Amaroswerin

Unravelling the Untapped Pharmacological Potential of Plant Molecules as Inhibitors of BACE1: In Silico Explorations for Alzheimer's Disease.[Pubmed:38158488]

Appl Biochem Biotechnol. 2023 Dec 30.

Alzheimer's disease (AD) is an extremely complex, heterogeneous, and multifactorial neurodegenerative disease clinically characterized by progressive memory loss and progressive decline in cognitive function. There is currently no effective treatment for the onset and/or progression of the pathophysiological diseases of AD. The global prevalence of this disease has increased in recent years due to modern lifestyle. Therefore, there is an urgent need to develop a drug with significant neuroprotective potential. Since plant metabolites, especially polyphenols, have important pharmacological properties acting against beta-amyloid (Abeta), Tau, neuroinflammation, and oxidative stress, such phytochemicals were selected in the present research. Using the Schrodinger tool (Maestro V.13.6), the drug potency of these metabolites was studied after installation in the highly configured workstation. Among the 120 polyphenols docked, amygdalin showed notable docking values of - 11.2638, followed by eriocitrin (- 10.9569), keracyanin (- 10.7086), and Amaroswerin (- 9.48126). The prominent MM-GBSA values of these molecules were - 62.8829, - 52.1914, - 68.6307, and - 63.1074, respectively. The MM-GBSA energy values demonstrated the drug stability of these molecules for beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1)-causing AD. In the absorption and distribution assessment, these phytochemicals showed significantly better values than the inhibitors CNP520. The chosen phytochemicals have been demonstrated as non-hepatotoxic; however, the BACE1 inhibitor CNP520 is hepatotoxic. In both the molecular docking and ADMET assessments, these natural chemicals have shown optimism as potential drug candidates for Alzheimer's disease. However, in order to understand the detailed biological metabolism of these compounds in AD, they need to be evaluated in in vivo studies to validate its efficacy.

A New RP-HPLC Method for Simultaneous Determination of Amaroswerin, Amarogentin and Andrographolide in a Herbal Drug "Chirayata".[Pubmed:35253055]

J Chromatogr Sci. 2023 Feb 3;61(2):172-176.

Chirayata-the whole dried plant of Swertia chirayita-is an important traditional drug of Indian System of Medicines. A novel reverse-phase high performance liquid chromatography (RP-HPLC) method has been developed for the simultaneous determination and quantification of Amaroswerin, amarogentin and andrographolide in a herbal drug "Chirayata," which is oftenly adulterated/substituted with herbal drug Kalmegh. The developed method is in accordance with International Council for Harmonization guidelines and is simple, precise, accurate, rapid, reproducible and specific to determine amarogentin, Amaroswerin and andrographolide. Reverse-phase column (Water's X-bridge C18, 5 mum, 4.6 mm x 250 mm) with high resolution for all marker compounds was used with binary gradient elution (methanol:water) with a flow rate of 1 mL/min and detection at 235 nm. The developed method showed good linearity (R2 > 0.999) in a relatively wider range of concentration 2.968-95.00 ppm for amarogentin, Amaroswerin and 5.625-180 ppm for andrographolide. The method is important for quality control analysis of drug Chirayata.

Anti-inflammatory activity of compounds isolated from Swertia mussotii.[Pubmed:29117731]

Nat Prod Res. 2019 Feb;33(4):598-601.

Six compounds were isolated from an ethanol extract of Swertia mussotii and identified as 2-phenylethyl-beta-D-glucoside (1), Amaroswerin (2), 1,3,7,8-tetrahydroxyxanthone (3), swertiamarine (4), 1,3,8-trihydroxy-5-methoxyxanthone (5) and methylswertianin (6). Compounds 1, 2 and 6 were isolated from S. mussotii for the first time. The anti-inflammatory activities of the compounds were evaluated by determining their effect on the production of NO by LPS-stimulated RAW264.7 cells. Amaroswerin was the most potent inhibitor of NO release, with an IC(50) value of 5.42 mug/mL. Treatment with Amaroswerin inhibited expression of iNOS at both protein and mRNA levels. Amaroswerin also dose-dependently suppressed production of TNF-alpha, IL-6 and IL-1beta and reduced expression of mRNA for these LPS-stimulated pro-inflammatory mediators. Amaroswerin thus inhibits the expression of iNOS, TNF-alpha, IL-6 and IL-1beta by downregulating transcription in LPS-induced RAW264.7 macrophage cells, indicating that Amaroswerin may be a valuable therapeutic agent for the treatment of inflammatory diseases.

Detection of intermediates through high-resolution mass spectrometry for constructing biosynthetic pathways for major chemical constituents in a medicinally important herb, Swertia chirayita.[Pubmed:25622657]

Nat Prod Res. 2015;29(15):1449-55.

Swertia chirayita is an endangered medicinal herb widely used as an antidiabetic. It contains two major classes of metabolites, secoiridoids and xanthones, i.e. swertiamarin, mangiferin, amarogentin and Amaroswerin. The biosynthetic pathways for these chemical constituents are not completely deciphered due to gaps and redundancy of routes proposed such as for mangiferin. The missing intermediates in pathways were detected through LC-ESI-QToF-HRMS/MS, including the detection of new secoiridoids, amaronitidin and gentiopicroside. The study also reports that the biosynthesis of amaronitidin occurs through the coupling of gentiopicroside and biphenyl acid derivatives such as amarogentin and Amaroswerin. This study reports for the first time complete biosynthetic pathways for gentiopicroside, mangiferin, amarogentin, Amaroswerin and amaronitidin in S. chirayita with the detection of intermediate metabolites iriflophenone, maclurin, deoxyloganic acid, loganic acid and 1,3,6,7-tetrahydroxy-9H-xanthen-9-one.

Protocol for in vitro regeneration and marker glycoside assessment in Swertia chirata Buch-Ham.[Pubmed:19521842]

Methods Mol Biol. 2009;547:139-53.

We have developed a rapid in vitro propagation system, via axillary shoot formation from nodal explants of Swertia chirata Buch Ham. Culture medium supplemented with 2 mg/L. BAP is best for direct shoot regeneration initially formed adventitious buds from axils of the nodal explants after 30 days. The reduced BAP concentration 0.5 mg/L proliferate shoots effectively. Kept the number of hyperhydrated shoots to minimal and induced on an average 22-38 shoots per flask (4.3 cm average length). The regenerated shoots (5- to 6-m long) formed roots very well in Murashige and Skoog (MS) medium devoid of any growth regulator and followed by acclimatization of plants in pre-sterilized sand containing 1% Trichoderma viride and Azatobactor chrococcum as bioinoculants. The regenerated plants don't show any genomic alterations. This protocol also outlines procedure of assessment of marker iridoid glycosides (amarogentin and Amaroswerin) from callus, roots, multiple shoots, regenerated plants, and mother plant. High propagation frequency, reproducibility of procedure, molecular, and phenotypic and chemical stability ensures the efficiency of the developed protocol.

Assessment of systemic interaction between Swertia chirata extract and its Bioactive constituents in rabbits.[Pubmed:19140153]

Phytother Res. 2009 Jul;23(7):1036-8.

The plant Swertia chirata (Gentianaceae) is known for its multifarious medicinal value in the Indian system of medicine (Ayurveda). Its methanol extracts having antidiabetic activity contains mangiferin, amarogentin, Amaroswerin, sweroside and swertiamarin as active constituents. The pharmacokinetics of mangiferin and amarogentin have been carried out after intravenous administration of pure standards and extract from S. chirata (CT) in rabbits to assess systemic interaction. The remaining three components were also monitored in plasma for pharmacokinetic estimation based on the ratio analysis method. Mangiferin was characterized by a relative low clearance ( approximately 0.14 L/h/kg) and a lesser volume of distribution ( approximately 0.15 L/kg), while amarogentin exhibited a rapid clearance ( approximately 2.62 L/h/kg) and wide distribution ( approximately 1.08 L/kg) from the systemic circulation. No significant difference was observed in pharmacokinetic parameters of mangiferin and amarogentin either administered alone or as CT formulation in rabbits.

Simultaneous estimation of mangiferin and four secoiridoid glycosides in rat plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study of herbal preparation.[Pubmed:17869193]

J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Oct 15;858(1-2):211-9.

Extracts from Swertia chirata (family Gentianaceae) have antidiabetics and antioxidant activity, largely attributed to the flavonoids and secoiridoids, which are a major class of functional components in methanolic extracts from aerial part of plants. In order to facilitate analysis of systemic exposure to S. chirata derived products in animals, we developed a liquid chromatography tandem mass spectrometry (LC-MS/MS) based method that is capable of routinely monitoring plasma levels of flavonoids and secoiridoids. An LC-MS/MS-based method has been developed for the simultaneous estimation of two bioactive markers, mangiferin and amarogentin along with three other components, Amaroswerin, sweroside and swertiamarin in rat plasma. All the analytes including the internal standard (kutkoside) were chromatographed on RP-18 column (250 mm x 4 mm i.d., 5 microm.) coupled with guard column using acetonitrile: 0.5 mM ammonium acetate buffer, pH approximately 3.0 as mobile phase at a flow rate of 1 ml/min in gradient mode. The final flow to source was splitted in 1:1 ratio. The detection of the analytes was performed on API 4000 LC-MS/MS system in the multiple reaction-monitoring (MRM) mode. The quantitation for analytes other than the pure markers was based on relative concentration. The method was validated in terms of establishing linearity, specificity, sensitivity, recovery, accuracy and precision (Intra- and Inter-day), freeze-thaw stability, peltier stability, dry residue stability and long-term stability. The recoveries from spiked control samples were >90% for all analytes and internal standard except mangiferin where recovery was >60%. Intra- and inter-day accuracy and precision of the validated method were within the acceptable limits of <15% at low and <10% at other concentrations. The quantitation method was successfully applied to generate pharmacokinetic (PK) profile of markers as well as to detect other components in plasma after intravenous dose administration of herbal preparation in male Sprague-Dawley (SD) rats.

Liquid chromatography/tandem mass spectrometric study and analysis of xanthone and secoiridoid glycoside composition of Swertia chirata, a potent antidiabetic.[Pubmed:17120271]

Rapid Commun Mass Spectrom. 2006;20(24):3761-8.

Swertia chirata is a bitter plant, used in the Indian system of medicine (Ayurveda) for various human ailments. The bioactive constituents include the xanthone and secoiridoid glycosides consisting of mangiferin, amarogentin, Amaroswerin, sweroside and swertiamarin. Methanolic extracts of S. chirata possess constituents with antidiabetic activities, which was investigated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). Preliminary HPLC analyses were performed on a reversed-phase C18 column using gradient elution. In the LC/ESI-MS spectra, predominant [M+H]+ and [M+Na]+ ions were observed in positive ion mode and provided molecular mass information. The five components of S. chirata were structurally correlated and confirmed based on the fragmentation characteristics and information available in the literature. The fragmentation behavior of [M+H]+/[M+Na]+ ions of these components were deduced from the collision-induced dissociation (CID) spectra obtained from the selective on-column information-dependant acquisition (IDA) approach. Xanthone-C-glycoside showed characteristic fragment ions due to fragmentation in the C-glycosidic unit while iridoid-O-glycosides showed characteristic fragment ions due to cleavage in the glycoside linkage and retro-Diels-Alder (RDA) cleavage within an iridoid aglycone. Furthermore, on the basis of this information, an analytical assay was developed and validated to determine relative concentrations of mangiferin, amarogentin, Amaroswerin, sweroside and swertiamarin. The detection was carried out using multiple reaction monitoring (MRM) in positive ionization mode with a total analysis time of 3.5 min. The method was successfully applied to standardize four different batches of herbal preparation on the basis of relative concentration of five bioactive components.

Synthesis of 3,3',5-trihydroxybiphenyl-2-carboxylic acid, a component of the bitterest natural product amarogentin and its coenzyme A and N-acetyl cysteamine thiol esters.[Pubmed:10757721]

J Nat Prod. 2000 Mar;63(3):371-4.

3,3',5-Trihydroxybiphenyl-2-carboxylic acid (6), an ester component of the bitter-tasting natural products amarogentin and Amaroswerin, was synthesized in six steps in 13.6% overall yield. Its N-acetyl cysteamine thiol ester (9) and its coenzyme A thiol ester (8), a likely biosynthetic precursor of the amarums, were also prepared.

Secoiridoids and xanthones from Gentianella nitida.[Pubmed:17252473]

Planta Med. 1996 Aug;62(4):365-8.

From Gentianella nitida twelve known metabolites were isolated and identified by HPLC-UV and/or by spectroscopic methods as secologanoside, Amaroswerin, amarogentin (secoiridoids), isoorientin (C-glucosylflavone), mangiferin, demethylbellidifolin 8-O-glucoside, norswertianine 1-O-glucoside, swertianine 1-O-primeveroside, swertianine 8-O-glucoside, norswertianine, demethylbellidifolin, and swertianine (xanthone glycosides and aglycones). Secologanoside is reported here for the first time in Gentianaceae species; the antioxidant mangiferin was obtained as the major compound in good yield.

Amarogentin, a naturally occurring secoiridoid glycoside and a newly recognized inhibitor of topoisomerase I from Leishmania donovani.[Pubmed:8984149]

J Nat Prod. 1996 Jan;59(1):27-9.

A MeOH extract of Swertia chirata found to inhibit the catalytic activity of topoisomerase I of Leishmania donovani was subjected to fractionation to yield three secoiridoid glycosides: amarogentin (1), Amaroswerin (2), and sweroside (3). Amarogentin is a potent inhibitor of type I DNA topoisomerase from Leishmania and exerts its effect by interaction with the enzyme, preventing binary complex formation.

[Simultaneous determination of five bitter secoiridoid glycosides in nine Chinese Gentiana species used as the Chinese drug "long dan" by high performance liquid chromatography].[Pubmed:1823982]

Yao Xue Xue Bao. 1991;26(11):864-70.

A new and rapid analytical method for the simultaneous determination of five bitter secoiridoid glycosides (gentiopicroside, GTP; swertiamarin, SWT; sweroside, SWO; amarogentin, AMG; Amaroswerin, AMS) in the Chinese drug "Long Dan", roots of Gentiana manshurica and 8 allied species by high performance liquid chromatography (HPLC) has been developed. The HPLC system consisting of an apparatus from Shimadzu (model LC-4A), with a UV-detector (SPD-2AS), a data processor (Chromatopac C-R2AX), a column oven (CTO-2AS), and a Zorbax ODS column (25 cm x 4.6 mm ID) was used. Using MeOH--H2O as the mobile phase, the linear concentration-program of methanol was [time (min):C (MeOH)]: [0:20]----[6:20]----[6.01:40]----[23:stop]. The temperature of column oven was 40 degrees C. The bitter secoiridoid glycosides eluted were detected at a wavelength of 254 nm and the analysis was successfully carried out within 23 minutes. This method is sensitive, rapid, accurate and has good reproducibility. Recoveries of each secoiridoid glycoside were 100.0-101.5% with coefficients of variation 0-2.5% (n = 3). The contents of five bitter secoiridoid glycosides in the roots of G. manshurica and eight allied species indigenous to China were determined and reported.

Desorption/Chemical ionization mass spectrometry of bitter glycosides from gentiana1.[Pubmed:17340340]

Planta Med. 1984 Oct;50(5):398-403.

A series of bitter secoiridoid glucosides isolated from various GENTIANA species (Gentianaceae) have been investigated by D/CI-MS. Amarogentin, amaropanin, Amaroswerin, deglucosyltrifloroside, desacetylcentapicrin, gentiopicrin, swertiamarin and sweroside have been characterized by quasimolecular ions and typical fragments, using NH (3) or CH (4) as reactant gas.