Computational and experimental approaches manifest the leishmanicidal potential of α-mangostin resourced from Garcinia cowa.

Owing to the persistent number of parasitic deaths, Visceral leishmaniasis continues to haunt several economically weaker sections of India. The disease causes over 30,000 deaths and threatens millions annually on a global scale. The standard pentavalent antimonials, on the other hand, are associated with health adversities and disease relapse. The current study is focused on the search for the most potential natural bioactive phytocompound from the bark extract of the Northeastern Indian plant, Garcinia cowa, that shows potent anti-leishmanial properties. The High Resonance Liquid Chromatography followed by Mass Spectrometry (HR-LCMS) study followed by an in silico molecular docking using computational tools revealed that α-mangostin might potentially possess antiparasitic activity. To validate the anti-leishmanial efficacy of the compound, a cell viability assay was performed, which demonstrated the parasite-specific inhibitory activity of α-mangostin; with IC50 values ranging from 4.95 - 7.37 µM against the different forms of Leishmania donovani parasite. The flow cytometric analysis of the phytocompound treated parasites indicated an oxidative and nitrosative stress-mediated apoptotic cell death in the parasites, by the suggestive surge in nuclear fragmentation and mitochondrial dysfunction. Simultaneously, a cytokine profiling study suggested approximate two-to-three-fold upregulated levels of pro-inflammatory cytokines post-compound treatment, which is predicted to actively contribute to parasite-killing. α-mangostin was also found to reduce the chances of parasite survival by inhibiting arginase enzyme activity, which in favorable conditions facilitates its sustenance. This study thereby substantiates that α-mangostin significantly possesses anti-leishmanial potentiality that can be developed into a cure for this infectious disease.

Quantification of mangiferin in streptozotocin-induced diabetic rat plasma using UPLC-MS/MS: Pharmacokinetic assessment of Gentiana rhodantha extract after oral administration.

Mangiferin, a key bioactive constituent in Gentiana rhodantha, has a favorable impact on reducing blood sugar. A selective and sensitive UPLC MS/MS approach was developed for determining mangiferin in diabetic rats. Employing acetonitrile protein precipitation, chromatographic separation utilized a 2.1×50 mm, 3.5µm C18 column with a mobile phase of 0.1% formic acid aqueous and 5mM ammonium acetate (A, 45%) and acetonitrile (B, 55%) at a 0.5mL min-1 flow rate. Quantification, employing the multiple reaction monitoring (MRM) mode, focused on precursor-to-product ion transitions at m/z 447.1→271.1 for baicalin m/z and 421.0→301.0 for mangiferin. Calibration curves demonstrated linearity in the 1.00~100ng/mL range, with a lower quantification limit for rat plasma set at 1.00ng/mL. Inter- and intra-day accuracies spanned -9.1% to 8.5% and mangiferin mean recovery varied from 82.3% to 86.7%. The adeptly utilized UPLC-MS/MS approach facilitated the exploration of mangiferin pharmacokinetics in diabetic rats.

Preliminary hazard assessment of a new nature-inspired antifouling (NIAF) agent.

A recently synthesized aminated 3,4-dioxygenated xanthone (Xantifoul2) was found to have promising antifouling (AF) effects against the settlement of the macrofouler Mytilus galloprovincialis larvae. Preliminary assessment indicated that Xantifoul2 has reduced ecotoxicological impacts: e.g., being non-toxic to the marine crustacea Artemia salina (<10 % mortality at 50 µM) and showing low bioconcentration factor in marine organisms. In order to meet the EU Biocidal Product Regulation, a preliminary hazard assessment of this new nature-inspired antifouling (NIAF) agent was conducted in this work. Xantifoul2 did not affect the swimming ability of the planktonic crustacean Daphnia magna, the growth of the diatom Phaeodactylum tricornutum, and the cellular respiration of luminescent Gram-negative bacteria Vibrio fischeri, supporting the low toxicity towards several non-target marine species. Regarding human cytotoxicity, Xantifoul2 did not affect the cell viability of retinal human cells (hTERT-RPE-1) and lipidomic studies revealed depletion of lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress only at a high concentration (10 µM). Accelerated degradation studies in water were conducted under simulated sunlight to allow the understanding of putative transformation products (TPs) that could be generated in the aquatic ecosystems. Both Xantifoul2 and photolytic-treated Xantifoul2 in the aqueous matrix were therefore evaluated on several nuclear receptors (NRs). The results of this preliminary hazard assessment of Xantifoul2, combined with the high degradation rates in water, provide strong evidence of the safety of this AF agent under the evaluated conditions, and provide the support for future validation studies before this compound can be introduced in the market.

Design, QSAR Methodology, Synthesis and Assessment of Some Structurally Different Xanthone Derivatives as Selective Cox-2 Inhibitors for their Anti-inflammatory Properties.

INTRODUCTION: Inflammation can be defined as a complex biological response that is produced by body tissues to harmful agents like pathogens, irritants, and damaged cells and thereby acts as a protective response incorporating immune cells, blood vessels, and molecular mediators. Histamine, serotonin, bradykinin, leukotrienes (LTB4), prostaglandins (PGE2), prostacyclins, reactive oxygen species, proinflammatory cytokines like IL-1, IL-11, TNF- anti-inflammatory cytokines like IL-4, IL-10, IL-11, IL-6 and IL-13, etc. all have different effects on both pro and anti-inflammatory mediators. Incorporation of combinatorial chemistry and computational studies have helped the researchers to design xanthones moieties with high selectivity that can serve as a lead compound and help develop potential compounds that can act as effective COX-2 inhibitors. The study aims to design and develop different series of substituted hydroxyxanthone derivatives with anti-inflammatory potential. METHODS: The partially purified synthetic xanthone derivatives were orally administered to the carrageenan induced paw oedemic rat models at the dose of 100 mg/kg, and their effect in controlling the degree of inflammation was measured at the time interval of 30 min, 1, 2, 3, 4 and 6 hrs. respectively. Further, these compounds were also subjected to modern analytical studies like UV, IR, NMR and mass spectrometry or their characterization. RESULTS: The results drawn out of the in silico, in vitro, in vivo and analytical studies concluded that the hydroxyxanthone derivatives can obstruct the enzyme COX-2 and produce anti-inflammatory action potentially. CONCLUSION: With the aim to evaluate the compounds for their anti-inflammatory activity, it was observed that the newly designed xanthonic compounds also possess a safe toxicity margin and hence can be utilized by the researchers to develop hybrid xanthonic moieties that can specifically target the enzyme COX-2.

Swertia chirayita: A comprehensive review on traditional uses, phytochemistry, quality assessment and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Swertia chirayita (Roxb.) H. Karst. is a traditionally used, well-recognized medicinal plant of the family Gentianaceae with significant therapeutic potential. It has been traditionally used to cure various ailments such as fever, vomiting, jaundice, digestive disorders, heart diseases, diabetes, malaria, scorpion bite, and skin diseases. AIM OF REVIEW: The present review emphasized the traditional uses, phytochemistry, pharmacology, toxicology, chemical profiling, and structural identification of isolated compounds by analytical and spectroscopic techniques. This review demonstrates the possibility of advanced ethnopharmacological research. MATERIALS AND METHODS: The literature on S. chirayita was obtained from bibliographic databases like Web of Science, PubMed, Science-Direct, American Chemical Society (ACS), Google Scholar, and SciFinder. The compiled review is covered up until March 2022. RESULTS: Approximately, 123 specialized metabolites including xanthones, seco-iridoids, terpenoids, alkaloids, and flavonoids have been isolated and characterized from S. chirayita. The extract and isolated compounds exhibited a wide spectrum of pharmacological effects such as anti-inflammatory, antioxidant, antitumor, hepatoprotective, antiviral, antimalarial, and antibacterial offering scientific evidence for traditional claims of this medicinal plant. In addition, various analytical methods using HPTLC, UPLC, HPLC, LC-MS, and GC-MS have also been documented to determine the phytochemicals of S. chirayita. CONCLUSION: The current article provides information on traditional usage, phytochemistry, chemical profiling, structure elucidation, pharmacological efficacy, toxicity, and future prospects of S. chirayita. This plant has long been traditionally used in a variety of ways by indigenous people. Numerous phytoconstituents and several pharmacological activities have been reported in S. chirayita. However, there are still some scientific gaps such as identification of bioactive compounds, structure-activity relationship and mechanistic action of isolated bioactive compounds, development of effective analytical methods for comprehensive quality control, and safety profiles that need to be addressed.

Fabrication and Biological Assessment of Antidiabetic α-Mangostin Loaded Nanosponges: In Vitro, In Vivo, and In Silico Studies.

Type 2 diabetes mellitus has been a major health issue with increasing morbidity and mortality due to macrovascular and microvascular complications. The urgent need for improved methods to control hyperglycemic complications reiterates the development of innovative preventive and therapeutic treatment strategies. In this perspective, xanthone compounds in the pericarp of the mangosteen fruit, especially α-mangostin (MGN), have been recognized to restore damaged pancreatic ß-cells for optimal insulin release. Therefore, taking advantage of the robust use of nanotechnology for targeted drug delivery, we herein report the preparation of MGN loaded nanosponges for anti-diabetic therapeutic applications. The nanosponges were prepared by quasi-emulsion solvent evaporation method. Physico-chemical characterization of formulated nanosponges with satisfactory outcomes was performed with Fourier transform infra-red (FTIR) spectroscopy, differential scanning calorimetry (DSC), and scanning electron microscopy (SEM). Zeta potential, hydrodynamic diameter, entrapment efficiency, drug release properties, and stability studies at stress conditions were also tested. Molecular docking analysis revealed significant interactions of α-glucosidase and MGN in a protein-ligand complex. The maximum inhibition by nanosponges against α-glucosidase was observed to be 0.9352 ± 0.0856 µM, 3.11-fold higher than acarbose. In vivo studies were conducted on diabetic rats and plasma glucose levels were estimated by HPLC. Collectively, our findings suggest that MGN-loaded nanosponges may be beneficial in the treatment of diabetes since they prolong the antidiabetic response in plasma and improve patient compliance by slowly releasing MGN and requiring less frequent doses, respectively.

Antiangiogenic properties of lichen secondary metabolites.

Lichens are symbiotic organisms which are composed fungi and algae and/or cyanobacteria. They produce a variety of characteristic secondary metabolites. Such substances have various biological properties including antimicrobial, antiviral, and antitumor activities. Angiogenesis, the growth of new vessels from pre-existing vessels, contributes to numerous diseases including cancer, arthritis, atherosclerosis, infectious, and immune disorders. Antiangiogenic therapy is a promising approach for the treatment of such diseases by inhibiting the new vessel formation. Technological advances have led to the development of various antiangiogenic agents and have made possible antiangiogenic therapy in many diseases associated with angiogenesis. Some lichens and their metabolites are used in the drug industry, but many have not yet been tested for their antiangiogenic effects. The cytotoxic and angiogenic capacities of lichen-derived small molecules have been demonstrated in vivo and in vitro experiments. Therefore, some of them may be used as antiangiogenic agents in the future. The secondary compounds of lichen whose antiangiogenic effect has been studied in the literature are usnic acid, barbatolic acid, vulpinic acid, olivetoric acid, emodin, secalonic acid D, and parietin. In this article, we review the antiangiogenic effects and cellular targets of these lichen-derived metabolites.

Gambogic acid: A shining natural compound to nanomedicine for cancer therapeutics.

The United States Food and Drug Administration has permitted number of therapeutic agents for cancer treatment. Most of them are expensive and have some degree of systemic toxicity which makes overbearing in clinical settings. Although advanced research continuously applied in cancer therapeutics, but drug resistance, metastasis, and recurrence remain unanswerable. These accounts to an urgent clinical need to discover natural compounds with precisely safe and highly efficient for the cancer prevention and cancer therapy. Gambogic acid (GA) is the principle bioactive and caged xanthone component, a brownish gamboge resin secreted from the of Garcinia hanburyi tree. This molecule showed a spectrum of biological and clinical benefits against various cancers. In this review, we document distinct biological characteristics of GA as a novel anti-cancer agent. This review also delineates specific molecular mechanism(s) of GA that are involved in anti-cancer, anti-metastasis, anti-angiogenesis, and chemo-/radiation sensitizer activities. Furthermore, recent evidence, development, and implementation of various nanoformulations of gambogic acid (nanomedicine) have been described.

An integrated approach for the valorization of mango seed kernel: Efficient extraction solvent selection, phytochemical profiling and antiproliferative activity assessment.

A novel valorization strategy is proposed in this work for the sustainable utilization of a major mango processing waste (i.e. mango seed kernel, MSK), integrating green pressurized-liquid extraction (PLE), bioactive assays and comprehensive HRMS-based phytochemical characterization to obtain bioactive-rich fractions with high antioxidant capacity and antiproliferative activity against human colon cancer cells. Thus, a two steps PLE procedure was proposed to recover first the non-polar fraction (fatty acids and lipids) and second the polar fraction (polyphenols). Efficient selection of the most suitable solvent for the second PLE step (ethanol/ethyl acetate mixture) was based on the Hansen solubility parameters (HSP) approach. A comprehensive GC- and LC-Q-TOF-MS/MS profiling analysis allowed the complete characterization of the lipidic and phenolic fractions obtained under optimal condition (100% EtOH at 150 °C), demonstrating the abundance of oleic and stearic acids, as well as bioactive xanthones, phenolic acids, flavonoids, gallate derivatives and gallotannins. The obtained MSK-extract exhibited higher antiproliferative activity against human colon adenocarcinoma cell line HT-29 compared to traditional extraction procedures described in literature for MSK utilization (e.g. Soxhlet), demonstrating the great potential of the proposed valorization strategy as a valuable opportunity for mango processing industry to deliver a value-added product to the market with health promoting properties.

LC-MSn and HR-MS characterization of secondary metabolites from Hypericum japonicum Thunb. ex Murray from Nepalese Himalayan region and assessment of cytotoxic effect and inhibition of NF-κB and AP-1 transcription factors in vitro.

Hypericum japonicum Thunb. ex Murray is traditionally used in Nepal to treat several diseases, among whom inflammation and acute pain. Although several secondary metabolites from the same Hypericum species have been already characterized and considered for their pharmacological use, an exhaustive phytochemical characterization of H. japonicum from Nepal is lacking, as well as the assessment of its potential pharmacological properties. Hence, the aims of this study were the characterization of a methanolic extract of H. japonicum (HJME) collected from the Northern region of Nepal by LC-MSn and UPLC-QTOF. The assessment of in vitro inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1) transcription factors and HJME's cytotoxic effect on human cell lines was performed to evaluate the potential use of this herb as a source of anti-inflammatory and cytotoxic lead compounds. Fifty-seven phytoconstituents were identified, being mainly flavonoids, phloroglucinols, phenolic acids and xanthones. Although compounds characteristic of H. japonicum were detected (quercetin, quercetin-7-O-α-l-rhamnoside, quercitrin and hyperoside), several others are here reported for the first time in this species. The results from bioassays indicated that HJME could significantly reduce the viability of human THP-1 cells (IC50 = 5.4 ±â€¯1.1 µg mL-1), showing the promising potential of HJME as anti-tumor agent. Furthermore, HJME significantly decreased the activation of both NF-κB and AP-1 at the concentration of 2 µg mL-1. Overall, these data suggest that H. japonicum from Nepal could be used as a source of potential natural anti-inflammatory and anti-tumor lead compounds.

PSYCHOMETRIC PROPERTIES OF THE ALABAMA PARENTING QUESTIONNAIRE ADAPTED TO FAMILIES OF CHILEAN PRESCHOOLERS.

The Alabama Parenting Questionnaire (APQ) is a well-known tool to assess empirically identified aspects of positive and negative parenting practices. This study evaluates the psychometric properties of an adapted version of the APQ for its use with parents of children between 2 and 6 years of age in Chile. The participants were 557 parents of children aged 2 to 6 years. A confirmatory factor analysis showed that the best fit was obtained by a four-factor model (positive reinforcement, parental involvement, inconsistency of disciplinary practices, and punitive practices). The invariance analysis for this model by sex and social composition was positive. Disciplinary inconsistency and punitive practices were correlated with externalized and internalized behaviors in children. Results suggest that this adaptation of the APQ may result in a useful tool for clinical and research purposes in this age group.

A novel procedure for the assessment of the antioxidant capacity of food components.

Carbonylation, an oxidative modification of the amino group of arginine and lysine residues caused by reactive oxygen species, has emerged as a new type of oxidative damage. Protein carbonylation has been shown to exert adverse effects on various protein functions. Recently, the role of food components in the attenuation of oxidative stress has been the focus of many studies. Most of these studies focused on the chemical properties of food components. However, it is also important to determine their effects on protein functions via post-translational modifications. In this study, we developed a novel procedure for evaluating the antioxidant capacity of food components. Hydrogen peroxide (H2O2)-induced protein carbonylation in HL-60 cells was quantitatively analyzed by using fluorescent dyes (Cy5-hydrazide dye and IC3-OSu dye), followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence determination. Among a panel of food components tested, quinic acid, kaempferol, saponin, squalene, trigonelline, and mangiferin were shown to be capable of suppressing protein carbonylation in HL-60 cells. Our results demonstrated that this fluorescence labeling/SDS-PAGE procedure allows for the detection of oxidative stress-induced protein carbonylation with high sensitivity and quantitative accuracy. This method should be useful for the screening of new antioxidant food components as well as the analysis of their suppression mechanism.

Preliminary assessment of mutagenic and anti-mutagenic potential of some aminoalkanolic derivatives of xanthone by use of the Vibrio harveyi assay.

The Vibrio harveyi assay was used to evaluate mutagenic and anti-mutagenic effects of four new aminoalkanolic derivatives of xanthone with anticonvulsant activity, to select the potentially safe compounds for further in vivo studies in animal models. The study showed that at a concentration of 40 ng/ml the test compounds were not mutagenic. Additionally, two of the investigated compounds, namely the (R,S)-N-methyl-1-amino-2-propanol derivative of 6-methoxyxanthone (compound III) and the (R)-N-methyl-2-amino-1-butanol derivative of 7-chloroxanthone (compound IV) were strong inhibitors of the mutagenicity induced by 4-nitroquinoline-N-oxide (4-NQO) in V. harveyi strains BB7M and BB7XM. The inhibition percentages for compound IV were 49 (in BB7M) and 69 (in BB7XM), whereas for compound III these percentages were 47 (in BB7M) and 42 (in BB7XM), respectively. The present study demonstrates that four bioactive derivatives of xanthone display no mutagenic activity in the V. harveyi assay. In addition, compounds III and IV demonstrated considerable anti-mutagenic activity in this test. Based on the results obtained here, these compounds could be selected for further studies in animal models, while compounds III and IV should be tested further for their anti-mutagenic properties.

Time-dependent approach to spin-vibronic coupling: implementation and assessment.

In this work, we present the generalization of a time-dependent method for the calculation of intersystem crossing (ISC) rates in the Condon approximation. When ISC takes place between electronic states with the same orbital type, i.e., when the transition is forbidden according to the El-Sayed rules, it is necessary to go beyond the Condon approximation. Similar to the Herzberg-Teller expansion of the vibronic interaction, the electronic spin-orbit matrix elements are assumed to depend linearly on the nuclear coordinates. The ISC rate is then a sum of three contributions: a direct, mixed direct-vibronic, and vibronic term. The method, presented in this work, is based on the generating function formalism and the multi-mode harmonic oscillator approximation. In addition to the zero-temperature case, we implemented formulae for finite-temperature conditions assuming a Boltzmann population of vibrational levels in the initial state. Tests have been carried out for a variety of molecules for which literature data were available. We computed vibronic one-photon spectra of free-base porphyrin and free-base chlorin and calculated ISC rates for xanthone, thioxanthone, thionine, as well as free-base porphyrin and found excellent agreement with previous results. Quantitative rates for triplet formation in rhodamine A have been determined theoretically for the first time. We find the S1↝ T2 channel to be the major source of triplet rhodamine formation in the gas phase.

A semi-automatic microextraction in packed sorbent, using a digitally controlled syringe, combined with ultra-high pressure liquid chromatography as a new and ultra-fast approach for the determination of prenylflavonoids in beers.

In this work a highly selective and sensitive analytical procedure based on semi-automatic microextraction by packed sorbents (MEPS) technique, using a new digitally controlled syringe (eVol(®)) combined with ultra-high pressure liquid chromatography (UHPLC), is proposed to determine the prenylated chalcone derived from the hop (Humulus lupulus L.), xanthohumol (XN), and its isomeric flavonone isoxanthohumol (IXN) in beers. Extraction and UHPLC parameters were accurately optimized to achieve the highest recoveries and to enhance the analytical characteristics of the method. Important parameters affecting MEPS performance, namely the type of sorbent material (C2, C8, C18, SIL, and M1), elution solvent system, number of extraction cycles (extract-discard), sample volume, elution volume, and sample pH, were evaluated. The optimal experimental conditions involves the loading of 500µL of sample through a C18 sorbent in a MEPS syringe placed in the semi-automatic eVol(®) syringe followed by elution using 250µL of acetonitrile (ACN) in a 10 extractions cycle (about 5min for the entire sample preparation step). The obtained extract is directly analyzed in the UHPLC system using a binary mobile phase composed of aqueous 0.1% formic acid (eluent A) and ACN (eluent B) in the gradient elution mode (10min total analysis). Under optimized conditions good results were obtained in terms of linearity within the established concentration range with correlation coefficients (R) values higher than 0.986, with a residual deviation for each calibration point below 12%. The limit of detection (LOD) and limit of quantification (LOQ) obtained were 0.4ngmL(-1) and 1.0ngmL(-1) for IXN, and 0.9ngmL(-1) and 3.0ngmL(-1) for XN, respectively. Precision was lower than 4.6% for IXN and 8.4% for XN. Typical recoveries ranged between 67.1% and 99.3% for IXN and between 74.2% and 99.9% for XN, with relative standard deviations %RSD no larger than 8%. The applicability of the proposed analytical procedure in commercial beers, revealed the presence of both target prenylchalcones in all samples being IXN the most abundant with concentration of between 0.126 and 0.200µgmL(-1).

Assessment of anxiolytic and panicolytic effects of dichloromethane fraction from stems of Kielmeyera coriacea.

Kielmeyera coriacea Mart. (Calophyllaceae) is known popularly as "Pau Santo". The hydroethanolic extract (HE) of Kielmeyera coriacea stems and its semi-pure dichloromethane (DCM) constituent produced an antidepressant-like effect in rats. The purpose of this study was to investigate the effects of repeated administration (21 days) by gavage of the DCM fraction (5, 10 or 15mg/kg) in rats submitted to the elevated T-maze (ETM), a model of generalized anxiety and panic disorders. The tricyclic antidepressant imipramine (15mg/kg) was used as a positive control. Rat locomotion was assessed using the open field test (OFT) following each drug treatment. The 2-hydroxy-1-methoxyxanthone (1), aucuparin (2), swertinin (3), 1,3,7-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (4) and 1,3,5-trihydroxy-2-(3-methylbut-2-enyl)-xanthone (5) were identified in DCM fraction, and suggest that the xanthone (4) is related with the antidepressant-like profile of this plant. Pharmacological evaluation showed that DCM fraction (10 and 15 mg/kg) decreased the inhibitory avoidance latency from the closed arm and increased the one-way escape latency from the open arm in the ETM, which is indicative of anxiolytic and panicolytic effects, respectively, as occurs with the positive control, imipramine (15 mg/kg), when compared to their control group (vehicle). Locomotor activity was not significantly altered by the different treatments. This study suggests that the DCM fraction from stems of Kielmeyera coriacea can be an important therapeutic alternative in the treatment of anxiety disorders, such as generalized anxiety and panic disorders.

Antimicrobial natural products: an update on future antibiotic drug candidates.

Over the last decade, it has become clear that antimicrobial drugs are losing their effectiveness due to the evolution of pathogen resistance. There is therefore a continuing need to search for new antibiotics, especially as new drugs only rarely reach the market. Natural products are both fundamental sources of new chemical diversity and integral components of today's pharmaceutical compendium, and the aim of this review is to explore and highlight the diverse natural products that have potential to lead to more effective and less toxic antimicrobial drugs. Although more than 300 natural metabolites with antimicrobial activity have been reported in the period 2000-2008, this review will describe only those with potentially useful antimicrobial activity, viz. with MICs in the range 0.02-10 microg mL(-1). A total of 145 compounds from 13 structural classes are discussed, and over 100 references are cited.

Validation of LC for the determination of alpha-mangostin in mangosteen peel extract: a tool for quality assessment of Garcinia mangostana L.

Mangosteen, Garcinia mangostana L., is known as the "Queen of fruits" and can be cultivated in the tropical rainforest such as Malaysia, Indonesia, and Thailand. Compounds isolated from the fruit peel of mangosteen contain abundant xanthones (especially alpha-mangostin). It has been used as traditional medicine such as anti-inflammatory and antibacterial and is popularly applied to cosmetic and pharmaceutical products. However, there is little information for quality and quantity determination of alpha-mangostin in mangosteen. Thus, the aim of this study was to set up a validated and stability-indicated isocratic reverse-phase high-performance liquid chromatographic (HPLC) method for quality control and quantity determination of a-mangostin from mangosteen peel extract. The assay was fully validated and shown to be linear (r(2) > 0.999), sensitive (LOD = 0.02 microg/mL and LOQ = 0.08 microg/mL), accurate (intra-day was between 98.1-100.8%, inter-day was between 90.0-101.3%), precise (intra-day variation < or = 1.8%, inter-day variation < or = 4.3%), specific, and with good recovery. Total analysis was approximately 8 min. The finalized method is also a stability-indicating assay. The present method should be useful for analytical research and for routine quality control analysis of alpha-mangostin in mangosteen peel extract and products of mangosteen.

Assessment of systemic interaction between Swertia chirata extract and its Bioactive constituents in rabbits.

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.

Assessment of the early effects of 5,6-dimethylxanthenone-4-acetic acid using macromolecular contrast media-enhanced magnetic resonance imaging: ectopic versus orthotopic tumors.

PURPOSE: To investigate the early effects of a vascular disrupting agent (VDA) in ectopic and orthotopic tumors by using macromolecular contrast media (MMCM)-enhanced magnetic resonance imaging (MMCM-MRI). METHODS AND MATERIALS: The MMCM-MRI of ectopic and orthotopic MCA205 murine fibrosarcomas was performed using the intravascular contrast agent albumin-(gadopentetate dimeglumine)(35). Change in longitudinal relaxation rate (DeltaR1) was measured 24 hours after treatment with 5,6-dimethylxanthenone-4-acetic acid (DMXAA; 30 mg/kg) and used to compute tumor vascular volume and permeability. Correlative histologic and immunohistochemical evaluation was carried out, along with measurement of tumor necrosis factor alpha and vascular endothelial growth factor levels in whole tumor extracts using the enzyme-linked immunosorbent assay. RESULTS: Orthotopic tumors showed higher vascular volume (p < 0.05) than ectopic tumors before treatment. Twenty-four hours after DMXAA treatment, a significant (p < 0.0001), but differential, decrease in DeltaR1 (70% in ectopic and 50% in orthotopic tumors) was observed compared with baseline estimates. Consistent with this observation, greater levels of tumor necrosis factor alpha, an important mediator of the antivascular activity of DMXAA, were measured in ectopic tumors 3 hours posttreatment compared with orthotopic tumors (p < 0.05). Immunohistochemical (CD31) and histologic (hematoxylin and eosin) sections of ectopic and orthotopic tumors showed highly tumor-selective vascular damage after treatment with the presence of viable surrounding normal tissue. CONCLUSIONS: The MMCM-MRI provided early quantitative estimates of change in tumor perfusion after VDA treatment that showed good correlation with cytokine induction. Differences in the response of ectopic and orthotopic tumors highlight the influence of the host microenvironment in modulating the activity of VDAs.