Isogentisin

Amarogentin as Topical Anticancer and Anti-Infective Potential: Scope of Lipid Based Vesicular in its Effective Delivery.[Pubmed:30210007]

Recent Pat Antiinfect Drug Discov. 2019;14(1):7-15.

There is a need for the development of liposomes based nanomedicines formulation for better efficacy and safety of the available drugs in the market. Liposomes have various applications in the field of pharmaceutical and medical field for their drug target potential, diagnostic importance and imaging techniques. Natural plant based drugs and their derivatives have been used in the medicine, nutraceuticals, perfumery, cosmetic and beverages industry. More than half of the prescribed drugs in the worldwide are mainly derived from different natural sources. Development of plant derived product is an emerging field of food, pharmaceutical and health industries. Plants belonging to the Gentianaecae family are well known for their bitter taste and Swertia chirata is one of best plants among them. Various active phytochemical of Swertia chirata are bitter secoiridoids like gentiopicroside, amarogentin, swertiamarin, isovitexin and Isogentisin. People use different species of Swertia in the form of decoction, infusion, paste and juice for the treatment of fever and enteric diseases. Swertia chirata possesses anticarcinogenic, antioxidative, hypoglycemic, antihepatotoxic, antimalarial, anti-inflammatory and antimicrobial activities. Amarogentin, a bitter secoiridoid glycoside present in Swertia chirata plant is an activator of human bitter taste receptor. Pharmacologically, amarogentin has antibacterial, antihepatitis, anticholinergic and chemopreventive activities, moreover, amarogentin has been proven for their anti-lieshmanial activity. Other studies also suggested that amarogentin acts on liver carcinogenesis, skin carcinogenesis and reduced tumour progression. In the present review, we have collected and compiled the data regarding biological sources, ethnomedicinal uses, phytochemistry, anticancer and anti-infective potential of amarogentin. For better understanding of various aspects of amarogentin, we have also discussed Swertia chirayita in a very concise manner. Further data related to various patents on amarogentin have also been discussed in this manuscript. However, we also admit that new advance biological research will also increase the medicinal and pharmacological value of amarogentin. Information regarding the chemistry of amarogentin, its biological sources, bioavailability as a pharmacological agent for the treatment and management of skin disorders and various forms of cancers will be beneficial to the scientists in the medicinal field.

Phytochemical analysis and antibacterial activity of Gentiana macrophylla extract against bacteria isolated from burn wound infections.[Pubmed:29111322]

Microb Pathog. 2018 Jan;114:25-28.

The management of burn wound victims is often considered a difficult task due to frequent infections. Moreover, the treatment with conventional antibiotics is associated with the upsurge of drug resistant bacterial strains. Therefore there is pressing need to explore antimicrobials that could overcome these problems. Plant extracts have been used as antimicrobials in different systems of medicine. Gentiana species have been widely used in Chinese system of traditional medicine for the treatment of various ailments including microbial infections. The aim of the present study was therefore to evaluate the antimicrobial activity of methanolic root extract of Gentiana macrophylla against bacterial strains isolated from wound burns. Preliminary phytochemical screening revealed the phenolic and flavonoids content of the extract to be 26.70 +/- 1.5 mg gallic acid equivalent (GAE)/g DW and 10.11 +/- 0.8 mg quercetin equivalent/g DW respectively. The phenolics and flavonoids content of the extract positively correlated with antioxidant activity of the extract. Evaluation of antimicrobial activity against bacterial strains isolated from wound burns revealed that the G. macrophylla extract exhibited significant antibacterial against all the tested bacterial strains. The MIC values ranged between 60 and 240 mug/ml. The lowest MIC was observed for S. epidermidis and the highest MIC was observed for E. coli. The MBCs also followed the similar trend and ranged between 106 to 300 mug/ml. To identify the active constituents responsible for the bioactivity of the extract LC/MS analysis was carried out which lead to the putative identification of five compounds including chlorogenic acid, rutin, sweroside, Isogentisin, and gentisin. Taken together, these results indicate G. macrophylla can prove to be an important source of antioxidants and antimicrobials and may be used for the management of wound burns.

Chromatographic Evaluation and Characterization of Components of Gentian Root Extract Used as Food Additives.[Pubmed:26726749]

Chem Pharm Bull (Tokyo). 2016;64(1):78-82.

Gentian root extract is used as a bitter food additive in Japan. We investigated the constituents of this extract to acquire the chemical data needed for standardized specifications. Fourteen known compounds were isolated in addition to a mixture of gentisin and Isogentisin: anofinic acid, 2-methoxyanofinic acid, furan-2-carboxylic acid, 5-hydroxymethyl-2-furfural, 2,3-dihydroxybenzoic acid, isovitexin, gentiopicroside, loganic acid, sweroside, vanillic acid, gentisin 7-O-primeveroside, Isogentisin 3-O-primeveroside, 6'-O-glucosylgentiopicroside, and swertiajaposide D. Moreover, a new compound, loganic acid 7-(2'-hydroxy-3'-O-beta-D-glucopyranosyl)benzoate (1), was also isolated. HPLC was used to analyze gentiopicroside and amarogentin, defined as the main constituents of gentian root extract in the List of Existing Food Additives in Japan.

Comparative HPLC/ESI-MS and HPLC/DAD study of different populations of cultivated, wild and commercial Gentiana lutea L.[Pubmed:25529701]

Food Chem. 2015 May 1;174:426-33.

The root of Gentiana lutea L., famous for its bitter properties, is often used in alcoholic bitter beverages, food products and traditional medicine to stimulate the appetite and improve digestion. This study presents a new, fast, and accurate HPLC method using HPLC/ESI-MS and HPLC/DAD for simultaneous analysis of iridoids (loganic acid), secoiridoids (gentiopicroside, sweroside, swertiamarin, amarogentin) and xanthones (Isogentisin) in different populations of G.lutea L., cultivated in the Monti Sibillini National Park, obtained wild there, or purchased commercially. Comparison of HPLC/ESI-MS and HPLC/DAD indicated that HPLC/ESI-MS is more sensitive, reliable and selective. Analysis of twenty samples showed that gentiopicroside is the most dominant compound (1.85-3.97%), followed by loganic acid (0.11-1.30%), Isogentisin (0.03-0.48%), sweroside (0.05-0.35%), swertiamarin (0.08-0.30%), and amarogentin (0.01-0.07%). The results confirmed the high quality of the G.lutea cultivated in the Monti Sibillini National Park.

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 profile, radical scavenging and cytotoxic activity of yellow gentian leaves (Genitaneae luteaefolium) grown in northern regions of Montenegro.[Pubmed:23285813]

Nat Prod Commun. 2012 Nov;7(11):1487-90.

LC-ESI-MS and HPLC were used for the identification of the constituents from G. lutea leaves collected at different localities, as well as for quantification of the main compounds. Seven secoiridoids, five C-glucoflavones and three xanthones, were identified. Swertiamarin derivatives, namely eustomorusside (2), eustomoside (3) and septemfidoside (5), were detected in G. lutea for the first time. Concentrations of five constituents (swertiamarin, gentiopicrin, isovitexin, mangiferin and Isogentisin) were determined. The relationship between concentrations of y-pyrones and altitude was observed with statistically significant correlation (r = 0.94). The extracts were also evaluated for their content of total phenolics, and antiradical and cytotoxic activities. The total phenolics content ranged from 7.7 to 12.7 mg GAE/g, and the IC50 values for DPPH radical scavenging activity varied between 0.45 to 2.02 mg/mL. The leaf extract exhibited moderate cytotoxic effects toward HeLa cells with an IC50 value of 41.1 microg/mL, while gentiopicrin, mangiferin and Isogentisin exerted strong activity against HeLa cells, with IC50 values ranging from 5.7 to 8.8 microg/mL. The results confirm the traditional usage of G. lutea leaves and also suggest their possible utilization as hepatoprotective, hypoglycemic and anti-inflammatory agents.

Antimicrobial activity of Gentiana lutea L. extracts.[Pubmed:19678535]

Z Naturforsch C J Biosci. 2009 May-Jun;64(5-6):339-42.

Methanolic extracts of flowers and leaves of Gentiana lutea L., together with the isolated compounds mangiferin, Isogentisin and gentiopicrin, were used to investigate the antimicrobial activity of the plant. A variety of Gram-positive and Gram-negative bacteria as well as the yeast Candida albicans has been included in this study. Both extracts and isolated compounds showed antimicrobial activity with MIC values ranging from 0.12-0.31 mg/ml. Our study indicated that the synergistic activity of the pure compounds may be responsible for the good antimicrobial effect of the extracts. Quantification of the secondary metabolites was performed using HPLC.

Determination of gentisin, isogentisin, and amarogentin in Gentiana lutea L. by capillary electrophoresis.[Pubmed:18064621]

J Sep Sci. 2008 Jan;31(1):195-200.

A novel, fast, and simple capillary electrophoresis method has been developed for the analysis of gentisin, Isogentisin, and amarogentin in roots of Gentiana lutea (yellow gentian), an herb traditionally used as gastric stimulant. Gentisin and Isogentisin are xanthones showing potent inhibition of monoamine oxidase type A and B, amarogentin represents one of the bitter principles of Gentiana, responsible for its gastric-roborant effects. Optimal CE-separation conditions comprise a 100 mM sodium tetraborate buffer of pH 9.3, containing 10 mM beta-cyclodextrin as additive; optimum temperature and applied voltage were found to be 30 degrees C and 25 kV, respectively. Direct diode array detection at 260 nm (gentisin, Isogentisin) and 242 nm (amarogentin) was performed, and the required analysis time was only 11 min. The developed method was validated for linearity, sensitivity, precision, and accuracy, and utilized to assay several commercially available G. lutea samples. Quantitative data obtained with the developed CE method are compared with HPLC results, and the advantages of each approach are discussed.

Isogentisin--a novel compound for the prevention of smoking-caused endothelial injury.[Pubmed:17141243]

Atherosclerosis. 2007 Oct;194(2):317-25.

The best strategy in the fight against tobacco-induced diseases is prevention. However, more than one billion people around the world are smokers. Most of these people will develop or already suffer from tobacco-induced diseases. In this project, we screened 22 natural alpine plant extracts for their potential to protect human vascular endothelial cells from cigarette smoke-induced cell damage. Extracts from Gentiana lutea (Yellow Gentian) proved to be effective, and were therefore subjected to bio-guided fractionation. Although our analyses suggest that G. lutea contains several active principles, fractions containing Isogentisin (1,3-dihydroxy-7-methoxyxanthone), and pure Isogentisin, were most effective. In experiments addressing the nature of the mechanism of protection, we were able to show that Isogentisin does not directly interfere with cigarette smoke chemicals. Addition of Isogentisin to the cells as long as 4.5h after exposure to cigarette smoke chemicals protected endothelial cells from cell death. Finally, detailed analyses of intracellular oxidative stress and protein oxidation suggest that Isogentisin promotes cell survival by activating cellular repair functions.

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.

Mutagenic activities of gentisin and isogentisin from Gentianae radix (Gentianaceae).[Pubmed:6338357]

Mutat Res. 1983 Feb;116(2):103-17.

The mutagenic activities of 2 hydroxyxanthones, gentisin and Isogentisin, obtained from the methanol extract of Gentianae radix (Gentianaceae) were investigated. The methanol extract of Gentianae radix, which showed mutagenicity in the Ames test in Salmonella typhimurium strain TA100 with S9 mix, was fractionated by column chromatography on Sephadex LH-20, and the fractions were purified by preparative TLC and column chromatography on polyamide. 2 mutagenic materials thus obtained, S1 and S2, each gave a single band on TLC. Identification of S1 and S2 was accomplished by comparing the analytical (mps, elementary analyses) and spectral (UV, IR, mass, NMR) results for S1 and S2 with literature data for gentisin and Isogentisin. At doses below 10 micrograms, S1 (gentisin) and S2 (Isogentisin) had similar specific mutagenic activities. At doses of over 10 to 50 micrograms, the mutagenic activities of S2 and S1 were 19.1 and 6.94 revertants per microgram respectively. This much lower activity of S1 than S2 may be a result of its poor solubility owing to the presence of the OMe group at C-3. The combined yield of S1 and S2 was about 76 mg (40 mg as S1 and 36 mg as S2), which accounted for 76% of the content of mutagenic compounds (100 mg) estimated roughly from the total mutagenic activity in the extract of the starting materials (100 g).