Norswertianolin

Effects of Four Compounds from Gentianella acuta (Michx.) Hulten on Hydrogen Peroxide-Induced Injury in H9c2 Cells.[Pubmed:30800665]

Biomed Res Int. 2019 Jan 20;2019:2692970.

In previous studies, Gentianella acuta (Michx.) Hulten was reported to contain xanthones, iridoids, terpenoids, and sterols and is mainly used to cure hepatitis, jaundice, fever, headache, and angina pectoris. In this study, we used bioassay guided fractionation to identify compounds from G. acuta and investigated their activity against hydrogen peroxide (H2O2)-induced apoptosis of H9c2 cells using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and glutamate-cysteine ligase catalytic (GCLC) expression were assessed using quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was evaluated using western blot. The results showed that all four compounds had protective effects on H9c2 cells. The transcription levels of HO-1 and GCLC significantly increased in H9c2 cells pretreated with Norswertianolin (1), swetrianolin (2), demethylbellidifolin (3), and bellidifolin (4). However, compared to the model group, the transcription levels of Nrf2 were not enhanced by pretreatment with compounds 1, 2, and 4. The protein expression levels of HO-1 and GCLC in H9c2 cells were greater than that in the H2O2-treated group, and the expression of Nrf2 was not significantly changed except by swetrianolin treatment; inhibitors can reverse the protective effect by ZnPP (15 muM), BSO (10 muM), and brusatol (10 muM). The results indicated that the four compounds isolated from G. acuta inhibited the oxidative injury induced by H2O2 by activating the Nrf2/ARE pathway in H9c2 cells and provide evidence that G. acuta may be a potential therapeutic agent for the treatment of cardiovascular diseases.

Chemical Composition, Antioxidant and Anticholinesterase Activities of Gentianella azurea from Russian Federation.[Pubmed:30549824]

Nat Prod Commun. 2017 Jan;12(1):55-56.

Phytochemical study of Gentianella azurea (Bunge) Holub (Gentianaceae) collected in Buryatia Republic (Russian Federation) resulted in the isolation of twenty-one compounds including bellidifolin, bellidin, isobellidifolin, Norswertianolin, isobellidifolin-8-O-beta-D-glucopyranoside, orientin, cynaroside, .cosmosiin, apigenin, 4'-O-caffeoylswertiamarin, swertiamarin-6'-O-beta-D-glucopyranoside and sweroside, firstly detected in this species. The extracts and individual compounds were shown to possess antioxidant and anticholinesterase potential.

Determination and pharmacokinetic study of four xanthones in rat plasma after oral administration of Gentianella acuta extract by UHPLC-ESI-MS/MS.[Pubmed:26297839]

J Ethnopharmacol. 2015 Nov 4;174:261-9.

ETHNOPHARMACOLOGICAL RELEVANCE: Gentianella acuta (Michx.) Hulten belonging to the family of Gentianaceae is an annual plant mainly distributed in north of China, Mongolia plateau, Siberia and Far East areas of Russia. The whole herb was used as folk medicine to treat hepatitis, jaundice, headache and fever in Mongolia native medicine. Xanthones are the main active compounds of G. acuta and possess a lot of pharmacological and biological activities AIM OF THE STUDY: A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of swertianolin, Norswertianolin, bellidifolin and demethylbellidifolin (DMB) in rat plasma after oral administration of G. acuta extract. MATERIALS AND METHODS: Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard. LC separation was achieved on an Agilent SB-C18 RRHD column (1.8 mum, 150 mm x 2.1 mm) at 30 degrees C with an isocratic mobile phase consisting of acetonitrile-water (0.1% formic acid) (90:10, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for swertianolin, Norswertianolin, bellidifolin, DMB and I.S. were 435.1/272.0, 420.8/258.9, 273.0/258.0, 258.9/214.9 and 193.0/92.0, respectively. RESULTS: The current UHPLC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four xanthones after oral administration of G. acuta extract. The time to reach the maximum plasma concentration (Tmax) was 0.40 +/- 0.12 h for swertianolin, 0.27 +/- 0.07 h for Norswertianolin, 1.00 +/- 0.18 h for bellidifolin and 0.94 +/- 0.15 h for demethylbellidifolin. The elimination half-time (t1/2) of swertianolin, Norswertianolin, bellidifolin and DMB, was 19.7 +/- 9.64 h, 11.3 +/- 4.51 h, 19.9 +/- 8.11 h and 24.9 +/- 8.19 h, respectively. CONCLUSION: This study described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of four xanthones in rat plasma after oral administration of G. acuta extract, and investigated on their pharmacokinetic studies as well.

[Chemical constituents of Gentiana rhodantha].[Pubmed:23668010]

Zhongguo Zhong Yao Za Zhi. 2013 Feb;38(3):362-5.

OBJECTIVE: To determine the chemical constituents of Gentiana rhodantha. METHOD: To isolate the constituents, column chromatography over silica gel, MCI, Sephadex LH-20 and C18 reverse-phased silica gel were used. Spectroscopic methods were used to elucidate the structures of the isolated compounds. RESULT: Sixteen compounds were isolated and elucidated as ten phonemic compounds, namely 1,3,7,8-tetrahydroxylxanthone (1), rhodanthenone D (2), 1,3,6,7-tetrahydroxylxanthone (3), 1,3,7-trihydroxy-4,8-dimethoxyxanthone (4), quercetin (5), isoorientin (6), mangiferin (7), Norswertianolin (8), gallic acid ethyl ester (9) and salicylic acid (10), and six triterpenes including alpha-amyrin (11), erythrodiol 3-O-palmitate (12), ursolic aldehyde (13), uvaol 3-O-acetyl (14), ursolic acid (15) and 2alpha-hydroxyursolic acid (16). CONCLUSION: Compounds 4-6, 8, 10-12, 15 and 16 were isolated from this plant for the first time. Compounds 1 and 3 were obtained firstly from the genus Gentiana and compounds 9, 13-14 were firstly from the family Gentianaceae.

Induction of apoptosis in human pancreatic MiaPaCa-2 cells through the loss of mitochondrial membrane potential (DeltaPsim) by Gentiana kurroo root extract and LC-ESI-MS analysis of its principal constituents.[Pubmed:23453831]

Phytomedicine. 2013 Jun 15;20(8-9):723-33.

The objective of the current study was to evaluate the methanolic root extract of Gentiana kurroo for antioxidant and antiproliferative activities as well as to study the effect of the extract on the induction of apoptosis in human pancreatic cancer cell line (MiaPaCa-2). The extract exerted significant antioxidant activity as verified by DPPH, hydroxyl radical, lipid peroxidation and protective oxidative DNA damage assays. The results were comparable to standard antioxidants like alpha-tocopherol, catechin and BHT used in such experiments. Antioxidant potential of G. kurroo may be attributed to the presence of high phenolic and flavonoid content (73+/-1.02 and 46+/-2.05 mg/g extract respectively). The anti-proliferative property of Gentiana kurroo root extract was determined by sulphorhodamine B (SRB) assay against Human colon cancer cell line (HCT-116), Lung carcinoma cell line (A-549), Pancreatic cancer cell line (MiaPaCa-2), Lung cancer cell line (HOP-62) and acute monocytic leukaemia cell line (THP-1). G. kurroo root extract inhibited cancer cell growth depending upon the cell line used and in a dose dependent manner. The extract induced potent apoptotic effects in MiaPaCa-2 cells. The population of apoptotic cells increased from 11.4% in case of control to 49.6% at 100 mug/ml of G. kurroo root extract. The extract also induced a remarkable decrease in mitochondrial membrane potential (DeltaPsim) leading to apoptosis of cancer cells used. The main chemical constituents identified by the liquid chromatography-tandem mass spectrometry (LC-ESI-MSMS) were found to be iridoid glucosides (iridoids and secoiridoids), xanthones and flavonoids. Iridoid glucosides are the bitter principles of Gentiana species. Loganic acid, Sweroside, Swertiamarin, Gentiopicroside, Gentisin, Isogentisin, Gentioside, Norswertianolin, Swertianolin, 4''-O-beta-D-glucosyl-6'-O-(4-O-beta-D-glucosylcaffeoyl)-linearoside and Swertisin were the principal compounds present in the methanol root extract of G. kurroo.

[Chemical constituents of Swertia macrosperma].[Pubmed:21355239]

Zhongguo Zhong Yao Za Zhi. 2010 Dec;35(23):3161-4.

OBJECTIVE: To study the chemical constituents of Swertia macrosperma. METHOD: The air-dried whole plants of Swertia macrosperma were extracted with boiling water. The extract was concentrated to a small amount of volume and extracted with petroleum ether, EtOAc and n-BuOH, successively. The compounds were isolated and purified by column chromatography from the EtOAc fraction, and identified based on spectral analyses (MS, 1H-NMR, 13C-NMR). RESULT: Thirteen compounds were isolated from S. macrosperma, and were characterized as norbellidifolin (1), 1-hydroxy-3,7, 8-trimethoxy-xanthone (2), Norswertianolin (3), swertianolin (4), 1,3,7,8-tetrahydroxyxanthone-8-O-beta-D-glucopyranoside (5), swertiamatin (6), decentapicrin (7), coniferl aldehyde (8), sinapaldehyde (9), balanophonin (10), together with beta-sitosterol, daucosterol, and oleanolic acid . CONCLUSION: Compounds 2, 4-10 were obtained from Swertia macrosperma for the first time.

[Determination of six active components in three species of genus Swertia by HPLC multiwavelength with detection].[Pubmed:19771868]

Zhongguo Zhong Yao Za Zhi. 2009 Jun;34(11):1384-9.

OBJECTIVE: To develop an HPLC method for the quantification of six active components in three species (Swertia davidi, S. nervosa and S. mussotii) . METHOD: The determination was performed on a Hypersil BDS colunm (4. 6 mm x 200 mm, 5 microm). Acetonitrile and 0.5% phosphoric acid solution were used as the mobile phases with a gradient elution. The flow rate was 1.0 mL x min(-1). The UV detection wavelength was at 240, 274, 325 and 334 nm. The column oven temperature was at 25 degrees C. RESULT: Six components were separated commendably in 60 minutes. The calibration curves of swertiamarin, gentiopicroside, Norswertianolin, swertianolin, demethylbellidifolin and bellidifolin were in good linearity over the range of 0.520-20.8, 0.202-8.06, 0.107-4.28, 0.097-3.86, 0.094-3.77, 0.101-4.02 microg, respectively (r = 0.999 9). The average recoveries were 98.7%, 98.1%, 98.3%, 98.8%, 98.1% and 98.6%, respectively, and the RSD were less than 3.0% (n = 6). CONCLUSION: The method is accurate,simple and reproducible, and can be used to control the quality of Swertia.

Xanthones from Gentianella amarella ssp. acuta with acetylcholinesterase and monoamine oxidase inhibitory activities.[Pubmed:18336006]

J Nat Prod. 2008 May;71(5):895-7.

Two new xanthone glycosides, corymbiferin 3-O-beta-D-glucopyranoside (1) and swertiabisxanthone-I 8'-O-beta- d-glucopyranoside (2), were isolated from Gentianella amarella ssp. acuta, along with eight known xanthones: triptexanthoside C, veratriloside, corymbiferin 1-O-glucoside, swertianolin, Norswertianolin, swertiabisxanthone-I, bellidin, and bellidifolin, four of them identified for the first time in G. amarella ssp. acuta. The isolation was conducted mainly by centrifugal partition chromatography, and the structures of the isolated compounds were established on the basis of spectrometric data including 2D NMR and mass spectrometry. Xanthones were weakly active against acetylcholinesterase (AChE), except triptexanthoside C, which inhibited AChE with an IC(50) of 13.8 +/- 1.6 microM. Some compounds were active against monoamine oxidases (MAO): bellidin and bellidifolin showed interesting inhibitory activity of MAO A, while swertianolin, the 8-O-glucopyranoside form of bellidifolin, gave 93.6% inhibition of MAO B activity at 10(-5) M.

Xanthones from Gentiana campestris as new acetylcholinesterase inhibitors.[Pubmed:15490334]

Planta Med. 2004 Oct;70(10):1011-4.

In order to discover new acetylcholinesterase (AChE) inhibitors, different plant extracts were screened by a previously established TLC bioautographic method. The methanol extract of Gentiana campestris leaves exhibited significant inhibition of AChE activity. A bioactivity-guided fractionation approach was undertaken to isolate the active components. Four xanthones, bellidin, bellidifolin, bellidin 8-O-beta-glucopyranoside (Norswertianolin), and bellidifolin 8-O-beta-glucopyranoside (swertianolin), were found to be responsible for the anti-AChE activity effects. Bellidifolin showed similar activity to galanthamine in this enzyme assay.

Mutagenicities of xanthone derivatives in Salmonella typhimurium TA100, TA98, TA97, and TA2637.[Pubmed:3889613]

Mutat Res. 1985 Jun-Jul;150(1-2):141-6.

The mutagenicities of naturally occurring xanthones were tested in Salmonella typhimurium TA100, TA98, TA97, and TA2637 by the preincubation method. Xanthydrol, gentisein, gentisin, isogentisin, 1-hydroxy-3,7-dimethoxyxanthone, 1,3,7-trimethoxyxanthone, desmethylbellidifolin, bellidifolin and dimethylbellidifolin were mutagenic, but unsubstituted xanthone was not mutagenic to TA100, TA98, TA97 and TA2637 with or without a metabolic activation system. The beta-O-glucosides, Norswertianolin and swertianolin, were only mutagenic when a metabolic activation system containing beta-glucosidase was used, and the C-glucoside mangiferin was not mutagenic even with this system.