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Background: Penthorum chinense has been used in East Asia for the treatment of cholecystitis, infectious hepatitis, and jaundice. So far there is no report regarding proprotein convertase subtilisin/kexin type 9 inhibitory constituents from this plant. The aim of the present study was to discover new active constituents with PCSK9 expression inhibitory activities from P. chinenseMethods: All structures were established by interpreting NMR spectroscopic data and MS data. Further experimental and calculated ECD data were used to determine the absolute configuration of the two new neolignans. To monitor the inhibitory activity on proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA expression and PCSK9-low density lipoprotein receptor (LDLR) interaction, quantitative real time-PCR, Western blot analysis, and an enzyme-linked immunosorbent assay (ELISA) method by a PCSK9-biotinylated-LDLR binding assay were performed.Results: 39 compounds were isolated and identified including two new oxepine-type neolignans, penthorinols A (1) and B (2) and a naturally occurring chalcone, 6'-hydroxy-2'-methoxychalcone-4'-O-β-D-glucopyranoside (20). Of all tested compounds, penthorin A (4) and methyl gallate (25) were found to suppress PCSK9 mRNA expression with IC50 values of 15.56 and 11.66 µM, respectively. Furthermore, penthorin A (4) and methyl gallate (25) downregulated PCSK9 protein expression. However, all compounds seemed to be inactive in PCSK9-LDLR interaction.Conclusion: In the present study, two new compounds was discovered from this plant and active constituents with PCSK9 expression inhibitory activities were suggested.

Cough and phlegm frequently occur in respiratory diseases like upper respiratory tract infections, acute bronchitis, and chronic obstructive pulmonary diseases. To relieve these symptoms and diseases, various ingredients are being used despite the debates on their clinical efficacy. We aimed to investigate the effects of the extract CKD-497, composed of Atractylodis Rhizoma Alba and Fructus Schisandrae, in relieving cough and facilitating expectoration of phlegm. CKD-497 was found to inhibit inflammatory mediators such as interleukin-8 (IL-8) and tumor necrosis factor &alpha, (TNF-&alpha, ) in lipopolysaccharide (LPS)-treated mouse macrophages and transient receptor potential cation channel 1 (TRPV-1)-overexpressed human bronchial epithelial cells stimulated by capsaicin. CKD-497 decreased the viscosity of the mucin solution. During in vivo experiments, CKD-497 reduced coughing numbers and increased expectoration of phlegm via mucociliary clearance enhancement. Collectively, these data suggest that CKD-497 possesses potential for cough and phlegm expectoration treatment.

Background Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Recently, the inhibitory effects of flavone glycosides isolated from Sicyos angulatus extract on hepatic lipid accumulation in vitro were demonstrated. However, the effects of S. angulatus extract and its major flavonoid glycoside on in vivo hepatic steatosis induced by a high-fat diet have not yet been established. Hypothesis/Purpose The aim of this study was to investigate the effects of S. angulatus extract and its major flavonoid glycoside, kaempferol 3-O-[α- l -rhamnopyranosyl-(1→6)]-β- d -glucopyranosyl-7-O-α- l -rhamnopyranoside, on hepatic steatosis in high-fat diet-fed mice, which serves as a model of NAFLD. In addition, attempts have been made to chemically profile the metabolites involved in the activity of the S. angulatus extract. Methods C57BL/6 J mice were divided into vehicle, total extract of S. angulatus (SA; 50, 100 and 200 mg/kg) and major active component (20 mg/kg) groups. The mice were fed a high-fat diet (HFD) with or without S. angulatus extract or its major single compound for 10 weeks. Chemical identification was carried out using ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-qTOF-MS/MS) and then quantified by HPLC-DAD. Results Administration of S. angulatus extract significantly lowered plasma ALT and AST levels in HFD-fed mice compared to those of the vehicle group. The hepatic lipid content, as evidenced by oil-red O staining and quantification, was significantly lower in the S. angulatus-administered group, and the effect was dose dependent. These beneficial effects of S. angulatus extract were related to the decreased expression of hepatic genes involved in fatty acid (ACC1, FAS and SCD1) and triglyceride (DGAT) synthesis. The expression levels of two key transcription factors regulating lipogenesis, SREBP-1c and PPARγ, were significantly suppressed in the liver by administration of S. angulatus extract with HFD. Treatment of the HFD-fed mice with the major compound isolated from S. angulatus extract resulted in improved liver function along with an anti-steatotic effect similar to the results seen with S. angulatus extract. For the standardization of the S. angulatus extract, 23 compounds were identified based on MS/MS fragmentation and UV spectroscopy. Quantitative analysis of the major compound showed that the major component was present in 15.35 ± 0.01 mg/g of total extract. Conclusion These findings suggest that S. angulatus extract and its major component have the potential to improve liver function and hepatic steatosis in diet-induced obese mice.

Diarylheptanoids have been the center of the intensive research efforts for Alzheimer's disease and other neurodegenerative diseases. The present study aimed to determine the effect of the standardized extract of B. platyphylla bark and its major diarylheptanoids in scopolamine-induced amnesic mice through cyclic AMP response element-binding protein (CREB) activation. Oral administration of the standardized extract of B. platyphylla bark (100 mg/kg body weight), aceroside VIII (1 mg/kg body weight) and platyphylloside (1 or 2 mg/kg body weight) significantly ameliorated scopolamine-induced amnesia in passive avoidance test. CREB phosphorylation and brain-derived neurotrophic factor (BDNF) expression in the cortex and hippocampus of the scopolamine-treated mice were markedly increased by the treatment of the standardized extract of B. platyphylla bark and platyphylloside. The standardized extract of B. platyphylla bark and its major diarylheptanoids also significantly protected HT22 cells against neurotoxicity induced by glutamate insult. The standardized extract of B. platyphylla bark and platyphylloside may ameliorate memory deficits by activating the CREB–BDNF pathway and prevent a neurodegeneration by inhibiting neuronal cell death.

The neuroprotective potential of flavonoids within the brain comprises anti-apoptosis of neuronal cells, anti-neuroinflammation and enhancement of cognitive function. We reported that Rhus vernciflua inhibits glutamate-induced neurotoxicity in primary cultured rat cortical cells. Here we narrowed it down to get neuroprotective fractions from the plant yielding flavonoid-rich ethyl acetate fraction (PREF). Among its active flavonoids, fisetin exhibited not only inhibitory effect against lipopolysaccharide (LPS)-induced neuroinflammation by suppressing inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 but also memory enhancing effects via reactivation of cAMP responsive element binding protein (CREB)-brain derived neurotrophic factor (BDNF) pathway in memory-impaired mice by scopolamine. Butein also showed a similar activity to fisetin even though to a lesser extent. The neuroprotection by PREF and selected flavonoids may involve maintenance of antioxidant defense mechanism including glutathione peroxidase (GSH-Px), glutathione reductase (GR) and superoxide dismutase (SOD). Conclusively, we demonstrate the R. vernciflua bark extract and its active flavonoids with potent neuroprotective and anti-inflammatory effects might be good therapeutic candidates as cognitive-enhancers.

A methanolic extract of the roots of Polygala tenuifolia (Polygalaceae) significantly attenuated nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Five xanthones, 1-hydroxy-7-methoxyxanthone (1), 3,6-dihydroxy-1,2,7-trimethoxyxanthone (2), 1,3,6-trihydroxy-2,7-dimethoxyxanthone (3), 1,7-dihydroxy-2,3-dimethoxyxanthone (4) and 1,7-dihydroxy-3-methoxyxanthone (5), and five phenylpropanoids, 4-hydroxy-3-methoxypropiophenone (6), methyl 4-hydroxy-3-methoxycinnamic acid (7), 3,4,5-trimethoxycinnamic acid (8), 4-methoxycinnamic acid (9) and β-d-(3-O-sinapoyl) fructofuranosyl-α-d-(6-O-sinapoyl)glucopyranoside (10), were isolated from CHCl(3) fraction using bioactivity-guided fractionation. Among these compounds, compounds 1, 2, 4, 5 and 7 showed significant inhibitory effects on LPS-induced NO production in BV2 microglia cells at the concentration ranging from 10.0 to 100.0 μM.