iridoids and mangiferin

In this study, response surface methodology (RSM) and artificial neural network (ANN) was used to construct the predicted models of linear, quadratic and interactive effects of two independent variables viz. salicylic acid (SA) and chitosan (CS) for the production of amarogentin (I), swertiamarin (II) and mangiferin (III) from shoot cultures of Swertia paniculata Wall. These compounds are the major therapeutic metabolites in the Swertia plant, which have significant role and demand in the pharmaceutical industries.. Present study highlighted that different concentrations of SA and CS elicitors substantially influenced the % yield of (I), (II) and (III) compounds in the shoot culture established on modified ½ MS medium (supplemented with 2.22 mM each of BA and KN and 2.54 mM NAA). In RSM, different response variables with linear, quadratic and 2 way interaction model were computed with five-factor-three level full factorial CCD. In ANN modelling, 13 runs of CCD matrix was divided into 3 subsets, with approximate 8:1:1 ratios to train, validate and test. The optimal enhancement of (I) (0.435%), (II) (4.987%) and (III) (4.357%) production was achieved in 14 days treatment in shoot cultures of S. paniculata elicited by 9 mM and 12 mg L

Topics: Chitosan; Glycosides; Iridoid Glucosides; Iridoids; Neural Networks, Computer; Pyrones; Salicylic Acid; Swertia; Xanthones

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.

Topics: Biosynthetic Pathways; Glucosides; Hypoglycemic Agents; Iridoid Glucosides; Iridoids; Plants, Medicinal; Pyrans; Secondary Metabolism; Swertia; Tandem Mass Spectrometry; Xanthones

Swertia chirayita, an endangered medicinal herb, contains three major secondary metabolites swertiamarin, amarogentin and mangiferin, exhibiting valuable therapeutic traits. No information exists as of today on the biosynthesis of these metabolites in S. chirayita. The current study reports the expression profiling of swertiamarin, amarogentin and mangiferin biosynthesis pathway genes and their correlation with the respective metabolites content in different tissues of S. chirayita. Root tissues of greenhouse grown plants contained the maximum amount of secoiridoids (swertiamarin, 2.8% of fr. wt and amarogentin, 0.1% of fr. wt), whereas maximum accumulation of mangiferin (1.0% of fr. wt) was observed in floral organs. Differential gene expression analysis and their subsequent principal component analysis unveiled ten genes (encoding HMGR, PMK, MVK, ISPD, ISPE, GES, G10H, 8HGO, IS and 7DLGT) of the secoiridoids biosynthesis pathway and five genes (encoding EPSPS, PAL, ADT, CM and CS) of mangiferin biosynthesis with elevated transcript amounts in relation to corresponding metabolite contents. Three genes of the secoiridoids biosynthesis pathway (encoding PMK, ISPD and IS) showed elevated levels (∼57-104 fold increase in roots), and EPSPS of mangiferin biosynthesis showed an about 117 fold increase in transcripts in leaf tissues of the greenhouse grown plants. The study does provide leads on potential candidate genes correlating with the metabolites biosynthesis in S. chirayita as an initiative towards its genetic improvement.

Topics: Iridoid Glucosides; Iridoids; Plant Roots; Plants, Medicinal; Pyrones; Swertia; Xanthones

The genus Swertia is reported to contain potent bitter compounds like iridoids, xanthones and c-glucoflavones that are known to heal many human disorders. In contrast to high ethnomedicinally valued Swertia chirayita, its other species have not been studied extensively, in spite of their common use in traditional medicinal system in Nepalese communities. So, the present study attempts to investigate the content of total polyphenols, flavonoids, antioxidant activity and estimate the rough content of amarogentin, swertiamarin and mangiferin from different species of Swertia from Nepalese Himalayas.. Whole plant parts of S. chirayita (SCH), S. angustifolia (SAN), S. paniculata (SPA), S. racemosa (SRA), S. nervosa (SNE), S. ciliata (SCI) and S. dilatata (SDI) were collected; total phenolic and flavonoid contents were quantified spectrophotometrically and in vitro DPPH free radical scavenging assay was measured. Thin layer chromatography was performed on TLC aluminium plates pre-coated with silica gel for identification of swertiamarin, amarogentin and mangiferin from those species and semi quantitative estimation was done using GelQuant.NET software using their standard compounds.. The phenolic content was highest in the methanol extract of SCH (67.49 ± 0.5 mg GAE/g) followed by SDI, SRA, SNE, SCI, SPA and SAN. The contents of flavonoids were found in the order of SCH, SPA, SRA, SNE, SDI, SCI and SAN. Promising concentration of phenolics and flavonoids produced promising DPPH free radical scavenging values. The IC50 values for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging test was lowest in SCH (23.35 ± 0.6 μg/ml), even lower than the standard ascorbic acid among the seven studied species. A significant correlation of 0.977 was observed between the polyphenol content and antioxidant values. The TLC profile showed the presence of all three major phytochemicals; amarogentin, swertiamarin and mangiferin in all of the plant samples.. Among the seven studied species, SCH showed anticipating results in total phenol content, flavonoid content and DPPH radical scavenging test. The less considered species of Swertia can be a potential source of bioactive amarogentin, and other useful therapeutic compounds in the alarming status of Swertia chirayita as shown by the phytochemical analysis.

Topics: Antioxidants; Chromatography, Thin Layer; Flavonoids; Free Radical Scavengers; Humans; Iridoid Glucosides; Iridoids; Methanol; Nepal; Phytochemicals; Plant Extracts; Plants, Medicinal; Polyphenols; Pyrones; Species Specificity; Swertia; Xanthones

The crude extract of Swertia chirayita, an important medicinal plant of Nepal, is locally used for many diseases including type 2 diabetes. In this study, crude aqueous and 12% ethanol solution extracts of S. chirayita collected from nine districts of Nepal were analyzed for anti-diabetic-linked anti-hyperglycemia potential using in vitro biochemical assays. There was moderate-to-high positive correlation between antioxidant activity and total phenolic content of both extracts and moderate-to-high α-glucosidase inhibitory activity. Although the anti-diabetic property of S. chirayita is mainly attributed to the phytochemical swerchirin present in its hexane fraction, we propose that the crude extract of this plant used in local healing also has anti-hyperglycemia potential. The crude extracts indicated the presence of three main phytochemicals mainly mangiferin, swertiamarin, and amarogentin and their derivatives. Among the standard compounds (mangiferin, swertiamarin, and amarogentin), mangiferin showed α-glucosidase and 2,2-diphenyl-1-picrylhydrazyl radical inhibitory activity indicating anti-hyperglycemia potential.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antioxidants; Biphenyl Compounds; Chromatography, High Pressure Liquid; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Inhibitory Concentration 50; Iridoids; Nepal; Phenols; Picrates; Plant Extracts; Swertia; Xanthones

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.

Topics: Animals; Drug Interactions; Glucosides; Iridoids; Male; Plant Extracts; Rabbits; Swertia; Tandem Mass Spectrometry; Xanthones

To develop a RP-HPLC method for determination of three glycosides in Swertia punicea.. Chromatographic column: Alltimal C18 (4.6 mm x 250 mm, 5 microm). Mobile phase: methanol-water (including 0.05% H3PO4), and gradient elution. Flow rate: 1 mL x min(-1). Wavelength: 254 nm. Column temperture: 30 degrees C.. The calibration curves of gentiopicroside, mangiferin and swertrianolin were in good linearity over the range of 31.3-281.7, 0.31-2.78, 0.55-4.91 microg, (r = 0.9996, 0.9993, 0.9995). The average recoveries were 103.36%, 101.42% and 97.39%, with RSD less then 3% (n = 5).. It is a simple and sensitive meathod in controlling the quality of S. punicea.

Topics: Calibration; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Glycosides; Iridoid Glucosides; Iridoids; Plants, Medicinal; Quality Control; Reproducibility of Results; Swertia; Xanthones

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.

Topics: Animals; Chromatography, Liquid; Cinnamates; Glucosides; Iridoid Glucosides; Iridoids; Male; Plant Preparations; Pyrones; Rats; Rats, Sprague-Dawley; Reference Standards; Reproducibility of Results; Swertia; Tandem Mass Spectrometry; Xanthones

To establish a quantitative method of simultaneously determination of swertiamarin, gentiopicroside, mangiferin, swertianolin, isoorientin, 1,8-drihydroxy-3-methoxy-xthanone in Swertia from Qinghai province and Sichuan province by HPLC.. The samples were separated on the column of Kromasil C18 (4. 6 mm x 250 mm, 5 microm) which eluted with methanol and water (content 0.02% phosphoric acid). The ratio of methanol increased from 20% to 80% during 20-50 min, and from 80% to 100% during 50-60 min, with detected wavelength 254 nm, flow rate at 1 mL x min(-1), column temperature 35 degrees C.. Six compounds were base-isolated, the linear ranges of swertiamarin, gentiopicroside, mangiferin, 4-swertianolin, 5-isoorientin, 1,8-drihydroxy-3-methoxy-xthanone were excellent.. The method was rapid and precise, and can be use for controlling medicinal materials quality.

Topics: China; Chromatography, High Pressure Liquid; Glucosides; Iridoid Glucosides; Iridoids; Luteolin; Plants, Medicinal; Pyrans; Pyrones; Quality Control; Reproducibility of Results; Swertia; Xanthones

Concentrations of seven phytochemical constituents (swertiamarin, mangiferin, swertisin, oleanolic acid, 1,5,8-trihydroxy-3-methoxyxanthone, 1,8-dihydroxy-3,7-dimethoxyxanthone and 1,8-dihydroxy-3,5-dimethoxyxanthone) of "ZangYinChen" (Swertia mussotii, a herb used in Tibetan folk medicine) were determined and compared in plants collected from naturally distributed high-altitude populations and counterparts that had been artificially cultivated at low altitudes. Levels of mangiferin, the most abundant active compound in this herb, were significantly lower in cultivated samples and showed a negative correlation with altitude. The other constituents were neither positively nor negatively correlated with cultivation at low altitude. Concentrations of all of the constituents varied substantially with growth stage and were highest at the bud stage in the cultivars, but there were no distinct differences between flowering and fruiting stages in this respect.

Topics: Agriculture; Altitude; Drug Evaluation, Preclinical; Flowers; Geography; Glucosides; Iridoid Glucosides; Iridoids; Medicine, Tibetan Traditional; Oleanolic Acid; Plant Physiological Phenomena; Plants, Medicinal; Pyrones; Seeds; Swertia; Time Factors; Xanthones

High-performance liquid chromatography was employed to determine the contents of several marker substances such as gentiopicroside, mangiferin, palmatine, berberine, baicalin, wogonin and glycyrrhizin in Sann-Joong-Kuey-Jian-Tang. The separation was performed on a Cosmosil 5C18-AR column by gradient elution with 0.03% (v/v) phosphoric acid-acetonitrile (0 min, 90:10; 10 min, 87:13; 17-27 min, 77:23; 40 min, 62:38; 50 min, 55:45) as the mobile phase at a flow-rate of 1.0 ml/min, with detection at 254 nm. n-Propylparaben was used as the internal standard and seven regression equations revealed linear relationships between the peak-area ratios (marker substances/internal standard) and concentrations. The repeatability and reproducibility (relative standard deviation) of the method were in the ranges 0.02-1.78% and 1.44-4.95%, respectively.

Topics: Berberine; Berberine Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucosides; Glycyrrhetinic Acid; Glycyrrhizic Acid; Iridoid Glucosides; Iridoids; Pyrans; Reproducibility of Results; Xanthenes; Xanthones