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Phytochemical investigation on the dried fruits of Casearia grewiifolia led to the identification of 10 new salicinoyl quinic acid derivatives (1-10), a new benzoyl quinic acid (11), and two known compounds (12 and 13). The structures of the new compounds were elucidated by interpreting 1D and 2D NMR spectroscopic data including HMBC and EXSIDE along with a chemical method for sugar unit analysis. All isolates were evaluated for their inhibitory activities against prostaglandin E2 (PGE2) production in ultraviolet B (UVB)-irradiated HaCat keratinocytes. Of the isolates tested, compounds 6 and 12 were found to inhibit PGE2 production with IC50 values of 20.5 and 28.8 μM, respectively.

Gaylussacin (1), a stilbene glucoside, has been isolated from Pentarhizidium orientale and is used in Korean folk medicine. Although it was first isolated in 1972, the synthesis of gaylussacin has ...

Phytochemical investigation of the methanol extract of the aerial parts of Salvia plebeia aided by a proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA expression screening assay in HepG2 cells led to the identification of 19 compounds including one new norsesquiterpene (1), six new eudesmane sesquiterpenoids (2-5, 8, and 11), and 12 known compounds. The structures of all compounds were elucidated by interpretation of their 1D and 2D NMR spectroscopic and MS data. Furthermore, computational prediction of ECD or chemical shifts was used to propose the absolute configurations of the new structures. All isolates were assessed for their inhibitory activities against PCSK9 mRNA expression and PCSK9-low-density lipoprotein receptor (LDLR) interactions. None of the isolated compounds inhibited PCSK9 and LDLR interactions. However, compounds 1, 9, and 10 downregulated PCSK9 mRNA expression.

Phytochemical investigation on the dried fruits of

Three acylated saponins and three flavonoid glycosides, along with nine known flavonoids, were isolated from the fruits of Stewartia koreana Nakai ex Rehder (Theaceae) using relative mass defect filtering analysis. The structures of these compounds were determined by performing spectroscopic analyses and using chemical methods. Furthermore, all the isolates were evaluated for their effects on the mRNA expression of the genes for proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) as well as their inhibitory activities on PCSK9 and LDLR binding. None of the isolates was deemed to be active in PCSK9-LDLR binding inhibition. However, (+)-catechin was found to inhibit PCSK9 expression and increase LDLR expression, suggesting the potential of (+)-catechin to lower cholesterol level via the downregulation of PCSK9 expression.

Ethnopharmacological relevance Penthorum chinense has been used in East Asia for the treatment of cholecystitis, infectious hepatitis, jaundice and to treat liver problems. Recent evidences provided the potential for the clinical use of P. chinense in the treatment of metabolic disease. Aim of the study: Based on the traditional use and recent evidences, we investigated the effects of constituents from P. chinense with modulation on proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptor (LDLR) expression, and the effect of the most active substance on cholesterol uptake, and genes relevant to lipid metabolism. Materials and methods The isolation of compounds from the BuOH-soluble extract of 80% methanol extract of P. chinense was conducted using chromatographic methods and the structures were established by interpreting spectroscopic data. Quantitative real time-PCR, and Western blot analysis were performed to monitor the regulatory activity on PCSK9 and LDLR expression. PCSK9-LDLR binding interaction was also tested. The cholesterol uptake in hepatocyte was measured using 1,1-dioctadecyl-3,3,3,3-tetramethylindocarbocyanine perchlorate (DiI)-labeled LDL cholesterol. Additionally, gene network analysis of LDLR and responses of its target proteins were carried out to discover genes germane to the effect of active compound on HepG2 cells. Moreover, we performed protein-protein interaction analysis via String and constructed the compound target network using Cytoscape. Results Two new neolignans and 37 known compounds were characterized from P. chinense. Of the isolated compounds, (7′E,8S)-2′,4,8-trihydroxy-3-methoxy-2,4′-epoxy-8,5′-neolign-7′-en-7-one (3), penthorin A (4) and methyl gallate (25) were found to suppress PCSK9 mRNA expression with IC50 values of 5.13, 15.56 and 11.66 μM, respectively. However, all the isolated compounds were found to be inactive in PCSK9-LDLR interaction assay. Additionally, a dibenzoxepine-type lignan analog, (7′E,8S)-2′,4,8-trihydroxy-3-methoxy-2,4′-epoxy-8,5′-neolign-7′-en-7-one (3) demonstrated to upregulate LDLR mRNA and protein expression via transcriptional factor sterol regulatory element-binding protein 2 (SREBP2). Furthermore, (7′E,8S)-2′,4,8-trihydroxy-3-methoxy-2,4′-epoxy-8,5′-neolign-7′-en-7-one (3) increase the LDL-cholesterol uptake in DiI-LDL assay. Conclusion (7′E,8S)-2′,4,8-trihydroxy-3-methoxy-2,4′-epoxy-8,5′-neolign-7′-en-7-one (3) seemed to increase potentially cholesterol uptake via the downregulation of PCSK9 and the activation of LDLR in hepatocytes. Moreover, SREBP2 was found to play an important role in regulation of PCSK9 and LDLR by (7′E,8S)-2′,4,8-trihydroxy-3-methoxy-2,4′-epoxy-8,5′-neolign-7′-en-7-one.

Phytochemical investigation of the methanol extract of the aerial parts of

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.

Six new dimeric lignans (1-6) and one new lignan glycoside (16) were isolated from Forsythia viridissima roots along with nine known lignans (7-15). Spectroscopic analyses and chemical methods were used to determine these new structures and their absolute configurations. Among these compounds, dimatairesinol (1) and viridissimaols A-E (2-6) were assigned as dimers of dibenzylbutyrolactone analogues. Furthermore, the isolated compounds were evaluated for their antiviral activities against coxsackievirus B3 (CVB3) and human rhinovirus 1B (HRV1B). In these tests, compounds 12 and 15 showed antiviral effects against CVB3 infection with IC50 values of 15.4 and 36.4 μM, respectively, while 2, 3, 8, and 9 showed activities against HRV1B with IC50 values of 45.7, 47.5, 13.0, and 43.2 μM, respectively.

Oligostilbenes are polyphenol oligomers derived from resveratrol and are commonly produced by members of the Gnetaceae family, and many researchers have focused on their anti-inflammatory activities. The EtOAc fraction of a Gnetum latifolium extract showed inhibitory activity against neuroinflammation induced by the transfection of Aβ1-42 into microglial BV-2 cells. The bioassay-guided isolation of the 70% EtOH extract of this plant resulted in three previously undescribed resveratrol oligostilbenes and ten known stilbene derivatives. The structures of the isolated compounds were established based on extensive NMR spectroscopic analysis. The absolute configurations of the three undescribed compounds were confirmed by comparison with available compounds with known stereochemistry and by ECD calculations and molecular modelling. Latifoliols A and B are the first reported oligostilbenes with a bridged 3-oxabicyclo[3.3.0]octane moiety, and latifoliol C was formed by the condensation of gnemontanin G with oxyresveratrol. Moreover, the hypothetical biogenetic pathway of latifoliols A, B and C was proposed. The potential anti-inflammatory activities of the thirteen isolated compounds were tested by measuring their effect on the secreted NO concentrations induced by transfection with plasmids expressing the Aβ1-42 gene in the BV-2 cell line. Interestingly, cis- and trans-shegansu B and latifolol, whose structures contained double bonds, strongly inhibited NO secretion in BV-2 cells, supporting the double binding effect of the stilbene derivative on inhibitory activity.

Thirteen C-methylated flavonoid glycosides (1–13), along with 15 previously known flavonoids (14–28), were isolated from rhizomes of Pentarhizidium orientale. Among these compounds, matteuorienates D–K (1–8) were obtained as analogues of matteuorienates A–C (14–16), which contain a characteristic 3-hydroxy-3-methylglutaryl (HMG) moiety. The structures of 1–13 were characterized by spectroscopic analysis and chemical derivatization. The isolates were evaluated for their antiviral activities against influenza virus (H1N1), with compounds 21, 22, 23, 25, and 26 showing inhibitory effects (IC50 of 23.9–30.3 μM) against neuraminidases.

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.

Ethnopharmacological relevance The fruits of Schisandra chinensis (Trucz.) Baill. (Schisandraceae) which have been used as a tonic especially for kidney yin deficiency in Chinese traditional medicine are recently receiving attention for its preventive activity on age-related neurodegenerative diseases. A variety of studies demonstrated the cognitive-enhancing effects of Schisandra chinensis through animal tests and also in clinical trials. Aim of study In this study, we attempted to investigate the effects of the lignan-riched extract of Schisandra chinensis fruits (ESP-806) on neurotoxicity and memory impairment induced by Aβ 1–42 injection in mice. Materials and methods The fruits of Schisandra chinensis were extracted with the mixture of n -hexane:ethanol (9:1), which is riched with bioactive dibenzocyclooctadiene lignans, schizandrin, gomisin N, wuweigisu C. After oral treatment of ESP-806 (100 mg/kg body weight) followed by injection of Aβ 1–42 (2 μg/mouse, i.c.v. ), novel object recognition and passive avoidance tests were evaluated. To verify the cognition enhancing effects of ESP-806, we examined the effects of ESP-806 on the activities of β -secretase and acetylcholinesterase, and the contents of Aβ and the reduced glutathione within the cortex and hippocampus of Aβ-injected mice. Results Oral treatment of ESP-806 (100 mg/kg body weight) significantly attenuated Aβ 1–42 -induced memory impairment evaluated by behavioral tests. Furthermore, the treatment of ESP-806 attenuated the elevation of β -secretase activity accompanying the reduced level of Aβ 1–42 in the cortex and hippocampus of the brain. ESP-806 also significantly inhibited the acetylcholinesterase activity in the hippocampus and increased the content of the reduced glutathione in the cortex and hippocampus of mouse brain. Conclusions These data suggested that the extract of Schisandra chinensis fruits riched with dibenzocyclooctadiene lignans may be useful in the prevention and treatment of Alzheimer's disease.

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.

Bioassay-guided fractionation of the EtOAc extract from Disporum viridescens roots led to the isolation of five new benzyl benzoate glycosides, BBGs (1-5). The neuroprotective activities of the BBGs were screened using neuronal HT22 hippocampal cells. BBG-D (4) significantly protected murine hippocampal HT22 cells against glutamate-induced neurotoxicity by maintaining the antioxidative defense systems such as superoxide dismutase, glutathione reductase, glutathione peroxidase, and the glutathione content. BBG-D, in a dose-and time-dependent manner, increased HO-1 expression through the selective activation of pERK signaling among the MAPK pathways. These results suggest that BBG-D could be a promising candidate for the treatment of neurodegenerative diseases related to glutamate-induced oxidative neuronal cytotoxicity.

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.