Mangiferin - a bioactive xanthonoid, not only from mango and not just antioxidant.
Matkowski Adam,Kuś Piotr,Góralska Edyta,Woźniak Dorota
Mini reviews in medicinal chemistry
Mangiferin is a plant natural polyphenol of C-glycosylxanthone structure and various pharmacological activities. It can be found in many plant species, among which the mango tree (Mangifera indica) is one of the primary sources. Mangiferin is also present in some medicinal herbs, influencing their therapeutic and preventive properties, and in honeybush (Cyclopia sp.), a popular South African herbal tea. Mangiferin dissolves well in water, so it can be easily extracted into infusions and decoctions. In the mangiferin molecule, four aromatic hydroxyl groups determine its strong antiradical and antioxidant properties. Mangiferin is also an efficient iron chelator, therefore preventing the generation of hydroxyl radical in Fenton-type reactions. Numerous published in vitro and in vivo pharmacological studies, demonstrated many other activities of mangiferin: analgesic, antidiabetic, antisclerotic, atimicrobial and antiviral, cardio-, hepato-, and neuroprotective, antiinflammatory, antiallergic, MAO inhibiting and memory improving, as well as radioprotective against X-ray, gamma, and UV radiation. Several studies indicated also its ability to inhibit cancerogenesis and cancer cells growth by apoptosis induction in vitro and in vivo. It is also used in cosmetics, due to antioxidant and UV-protecting properties.
Iron complexing activity of mangiferin, a naturally occurring glucosylxanthone, inhibits mitochondrial lipid peroxidation induced by Fe2+-citrate.
Andreu Gilberto Pardo,Delgado René,Velho Jesus A,Curti Carlos,Vercesi Anibal E
European journal of pharmacology
Mangiferin, a naturally occurring glucosylxanthone, has been described as having antidiabetic, antiproliferative, immunomodulatory and antioxidant activities. In this study we report for the first time the iron-complexing ability of mangiferin as a primary mechanism for protection of rat liver mitochondria against Fe(2+)-citrate induced lipid peroxidation. Thiobarbituric acid reactive substances and antimycin A-insensitive oxygen consumption were used as quantitative measures of lipid peroxidation. Mangiferin at 10 microM induced near-full protection against 50 microM Fe(2+)-citrate-induced mitochondrial swelling and loss of mitochondrial transmembrane potential (DeltaPsi). The IC(50) value for mangiferin protection against Fe(2+)-citrate-induced mitochondrial thiobarbituric acid reactive substance formation (9.02+/-1.12 microM) was around 10 times lower than that for tert-butylhydroperoxide mitochondrial induction of thiobarbituric acid reactive substance formation. The xanthone derivative also inhibited the iron citrate induction of mitochondrial antimycin A-insensitive oxygen consumption, stimulated oxygen consumption due to Fe(2+) autoxidation and prevented Fe(3+) ascorbate reduction. Absorption spectra of mangiferin-Fe(2+)/Fe(3+) complexes also suggest the formation of a transient charge transfer complex between Fe(2+) and mangiferin, accelerating Fe(2+) oxidation and the formation of a more stable Fe(3+)-mangiferin complex unable to participate in Fenton-type reaction and lipid peroxidation propagation phase. In conclusion, these results show that in vitro antioxidant activity of mangiferin is related to its iron-chelating properties and not merely due to the scavenging activity of free radicals. These results are of pharmacological relevance since mangiferin and its naturally contained extracts could be potential candidates for chelation therapy in diseases related to abnormal intracellular iron distribution or iron overload.
10.1016/j.ejphar.2005.03.007
[Design of acetylcholinesterase inhibitor for Alzheimer's disease therapy: from multi-binding site inhibitors to multi-target directed ligands].
Yang Wen-Chao,Sun Qi,Yu Ning-Xi,Zhu Xiao-Lei,Yang Guang-Fu
Yao xue xue bao = Acta pharmaceutica Sinica
Alzheimer's disease (AD) is a complex neurodegenerative disorder which seriously causes the dementia in elderly people and afflicts millions of people worldwide. Drug discovery for Alzheimer's disease therapy has been a hot research area and a big challenge, in which development of acetylcholinesterase (AChE) inhibitors design was the most active and some AChE inhibitors are commercially available for AD medication already. However, practical using of commercial AChE inhibitors showed their limited usefulness and related adverse effects. Thus, it is extremely urgent to find novel AChE inhibitors with higher potency and less adverse effects. Based on the accurate crystallographic studies about AChE, strategies for multi-binding site AChE inhibitors have been formed, followed by design of the multi-target directed ligands. In this review, the structures and binding modes of commercial AChE inhibitors were briefly discussed, together with the development of AChE inhibitor design for AD therapy: from multi-binding site inhibitors to multi-target directed ligands.
Design, synthesis and biological evaluation of 1,3-dihydroxyxanthone derivatives: Effective agents against acetylcholinesterase.
Menéndez Cintia A,Biscussi Brunella,Accordino Sebastián,Paula Murray A,Gerbino Darío C,Appignanesi Gustavo A
Bioorganic chemistry
The present work concerns the rational design and development of new inhibitors of acetylcholinesterase (AChE) based on the privileged xanthone scaffold. In order to understand and rationalize the mode of action of these target structures a theoretical study was initially conducted. From the results of rational design, a new variety of amphiphilic xanthone derivatives were synthesized, structurally characterized and evaluated as potential anti-Alzheimer agents. The results showed that most of the synthesized compounds exhibited high AChE inhibitory activity at the micromolar range (IC, 0.46-12.09μM). The synthetic xanthone 11 showed the best inhibitory effect on AChE and a molecular modeling study revealed that 11 targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Therefore, this compound could be considered asa potential lead compound towards new drugs for the treatment of Alzheimer's disease.
10.1016/j.bioorg.2017.09.012
Xanthones from mangosteen (Garcinia mangostana): multi-targeting pharmacological properties.
Jindarat Sarawut
Journal of the Medical Association of Thailand = Chotmaihet thangphaet
OBJECTIVE:This review focuses on mangosteen pericarp extracts, xanthones and derivatives for the future laboratory experiment and development in pharmacological aspects. MATERIAL AND METHOD:All relevant literature databases were searched up to 2 March 2014. The search terms included mangosteen, xanthone, mangostin, and gatanin in all of the human, animal, in vitro and in vivo studies. Anti-intflammation, antioxidant, antibacterial, anticancer and antiulcer properties of each substance were the key parameters. RESULTS:Xanthones are a group of oxygen-containing heterocyclic compounds including alpha-mangostin, gamma-mangostin, mangosteen extract, xanthone derivatives and synthetic xanthones, which provide remarkable and diverse pharmacological effects such as anticancer, antioxidant, anti-inflammatory and antimicrobial activities. CONCLUSION:These xanthone compounds may play a major role in therapeutic treatment ofthe diseases but precise mechanisms ofaction are still unclear and needfurther investigation.
Lyophilized aqueous extracts of Mori Fructus and Mori Ramulus protect Mesenchymal stem cells from •OH-treated damage: bioassay and antioxidant mechanism.
Jiang Qian,Li Xican,Tian Yage,Lin Qiaoqi,Xie Hong,Lu Wenbiao,Chi Yuguang,Chen Dongfeng
BMC complementary and alternative medicine
BACKGROUND:Mori Fructus and Mori Ramulus are two traditional Chinese herbal medicines from mulberries. The present work explores their beneficial effects on •OH-treated mesenchymal stem cells (MSCs) and discusses possible mechanisms. METHODS:Lyophilized aqueous extracts of Mori Fructus (LAMF) and Mori Ramulus (LAMR) were prepared and analyzed using HPLC. LAMF and LAMR (along with morin) were further investigated for their effects on •OH-treated MSCs using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl (MTT) assay. The direct antioxidation mechanisms were studied using 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (PTIO•)-scavenging, 2,2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS•)-scavenging and 1,1-diphenyl-2-picryl-hydrazl (DPPH•)-scavenging, as well as Cu-reducing and Fe-reducing antioxidant power. Finally, the indirect antioxidant mechanism was investigated based on the UV-vis spectra of Fe-chelation. RESULTS:In each LAMF and LAMR, seven phytophenols were successfully measured by HPLC, including five flavonoids (morin, rutin, astragalin, isoquercitrin and luteolin) and two non-flavonoids (chlorogenic acid and maclurin). MTT assays revealed that LAMF, LAMR and morin could effectively increase the survival of •OH-treated MSCs at 10-100 μg/mL, and could effectively scavenge PTIO• (IC 6609.7 ± 756.6, 4286.9 ± 84.9 and 103.4 ± 0.9 μg/mL, respectively), DPPH• (IC 208.7 ± 3.0, 97.3 ± 3.1 and 8.2 ± 0.7 μg/mL, respectively) and ABTS• (IC 73.5 ± 5.8, 34.4 ± 0.1 and 4.2 ± 0.2 μg/mL, respectively), and reduce Cu (IC 212.5 ± 7.0, 123.2 ± 0.9 and 14.1 ± 0.04 μg/mL, respectively) & Fe (IC 277.0 ± 3.1, 191.9 ± 5.2 and 5.0 ± 0.2 μg/mL, respectively). In the Fe-chelating assay, the five flavonoids produced much stronger shoulder-peaks than the two non-flavonoids within 420-850 nm. CONCLUSION:Mori Fructus and Mori Ramulus, can protect MSCs from •OH-induced damage. Such beneficial effects can mainly be attributed to the antioxidant action of phytophenols, which occurs via direct (ROS-scavenging) and indirect mechanism (Fe-chelating). The ROS-scavenging mechanism, however, include at least a H-transfer and an electron-transfer (ET), and possibly includes a hydrogen-atom-transfer (HAT). In the Fe-chelating, flavonoids are more effective than non-flavonoids. This can be attributed to several adjacent planar chelating-sites between the 3-OH and 4-C = O, between the 4-C = O and 5-OH, or between the 3'-OH and 4'-OH in flavonoids. Such multiple-Fe-chelating reactions cause overlap in the UV-vis absorptions to deepen the complex color, enhance the peak strength, and form shoulder-peaks. By comparison, two non-flavonoids with catechol moiety produce only a weak single peak.
10.1186/s12906-017-1730-3
Xanthone Glucosides: Isolation, Bioactivity and Synthesis.
Huang Qing,Wang Youyi,Wu Huaimo,Yuan Man,Zheng Changwu,Xu Hongxi
Molecules (Basel, Switzerland)
Xanthones are secondary metabolites found in plants, fungi, lichens, and bacteria from a variety of families and genera, with the majority found in the Gentianaceae, Polygalaceae, and Clusiaceae. They have a diverse range of bioactivities, including anti-oxidant, anti-bacterial, anti-malarial, anti-tuberculosis, and cytotoxic properties. Xanthone glucosides are a significant branch of xanthones. After glycosylation, xanthones may have improved characteristics (such as solubility and pharmacological activity). Currently, no critical review of xanthone glucosides has been published. A literature survey including reports of naturally occurring xanthone glucosides is included in this review. The isolation, structure, bioactivity, and synthesis of these compounds were all explored in depth.
10.3390/molecules26185575
Activity-guided isolation of antioxidant xanthones from Swertia chirayita (Roxb.) H. Karsten (Gentianaceae).
Singh Pradeep Pratap,Ambika ,Chauhan Shive Murat Singh
Natural product research
An activity-guided isolation and purification process was used to identify the DPPH (l,l-diphenyl-2-picrylhydrazyl) radical-scavenging components of Swertia chirayita. A dry, whole plant of S. chirayita was extracted with different solvents and tested for its DPPH radical-scavenging activity. The acetone : water (8 : 2) extract showed the highest total phenolic content (TPC) and DPPH radical-scavenging activity, which was column chromatographed to obtain decussatin, swertianin, bellidifolin, isobellidifolin, amarogentin, swertianolin and mangiferin as active components. Good correlation was observed between TPC and DPPH scavenging activity among the extracts. The unique structure of xanthones, including the catecholic moiety and the completely conjugated system, enables them to be promising antioxidants.
10.1080/14786419.2011.592836
Antioxidant xanthones from Swertia mussotii, a high altitude plant.
Luo Cui-Ting,Mao Shuang-Shuang,Liu Fang-Lan,Yang Mao-Xun,Chen Heru,Kurihara Hiroshi,Li Yulin
Fitoterapia
Four new xanthones, 3,5,6,8-tetrahydroxyxanthone-1-C-β-D-glucoside (1), 7-hydroxy-3,4,8-trimethoxyxanthone-1-O-(β-D-glucoside) (2), 6-hydroxy-3,5-dimethoxyxanthone-1-O-(β-D-glucoside) (3), 3,4,7,8-tetramethoxyxanthone-1-O-(β-D-glucoside) (4), together with twenty-one known xanthones (5-25) were isolated from the ethanol aqueous extract of Swertia mussotii. Their structures were elucidated via spectroscopic analyses. Oxygen radical absorbance capacity of all the isolated xanthones was systematically evaluated by ORAC(FL) assay. Results disclose that all the tested xanthones display moderate to excellent antioxidant activity, where 1 is the most active compound and 13 is the least one. A preliminary structure-activity relationship is also discussed.
10.1016/j.fitote.2013.08.021
Hydroxyl radical and hypochlorous acid scavenging activity of small centaury (Centaurium erythraea) infusion. A comparative study with green tea (Camellia sinensis).
Valentão P,Fernandes E,Carvalho F,Andrade P B,Seabra R M,Bastos M L
Phytomedicine : international journal of phytotherapy and phytopharmacology
Small centaury (Centaurium erythraea Rafin.) is a herbal species with a long use in traditional medicine due to its digestive, stomachic, tonic, depurative, sedative and antipyretic properties. This species is reported to contain considerable amounts of polyphenolic compounds, namely xanthones and phenolic acids as the main constituents. Although the antiradicalar activity of some pure polyphenolic compounds is already known, it remains unclear how a complex mixture obtained from plant extracts functions against reactive oxygen species. Thus, the ability of small centaury infusion to act as a scavenger of the reactive oxygen species hydroxyl radical and hypochlorous acid was studied and compared with that of green tea (Camellia sinensis L.). Hydroxyl radical was generated in the presence of Fe3+-EDTA, ascorbate and H2O2 (Fenton system) and monitored by evaluating hydroxyl radical-induced deoxyribose degradation. The reactivity towards hypochlorous acid was determined by measuring the inhibition of hypochlorous acid-induced 5-thio-2-nitrobenzoic acid oxidation to 5,5'-dithiobis(2-nitrobenzoic acid). The obtained results demonstrate that small centaury infusion exhibits interesting antioxidant properties, expressed both by its capacity to effectively scavenge hydroxyl radical and hypochlorous acid, although with a lower activity against the second than that observed for green tea. Green tea exhibited a dual effect at the hydroxyl radical scavenging assay, stimulating deoxyribose degradation at lower dosages.
10.1078/094471103322331485
Antioxidant activity of Centaurium erythraea infusion evidenced by its superoxide radical scavenging and xanthine oxidase inhibitory activity.
Valentão P,Fernandes E,Carvalho F,Andrade P B,Seabra R M,Bastos M L
Journal of agricultural and food chemistry
Centaurium erythraea Rafin. (Gentianaceae) has long been used in traditional medicine. This plant contains considerable amounts of polyphenolic compounds, namely, xanthones and phenolic acids as the main constituents. Because phenolic groups exhibit activity as radical scavengers and/or metal chelators, this study evaluated the superoxide radical scavenging properties of a lyophilized infusion obtained from C. erythraea flowering tops. Superoxide radical scavenging activity was assayed using enzymatic (xanthine/xanthine oxidase) and nonenzymatic (NADH/phenazine methosulfate) superoxide generating systems. This study provided evidence that C. erythraea exhibits interesting antioxidant properties, expressed either by the capacity to scavenge superoxide radical or to noncompetitively inhibit xanthine oxidase. The main phenolic compounds present in this extract were several esters of hydroxycinnamic acids, namely, p-coumaric, ferulic, and sinapic acids.
10.1021/jf001145s
Prostaglandin E receptors in myometrial cells.
Asbóth G,Phaneuf S,López Bernal A L
Acta physiologica Hungarica
Prostaglandins (PGs) exert their effects via binding to specific cell surface receptors and influencing second messenger systems through G-proteins. PGE2 may interact with at least four receptor subtypes (EP1, EP2, EP3, EP4), each showing different pharmacological profiles. The second messengers calcium, inositol phosphates (InsPs) and cyclic nucleotides play decisive roles in uterine contractility. The question in this investigation was, which EP receptors, G-proteins and second messenger systems transmit PGE2 induced signals in human myometrium. We have measured changes in InsPs and cAMP formation and also in intracellular calcium concentration ([Ca2+]i) induced by PGE2 and receptor subtype selective analogues in cultured human myometrial cells. PGE2 increased cAMP level and this effect was shared by the EP2 receptor subtype selective agonist Butaprost and by Misoprostol (EP3 > EP2 > EP1). Sulprostone (EP3 > EP1) did not stimulate adenylyl cyclase activity per se, but inhibited forskolin-stimulated adenylyl cyclase in a pertussis toxin (PT) sensitive way. PGE2, GR63799X (EP3 selective), Sulprostone and Misoprostol activated phospholipase-C (PLC), this effect was resistant to PT treatment. PGE2 also elevated [Ca2+]i from the resting level of 60-90 nM up to 350 nM. Low concentrations (1-300 nM) of PGE2 increased [Ca2+]i without PLC activation. The selective EP1 inhibitor AH6809, Nifedipine, Verapamil and PT treatment inhibited this effect of PGE2. In cultured human myometrial cells PGE2 interacts with EP1 receptors, which elevate [Ca2+]i independently from PLC, but involving a Gi protein and plasmamembrane calcium channels; EP2 receptors which stimulate adenylyl cyclase; EP3A receptors, which inhibit adenylyl cyclase activity through Gi activation and EP3D receptors which activate PLC through a PT-insensitive pathway and also elevate [Ca2+]i.
Insights into molecular interactions between CaM and its inhibitors from molecular dynamics simulations and experimental data.
González-Andrade Martin,Rodríguez-Sotres Rogelio,Madariaga-Mazón Abraham,Rivera-Chávez José,Mata Rachel,Sosa-Peinado Alejandro,Del Pozo-Yauner Luis,Arias-Olguín Imilla I
Journal of biomolecular structure & dynamics
In order to contribute to the structural basis for rational design of calmodulin (CaM) inhibitors, we analyzed the interaction of CaM with 14 classic antagonists and two compounds that do not affect CaM, using docking and molecular dynamics (MD) simulations, and the data were compared to available experimental data. The Ca(2+)-CaM-Ligands complexes were simulated 20 ns, with CaM starting in the "open" and "closed" conformations. The analysis of the MD simulations provided insight into the conformational changes undergone by CaM during its interaction with these ligands. These simulations were used to predict the binding free energies (ΔG) from contributions ΔH and ΔS, giving useful information about CaM ligand binding thermodynamics. The ΔG predicted for the CaM's inhibitors correlated well with available experimental data as the r(2) obtained was 0.76 and 0.82 for the group of xanthones. Additionally, valuable information is presented here: I) CaM has two preferred ligand binding sites in the open conformation known as site 1 and 4, II) CaM can bind ligands of diverse structural nature, III) the flexibility of CaM is reduced by the union of its ligands, leading to a reduction in the Ca(2+)-CaM entropy, IV) enthalpy dominates the molecular recognition process in the system Ca(2+)-CaM-Ligand, and V) the ligands making more extensive contact with the protein have higher affinity for Ca(2+)-CaM. Despite their limitations, docking and MD simulations in combination with experimental data continue to be excellent tools for research in pharmacology, toward a rational design of new drugs.
10.1080/07391102.2015.1022225
Progress in the Development of Platelet-Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases.
Hyland Isabel K,O'Toole Ronan F,Smith Jason A,Bissember Alex C
ChemMedChem
Platelet-activating factor (PAF) and its receptor (PAFr) have been implicated in a wide range of diseases and disorders that originate from the activation of inflammatory pathways. Although the exact structure of the binding site on the PAFr remains unknown, the PAFr is a well-established therapeutic target, and an array of structurally diverse PAFr antagonists have been identified. These include compounds that are structurally similar to the natural PAF ligand, synthetic heterocycles, complex polycyclic natural products, and various metal complexes. This review provides an update on more than 20 years of progress in this area. The development and synthesis of new PAFr antagonists, structure-activity relationship studies, the biological activity of these molecules, and their therapeutic potential are discussed.
10.1002/cmdc.201800401
Oxygen transfer from sulfoxides: oxidation of alkylarenes catalyzed by a polyoxomolybdate, [PMo12O40]3-.
Khenkin Alexander M,Neumann Ronny
Journal of the American Chemical Society
The polyoxomolydate of the Keggin structure, PMo12O403-, catalyzes, under anaerobic conditions, oxygen transfer from sulfoxides to alkylarenes such as xanthene and diphenylmethane to yield xanthen-9-one and benzophenone, respectively. With use of 17O and 18O labeled phenylmethylsulfoxide it was shown that the sulfoxide is complexed by the polyoxometalate and the oxygen is transferred from the sulfoxide to the alkylarene. There is a good correlation between the reaction rate and the heterolytic benzylic C-H bond energy indicating a hydride transfer reaction from the alkylarene to the polyoxometalate-sulfoxide complex. In the case of triphenylmethane the resulting carbocation reacts to yield 9-phenylfluorene as the major product. The reaction kinetics supports such a reaction pathway.
10.1021/ja0178721
Mangostin inhibits the oxidative modification of human low density lipoprotein.
Williams P,Ongsakul M,Proudfoot J,Croft K,Beilin L
Free radical research
The oxidation of low density lipoprotein (LDL) may play an important role in atherosclerosis. We investigated the possible antioxidant effects of mangostin, isolated from Garcinia mangostana, on metal ion dependent (Cu2+) and independent (aqueous peroxyl radicals) oxidation of human LDL. Mangostin prolonged the lagtime to both metal ion dependent and independent oxidation of LDL in a dose dependent manner over 5 to 50 microM as monitored by the formation of conjugated dienes at 234 nm (P < 0.001). There was no significant effect of mangostin on the rate at which conjugated dienes were formed in the uninhibited phase of oxidation. Levels of thiobarbituric reactive substances (TBARS) generated in LDL were measured 4 and 24 hours after oxidation with 5 microM Cu2+ in the presence or absence of 50 microM or 100 microM mangostin. We observed an inhibition of TBARS formation with 100 microM mangostin at 4 hours (P = 0.027) but not at 24 hours (P = 0.163). Similar results were observed in the presence of 50 microM mangostin. Mangostin, at 100 microM, retarded the relative electrophoretic mobility of LDL at both 4 and 24 hours after Cu2+ induced oxidation. Mangostin (100 microM) significantly inhibited the consumption of alpha-tocopherol in the LDL during Cu2+ initiated oxidation over a 75 minute period (P < 0.001). From these results, we conclude that mangostin is acting as a free radical scavenger to protect the LDL from oxidative damage in this in vitro system.
Fe(III) shifts the mitochondria permeability transition-eliciting capacity of mangiferin to protection of organelle.
Pardo-Andreu Gilberto L,Cavalheiro Renata A,Dorta Daniel J,Naal Zeki,Delgado René,Vercesi Aníbal E,Curti Carlos
The Journal of pharmacology and experimental therapeutics
Mangiferin acts as a strong antioxidant on mitochondria. However, when in the presence of Ca(2+), mangiferin elicits mitochondrial permeability transition (MPT), as evidenced by cyclosporin A-sensitive mitochondrial swelling. We now provide evidence, by means of electrochemical and UV-visible spectroscopical analysis, that Fe(III) coordinates with mangiferin. The resulting mangiferin-Fe(III) complex does not elicit MPT and prevents MPT by scavenging reactive oxygen species. Indeed, the complex protects mitochondrial membrane protein thiols and glutathione from oxidation. Fe(III) also significantly increases the ability of mangiferin to scavenge the 2,2-diphenyl-1-picrylhydrazyl radical, as well as to display antioxidant activity toward antimycin A-induced H(2)O(2) production and t-butyl hydroperoxide-promoted membrane lipid peroxidation in mitochondria. We postulate that coordination with Fe(III) constitutes a potential protective mechanism toward the prooxidant action of mangiferin and other catechol-containing antioxidants regarding MPT induction. Potential therapeutic relevance of this finding for conditions of pathological iron overload is discussed.
10.1124/jpet.106.112003
Dual mechanism of mangiferin protection against iron-induced damage to 2-deoxyribose and ascorbate oxidation.
Pardo-Andreu Gilberto Lázaro,Delgado René,Núñez-Sellés Alberto J,Vercesi Anibal E
Pharmacological research
We studied mangiferin effects on the degradation of 2-deoxyribose induced by Fe(III)-EDTA/citrate plus ascorbate, in relation to ascorbate oxidation (measured at 265 nm). Results revealed that mangiferin was equally effective in preventing degradation of both 15 and 1.5 mM 2-deoxyribose. At a fixed Fe(III) concentration, increasing the concentration of ligands (either EDTA or citrate) caused a significant reduction in the protective effects of mangiferin. Interestingly, mangiferin strongly stimulated Fe(III)-EDTA ascorbate oxidation, but inhibited it when citrate was used as iron co-chelator. Mangiferin stimulated O2 consumption due to Fe(II) (formed by Fe(III) ascorbate reduction) autoxidation when the metal ligand was EDTA, but inhibited it when citrate was used. These results suggest that mangiferin removes iron from citrate, but not from EDTA, forming an iron-mangiferin complex that cannot induce ascorbate oxidation effectively, thus inhibiting iron-mediated oxyradical formation. Taken together, these results indicate that mangiferin works mainly by a mechanism different from the classical hydroxyl radical scavengers, keeping iron in its ferric form, by complexing Fe(III), or stimulating Fe(II) autoxidation.
10.1016/j.phrs.2005.06.006
Protective effects of Mangifera indica L extract (Vimang), and its major component mangiferin, on iron-induced oxidative damage to rat serum and liver.
Pardo-Andreu Gilberto L,Barrios Mariela Forrellat,Curti Carlos,Hernández Ivones,Merino Nelson,Lemus Yeny,Martínez Ioanna,Riaño Annia,Delgado René
Pharmacological research
In vivo preventive effects of a Mangifera indica L extract (Vimang) or its major component mangiferin on iron overload injury have been studied in rats given respectively, 50, 100, 250 mg kg(-1) body weight of Vimang, or 40 mg kg(-1) body weight of mangiferin, for 7 days prior to, and for 7 days following the administration of toxic amounts of iron-dextran. Both Vimang or mangiferin treatment prevented iron overload in serum as well as liver oxidative stress, decreased serum and liver lipid peroxidation, serum GPx activity, and increased serum and liver GSH, serum SOD and the animals overall antioxidant condition. Serum iron concentration was decreased although at higher doses, Vimang tended to increase it; percent tranferrin saturation, liver weight/body mass ratios, liver iron content was decreased. Treatment increased serum iron-binding capacity and decreased serum levels of aspartate-amine transferase (ASAT) and alanine-amine transferase (ALAT), as well as the number of abnormal Kupffer cells in iron-loaded livers. It is suggested that besides acting as antioxidants, Vimang extract or its mangiferin component decrease liver iron by increasing its excretion. Complementing earlier in vitro results from our group, it appears possible to support the hypothesis that Vimang and mangiferin present therapeutically useful effects in iron overload related diseases.
10.1016/j.phrs.2007.12.004
[Study on the interactions of Eu(III) complex of O-(thioxanthone-[2]-yl)-oxyacetic acid with DNA].
Yang Wu,Gao Qi-Kuan,Lu Xiao-Lin,Wu Jin-Xiu
Guang pu xue yu guang pu fen xi = Guang pu
The interaction of the Eu(III) complex of O-(thioxanthone-[2]-yl)-oxyacetic acid and calf thymus DNA was studied using fluorimetric, UV-Vis and CD(circular dichroism) methods. It was found that the ultraviolet absorption intensity of Eu(III) complex of O-(thioxanthone-[2]-yl)-oxyacetic acid decreased as the concentration of DNA increased under the physiological condition of pH 7.10, and the compound remarkably influenced the negative peak in CD spectra of DNA when Eu(III) complex of O-(thioxanthone-[2]-yl)-oxyacetic acid interacted with DNA. The emission intensity of the Eu(III) complex evidently increased in the presence of DNA. The emission intensity of the DNA-EB system decreased as the concentration of the complex increasesd. And the presence of EB also led to the decrease in the emission intensity of the DNA-complex system. These changes observed here are often characteristic of intercalation. The above results strongly suggest that the complex can bind to DNA mainly by intercalation.
Antitumor activity and DNA-binding investigations of the Zn(II) and Cu(II) complexes with isoeuxanthone.
Wang Huifang,Shen Rui,Wu Jincai,Tang Ning
Chemical & pharmaceutical bulletin
Two new complexes ZnL(2) (1) and CuL(2) (2) (here, HL=isoeuxanthone) have been synthesized and characterized by elemental analyses, molar conductance, infrared spectra (IR), (1)H-NMR and UV-Vis measurements. The interactions of them with calf thymus DNA (ct DNA) have been investigated by absorption spectroscopy, fluorescence spectroscopy, circular dichroism spectroscopy and viscosity measurements. Experimental results revealed an intercalative interaction with DNA for the complexes; furthermore the binding affinity of 2 is higher than that of 1 according to the calculated binding constant values. In addition, they were evaluated for their cytotoxic activities toward human esophageal cancer (ECA109) and human gastric cancer (SGC7901) cells by MTT assay. Both of them showed significant cytotoxic potency.
10.1248/cpb.57.814
Antigenotoxic effect of mangiferin and changes in antioxidant enzyme levels of Swiss albino mice treated with cadmium chloride.
Viswanadh E Kasi,Rao B Nageshwar,Rao B S Satish
Human & experimental toxicology
Cadmium is an environmental metal toxin implicated in human diseases. Mangiferin (MGN), a naturally occurring glucosylxanthone, is present in Mangifera indica. In this study, the protective role of MGN against cadmium chloride (CdCl(2))-induced genotoxicity was studied in Swiss albino mice. Mice were administered with single intra-peritoneal (i.p.) optimal dose of MGN (2.5 mg/kg b.wt.) before treatment with various concentrations of CdCl(2) (7, 8, 9, 10 and 11 mg/kg b.wt.). The LD( 50(30)) was found to be 8.5 mg/kg b.wt. for DDW + CdCl(2) group, while it was increased to 9.77 mg/kg after MGN treatment resulting in increase in the LD(50(30)) value by 1.26 mg, with a dose reduction factor (DRF) of 1.14. Treatment of mice to various doses of CdCl(2) resulted in a dose-dependent increase in the frequency of micronucleated polychromatic (MnPCE) and normochromatic erythrocytes (MnNCE), with corresponding decrease in the polychromatic / normochromatic erythrocyte ratio (PCE/NCE ratio) at various post-treatment times. MGN (2.5 mg/kg b.wt.) pretreatment significantly (p < .001) reduced the frequency of MnPCE, MnNCE and increased PCE/NCE ratio when compared with the DDW + CdCl(2) group at all post-treatment times indicating its antigenotoxic effect. Further, pretreatment of MGN declined the lipid peroxidation (LPx) content in liver, whereas significant increase was observed in hepatic Glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) activity. Our study revealed that MGN has potent antigenotoxic effect against CdCl(2)-induced toxicity in mice, which may be due to the scavenging of free radicals and increased antioxidant status.
10.1177/0960327110361752
Selective colorimetric and fluorescent detection of HSO4- with sodium(I), magnesium(II) and aluminium(III) xanthone-crown ether complexes.
Shen Rui,Pan Xiaobo,Wang Huifang,Yao Lihui,Wu Jincai,Tang Ning
Dalton transactions (Cambridge, England : 2003)
Xanthone-crown ether (1) reacts with NaClO(4), Mg(ClO(4))(2) and Al(ClO(4))(3) forming the one-dimensional chain dinuclear polymer [Na(2).1.(ClO(4))(2)] (2), the mononuclear complex [Mg.1.(H(2)O)(2)](ClO(4))(2) (3) and an interesting sandwich complex [Al.(1)(2).(H(2)O)(6)](ClO(4))(3) (4) with different ratios of metal-to-ligand, respectively. The anion recognition experiment results show that the magnesium complex (3) is a good colorimetric and fluorescent detector for HSO(4)(-) with high sensitivity and selectivity.
10.1039/b719407b
Mangiferin attenuates methylmercury induced cytotoxicity against IMR-32, human neuroblastoma cells by the inhibition of oxidative stress and free radical scavenging potential.
Das Shubhankar,Nageshwar Rao B,Satish Rao B S
Chemico-biological interactions
Mangiferin (MGN), a C-glucosylxanthone was investigated for its ability to protect against methylmercury (MeHg) induced neurotoxicity by employing IMR-32 (human neuroblastoma) cell line. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and clonogenic cell survival assays confirmed the efficacy of MGN supplementation in attenuating MeHg-induced cytotoxicity. Pre-treatment with MGN significantly (p<0.01) inhibited MeHg-induced DNA damage (micronuclei, olive tail moment and % tail DNA) thereby demonstrating MGN's antigenotoxic potential. Also, pre-treatment with MGN significantly reduced MeHg-induced oxidative stress, intra-cellular Ca(2+) influx and inhibited depolarization of mitochondrial membrane. MGN pre-treated cells demonstrated a significant (p<0.05) increase in the GSH and GST levels followed by a significant (p<0.05) decrease in malondialdehyde (MDA) formation. In addition, inhibition of MeHg induced apoptotic cell death by MGN was demonstrated by microscopic, Annexin-V FITC and DNA fragmentation assays and further confirmed by western blot analysis. The present findings indicated the protective effect of MGN against MeHg induced toxicity, which may be attributed to its anti-genotoxic, anti-apoptotic and anti-lipid peroxidative potential plausibly because of its free radical scavenging ability, which reduced the oxidative stress and in turn facilitated the down-regulation of mitochondrial apoptotic signalling pathways.
10.1016/j.cbi.2011.06.002
Synthesis, crystal structure, DNA-binding properties and cytotoxic activity of the copper (II) complex involving xanthone.
Shen Rui,Wang Peng,Tang Ning
Journal of fluorescence
1, 8-(3, 6, 9-Trioxaundecane-1, 11-diyldioxy)xanthone (L), and its new Cu (II) complex [Cu.L.(CH3CN)2](ClO4)2 have been synthesized and characterized by 1H NMR, electrospray mass spectra (ESI-MS), elemental analyses, infrared spectra (IR) and X-ray single crystal diffraction. The crystal structure of complex shows that Cu (II) ion is encapsulated within the macrocycle of L. The geometry around copper is a distorted square bipyramid with two acetonitrile molecules at axial position, and four macrocyclic oxygens including the carbonyl oxygen on the equatorial positions. The interaction of Cu (II) complex with calf thymus DNA (ct DNA) has been investigated by spectrophotometric titrations, ethidium bromide (EB) displacement experiments, circular dichroism (CD) spectra and viscosity measurements. Results indicate that Cu (II) complex can intercalate into the DNA base pairs by the plane of xanthone ring. Furthermore, the Cu (II) complex was tested against tumor cell lines including ECA109, SGC7901 and GLC-82 by MTT (microculture tetrazolium) method. The studies of DNA-binding agree with the effects on the inhibition of tumor cells in vitro.
10.1007/s10895-009-0507-6
Synthesis and characterization of the Zn(II) and Cu(II) piperidinyl isoeuxanthone complexes: DNA-binding and cytotoxic activity.
Wang Hui-Fang,Shen Rui,Tang Ning
European journal of medicinal chemistry
Two new complexes ZnL(2)x2H(2)O (1) and CuL(2)x2H(2)O (2) (HL=1-hydroxy-6-(2-(1-piperidinyl)ethoxy)xanthone) have been synthesized and characterized. Their interactions with calf thymus DNA (ct DNA) were investigated by absorption spectroscopy, fluorescence spectroscopy, ethidium bromide (EB) displacement experiments, circular dichroism spectroscopy and viscosity measurements. Experimental results suggested that there were intercalative interactions of the complexes with DNA. The binding affinity of complex 2 was higher than that of 1. In addition, the cytotoxic effects of both complexes were evaluated with lung adenocarcinoma (GLC-82), esophagus squamous cancer (ECA109) and human gastric cancer (SGC7901) cells using MTT assay. Both were potent exhibiting significant cytotoxicity in vitro.
10.1016/j.ejmech.2009.06.019
Structure-activity relationships in hydroxy-2,3-diarylxanthone antioxidants. Fast kinetics spectroscopy as a tool to evaluate the potential for antioxidant activity in biological systems.
Santos Clementina M M,Silva Artur M S,Filipe Paulo,Santus René,Patterson Larry K,Mazière Jean-Claude,Cavaleiro José A S,Morlière Patrice
Organic & biomolecular chemistry
A structure-activity relationship has been established for eight hydroxy-2,3-diarylxanthones (XH) bearing hydroxy groups on the two aryl rings. One-electron oxidation by superoxide radical-anions (˙O(2)(-)) and ˙Trp radicals as well as reaction with ˙CCl(3)O(2) and ˙CHCl(2)O(2) radicals demonstrates that two OH groups are required for efficient antioxidant reactivity in cetyltrimethylammonium bromide micelles. Hydroxy groups at the meta and para positions on either of the two phenyl rings confer enhanced reactivity, but XH bearing an OH at the para position of either phenyl ring is unreactive. While oxidation is favoured by OH in both meta and para positions of 2-aryl xanthone substituents, addition of a third and/or fourth OH enhances electron-donating capacity. In Cu(2+)-induced lipid peroxidation of human LDL, the lag period preceding the commencement of lipid peroxidation in the presence of XH bearing OH at meta and para positions on the 3-phenyl ring is extended to twice that observed with a comparable concentration of quercetin, a reference antioxidant. These antioxidants are also superior to quercetin in protecting human skin keratinocytes against tert-butylhydroperoxide-induced oxidative stress. While XH antioxidant activity in model biological systems is consistent with the structure-activity relationship, their response is also modulated by the localization of XH and by structural factors.
10.1039/c0ob00841a
Neuroprotective effects of xanthone derivative of Garcinia mangostana against lead-induced acetylcholinesterase dysfunction and cognitive impairment.
Phyu Moe Pwint,Tangpong Jitbanjong
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
Lead poisoning is a common environmental toxicity and low level of lead exposure is responsible for neurobehavioral or intelligence defects. This study was designed to investigate the protective effect of a xanthone derivative of Garcinia mangostana against lead-induced acetycholinesterase (AChE) dysfunction and cognitive impairment in mice. ICR mice were exposed to lead acetate (Pb) in drinking water (1%) with or without xanthone co-administration (100 and 200mg/kgBW/day) for 38days. Xanthone possesses a high phenolic content, which is positive correlation with its antioxidant activity (R(2)=0.98). The IC50 of xanthone on scavenging free radical activities, hydroxyl radical, superoxide radical, hydrogen peroxide and nitric oxide in cell-free system were 0.48±0.08, 1.88±0.09, 2.20±0.03 and 0.98±0.40mg/mL, respectively. We found that Pb induced AChE dysfunction and memory deficit in a dose dependent manner, indicated by in vitro and in vivo studies. However, xanthone significantly restored AChE activity in the blood and brains of mice and prevented Pb-induced neurobehavioral defect indicators with Forced Swimming and Morris water maze tests. Xanthone treatment improved all indicators compared to the Pb-treated group. In conclusion, xanthone alleviates Pb-induced neurotoxicity, in part, by suppression of oxidative damage and reversing AChE activity with a reduction in learning deficit and memory loss.
10.1016/j.fct.2014.04.035
Chitosan/mangiferin particles for Cr(VI) reduction and removal.
Sampaio Caroline de G,Frota Lucas S,Magalhães Herbert S,Dutra Lilian M U,Queiroz Danilo C,Araújo Rinaldo S,Becker Helena,de Souza José R R,Ricardo Nágila M P S,Trevisan Maria T S
International journal of biological macromolecules
In this work, chitosan/mangiferin particles (CMP) were prepared by spray-drying technique and characterized by SEM, DLS, FTIR, HPLC-UV and adsorption studies to investigate a possible application as a preventive material in cases of human and animal contamination with Cr(VI). CMP presented sizes ranging from nano to micrometers. Chitosan and mangiferin (MA) presence in the powder was confirmed by FTIR and MA quantification (136 μg/mg) was performed using a calibration curve prepared by HPLC-UV. Adsorption capacity of Cr(VI) onto CMP was compared with chitosan and investigated in a batch system by considering the effects of various parameters like contact time, initial concentration of adsorbent and pH. Cr(VI) removal is pH dependent and it was found to be maximum at pH 5.0. The results showed that CMP has a potential application as a preventive material in cases of human or animal contamination with Cr(VI).
10.1016/j.ijbiomac.2015.03.038
Protective effect of α-mangostin against CoCl2-induced apoptosis by suppressing oxidative stress in H9C2 rat cardiomyoblasts.
Fang Zhao,Luo Wanjun,Luo Yanli
Molecular medicine reports
Garcinia mangostana (a fruit) has been commonly used as a traditional drug in the treatment of various types of diseases. The aim of the present study was to evaluate the potential protective effect of α‑mangostin (α‑MG), a primary constituent extracted from the hull of the G. mangostana fruit (mangosteen), against CoCl2‑induced apoptotic damage in H9C2 rat cardiomyoblasts. α‑MG was demonstrated to significantly improve the viability of the CoCl2‑treated cells by up to 79.6%, attenuating CoCl2‑induced damage. Further studies revealed that α‑MG exerted a positive effect in terms of decreased reactive oxygen species generation, malondialdehyde concentration, cellular apoptosis, and increased superoxide dismutase activity. Furthermore, treatment with CoCl2 increased the cleavage of caspase‑9, caspase‑3 and apoptosis regulator BAX, and reduced apoptosis regulator Bcl‑2 in H9C2 cells, as measured by reverse transcription‑quantitative polymerase chain reaction and western blotting, which were significantly reversed by co‑treatment with α‑MG (0.06 and 0.3 mM). In conclusion, these results demonstrated that α‑MG protects H9C2 cells against CoCl2‑induced hypoxic injury, indicating that α‑MG is a potential therapeutic agent for cardiac hypoxic injury.
10.3892/mmr.2018.8680
Mangiferin and Morin Attenuate Oxidative Stress, Mitochondrial Dysfunction, and Neurocytotoxicity, Induced by Amyloid Beta Oligomers.
Alberdi Elena,Sánchez-Gómez María Victoria,Ruiz Asier,Cavaliere Fabio,Ortiz-Sanz Carolina,Quintela-López Tania,Capetillo-Zarate Estibaliz,Solé-Domènech Santiago,Matute Carlos
Oxidative medicine and cellular longevity
Amyloid beta- (A-) mediated ROS overproduction disrupts intraneuronal redox balance and exacerbates mitochondrial dysfunction which leads to neuronal injury. Polyphenols have been investigated as therapeutic agents that promote neuroprotective effects in experimental models of brain injury and neurodegenerative diseases. The aim of this study was to identify the neuroprotective effects of morin and mangiferin against A oligomers in cultured cortical neurons and organotypic slices as well as their mechanisms of action. Cell death caused by A oligomers in neuronal cultures was decreased in the presence of micromolar concentrations of mangiferin or morin, which in turn attenuated oxidative stress. The neuroprotective effects of antioxidants against A were associated with the reduction of A-induced calcium load to mitochondria; mitochondrial membrane depolarization; and release of cytochrome c from mitochondria, a key trigger of apoptosis. Additionally, we observed that both polyphenols activated the endogenous enzymatic antioxidant system and restored oxidized protein levels. Finally, A induced an impairment of energy homeostasis due to a decreased respiratory capacity that was mitigated by morin and mangiferin. Overall, the beneficial effects of polyphenols in preventing mitochondrial dysfunction and neuronal injury in AD cell models suggest that morin and mangiferin hold promise for the treatment of this neurological disorder.
10.1155/2018/2856063
2,3-diarylxanthones as strong scavengers of reactive oxygen and nitrogen species: a structure-activity relationship study.
Santos Clementina M M,Freitas Marisa,Ribeiro Daniela,Gomes Ana,Silva Artur M S,Cavaleiro José A S,Fernandes Eduarda
Bioorganic & medicinal chemistry
Xanthones are a class of oxygen-containing heterocyclic compounds widely distributed in nature. The natural derivatives can present different substitutions in the xanthone core that include hydroxyl, methoxyl, prenyl and glycosyl groups. The inclusion of aryl groups has only been reported for a few synthetic derivatives, the 2,3-diaryl moiety being recently introduced by our group. Xanthones are endowed with a broad spectrum of biological activities, many of them related to their antioxidant ability, including the scavenging of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as metal chelating effects. Considering the interesting and promising antioxidant activities present in compounds derived from the xanthone core, the main goal of this work was to evaluate the scavenging activity of the new 2,3-diarylxanthones for ROS, including superoxide radical (O2-), hydrogen peroxide (H2O2), singlet oxygen (1O2), peroxyl radical (ROO.) and hypochlorous acid (HOCl), and RNS, including nitric oxide (.NO) and peroxynitrite anion (ONOO-). The obtained results revealed that the tested 2,3-diarylxanthones are endowed with outstanding ROS and RNS scavenging properties, considering the nanomolar to micromolar range of the IC50 values found. The xanthones with two catechol rings were the most potent scavengers of all tested ROS and RNS. In conclusion, the new 2,3-diarylxanthones are promising molecules to be used for their potential antioxidant properties.
10.1016/j.bmc.2010.07.044
The Role of Mangiferin in the Prevention of Experimentally Induced Iron Overload in an Animal Model.
Estuningtyas Ari,Setiabudy Rianto,Wahidiyat Pustika Amalia,Freisleben Hans-Joachim
Drug research
BACKGROUND:The leaves, fruit peels, and bark of mango trees (Mangifera indica L) contain mangiferin as an active compound with known anti-oxidative and iron chelating properties. This study aims to evaluate the benefits of mangiferin in the management of iron overload. METHODS:Thirty rats were divided into five groups: normal control, rats with iron overload, and rats with iron overload treated with oral mangiferin doses of 50, 100, or 200 mg/kg BW, respectively. The iron overload in this rat model was induced by means of 15 mg intraperitoneal iron dextran, twice a week for 4 weeks. Plasma mangiferin was measured using high performance liquid chromatography, plasma ferritin by using enzyme linked immunosorbent assay, and iron contents of plasma, urine, and tissues by using atomic absorbance spectrophotometry. RESULTS:Plasma mangiferin concentration at doses of 50, 100, or 200 mg/kg BW were 416.10±112.04, 310.55±134.18, and 450.11±165.99 ng/mL, respectively. At 50 mg/kg BW, mangiferin significantly decreased plasma ferritin levels (from 7051.14±1368.24 to 5543.80±1225.53 ng/mL, (p=0.037). Mangiferin also showed tendency to increase urinary iron excretion and to decrease cardiac and hepatic iron accumulation. CONCLUSION:In our model, oral administration of mangiferin showed non-linear pharmacokinetics and low bioavailability. At a dose of 50 mg/kg BW, mangiferin decreased plasma ferritin levels significantly. Mangiferin did not prevent the increase of plasma iron, although it exerted tendency to increase urinary iron excretion and to decrease iron accumulation in liver and heart.
10.1055/a-0667-8530
Harmonization of Mangiferin on methylmercury engendered mitochondrial dysfunction.
Das Shubhankar,Paul Ajanta,Mumbrekar Kamalesh D,Rao Satish B S
Environmental toxicology
Mangiferin (MGN), a C-glucosylxanthone abundantly found in mango plants, was studied for its potential to ameliorate methylmercury (MeHg) induced mitochondrial damage in HepG2 (human hepatocarcinoma) cell line. Cell viability experiments performed using 3-[4,5-dimethylthiazol-2-yl]-2,5- diphenyltetrazolium bromide (MTT) showed protective property of MGN in annulling MeHg-induced cytotoxicity. Conditioning the cells with optimal dose of MGN (50 µM) lowered MeHg-induced oxidative stress, calcium influx/efflux, depletion of mitochondrial trans-membrane potential and prevented mitochondrial fission as observed by decrease in Mitotracker red fluorescence, expression of pDRP1 (serine 616), and DRP1 levels. MGN pre-treated cells demonstrated elevation in the activities of glutathione (GSH), Glutathione-S-transferase (GST), Glutathione peroxidase (GPx), Glutathione reductase (GR), reduced levels of Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) and mitochondrial electron transport chain (ETC) enzyme complexes. In addition, the anti-apoptotic effect of MGN was clearly indicated by the reduction in MeHg-induced apoptotic cells analyzed by flowcytometric analysis after Annexin V-FITC/propidium iodide staining. In conclusion, the present work demonstrates the ability of a dietary polyphenol, MGN to ameliorate MeHg-mediated mitochondrial dysfunction in human hepatic cells in vitro. This hepatoprotective potential may be attributed predominantly to the free radical scavenging/antioxidant property of MGN, by facilitating the balancing of cellular Ca ions, maintenance of redox homeostasis and intracellular antioxidant activities, ultimately preserving the mitochondrial function and cell viability after MeHg intoxication. As MeHg intoxication occurs over a period of time, continuous consumption of such dietary compounds may prove to be very useful in promoting human health. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 630-644, 2017.
10.1002/tox.22265
Mangiferin, a natural xanthone, protects murine liver in Pb(II) induced hepatic damage and cell death via MAP kinase, NF-κB and mitochondria dependent pathways.
Pal Pabitra Bikash,Sinha Krishnendu,Sil Parames C
PloS one
One of the most well-known naturally occurring environmental heavy metals, lead (Pb) has been reported to cause liver injury and cellular apoptosis by disturbing the prooxidant-antioxidant balance via oxidative stress. Several studies, on the other hand, reported that mangiferin, a naturally occurring xanthone, has been used for a broad range of therapeutic purposes. In the present study, we, therefore, investigated the molecular mechanisms of the protective action of mangiferin against lead-induced hepatic pathophysiology. Lead [Pb(II)] in the form of Pb(NO3)2 (at a dose of 5 mg/kg body weight, 6 days, orally) induced oxidative stress, hepatic dysfunction and cell death in murine liver. Post treatment of mangiferin at a dose of 100 mg/kg body weight (6 days, orally), on the other hand, diminished the formation of reactive oxygen species (ROS) and reduced the levels of serum marker enzymes [alanine aminotranferase (ALT) and alkaline phosphatase (ALP)]. Mangiferin also reduced Pb(II) induced alterations in antioxidant machineries, restored the mitochondrial membrane potential as well as mutual regulation of Bcl-2/Bax. Furthermore, mangiferin inhibited Pb(II)-induced activation of mitogen-activated protein kinases (MAPKs) (phospho-ERK 1/2, phosphor-JNK phospho- p38), nuclear translocation of NF-κB and apoptotic cell death as was evidenced by DNA fragmentation, FACS analysis and histological assessment. In vitro studies using hepatocytes as the working model also showed the protective effect of mangiferin in Pb(II) induced cytotoxicity. All these beneficial effects of mangiferin contributes to the considerable reduction of apoptotic hepatic cell death induced by Pb(II). Overall results demonstrate that mangiferin exhibit both antioxidative and antiapoptotic properties and protects the organ in Pb(II) induced hepatic dysfunction.
10.1371/journal.pone.0056894
Alpha-Mangostin Improves Insulin Secretion and Protects INS-1 Cells from Streptozotocin-Induced Damage.
Lee Dahae,Kim Young-Mi,Jung Kiwon,Chin Young-Won,Kang Ki Sung
International journal of molecular sciences
Alpha (α)-mangostin, a yellow crystalline powder with a xanthone core structure, is isolated from mangosteen (), which is a tropical fruit of great nutritional value. The aim of the present study was to investigate the anti-diabetic effects of α-mangostin and to elucidate the molecular mechanisms underlying its effect on pancreatic beta (β)-cell dysfunction. To assess the effects of α-mangostin on insulin production, rat pancreatic INS-1 cells were treated with non-toxic doses of α-mangostin (1⁻10 μM) and its impact on insulin signaling was examined by Western blotting. In addition, the protective effect of α-mangostin against pancreatic β-cell apoptosis was verified by using the β-cell toxin streptozotocin (STZ). Our results showed that α-mangostin stimulated insulin secretion in INS-1 cells by activating insulin receptor (IR) and pancreatic and duodenal homeobox 1 (Pdx1) followed by phosphorylation of phospho-phosphatidylinositol-3 kinase (PI3K), Akt, and extracellular signal regulated kinase (ERK) signaling cascades, whereas it inhibited the phosphorylation of insulin receptor substrate (IRS-1) (Ser1101). Moreover, α-mangostin was found to restore the STZ-induced decrease in INS-1 cell viability in a dose-dependent manner. In addition, treatment of INS-1 cells with 50 μM STZ resulted in an increase in intracellular reactive oxygen species (ROS) levels, which was represented by the fluorescence intensity of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). This oxidative stress was decreased by co-treatment with 5 μM α-mangostin. Similarly, marked increases in the phosphorylation of P38, c-Jun N-terminal kinase (JNK), and cleavage of caspase-3 by STZ were decreased significantly by co-treatment with 5 μM α-mangostin. These results suggest that α-mangostin is capable of improving insulin secretion in pancreatic β-cells and protecting cells from apoptotic damage.
10.3390/ijms19051484
Mangiferin improves hepatic damage-associated molecular patterns, lipid metabolic disorder and mitochondrial dysfunction in alcohol hepatitis rats.
Li Mengran,Wu Chunxiao,Guo Hongbin,Chu Ce,Hu Mingye,Zhou Chengyan
Food & function
This study was conducted to investigate the beneficial effects and possible mechanism of action of mangiferin (MF) in alcohol hepatitis (AH) rats. Building on our previous study, the damage-associated molecular patterns (DAMPs), lipid metabolic disorder and mitochondrial dysfunction were investigated. MF effectively regulated the abnormal liver function, the levels of alcohol, FFAs and metal elements in serum. More importantly, MF improved the expression levels of mRNA and protein of PPAR-γ, OPA-1, Cav-1, EB1, NF-κB p65, NLRP3, Cas-1 and IL-1β, and decreased the positive protein expression rates of HSP90, HMGB1, SYK, CCL20, C-CAS-3, C-PARP and STARD1. Additionally, MF decreased the levels of fumarate, cAMP, xanthurenic acid and d-glucurone-6,3-lactone, and increased the levels of hippuric acid and phenylacetylglycine, and then adjusted the changes of phenylalanine metabolism, TCA cycle and ascorbate and aldarate metabolic pathways. The above results suggested that MF can effectively prevent AH by modulating specific AH-associated genes, potential biomarkers and metabolic pathways in AH rats, etc.
10.1039/c9fo00153k
Rhodol-derived turn-on fluorescent probe for copper ions with high selectivity and sensitivity.
Zeng Xiaodan,Gao Song,Jiang Cheng,Duan Qingxia,Ma Mingshuo,Liu Zhigang,Chen Jie
Luminescence : the journal of biological and chemical luminescence
A new rhodol-derived fluorescent probe 1 with picolinate as the recognition receptor was designed and simply synthesized using a one-step reaction. With the concentration of added Cu increases, it gradually turns pink, so the effect of naked eye detection can be achieved. The detection limit of probe 1 for Cu is 42 nM, and the linear detection range was 0-2 μM. The experimental results showed that 1 was a fluorescent probe with high selectivity, good water solubility, and high sensitivity to Cu . Probe 1 was successfully applied in cell imaging experiments and can detect the concentration of Cu in water samples. All these indicate that probe 1 has the potential to be applied to the detection of Cu concentration in the real environment.
10.1002/bio.4118
Preparation and mechanistic aspect of natural xanthone functionalized gold nanoparticle.
Patra Nabanita,Dehury Niranjan,Pal Abhisek,Behera Anindita,Patra Srikanta
Materials science & engineering. C, Materials for biological applications
Herein, a facile scale up and shape variable synthesis of gold nanoparticle (AuNP) and reaction mechanism by natural xanthone derivative (mangiferin) has been reported. Mangiferin (CHO; 1,3,6,7-tetrahydroxyxanthone-C2-β-d-glucoside), a xanthone derivative is isolated from Mangifera indica L. leaves which efficiently reduces Au ions to Au and stabilizes the formed AuNP. The structural, optical and plasmonic properties of synthesized AuNP have been investigated through different instrumental techniques like UV-Vis and FTIR spectroscopy, powder XRD, FESEM and TEM analysis. It is observed that variation of the concentration of Au ions and mangiferin has a great effect on controlling size and shape of nanoparticles. The role of reaction temperature is also notable. An interesting observation is that with same concentration ratio of HAuCl/mangiferin (0.025 mM/0.002%) at the room temperature kidney shaped AuNP is produced, whereas it is spherical at boiling temperature. Moreover, mangiferin allows high scale synthesis of AuNPs (0.025 mM to 10 mM) without changing the particles size and shape. The mechanistic investigation through UV-Vis, FTIR and GCMS analyses reveal the cleavage of glucose unit and oxidation of phenolic OH groups during AuNP formation. Non-toxicity of mangiferin conjugated AuNP on normal human breast cell line (MCF-10A) suggesting its future application as a drug delivery system and other related medicinal purposes.
10.1016/j.msec.2018.04.091
Protective Effect of γ-mangostin Isolated from the Peel of against Glutamate-Induced Cytotoxicity in HT22 Hippocampal Neuronal Cells.
Biomolecules
The aim of the present study was to examine the protective effect of γ-mangostin, a component of the mangosteen shell, against oxidative damage to nerve cells induced by excessive glutamate, a known excitatory neurotransmitter. To investigate the effect of γ-mangostin on apoptosis, 5 mM of glutamate was used to induce apoptotic cell death in mouse hippocampal HT22 cells. In this study, γ-mangostin was found to exert a stronger protection than N-acetyl cysteine against glutamate-induced cell damage. γ-Mangostin showed prevented glutamate-induced apoptosis in HT22 cells by reducing the production of reactive oxygen species and stimulating the expression of heme oxygenase-1 protein. In addition, glutamate significantly induced the accumulation of intracellular calcium ions, whereas treatment with γ-mangostin markedly reduced it. Hoechst 33342 staining showed an improvement in glutamate-induced nuclear condensation following γ-mangostin treatment. Furthermore, the number of annexin V-positive cells was significantly reduced following treatment with γ-mangostin. Western blot analysis showed the inhibition of glutamate-induced mitogen-activated protein kinase phosphorylation by γ-mangostin. γ-mangostin also inhibited the regulation of the intrinsic mitochondrial apoptotic pathway. Thus, the results of this study suggest that γ-mangostin is an active ingredient of mangosteen and exerts neuroprotective activities in HT22 cells.
10.3390/biom11020170
Multifunctional thioxanthone derivatives with acetylcholinesterase, monoamine oxidases and β-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease.
Luo Li,Li Yan,Qiang Xiaoming,Cao Zhongcheng,Xu Rui,Yang Xia,Xiao Ganyuan,Song Qing,Tan Zhenghuai,Deng Yong
Bioorganic & medicinal chemistry
A series of 1-hydroxyl-3-aminoalkoxy-thioxanthone derivatives were designed, synthesized and evaluated as potential multifunctional agents against Alzheimer's disease (AD). The results indicated that most of these compounds exhibited good AChE and MAOs inhibitory activities, significant inhibition of self- and Cu-induced Aβ aggregation, and moderate to good antioxidant activities. Specifically, compound 9e displayed high inhibitory potency toward AChE (IC=0.59±0.02μM), MAO-A and MAO-B (IC=1.01±0.02μM and 0.90±0.01μM respectively), excellent efficiency to block both self- and Cu-induced Aβ aggregation (74.8±1.2% and 87.7±1.9% at 25μM, respectively), good metal-chelating property and a low toxicity in SH-SY5Y cells. Furthermore, kinetic and molecular modeling studies revealed that compound 9e binds simultaneously to the catalytic active site and peripheral anionic site of AChE, and could penetrate the BBB. Collectively, these results suggested that 9e might be a potential multifunctional agent for further development in the treatment of AD.
10.1016/j.bmc.2017.02.027
Development of the fluorescent biosensor hCalmodulin (hCaM)L39C-monobromobimane(mBBr)/V91C-mBBr, a novel tool for discovering new calmodulin inhibitors and detecting calcium.
Gonzalez-Andrade Martin,Rivera-Chavez Jose,Sosa-Peinado Alejandro,Figueroa Mario,Rodriguez-Sotres Rogelio,Mata Rachel
Journal of medicinal chemistry
A novel, sensible, and specific fluorescent biosensor of human calmodulin (hCaM), namely hCaM L39C-mBBr/V91C-mBBr, was constructed. The biosensor was useful for detecting ligands with opposing fluorescent signals, calcium ions (Ca(2+)) and CaM inhibitors in solution. Thus, the device was successfully applied to analyze the allosteric effect of Ca(2+) on trifluoroperazine (TFP) binding to CaM (Ca(2+)K(d) = 0.24 μM ± 0.03 with a stoichiometry 4.10 ± 0.15; TFPK(d) ∼ 5.74-0.53 μM depending on the degree of saturation of Ca(2+), with a stoichiometry of 2:1). In addition, it was suitable for discovering additional xanthones (5, 6, and 8) with anti-CaM properties from the fungus Emericella 25379. The affinity of 1-5, 7, and 8 for the complex (Ca(2+))(4)-CaM was excellent because their experimental K(d)s were in the nM range (4-498 nM). Docking analysis predicted that 1-8 bind to CaM at sites I, III, and IV as does TFP.
10.1021/jm200167g
Mangiferin functionalized radioactive gold nanoparticles (MGF-AuNPs) in prostate tumor therapy: green nanotechnology for production, in vivo tumor retention and evaluation of therapeutic efficacy.
Al-Yasiri A Y,Khoobchandani M,Cutler C S,Watkinson L,Carmack T,Smith C J,Kuchuk M,Loyalka S K,Lugão A B,Katti K V
Dalton transactions (Cambridge, England : 2003)
We report here an innovative feature of green nanotechnology-focused work showing that mangiferin-a glucose functionalized xanthonoid, found in abundance in mango peels-serves dual roles of chemical reduction and in situ encapsulation, to produce gold nanoparticles with optimum in vivo stability and tumor specific characteristics. The interaction of mangiferin with a Au-198 gold precursor affords MGF-AuNPs as the beta emissions of Au-198 provide unique advantages for tumor therapy while gamma rays are used for the quantitative estimation of gold within the tumors and various organs. The laminin receptor specificity of mangiferin affords specific accumulation of therapeutic payloads of this new therapeutic agent within prostate tumors (PC-3) of human prostate tumor origin induced in mice which overexpress this receptor subtype. Detailed in vivo therapeutic efficacy studies, through the intratumoral delivery of MGF-AuNPs, show the retention of over 80% of the injected dose (ID) in prostate tumors up to 24 h. By three weeks post treatment, tumor volumes of the treated group of animals showed an over 5 fold reduction as compared to the control saline group. New opportunities for green nanotechnology and a new paradigm of using mangiferin as a tumor targeting agent in oncology for the application of MGF-AuNPs in the treatment of cancer are discussed.
10.1039/c7dt00383h
Zinc Photocages with Improved Photophysical Properties and Cell Permeability Imparted by Ternary Complex Formation.
Basa Prem N,Barr Chelsea A,Oakley Kady M,Liang Xiaomeng,Burdette Shawn C
Journal of the American Chemical Society
Photocaged complexes can control the availability of metal ions to interrogate cellular signaling pathways. We describe a new photocage, {bis[(2-pyridyl)methyl]amino}(9-oxo-2-xanthenyl)acetic acid (XDPAdeCage, ), which utilizes a 2-xanthone acetic acid group to mediate a photodecarboxylation reaction. XDPAdeCage photolyzes with a quantum yield of 27%, and binds Zn with 4.6 pM affinity, which decreases by over 4 orders of magnitude after photolysis. For comparison to our previous approach to Zn release via photodecarboxylation, the analogous photocage {bis[(2-pyridyl)methyl]amino}(-nitrophenyl)acetic acid (DPAdeCage, ), which uses a -nitrobenzyl chromophore, was also prepared and characterized. The advantages of the 2-xanthone acetic acid chromophore include red-shifted excitation and a higher extinction coefficient at the preferred uncaging wavelength. The neutral ternary complex of [Zn(XDPAdeCage)] with the anionic ligand pyrithione is membrane permeable, which circumvents the need to utilize invasive techniques to introduce intracellular Zn fluctuations. Using fluorescent imaging, we have confirmed transport of Zn across membranes; in addition, RT-PCR experiments demonstrate changes in expression of Zn-responsive proteins after photolysis.
10.1021/jacs.9b05504
Design, synthesis and anti-Alzheimer's disease activity study of xanthone derivatives based on multi-target strategy.
Kou Xiaodi,Song Lulu,Wang Yunhua,Yu Qiao,Ju Hui,Yang Aihong,Shen Rui
Bioorganic & medicinal chemistry letters
A series of xanthone derivatives were designed, synthesized and evaluated as multifunctional ligands against Alzheimer's disease (AD). In vitro studies showed all xanthone derivatives had good metal chelating property and exhibited selective inhibitory activity against Acetylcholinesterase (AChE). In particular, compound 2a showed the highest inhibitory activity against AChE, and the IC value was (0.328 ± 0.001) μM, which was comparable to tacrine. Kinetic analysis and molecular docking studies indicated that these derivatives targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of AChE. Moreover, all derivatives showed higher anti-oxidative activity than vitamin C. Furthermore, copper complex had higher anti-AChE activity and antioxidant activity. Thus, these xanthone derivatives are potential multi-targeted-directed ligands for further development for the treatment of AD.
10.1016/j.bmcl.2019.126927
Design, synthesis, and biological evaluation of novel xanthone-alkylbenzylamine hybrids as multifunctional agents for the treatment of Alzheimer's disease.
Zhang Zhipeng,Guo Jie,Cheng Maojun,Zhou Weixin,Wan Yang,Wang Rikang,Fang Yuanying,Jin Yi,Liu Jing,Xie Sai-Sai
European journal of medicinal chemistry
In this study, a series of multifunctional hybrids against Alzheimer's disease were designed and obtained by conjugating the pharmacophores of xanthone and alkylbenzylamine through the alkyl linker. Biological activity results demonstrated that compound 4j was the most potent and balanced dual ChEs inhibitor with IC values 0.85 μM and 0.59 μM for eeAChE and eqBuChE, respectively. Kinetic analysis and docking study indicated that compound 4j was a mixed-type inhibitor for both AChE and BuChE. Additionally, it exhibited good abilities to penetrate BBB, scavenge free radicals (4.6 trolox equivalent) and selectively chelate with Cu and Al at a 1:1.4 ligand/metal molar ratio. Importantly, after assessments of cytotoxic and acute toxicity, we found compound 4j could improve memory function of scopolamine-induced amnesia mice. Hence, the compound 4j can be considered as a promising lead compound for further investigation in the treatment of AD.
10.1016/j.ejmech.2021.113154
Theoretical study of chromophores for biological sensing: Understanding the mechanism of rhodol based multi-chromophoric systems.
Rivera-Jacquez Hector J,Masunov Artëm E
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
Development of two-photon fluorescent probes can aid in visualizing the cellular environment. Multi-chromophore systems display complex manifolds of electronic transitions, enabling their use for optical sensing applications. Time-Dependent Density Functional Theory (TDDFT) methods allow for accurate predictions of the optical properties. These properties are related to the electronic transitions in the molecules, which include two-photon absorption cross-sections. Here we use TDDFT to understand the mechanism of aza-crown based fluorescent probes for metals sensing applications. Our findings suggest changes in local excitation in the rhodol chromophore between unbound form and when bound to the metal analyte. These changes are caused by a charge transfer from the aza-crown group and pyrazol units toward the rhodol unit. Understanding this mechanism leads to an optimized design with higher two-photon excited fluorescence to be used in medical applications.
10.1016/j.saa.2018.02.047
Green nanotechnology of MGF-AuNPs for immunomodulatory intervention in prostate cancer therapy.
Scientific reports
Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.
10.1038/s41598-021-96224-8
DNA protective effect of mangosteen xanthones: an in vitro study on possible mechanisms.
Lin Jing,Gao Yaoxiang,Li Haiming,Zhang Lulu,Li Xican
Advanced pharmaceutical bulletin
PURPOSE:The aim of this study was to evaluate antioxidant ability of mangosteen shell and explore the non-enzymatic repair reaction and possible mechanism of xanthones in mangosteen shell. METHODS:Mangosteen shell was extracted by methanol to obtain the extract of mangosteen shell. The extract was then determined by various antioxidant assays in vitro, including protection against DNA damage, •OH scavenging,DPPH• (1,1-diphenyl-2-picryl-hydrazl radical) scavenging, ABTS(+)• (2,2'-azino-bis(3-ethylbenzo- thiazoline-6-sulfonic acid diammonium) scavenging, Cu(2+)-chelating, Fe(2+)-chelatingand Fe(3+) reducing assays. RESULTS:Mangosteen shell extract increased dose-dependently its percentages in all assays. Its IC50 values were calculated as 727.85±2.21,176.94±19.25, 453.91±6.47, 84.60±2.47, 6.81±0.28, 1.55±0.10, 3.93±0.17, and 9.52±0.53μg/mL, respectively for DNA damage assay, •OH scavenging assay, Fe(2+)-Chelating assay, Cu(2+)-Chelating assay, DPPH• scavenging assay, ABTS(+)•scavenging assay, Fe(3+) reducing assay and Cu(2+) reducing assay. CONCLUSION:On the mechanistic analysis, it can be concluded that mangosteen shell can effectively protect against hydroxyl-induced DNA oxidative damage. The protective effect can be attributed to the xanthones. One approach for xanthones to protect against hydroxyl-induced DNA oxidative damage may be ROS scavenging. ROS scavenging may be mediated via metal-chelating, and direct radical-scavenging which is through donating hydrogen atom (H·) and electron (e). However, both donating hydrogen atom (H·) and electron (e) can result in the oxidation of xanthone to stable quinone form.
10.5681/apb.2014.022
Design, Synthesis and Biological Evaluation of Xanthone Derivatives for Possible Treatment of Alzheimer's Disease Based on Multi-Target Strategy.
Yang Aihong,Yu Qiao,Ju Hui,Song Lulu,Kou Xiaodi,Shen Rui
Chemistry & biodiversity
Four xanthone derivatives were synthesized and evaluated as acetylcholinesterase inhibitors (AChEIs) with metal chelating ability and antioxidant ability against Alzheimer's disease (AD). Most of them exhibited potential acetylcholinesterase (AChE), butylcholinesterase (BuChE) inhibitory, antioxidant and metal chelating properties. Among them, 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one had the highest ability to inhibit AChE and displayed high selectivity towards AChE (IC =2.403±0.002 μM for AChE and IC =31.221±0.002 μM for BuChE), and it was also a good antioxidant (IC =2.662±0.003 μM). Enzyme kinetic studies showed that this compound was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Interestingly, its copper complex showed more significant inhibitory activity for AChE (IC =0.934±0.002 μM) and antioxidant activity (IC =1.064±0.003 μM). Molecular dockings were carried out for the four xanthone derivatives in order to further investigate the binding modes. Finally, the blood-brain barrier (BBB) penetration prediction indicated that all compounds might penetrate BBB. These results suggested that 1-hydroxy-3-[2-(pyrrolidin-1-yl)ethoxy]-9H-xanthen-9-one was promising AChEI with metal chelating ability and antioxidant ability for the further investigation.
10.1002/cbdv.202000442
Inhibitory effect of xanthones isolated from the pericarp of Garcinia mangostana L. on rat basophilic leukemia RBL-2H3 cell degranulation.
Itoh Tomohiro,Ohguchi Kenji,Iinuma Munekazu,Nozawa Yoshinori,Akao Yukihiro
Bioorganic & medicinal chemistry
Mangostin, Garcinia mangostana L. is used as a traditional medicine in southeast Asia for inflammatory and septic ailments. Hitherto we indicated the anticancer activity induced by xanthones such as alpha-, beta-, and gamma-mangostin which were major constituents of the pericarp of mangosteen fruits. In this study, we examined the effect of xanthones on cell degranulation in rat basophilic leukemia RBL-2H3 cells. Antigen (Ag)-mediated stimulation of high affinity IgE receptor (FcepsilonRI) activates intracellular signal transductions resulting in the release of biologically active mediators such as histamine. The release of histamine and other inflammatory mediators from mast cell or basophils is the primary event in several allergic responses. These xanthones suppressed the release of histamine from IgE-sensitized RBL-2H3 cells. In order to reveal the inhibitory mechanism of degranulation by xanthones, we examined the activation of intracellular signaling molecules such as Lyn, Syk, and PLCgammas. All the xanthones tested significantly suppressed the signaling involving Syk and PLCgammas. In Ag-mediated activation of FcepsilonRI on mast cells, three major subfamilies of mitogen-activated protein kinases were activated. The xanthones decreased the level of phospho-ERKs. Furthermore, the levels of phospho-ERKs were observed to be regulated by Syk/LAT/Ras/ERK pathway rather than PKC/Raf/ERK pathway, suggesting that the inhibitory mechanism of xanthones was mainly due to suppression of the Syk/PLCgammas/PKC pathway. Although intracellular free Ca(2+) concentration ([Ca(2+)](i)) was elevated by FcepsilonRI activation, it was found that alpha- or gamma-mangostin treatment was reduced the [Ca(2+)](i) elevation by suppressed Ca(2+) influx.
10.1016/j.bmc.2008.02.054
Antioxidant and structure-activity relationships of five tetraoxygenated xanthones from Swertia minor (Griscb.) Knobl.
Uvarani Chokkalingam,Chandraprakash Kumarasamy,Sankaran Mathan,Ata Athar,Mohan Palathurai Subramaniam
Natural product research
Antioxidant activity-guided fractionations of chloroform extract of Swertia minor yielded five known tetraoxygenated xanthones (1-5), of which compound 3 was isolated for the first time from plant sources. Compounds 1-5 were identified with the aid of extensive NMR spectroscopic studies. A relationship between the structural features of 1-5 and their antioxidant activity was also determined. Among these bioactive isolates (1-5), compound 4 exhibited strong scavenging effect in DPPH (IC(50) = 10.31 µg mL(-1)), FRAP (8536.32 ± 34.1 Mmol Fe (II) g(-1)) and metal chelating (17.2 ± 0.88 mg EDTA g(-1)) assays. Compound 5 was potently active in secondary antioxidant assay (i.e. binding to metal ions strongly); however, its primary antioxidant capacity was found to be feeble.
10.1080/14786419.2011.561494
Development of a fluorometric measurement system used in biological samples upon the determination of iron (II) metal ion.
Toksöz Yavuz Selim,Özyiğit İbrahim Ethem,Bilen Çiğdem,Arsu Nergis,Karakuş Emine
Preparative biochemistry & biotechnology
2-thioxanthone thioacetic acid (TXSCHCOOH, T), which has a fluorometric character, was used for new fluorometric system upon Fe(II) analysis in biological samples as the main target. T-BSA binary complex was firstly consisted with non-covalent interactions between T and BSA at the equilibrium concentration as 1.77 × 10M. T-BSA binary complex emission was increased at the ratio of 24.40% due to stabilization property of BSA (pH:7), compared with T emission intensity. Fluorescence emission spectroscopy was used for the all measurements because of an economic, a sensitive and a practical method compared with other spectroscopic analysis. T-BSA-Fe(II) triple complex was also obtained by adding Fe(II) ion to T-BSA binary complex solution. Its characterization was performed to be investigated with optimum excitation wavelength, buffer concentration, pH and temperature as 297 nm, 10 M Tris HCl (10M NaCI), pH:7.2 at 25 °C, respectively. The results of Fe(II) analysis in serum showed a certain response in fluorometric T-BSA-Fe(II) triple complex measurement system as 50.42 ± 5.8 µg/dL. The analyses of our fluorometric triple complex system were compared with the reference electrochemiluminescence method and similar results were obtained. Fluorometric measurements of T-BSA-Fe(II) triple complex, its characterization and Fe(II) analysis in this system have not been investigated in literature gives originality to our study.
10.1080/10826068.2020.1818257
Ru(II)-catalyzed selective C-H amination of xanthones and chromones with sulfonyl azides: synthesis and anticancer evaluation.
Shin Youngmi,Han Sangil,De Umasankar,Park Jihye,Sharma Satyasheel,Mishra Neeraj Kumar,Lee Eui-Kyung,Lee Youngil,Kim Hyung Sik,Kim In Su
The Journal of organic chemistry
A ketone-assisted ruthenium-catalyzed selective amination of xanthones and chromones C-H bonds with sulfonyl azides is described. The reactions proceed efficiently with a broad range of substrates with excellent functional group compatibility. This protocol provides direct access to 1-aminoxanthones, 5-aminochromones, and 5-aminoflavonoid derivatives known to exhibit potent anticancer activity.
10.1021/jo501709f
Mechanism of the vasodilator effect of mono-oxygenated xanthones: a structure-activity relationship study.
Diniz Thiago F,Pereira Aline C,Capettini Luciano S A,Santos Marcelo H,Nagem Tanus J,Lemos Virginia S,Cortes Steyner F
Planta medica
The present study characterized the mechanisms involved in the vasodilator effect of two mono-oxygenated xanthones, 4-hydroxyxanthone and 4-methoxyxanthone. 9-Xanthenone, the base structure of xanthones, was used for comparison. 4-Hydroxyxanthone and 9-xanthenone induced a concentration-dependent and endothelium-independent vasodilator effect in arteries precontracted with phenylephrine (0.1 µmol · L-1) or KCl (50 mmol · L-1). 4-Methoxyxanthone induced a concentration-dependent vasodilator effect in arteries precontracted with phenylephrine, which was partially endothelium-dependent, and involved production of nitric oxide. In endothelium-denuded arteries precontracted with KCl, the vasodilator effect of 4-methoxyxanthone was abolished. The vasodilator effect of 4-hydroxyxanthone (96.22 ± 2.10 %) and 4-methoxyxanthone (96.57 ± 12.40 %) was significantly higher than observed with 9-xanthenone (53.63 ± 8.31 %). The presence of an oxygenated radical in position 4 made 4-hydroxyxanthone (pIC50 = 4.45 ± 0.07) and 4-methoxyxanthone (pIC50 = 5.04 ± 0.09) more potent as a vasodilator than 9-xanthenone (pIC50 = 3.92 ± 0.16). In addition, 4-methoxyxanthone was more potent than the other two xanthones. Ca2+ transients in vascular smooth muscle cells elicited by high K+ were abolished by 4-hydroxyxanthone and 9-xanthenone. The endothelium-independent effect of 4-methoxyxanthone was abolished by inhibition of K+ channels by tetraethylammonium. The current work shows that an oxygenated group in position 4 is essential to achieve Emax and to increase the potency of xanthones as vasodilators. Substitution of an OH by OCH3 in position 4 increases the potency of the vasodilator effect and changes the underling mechanism of action from the blockade of L-type calcium channels to an increase in NO production and activation of K+ channels.
10.1055/s-0033-1350803
Mangiferin offers protection against deleterious effects of pharmaceuticals, heavy metals, and environmental chemicals.
Naraki Karim,Rezaee Ramin,Mashayekhi-Sardoo Habibeh,Hayes A Wallace,Karimi Gholamreza
Phytotherapy research : PTR
Mangiferin (MGF) is a polyphenolic C-glucosyl-xanthone extracted from the mango tree (Mangifera indica). MGF has shown diverse effects such as antioxidant, antiapoptotic, radical scavenging, and chelating properties. MGF also has been shown to modulate inflammatory pathways. In this review, we examined and evaluated the literature dealing with the protective effects of MGF against various chemical toxicities. Our literature review indicated that the MGF-induced protective effects against the toxic effects of pharmaceuticals, heavy metals and environmental chemicals were mainly mediated via suppression of lipid peroxidation, oxidative stress (along with enhancement of the antioxidant enzyme), inflammatory factors (TNF-α, IL-6, IL-10, and IL-12), and activation of PI3K/Akt and the MAPK survival signaling pathway.
10.1002/ptr.6864
Synthesis of Succinimide-Containing Chromones, Naphthoquinones, and Xanthones under Rh(III) Catalysis: Evaluation of Anticancer Activity.
Han Sang Hoon,Kim Saegun,De Umasankar,Mishra Neeraj Kumar,Park Jihye,Sharma Satyasheel,Kwak Jong Hwan,Han Sangil,Kim Hyung Sik,Kim In Su
The Journal of organic chemistry
The weakly coordinating ketone group directed C-H functionalizations of chromones, 1,4-naphthoquinones, and xanthones with various maleimides under rhodium(III) catalysis are described. These protocols efficiently provide a range of succinimide-containing chromones, naphthoquinones, and xanthones with excellent site selectivity and functional group compatibility. All synthetic compounds were screened for in vitro anticancer activity against human breast adenocarcinoma cell lines (MCF-7). In particular, compounds 7aa and 7ca with a naphthoquinone scaffold were found to be highly cytotoxic, with an activity competitive with anticancer agent doxorubicin.
10.1021/acs.joc.6b02577
Efficacy, Stability, and Safety Evaluation of New Polyphenolic Xanthones Towards Identification of Bioactive Compounds to Fight Skin Photoaging.
Resende Diana I S P,Almeida Mariana C,Maciel Bruna,Carmo Helena,Sousa Lobo José,Dal Pozzo Carlotta,Cravo Sara M,Rosa Gonçalo P,Kane-Pagès Aida,do Carmo Barreto Maria,Almeida Isabel F,de Sousa Maria Emília,Pinto Madalena M M
Molecules (Basel, Switzerland)
Antioxidants have long been used in the cosmetic industry to prevent skin photoaging, which is mediated by oxidative stress, making the search for new antioxidant compounds highly desirable in this field. Naturally occurring xanthones are polyphenolic compounds that can be found in microorganisms, fungi, lichens, and some higher plants. This class of polyphenols has a privileged scaffold that grants them several biological activities. We have previously identified simple oxygenated xanthones as promising antioxidants and disclosed as hit, 1,2-dihydroxyxanthone (). Herein, we synthesized and studied the potential of xanthones with different polyoxygenated patterns as skin antiphotoaging ingredients. In the DPPH antioxidant assay, two newly synthesized derivatives showed IC values in the same range as ascorbic acid. The synthesized xanthones were discovered to be excellent tyrosinase inhibitors and weak to moderate collagenase and elastase inhibitors but no activity was revealed against hyaluronidase. Their metal-chelating effect (FeCl and CuCl) as well as their stability at different pH values were characterized to understand their potential to be used as future cosmetic active agents. Among the synthesized polyoxygenated xanthones, 1,2-dihydroxyxanthone () was reinforced as the most promising, exhibiting a dual ability to protect the skin against UV damage by combining antioxidant/metal-chelating properties with UV-filter capacity and revealed to be more stable in the pH range that is close to the pH of the skin. Lastly, the phototoxicity of 1,2-dihydroxyxanthone () was evaluated in a human keratinocyte cell line and no phototoxicity was observed in the concentration range tested.
10.3390/molecules25122782