Cycloartane-type triterpenoids from Combretum quadrangulare Kurz with PCSK9 secretion inhibitory activities.

Nine previously undescribed (1-9) and seven known (10-16) cycloartane-type triterpenoids were isolated and characterized from Combretum quadrangulare Kurz using physicochemical and spectroscopic methods. The absolute configurations of these compounds were determined through modified Mosher's method and quantum chemical calculation of electronic circular dichroism (ECD) and vibrational circular dichroism (VCD) spectra. Their inhibitory activities against PCSK9 secretion were assessed, and a plausible structure-activity relationship was delineated.

Butanolides and clerodane diterpenes from the twigs of Casearia grewiifolia and their effects on adiponectin secretion.

Three butanolides derivatives, grewiifolides A-C, and nine clerodane diterpenes, grewiifolins M-U, as well as a known sterol were isolated from the twigs of Casearia grewiifolia. The chemical structures and configurations of all isolates were established by various spectroscopic means and chemical derivatization. In a cell-based phenotypic assay using the adipogenesis model of human bone marrow mesenchymal stem cells (hBM-MSCs), grewiifolide B significantly promoted adiponectin-secretion with EC value of 24.

Chemical constituents from the roots of Cynanchum wilfordii with PCSK9 secretion inhibitory activities.

From the Cynanchum wilfordii roots, 32 compounds, including 5 previously undescribed (1, 4-6, 12) and 27 known (2, 3, 7-11, 13-32) compounds, were isolated, and their structures were elucidated using NMR spectroscopic data and MS data aided by ECD calculations or the modified Mosher's reaction. All isolates were tested for their inhibitory effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion. Among the isolates, compound 4, a methyl cholesterol analog, exhibited the most potent effect in reducing PCSK9 secretion, along with PCSK9 downregulation at the mRNA and protein levels via FOXO1/3 upregulation.

Stereochemical assignment of clerodane-type diterpenes from the fruits of Casearia grewiifolia and their ability to inhibit PCSK9 expression.

More than 20 natural products have been reported to modulate PCSK9-mediated cholesterol regulation, and small-molecule-derived proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors continue to be developed and identified. Here, twelve undescribed clerodane-type diterpenes (1-9 and 12-14) and two known compounds were isolated from the chloroform-soluble extract of the dried fruits of Casearia grewiifolia Vent. using a PCSK9 mRNA expression monitoring assay.

Chemical constituents from with proprotein convertase subtilisin/kexin type 9 expression and secretion inhibitory activity.

Six new flavanones, including sanggenol W (1), morusalnol D-F (2-4) and neovanone A and B (5 and6), and fourteen known compounds were isolated from the methanol extract of the dried root bark of using various column chromatographic methods. Their structures were elucidated using spectroscopic methods. The isolated compounds were tested for LDLR, PCSK9 and IDOL mRNA regulatory activity, and it was found that betulinic acid (13) showed the most potent effect on downregulation of PCSK9 and upregulation of LDLR at both mRNA and protein levels, showing comparable results to berberine, the positive control.

Isocoumarins and Benzoquinones with Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activities from Dried Roots of .

A phytochemical investigation of the -hexane-soluble chemical constituents roots allowed for selection using a proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells. This led to the isolation of two previously undescribed isocoumarins of natural origin, 8'Z,11'Z-octadecadienyl-6,8-dihydroxyisocoumarin () and 3-pentadecyl-6,8-dihydroxyisocoumarin (), along with 20 previously reported compounds (-). All of the structures were established using NMR spectroscopic data and MS analysis.

Alkaloids and Coumarins with Adiponectin-Secretion-Promoting Activities from the Leaves of .

Fractionation of a methanol extract of leaves led to the identification of five new quinoline alkaloids (, , , , and ), three new coumarins (, , and ), and 20 known compounds. The structures were determined by analysis of 1D and 2D NMR spectroscopic data. The absolute configuration of was proposed by electronic circular dichroism calculation.

Analgesic effects of saikosaponin A in a rat model of chronic inflammatory pain.

Saikosaponin A (SSA) is the main active ingredient of roots of the East Asian medicinal plant, L. The present study was aimed at delving into the analgesic properties of SSA in a model of chronic inflammatory pain. To this end, rats were initially treated intraplantarly with complete Freund's adjuvant for induction of hyperalgesia.

Chemical Constituents from the Roots and Rhizomes of and Their Effects on Proprotein Convertase Substilisin/Kexin Type 9 Expression.

This study was conducted to further investigate bioactive molecules from that can inhibit proprotein convertase substilisin/kexin type 9 (PCSK9) expression. After interpreting NMR spectroscopic data and MS spectral data of all isolates, a new naturally occurring compound, 6-hydroxy-vitexin-2″--rhamnoside (), was identified along with 30 known compounds. The calculation of the gauge-including atomic orbital (GAIO) and electronic circular dichroism (ECD) proposed the absolute configuration of as (2,3)-methyl-2-(4-hydroxybenzyl)tartrate by comparing the calculated ECD with experimental data.

Suppressing effect of a saikosaponin-enriched extract of on alcohol and chocolate self-administration in rats.

Recent studies demonstrated that saikosaponin (SS) A and other SSs extracted from L (Apiaceae) roots abolished different behaviours motivated by drugs of abuse and palatable foods in rats. The present study was designed to investigate the effect of an SS-enriched extract fraction of roots on operant, oral self-administration of alcohol and chocolate in rats. To this end, female Sardinian alcohol-preferring and Wistar rats were trained to lever-respond for alcohol (15% v/v) and chocolate (5% w/v powdered Nesquik in water), respectively.

Salicinoyl Quinic Acids and Their Prostaglandin E Production Inhibitory Activities from the Fruits of .

Phytochemical investigation on the dried fruits of led to the identification of 10 new salicinoyl quinic acid derivatives (-), a new benzoyl quinic acid (), and two known compounds ( and ). 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 E (PGE) production in ultraviolet B (UVB)-irradiated HaCat keratinocytes.

Identification of neolignans with PCSK9 downregulatory and LDLR upregulatory activities from Penthorum chinense and the potential in cholesterol uptake by transcriptional regulation of LDLR via SREBP2.

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.

Dilignans with a Chromanol Motif Discovered by Molecular Networking from the Stem Barks of and Their Proprotein Convertase Subtilisin/Kexin Type 9 Expression Inhibitory Activity.

Natural products have been fundamental materials in drug discovery. Traditional strategies for observing natural products with novel structure and/or biological activity are challenging due to large cost and time consumption. Implementation of the MS/MS-based molecular networking strategy with the in silico annotation tool is expected to expedite the dereplication of secondary metabolites.

Sesquiterpenoids from the Aerial Parts of with Inhibitory Activities on Proprotein Convertase Subtilisin/Kexin Type 9 Expression.

Phytochemical investigation of the methanol extract of the aerial parts of 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 (), six new eudesmane sesquiterpenoids (-, , and ), 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.

Standardized Extract of Atractylodis Rhizoma Alba and Fructus Schisandrae Ameliorates Coughing and Increases Expectoration of Phlegm.

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.

A stilbene dimer and flavonoids from the aerial parts of Chromolaena odorata with proprotein convertase subtilisin/kexin type 9 expression inhibitory activity.

Investigation of components of the chloroform-soluble and ethyl acetate-soluble extracts of the aerial parts of Chromolaena odorata L. selected by PCSK9 mRNA expression monitoring assay in HepG2 cells led to the isolation of a new stilbene dimer, (+)-8b-epi-ampelopsin A (1), and 30 known compounds (2-31). The structures of the isolates were established by interpretation of NMR spectroscopic data and the stereochemistry of the new stilbene (1) was proposed based on ECD and NMR calculations.

Discovery of Flavonoids from Scutellaria baicalensis with Inhibitory Activity Against PCSK 9 Expression: Isolation, Synthesis and Their Biological Evaluation.

Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data and comparing measured values from those in the literature. All compounds were assessed for their ability to inhibit PCSK9 mRNA expression; compounds (3,7,2'-trihydroxy-5-methoxy-flavanone) and (skullcapflavone II) were found to suppress PCSK9 mRNA via SREBP-1.

Chemical Constituents with Proprotein Convertase Subtilisin/Kexin Type 9 mRNA Expression Inhibitory Activity from Dried Immature Morus alba Fruits.

Phytochemical investigation for a chloroform-soluble extract of dried Morus alba fruits, selected by proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression monitoring assay in HepG2 cells, led to the isolation of a new benzofuran, isomoracin D (1), and a naturally occurring compound, N-(N-benzoyl-l-phenylalanyl)-l-phenylalanol (2), along with 13 known compounds (3-15). All of the structures were established by NMR spectroscopic data as well as MS analysis. Of the isolates, moracin C (7) was found to inhibit PCSK9 mRNA expression with an IC value of 16.

Lignans from the fruits of Schisandra chinensis (Turcz.) Baill inhibit proprotein convertase subtilisin/kexin type 9 expression.

Bioactivity-guided fractionation of the fruits of Schisandra chinensis, using the proprotein convertase subtilisin-kexin type 9 (PCSK9) mRNA expression screening assay, led to isolation of two previously unknown lignans, 14-tigloylschinlignan D and rel-(7R, 8R, 7'R, 8'R)-manglisin E, along with 28 known compounds. All structures were established by NMR spectroscopic data as well as CD and MS analysis. All isolates were tested for their inhibitory activities on the mRNA expression of PCSK9.