Antioxidant and Inhibitory Activities of Filipendula glaberrima Leaf Constituents against HMG-CoA Reductase and Macrophage Foam Cell Formation.

In our search for bioactive components, various chromatographic separations of the organic fractions from Filipendula glaberrima leaves led to the isolation of a new ellagitannin and a triterpenoid, along with 26 known compounds. The structures of the isolates were determined based on their spectroscopic properties and chemical evidence, which were then evaluated for their antioxidant activities, inhibitory activities on 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and foam cell formation in THP-1 cells to prevent atherosclerosis. Rugosin B methyl ester (1) showed the best HMG-CoA reductase inhibition and significantly reduced ox-low-density lipoprotein-induced THP-1 macrophage-derived foam cell formation at 25 µM. In addition, no cytotoxicity was observed in THP-1 cells at 50 µg/mL of all extracts in the macrophage foam cell formation assay. Therefore, F. glaberrima extract containing 1 is promising in the development of dietary supplements due to its potential behavior as a novel source of nutrients for preventing and treating atherosclerosis.

Anti-inflammatory effect and metabolic mechanism of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on atopic dermatitis in vivo and in vitro.

BACKGROUND: Atopic dermatitis (AD) is a chronic, relapsing skin disease accompanied by itchy and dry skin. AD is caused by complex interactions between innate and adaptive immune response. AD treatment include glucocorticoids and immunosuppressants. However, long-term treatment can have serious side effects. Thus, an effective AD treatment with fewer side effects is required. Natural materials, including herbal medicines, have potential applications. PURPOSE: This study evaluated the in vivo and in vitro therapeutic effects of BS012, a mixture of Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts, on AD and investigated the underlying metabolic mechanisms. METHODS: The anti-inflammatory effects of BS012 were assessed using a mouse model of AD induced by 1­chloro-2,4-dinitrobenzene (DNCB) and in tumor necrosis factor-alpha/interferon-gamma (TNF-α/IFN-γ) stimulated normal human epidermal keratinocytes (NHEKs). In DNCB-induced mice, total dermatitis score, histopathological analysis, and immune cell factors were assessed to evaluate the anti-atopic activity. In TNF-α/IFN-γ-stimulated NHEKs, pro-inflammatory cytokines, chemokines, and related signaling pathways were investigated. Serum and intracellular metabolomics were performed to identify the metabolic mechanism underlying the therapeutic effects of BS012 treatment. RESULTS: In DNCB-induced mice, BS012 showed potent anti-atopic activity, including reducing AD-like skin lesions and inhibiting the expression of Th2 cytokines and thymic stromal lymphopoietin. In TNF-α/IFN-γ-stimulated keratinocytes, BS012 dose-dependently inhibited the expression of pro-inflammatory cytokines and chemokines by blocking nuclear factor-kappa B and signal transducer and activator of transcription signaling pathways. Serum metabolic profiles of mice revealed significant changes in lipid metabolism related to inflammation in AD. Intracellular metabolome analysis revealed that BS012 treatment affected the metabolism associated with inflammation, skin barrier function, and lipid organization of the stratum corneum. CONCLUSION: BS012 exerts anti-atopic activity by reducing the Th2-specific inflammatory response and improving skin barrier function in AD in vivo and in vitro. These effects are mainly related to the inhibition of inflammation and recovery of metabolic imbalance in lipid organization. BS012, a novel combination with strong activity in suppressing the Th2-immune response, could be a potential alternative for AD treatment. Furthermore, the metabolic mechanism in vivo and in vitro using a metabolomics approach will provide crucial information for the development of natural products for AD treatment.

Metabolites identification for major active components of Agastache rugosa in rat by UPLC-Orbitap-MS: Comparison of the difference between metabolism as a single component and as a component in a multi-component extract.

Agastache rugosa (fisch. & C.A. Mey.) Kuntze (A. rugosa) is used in traditional medicine in Korea since it has variety of medicinal activities, such as antioxidant, anti-inflammatory, anti-photoaging. Acacetin, tilianin, and rosmarinic acid are the active components of A. rugosa but their metabolites have not yet been fully identified. The purpose of this study was to identify the metabolites of A. rugosa after oral administration in Sprague-Dawley rats. For this study, active components (acacetin, tilianin, rosmarinic acid) and A. rugosa extract were dissolved in 0.5% carboxymethyl cellulose sodium solution respectively and treated by oral gavage at a dose of 50 mg/kg (for single compounds) and 200 mg/kg (for A. rugosa extract). For metabolite identification, plasma, urine, and fecal samples were collected after oral administration and analyzed using liquid chromatography coupled with Orbitrap mass spectrometry (UPLC-Orbitrap-MS) for data acquisition and metabolite identification. Metabolite identification was performed by considering the mass difference of the metabolites from the parent compounds and using their exact m/z and MS/MS fragments. The main biotransformation of the major components of A. rugosa was hydrolysis to acacetin, followed by demethylation, methylation, and conjugation. That of rosmarinic acid is methylated and conjugated. There were differences in metabolism between the treatment of single active components and extract; some sulfate-conjugated metabolites or metabolic intermediates were only detected in the treatment of single active components. The reason for this is thought to be the low content of the active components in the extract, which react competitively with the components present in the extract in the metabolic process. This study provides valuable evidence for a comprehensive understanding of the metabolism of A. rugosa.

Astrocytes Control Sensory Acuity via Tonic Inhibition in the Thalamus.

Sensory discrimination is essential for survival. However, how sensory information is finely controlled in the brain is not well defined. Here, we show that astrocytes control tactile acuity via tonic inhibition in the thalamus. Mechanistically, diamine oxidase (DAO) and the subsequent aldehyde dehydrogenase 1a1 (Aldh1a1) convert putrescine into GABA, which is released via Best1. The GABA from astrocytes inhibits synaptically evoked firing at the lemniscal synapses to fine-tune the dynamic range of the stimulation-response relationship, the precision of spike timing, and tactile discrimination. Our findings reveal a novel role of astrocytes in the control of sensory acuity through tonic GABA release.

Analysis of plasma metabolic profiling and evaluation of the effect of the intake of Angelica keiskei using metabolomics and lipidomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Angelica keiskei contains many bioactive components with anti-oxidative and anti-inflammatory effects. It is also effective for the treatment of diabetes mellitus, hypertension, and arteriosclerosis, but the relationships between these effects and the active components in the herb have not been studied. AIM OF THE STUDY: We aimed to confirm the effects of Angelica keiskei on humans. MATERIALS AND METHODS: A metabolomics and lipidomics study was performed using human plasma samples from 20 subjects after the intake of Angelica keiskei, and the components of Angelica keiskei in the plasma were profiled. UPLC-Orbitrap-MS was used to analyze the plasma and plant extracts, and multivariate analysis and correlation studies between the exogenous components from plant and endogenous metabolite in plasma were performed. RESULTS: The levels of the 14 metabolites including kynurenic acid, prostaglandin E1, chenodeoxycholic acid, lysoPC (18:1), lysoPC (18:2), lysoPC (20:3), lysoPC (20:4), lysoPC (22:6), PC (34:1), PC (34:2), PC (38:3), PC (38:4), PC (38:6) and PC (40:7) in the plasma were changed. By monitoring the components originating from Angelica keiskei in plasma, five components including 5-methoxypsoralen, 8-methoxypsoralen, 4-hydroxyderricin, xanthoangelol B and xanthoangelol F were detected and they reduced the levels of bile acids and fatty acids. CONCLUSIONS: The levels of the metabolites, including bile acids, amino acids, glycerophospholipids and fatty acids, in the plasma were changed, and 14 significantly changed metabolites were closely related to the preventive effect against liver diseases, type 2 diabetes, anemia, obesity, atherosclerosis, depression and anti-inflammatory effects. The five components of Angelica keiskei were related the modulatory activity of reducing the levels of bile acids and fatty acids.

Identification of interactions between multiple components in Socheongryong-tang using a plant profiling approach.

Traditional herbal medicine consists of multiple components. There are interactions among the components, which affect both potency and toxicity. The preparation of herbal medicines can be a cause of interactions between multicomponents in herbs. To demonstrate the differences in multiherb interactions based on the preparation methods, the changes in the active components in the different preparations of Socheongryong-tang (SCRT) were evaluated using metabolomics profiling. We performed multicomponent profiling of the decoction of SCRT (SCRTD) and individual herb mixture (SCRTM) using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Active compounds from SCRTD and SCRTM were identified using multivariate analysis, and the activities between the two groups were compared. We also evaluated the anti-inflammatory effect of SCRT through investigating the protein expression of iNOS and COX-2 in lipopolysaccharide-induced macrophage RAW 264.7 cells in both groups. From the multivariate analysis, 53 active compounds that have different intensities between SCRTD and SCRTM were identified. The intensities of those components, such as ephedrines, glycyrrhizic acid, 6-gingerol and (2E,4E,8Z,10E)-N-isobutyl-2,4,8,10-dodecatetraenamide, which is newly identified in Asiasarum heterotropoides, were mostly higher in SCRTD than in SCRTM, which was related to the anti-inflammatory effect. From the iNOS inhibition test, it was found that SCRTD had a stronger anti-inflammatory effect than SCRTM. It was demonstrated that multicomponent interactions can be changed by the preparation method, and finally the anti-inflammatory effect in SCRT can be affected.