory, anti-viral, tumoricidal, and analgesic effects. Moreover, it is applied to prevent metabolic disorders, such as type 2 diabetes and arteriosclerosis.

Ameliorative effect of panaxynol on the reduction in high-molecular-weight adiponectin secretion from 3T3-L1 adipocytes treated with palmitic acids.

Reduced plasma levels of the high-molecular weight (HMW) form of adiponectin, rather than total adiponectin levels, have been shown to be closely associated with various metabolic diseases including insulin resistance, type 2 diabetes, and cardiovascular disease. Therefore, we sought to explore active, naturally occurring compounds that promote the recovery of HMW adiponectin secretion suppressed by palmitic acid in our model. A total of 90 crude drug extracts were screened for the ability to augment HMW adiponectin secretion from 3T3-L1 adipocytes treated with palmitic acid.

Gerontoxanthone B from Maclura cochinchinensis var. gerontogea exhibits anti-inflammatory potential as an aryl hydrocarbon receptor agonist.

The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcriptional factor belonging to the basic helix-loop-helix-Per-Ahr/Arnt-Sim family. In this study, we evaluated the AhR agonistic activities of 12 xanthones isolated from the roots of M. cochinchinensis var.

Pteleifolols A-E, acetophenone di-C-glycosides and a benzopyran dimer from the leaves of Melicope pteleifolia.

Four new acetophenone di-C-glycosides, pteleifolols A-D (1-4) and a new dimeric benzopyran, pteleifolol E (5), were isolated from the leaves of Melicope pteleifolia. Seven known compounds, including 2,4,6-trihydroxyacetophenone-3,5-di-C-glucopyranoside (6), were also isolated. Structures of the new compounds (1-5) were established by using spectroscopic and spectrometric techniques, including 1D and 2D nuclear magnetic resonance (NMR), UV, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data.

Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa.

The emergence and spread of multidrug-resistant P. aeruginosa infections is of great concern, as very few agents are effective against strains of this species. Methanolic extracts from the Coptidis Rhizoma (the rhizomes of Coptis japonica var.

Yuccalides A-C, three new phenolic compounds with spiro-structures from the roots of Yucca gloriosa.

Three new phenolic compounds, yuccalides A-C (1-3), were isolated from the roots of Yucca gloriosa L., along with four known compounds (4-7). The structures of the new compounds were established by extensive NMR spectroscopic analyses.

Atranorin and lecanoric acid antagonize TCDD-induced xenobiotic response element-driven activity, but not xenobiotic response element-independent activity.

Lichens are symbiotic organisms that consist of fungi and photosynthetic symbionts (algae and/or cyanobacteria). Previous studies of their constituents suggested lichens produce many kinds of aromatic secondary metabolites, such as depsides, quinones, and dibenzofurans. In this study, we evaluated the aryl hydrocarbon receptor (AhR) antagonistic activity of 17 lichen substances and demonstrated that atranorin (1) and lecanoric acid (2), isolated from Parmotrema tinctorum Hale, showed an inhibitory effect on luciferase activity increased by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), using an XRE-driven pX4TK-Luc reporter gene assay.