mangostin and Disease-Models--Animal

Crohn's disease and ulcerative colitis presently have no cure and are treated with anti-inflammatory drugs or monoclonal antibodies targeting pro-inflammatory cytokines. A variety of rodent models have been used to model chronic and acute colitis. Dietary polyphenols in foods and botanicals are of considerable interest for prevention and treatment of colitis. Many dietary polyphenols have been utilized for prevention of colitis in rodent models. Berries, green tea polyphenols, curcumin, and stilbenes have been the most extensively tested polyphenols in rodent models of colitis. The majority of polyphenols tested have inhibited colitis in rodents, but increasing doses of EGCG and green tea, isoflavones, flaxseed, and α-mangostin have exacerbated colitis. Few studies have examined combination of polyphenols or other bioactives for inhibition of colitis. Translating polyphenol doses used in rodent models of colitis to human equivalent doses reveals that supplemental doses are most likely required to inhibit colitis from a single polyphenol treatment. The ability to translate polyphenol treatments in rodent models is likely to be limited by species differences in xenobiotic metabolism and microbiota. Given these limitations, data from polyphenols in rodent models suggests merit for pursuing additional clinical studies for prevention of colitis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Coumaric Acids; Dietary Supplements; Disease Models, Animal; Flavonoids; Functional Food; Gastrointestinal Agents; Humans; Inflammatory Bowel Diseases; Phenols; Plant Extracts; Polyphenols; Stilbenes; Xanthones

Antimicrobial resistance in

Topics: Animals; Anti-Bacterial Agents; Anti-Inflammatory Agents; Cats; Disease Models, Animal; Dogs; Drug Resistance, Bacterial; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pets; Staphylococcal Infections; Staphylococcus; Xanthones

Neurodegenerative disease, for instance, Parkinson's disease (PD), is associated with substantia nigra dopaminergic neuronal loss with subsequent striatal dopamine reduction, leading to motor deficits. Currently, there is no available effective therapy for PD; thus, novel therapeutic agents such as natural antioxidants with neuroprotective effects are emerging. Alpha-mangostin (αM) is a xanthone derivative compound from mangosteen peel with a cytoprotective effect depicted in neurodegenerative disease models. However, αM has low aqueous solubility and low biodistribution in the brain. Nanostructured lipid carriers (NLC) have been used to encapsulate bioactive compounds delivered to target organs to improve the oral bioavailability and effectiveness. This study aimed to investigate the effect of αM and αM encapsulated in NLC (αM-NLC) in mice with rotenone-induced PD-like neurodegeneration. Forty male ICR mice were divided into normal, PD, PD + αM, and PD + αM-NLC groups. Vehicle, αM (25 mg/kg/48 h), and αM-NLC (25 mg/kg/48 h) were orally administered, along with PD induction by intraperitoneal injection of rotenone (2.5 mg/kg/48 h) for 4 consecutive weeks. Motor abilities were assessed once a week using rotarod and hanging wire tests. Biochemical analysis of brain oxidative status was conducted, and neuronal populations in substantia nigra par compacta (SNc), striatum, and motor cortex were evaluated using Nissl staining. Tyrosine hydroxylase (TH) immunostaining of SNc and striatum was also evaluated. Results showed that rotenone significantly induced motor deficits concurrent with significant SNc, striatum, and motor cortex neuronal reduction and significantly decreased TH intensity in SNc (p < 0.05). The significant reduction of brain superoxide dismutase activity (p < 0.05) was also detected. Administrations of αM and αM-NLC significantly reduced motor deficits, prevented the reduction of TH intensity in SNc and striatum, and prevented the reduction of neurons in SNc (p < 0.05). Only αM-NLC significantly prevented the reduction of neurons in both striatum and motor cortex (p < 0.05). These were found concurrent with significantly reduced malondialdehyde level and increased catalase and superoxide dismutase activities (p < 0.05). Therefore, this study depicted the neuroprotective effect of αM and αM-NLC against rotenone-induced PD-like neurodegeneration in mice. We indicated an involvement of NLC, emphasizing the protective effect of αM against oxidative

Topics: Animals; Disease Models, Animal; Dopamine; Dopaminergic Neurons; Lipids; Male; Mice; Mice, Inbred ICR; Nanostructures; Neuroprotective Agents; Parkinson Disease, Secondary; Rotenone; Substantia Nigra; Superoxide Dismutase; Tissue Distribution; Tyrosine 3-Monooxygenase; Xanthones

Cardiac hypertrophy and fibrosis are significant risk factors for chronic heart failure (HF). Since pharmacotherapy agents targeting these processes have not been established, we investigated the effect of alpha-magostin (α-man) on cardiomyocyte hypertrophy and fibrosis in vitro. Primary cultured cardiomyocytes and cardiac fibroblasts were prepared from neonatal rats. After α-man treatment, phenylephrine (PE) and transforming growth factor-beta (TGF-β) were added to the cardiomyocytes and cardiac fibroblasts to induce hypertrophic and fibrotic responses, respectively. Hypertrophic responses were assessed by measuring the cardiomyocyte surface area and hypertrophic gene expression levels. PE-induced phosphorylation of Akt, extracellular signal-regulated kinase (ERK)1/2, and p38 was examined by Western blotting. Fibrotic responses were assessed by measuring collagen synthesis, fibrotic gene expression levels, and myofibroblast differentiation. In addition, TGF-β-induced reactive oxygen species (ROS) production was investigated. In cultured cardiomyocytes, α-man significantly suppressed PE-induced increases in the cardiomyocyte surface area, and the mRNA levels (atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP)). Treatment with α-man significantly suppressed PE-induced Akt phosphorylation, but not ERK and p38 phosphorylation. In cultured cardiac fibroblasts, α-man significantly suppressed TGF-β-induced increases in L-proline incorporation, mRNA levels (POSTN and alpha-smooth muscle actin (α-SMA)), and myofibroblast differentiation. Additionally, it significantly inhibited TGF-β-induced reduced nicotinamide adenine dinucleotide phosphate oxidase4 (NOX4) expression and ROS production in cardiac fibroblasts. Treatment with α-man significantly ameliorates hypertrophy by inhibiting Akt phosphorylation in cardiomyocytes and fibrosis by inhibiting NOX4-generating ROS in fibroblasts. These findings suggest that α-man is a possible natural product for the prevention of cardiac hypertrophy and fibrosis.

Topics: Animals; Cardiomegaly; Cells, Cultured; Disease Models, Animal; Fibroblasts; Fibrosis; Garcinia; Heart; Humans; Myocardium; Myocytes, Cardiac; NADPH Oxidase 4; Primary Cell Culture; Rats; Reactive Oxygen Species; Xanthones

Diabetes mellitus (DM) is concomitant with significant morbidity and mortality and its prevalence is accumulative in worldwide. The conventional antidiabetic agents are known to mitigate the symptoms of diabetes; however, they may also cause side and adverse effects. There is an imperative necessity to conduct preclinical and clinical trials for the discovery of alternative therapeutic agents that can overcome the drawbacks of current synthetic antidiabetic drugs. This study aimed to investigate the efficacy of lowering blood glucose and underlined mechanism of γ-mangostin, mangosteen (Garcinia mangostana) xanthones. The results showed γ-Mangostin had a antihyperglycemic ability in short (2 h)- and long-term (28 days) administrations to diet-induced diabetic mice. The long-term administration of γ-mangostin attenuated fasting blood glucose of diabetic mice and exhibited no hepatotoxicity and nephrotoxicity. Moreover, AMPK, PPARγ, α-amylase, and α-glucosidase were found to be the potential targets for simulating binds with γ-mangostin after molecular docking. To validate the docking results, the inhibitory potency of γ-mangostin againstα-amylase/α-glucosidase was higher than Acarbose via enzymatic assay. Interestingly, an allosteric relationship between γ-mangostin and insulin was also found in the glucose uptake of VSMC, FL83B, C2C12, and 3T3-L1 cells. Taken together, the results showed that γ-mangostin exerts anti-hyperglycemic activity through promoting glucose uptake and reducing saccharide digestion by inhibition of α-amylase/α-glucosidase with insulin sensitization, suggesting that γ-mangostin could be a new clue for drug discovery and development to treat diabetes.

Topics: 3T3-L1 Cells; alpha-Amylases; AMP-Activated Protein Kinases; Animals; Biomarkers; Blood Glucose; Diabetes Mellitus; Diet, High-Fat; Disease Models, Animal; Down-Regulation; Garcinia mangostana; Glycoside Hydrolase Inhibitors; Insulin Resistance; Male; Mice; Mice, Inbred ICR; Plant Extracts; PPAR gamma; Signal Transduction; Time Factors; Xanthones

Ulcerative colitis (UC) is an inflammatory disorder of the colon. Garcinia mangostana Linn. (GM) has been traditionally used for its anti-inflammatory and antioxidant activities.. The effects of GM and its bioactive constituent α-mangostin on dextran sulfate sodium (DSS)-induced UC in mice were investigated.. Adult ICR mice (n = 63) were pretreated with ethanolic GM extract at 40, 200, and 1000 mg/kg/day (GM40, GM200, and GM1000), α-mangostin at 30 mg/kg/day, or sulfasalazine at 100 mg/kg/day (SA) for 7 consecutive days. On days 4-7, UC was induced in the mice by the oral administration of DSS (40 kDa, 6 g/kg/day), while control mice received distilled water. The UC disease activity index (DAI) and histological changes were recorded. The activities of myeloperoxidase, catalase, and superoxide dismutase, and the levels of reactive oxygen species (ROS), nitric oxide (NO), and malondialdehyde (MDA) were determined. The mRNA expression of inflammatory related genes including proinflammatory cytokine Tnf-α, Toll-like receptor (Tlr-2), adhesion molecules (Icam-1 and Vcam-1), and monocyte chemoattractant protein (Mcp-1) were evaluated.. Treatment with GM or α-mangostin decreased the UC DAI and protected against colon shortening and spleen and kidney enlargement. GM and α-mangostin prevented histological damage, reduced mast cell infiltration in the colon, and decreased myeloperoxidase activity. GM and α-mangostin increased catalase and superoxide dismutase activity and decreased ROS, NO, and MDA production. GM downregulated mRNA expression of Tnf-α, Tlr-2, Icam-1, Vcam-1, and Mcp-1.. GM and α-mangostin attenuated the severity of DSS-induced UC via anti-inflammatory and antioxidant effects. Therefore, GM is a promising candidate for development into a novel therapeutic agent for UC.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Colitis, Ulcerative; Dextran Sulfate; Disease Models, Animal; Dose-Response Relationship, Drug; Ethanol; Garcinia mangostana; Male; Mice; Mice, Inbred ICR; Nitric Oxide; Oxidative Stress; Plant Extracts; Xanthones

α-mangostin, a polyphenolic xanthone derivative of mangosteen, has been reported to possess multiple therapeutic properties, such as anti-cancer, anti-allergy and anti-inflammatory activity. However, its anti-inflammatory effects in autoimmune diseases such as lupus nephritis (LN) remain unclear. In this study, we want to investigate the therapeutic effect of α-mangostin in LN.. First, we elucidated the retinoic acid receptor related orphan receptor gamma t (RORγt) inhibitory activity of α-mangostin in cell-based assay and T helper 17 (Th17) differentiation in vitro assay. Then, we established a pristane-induced LN mouse model and randomly divided these into a normal control group, model control group, α-mangostin group and prednisone acetate group. Finally, anti-double-stranded DNA (anti-dsDNA) level in serum was detected by enzyme-linked immunosorbent assay, interleukin (IL)-17A and interferon (IFN)-γ expression in spleen cells by flow cytometry; histomorphology examination of kidneys was performed by periodic acid-Schiff staining and immunofluorescence analysis with an anti-immunoglobulin G (anti-IgG) and anti-IgM antibodies.. We found that α-mangostin inhibited RORγt transcription activity in a cell-based assay and also polarized Th17 cells in an in vitro induction experiment. Our results also showed that α-mangostin could significantly decrease serum anti-dsDNA antibody levels, IL-17A and IFN-γ expression and alleviate renal pathological damage in the α-mangostin-treated group mice than in the model group mice.. Thus, α-mangostin demonstrated its potential as a candidate therapeutic drug for LN and other Th17-mediated autoimmune diseases by inhibiting the function of Th17.

Topics: Animals; Cell Differentiation; Disease Models, Animal; Female; Immunity, Cellular; Lupus Nephritis; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Terpenes; Th17 Cells; Xanthones

Topics: Animals; Cartilage, Articular; Cell Line; Cyclooxygenase 2; Disease Models, Animal; Fibroblasts; Garcinia mangostana; Gene Expression; Humans; Interferon-gamma; Interleukin-6; Mice; MicroRNAs; NF-kappa B; Osteoarthritis; Papain; Phytotherapy; Plant Preparations; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha; Xanthones

Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect.. In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats.. HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity.. However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

Topics: Animals; Behavior, Animal; Brain; Brain-Derived Neurotrophic Factor; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic Disease; Cognition; Cognitive Dysfunction; Disease Models, Animal; Garcinia mangostana; Male; Memory; Neuroprotective Agents; Plant Extracts; Rats, Sprague-Dawley; Spatial Learning; Xanthones

The oxysterone α-mangostin is isolated from mangosteen husks and is widely used in the treatment of abdominal pain, diarrhea, and dysentery. In this study, we established a lipopolysaccharide (LPS)-induced inflammatory model of rat intestinal epithelial cells (IEC-6 cells), at the same time we used differently concentration α-mangostin to detect its anti-inflammatory activity. We applied doses of α-mangostin (2.5, 5, and 10 μM) and detected apoptosis by flow cytometry, and the Griess reagent and the enzyme-linked immunosorbent assay (ELISA) method detected inflammatory factors such as nitric oxide (NO), prostaglandin (PG) E2, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. We also used quantitative real-time PCR (Q-PCR) to examine inflammatory factors and western blotting to examine the activation of transforming growth factor-activated kinase (TAK)-1-nuclear factor (NF)-κB signaling pathway-related proteins. Finally, we used laser confocal microscopy to detect the effect of the 10 μM α-mangostin on the nuclear import of NF-κB-p65. The results showed that α-mangostin treatment significantly reduced the apoptosis of LPS-stimulated IEC-6 cells, the production of inflammatory factors, the activation of TAK1-NF-κB signaling pathway-related proteins, and the entry of p65 into the nucleus. In conclusion, α-mangostin exerts its anti-inflammatory effects by inhibiting the activation of TAK1-NF-κB and it may be a potential choice for the treatment of inflammation diseases.

Topics: Animals; Apoptosis; Cells, Cultured; Disease Models, Animal; Dose-Response Relationship, Drug; Epithelial Cells; Inflammation; Intestinal Mucosa; MAP Kinase Kinase Kinases; NF-kappa B; Protein Kinase Inhibitors; Rats; Signal Transduction; Xanthones

The purpose of this study was to investigate the hepatoprotective effect of α-mangostin (α-MG) on lipopolysaccharide/d-galactosamine (LPS/D-GalN)-induced acute liver failure and discover its potential mechanisms in mice. The results showed that α-MG could attenuate LPS/D-GalN-induced liver pathological injury, and decrease the hepatic malondialdehyde (MDA) level, serum alanine aminotransferase (ALT), aspartate transaminase (AST), tumor necrosis factor (TNF-α), interleukin-1β and 6 (IL-1β, IL-6) levels and recovery hepatic glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) activities. The results also indicated that α-MG inhibited LPS/D-GalN-induced toll-like receptor 4 (TLR4) expression and NF-κB activation. In addition, α-MG up-regulated the expressions of Nrf2 and heme oxygenase-1 (HO-1). In conclusion, the results indicated that α-MG could protect against LPS/D-GalN-induced liver failure by activating Nrf2 to induce antioxidant defense and inhibiting TLR4 signaling pathway to induce anti-inflammatory effect.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Cytoprotection; Disease Models, Animal; Dose-Response Relationship, Drug; Galactosamine; Heme Oxygenase-1; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Membrane Proteins; Mice, Inbred ICR; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Toll-Like Receptor 4; Xanthones

To observe the protective effect of alpha-mangostin (α-MG) on focal segmental glomurular sclerosis (FSGS) induced by adriamycin.
 Methods: Adriamycin nephropathy (AN) model was induced by adriamycin (10 mg/kg) via a tail vein. Then the mice were treated with α-MG (12.5 mg/kg) or normal salin once daily for 6 weeks. At the end of 6 weeks, the mice were sacrificed, and the kidneys and blood samples were collected. Histopathology of the kidneys were analyzed under the optical microscope. The serum levels of biochemical indicators, such as serum creatinine (SCr), blood urea nitrogen (BUN) and cholesterol were determined. The levels of superoxide anion, malondialdehyde (MDA), and glutathione (GSH), the activity of superoxide dismutase (SOD) and catalase (CAT) in kidney tissues were determined. Serum levels of IL-1β, IL-18, IL-10 and adiponectin were determined. The levels of TGF-β1, collagen I (Col I), α-SMA, silent information regulator 1 (Sirt1) and the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) in kidney tissues were determined using immunohistochemical staining, Western blot, and RT-PCR.
 Results: The levels of SCr, proteinuria, urine protein to creatinine ratio and serum cholesterol were attenuated in AN mice after α-MG treatment, while creatinine clearance rate and serum albumin were upregulated (P<0.05). α-MG treatment alleviated the glomerular and interstitial fibrosis, downregulated the expression of fibrosis markers, such as Col I and α-SMA (P<0.05). α-MG treatment reduced the production of superoxide anion, the levels of MDA and GSH, and increased the activity of CAT and SOD (P<0.05). α-MG treatment inhibitd the generation of pro-inflammatory cytokines, such as IL-1β and IL-18 and promoted the production of anti-inflammatory cytokines, such as the IL-10 and adiponectin (P<0.05); α-MG treatment promoted the expression of Sirt1, inhibitd the expression of NLRP3 in kidney tissues (P<0.05).
 Conclusion: α-MG could attenuates FSGS of mice induced by adriamycin ameliorate and improve renal function. α-MG exerts its anti-inflammatory and anti-oxidative effects by up-regulation the expression of Sirt1 and suppression of NLRP3.. 目的：观察α-倒捻子素(alpha-mangostin，α-MG)治疗对阿霉素诱导的局灶节段性肾小球硬化(focal segmental glomurular sclerosis，FSGS)的肾脏保护作用。方法：BALB/c小鼠尾静脉注射阿霉素(10 mg/kg)诱导阿霉素肾病(adriamycin nephropathy，AN)模型后分为两组：1)AN+生理盐水组，用生理盐水灌胃；2)AN+α-MG组，用α-MG(12.5 mg/kg)灌胃。灌胃每日1次，从阿霉素注射当日开始。另取10只小鼠作为对照组。6周后处死小鼠，在光学显微镜下观察肾组织病理学改变；检测血肌酐(SCr)、血尿素氮(BUN)、血胆固醇等肾功能相关生化指标水平；检测肾组织中超氧阴离子，丙二醛(MDA)和谷胱甘肽(GSH)水平以及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性；检测血清中IL-1β，IL-18，IL-10，脂联素水平；用免疫组织化学、RT-PCR和Western印迹检测肾组织中TGF-β1，I型胶原蛋白(collagen I，Col I)，α-SMA，沉默信息调控因子1(silent information regulator 1，Sirt1)，核苷酸结合结构域样受体蛋白3(NLRP3)水平。结果：α-MG治疗可降低AN小鼠血肌酐、蛋白尿、尿蛋白/尿肌酐、血胆固醇，增加肌酐清除率、血浆白蛋白(P<0.05)；缓解肾小球硬化和间质纤维化；下调纤维化指标Col I和α-SMA的表达(P<0.05)；减少肾组织超氧阴离子的产生，降低MDA和GSH水平以及增加CAT和SOD活性(P<0.05)；降低血清炎性因子IL-1β和IL-18水平，升高抗炎因子IL-10和脂联素水平(P<0.05)；促进肾组织中Sirt1表达，抑制NLRP3的表达(P<0.05)。结论：α-MG治疗能够改善阿霉素诱导的FSGS小鼠肾功能，延缓肾小球硬化和间质纤维化进程。α-MG通过促进肾脏Sirt1表达和抑制NLRP3表达而发挥抗炎和抗氧化作用。.

Topics: Animals; Disease Models, Animal; Doxorubicin; Glomerulosclerosis, Focal Segmental; Kidney; Mice; Mice, Inbred NOD; Protein Kinase Inhibitors; Xanthones

Alpha-mangostin, a natural xanthonoid, has been reported to possess the anti-cancer property in various types of human cancer. However, its effects and mechanism of α-mangostin in cervical cancer remain unclear. We found that α-mangostin effectively inhibited cell viability, resulted in loss of mitochondrial membrane potential (MMP), release of cytochrome C, increase of Bax, decrease of Bcl-2, and activation of caspase-9/caspase-3 cascade in cervical cancer cells. Alpha-mangostin elevated the contents of reactive oxygen species (ROS) to activate p38. Disrupting ASK1/p38 signaling pathway by a specific inhibitor of p38, or by the siRNAs against ASK1, MKK3/6, or p38, significantly abolished α-mangostin-induced cell death and apoptotic responses. Moreover, α-mangostin also repressed tumor growth in accordance with increased levels of p-ASK1, p-p38, cleaved-PARP and cleaved-caspase-3 in the tumor mass from the mouse xenograft model of cervical cancer. In the current study, we provided first evidence to demonstrate that dietary antioxidant α-mangostin could inhibit the tumor growth of cervical cancer cells through enhancing ROS amounts to activate ASK1/p38 signaling pathway and damage the integrity of mitochondria and thereby induction of apoptosis in cervical cancer cells.

Topics: Animals; Antineoplastic Agents; Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cytochromes c; Disease Models, Animal; Female; Humans; MAP Kinase Kinase Kinase 5; Matrix Metalloproteinases; Membrane Potential, Mitochondrial; Mice; Mitochondria; Models, Biological; p38 Mitogen-Activated Protein Kinases; Protein Kinase Inhibitors; Reactive Oxygen Species; Signal Transduction; Xanthones; Xenograft Model Antitumor Assays

Obesity induces various metabolic diseases such as dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. Fat expansion in adipose tissue induces adipose tissue dysfunction and inflammation, insulin resistance, and other metabolic syndromes. α-Mangostin (α-MG) has been previously studied for its anti-cancer, anti-inflammatory, and antioxidant activities. In this study, we investigated the effects of α-MG on adipose tissue inflammation and hepatic steatosis. We categorized study animals into four groups: regular diet control mice, RD mice treated with α-MG, high fat diet-induced obese mice, and HFD mice treated with α-MG. α-MG treatment significantly reduced not only the body, liver, and fat weights, but also plasma glucose, insulin, and triglyceride levels in HFD mice. Additionally, adiponectin levels of α-MG-treated mice were significantly higher than those of control HFD mice. Immunohistochemistry of liver and adipose tissue showed that CD11c expression was reduced in α-MG fed obese mice. α-MG treatment of HFD mice down-regulated the adipose-associated inflammatory cytokines and CCR2 in both liver and adipose tissue. Moreover, glucose tolerance and insulin sensitivity were significantly improved in α-MG fed obese mice. α-Mangostin ameliorates adipose inflammation and hepatic steatosis in HFD-induced obese mice.

Topics: Adipose Tissue; Animals; Body Weight; Bone Marrow Cells; Cell Line; Cytokines; Diet, High-Fat; Disease Models, Animal; Fatty Acids; Glucose Tolerance Test; Inflammation Mediators; Insulin Resistance; Liver; Macrophages; Mice; Non-alcoholic Fatty Liver Disease; Obesity; Protein Kinase Inhibitors; Receptors, CCR2; Xanthones

Osteoarthritis (OA) is a chronic degenerative joint disease that is characterized by progressive joint dysfunction and pain. Apoptosis and catabolism in chondrocytes play critical roles in the development of OA. Alpha-Mangostin (α-MG), one of the main components of the mangosteen, has been reported to have anti-apoptotic, anti-inflammatory and antioxidant effects. We investigated the therapeutic effects of α-MG on OA through experiments on rat chondrocytes in vitro and in a rat model of OA induced by destabilization of the medial meniscus (DMM). In vitro, we provided experimental evidence that α-MG inhibits the expression of MMP-13 and ADAMTs-5, and promotes the expression of SOX-9 in rat chondrocytes stimulated with interleukin-1β (IL-1β). In addition, we also found that α-MG can inhibit the expression of pro-apoptotic proteins such as Bax, Cyto-c, and C-caspase3, and increase the expression of the anti-apoptotic protein Bcl-2. These changes may be related to an α-MG induced inhibition of the IL-1β-induced activation of the NF-kB signaling pathway. In vivo, we also found that α-MG can limit the development of OA in rat models. The above results show that α-MG has a potential therapeutic effect on OA, and that this effect may be achieved by inhibiting the mitochondrial apoptosis of chondrocytes induced by an activation of the NF-kB pathway.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cells, Cultured; Chondrocytes; Disease Models, Animal; Disease Progression; Humans; Immunosuppression Therapy; Interleukin-1beta; Male; NF-kappa B; Osteoarthritis; Rats; Rats, Sprague-Dawley; Signal Transduction; Xanthones

β-Mangostin (BM) from Cratoxylum arborescens demonstrated various pharmacological activities such as anticancer and anti-inflammatory. In this study, we aimed to investigate its antiulcer activity against ethanol ulcer model in rats.. BM was isolated from C. arborescens. Gastric acid output, ulcer index, gross evaluation, mucus production, histological evaluation using hematoxylin and eosin and periodic acid-Schiff staining and immunohistochemical localization for heat shock protein 70 (HSP70) and Bax proteins were investigated. Possible involvement of reduced glutathione, lipid peroxidation, prostaglandin E2, antioxidant enzymes, superoxide dismutase and catalase enzymes, radical scavenging, nonprotein sulfhydryl compounds, and anti-Helicobacter pylori were investigated.. BM showed antisecretory activity against the pylorus ligature model. The pretreatment with BM protect gastric mucosa from ethanol damaging effect as seen by the improved gross and histological appearance. BM significantly reduced the ulcer area formation, the submucosal edema, and the leukocytes infiltration compared to the ulcer control. The compound showed intense periodic acid-Schiff staining to the gastric mucus layer and marked amount of alcian blue binding to free gastric mucus. BM significantly increased the gastric homogenate content of prostaglandin E2 glutathione, superoxide dismutase, catalase, and nonprotein sulfhydryl compounds. The compound inhibited the lipid peroxidation revealed by the reduced gastric content of malondialdehyde. Moreover, BM upregulate HSP70 expression and downregulate Bax expression. Furthermore, the compound showed interesting anti-H. pylori activity.. Thus, it could be concluded that BM possesses gastroprotective activity, which could be attributed to the antisecretory, mucus production, antioxidant, HSP70, antiapoptotic, and anti-H. pylori mechanisms.

Topics: Animals; Anti-Ulcer Agents; Apoptosis; bcl-2-Associated X Protein; Clusiaceae; Disease Models, Animal; Down-Regulation; Ethanol; Female; Gastric Mucosa; Helicobacter pylori; HSP70 Heat-Shock Proteins; Lipid Peroxidation; Male; Malondialdehyde; Rats; Rats, Sprague-Dawley; Stomach Ulcer; Up-Regulation; Xanthones

Garcinia mangostana Linn. (Guttiferae) (GM) pericarp has been shown to exhibit good in vitro antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA); however, there is currently no available information regarding its in vivo antibacterial activity.. To examine in vivo antibacterial activity of G. mangostana extract against MRSA.. GM pericarp was extracted by ethanol (GM-EtOH) and methanol (GM-MeOH). The crude extracts were examined for in vitro antibacterial activity against MRSA using broth microdilution assay. The in vivo antibacterial activity of 10% GM-EtOH against MRSA was determined in a tape stripping mouse model of superficial skin infection for 9 days by evaluating transepidermal water loss (TEWL) and performing colony counts from cultured swabs.. GM-EtOH showed greater in vitro activity against MRSA than GM-MeOH in broth microdilution assay with minimum inhibitory concentration 17 versus 20 μg/mL and minimum bactericidal concentration 30 versus 35 μg/mL, respectively. The GM-EtOH (13.20 ± 0.49%) contained α-mangostin more than the GM-MeOH (9.83 ± 0.30%). In the tape stripping mouse model, 10% GM-EtOH reduced the number of MRSA colonies (0-1) recovered from infected wounds (>100 colonies) on the first day of treatment, restored TEWL to normal levels on the fourth day, and had completely healed the wounds by day 9.. GM-EtOH showed promising in vivo antibacterial activity against MRSA in a superficial skin infection model in mice. It is of interest to develop a topical formulation of GM-EtOH to further study its potential as a novel antibacterial agent.

Topics: Animals; Anti-Bacterial Agents; Disease Models, Animal; Erythromycin; Garcinia mangostana; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred ICR; Microbial Sensitivity Tests; Plant Extracts; Staphylococcal Skin Infections; Wound Healing; Xanthones

Neuroinflammation is an important feature in the pathogenesis and progression of neurodegenerative diseases. Molecules with anti-inflammatory properties have been evaluated in animal models of neuroinflammation and neurodegeneration as an adjuvant therapeutic strategy. In the present study we have demonstrated that alpha-mangostin (α-MG), a natural xanthone purified from mangosteen pericarp, reduced brain levels of pro-inflammatory cytokine interleukin-6 (IL-6), cyclooxygenase-2 (COX-2) and 18 kDa translocator protein (TSPO) in an animal model of peripheral LPS-induced neuroinflammation. We think that evaluation of α-MG as an adjuvant treatment in preclinical models of AD, PD, multiple sclerosis and other diseases with known shared pathology merits further consideration.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Calcium-Binding Proteins; Cyclooxygenase 2; Cytokines; Disease Models, Animal; Encephalitis; Female; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Microfilament Proteins; Microglia; Receptors, GABA; Xanthones

Elucidate the antinociceptive mechanisms of α-mangostin isolated from Garcinia malaccensis Linn.. Male mice/rats (n = 6/group) were used in this between-group study. To determine α-mangostin's antinociceptive profile, animals were given α-mangostin orally (3, 30, or 100 mg/kg) 60 min before the start of the abdominal constriction or formalin tests. In the hot plate test, the noxious stimulus was applied before and 60, 90, 120, 150, 180, and 210 min after treatment with test solutions. Positive controls received 100 mg/kg acetylsalicylic acid (ASA; oral) or 5 mg/kg morphine (intraperitoneal injection) for the abdominal constriction and hot plate tests, respectively, and either ASA or morphine for the formalin test. Negative controls received vehicle only. To explore α-mangostin's mechanisms of action, we performed (i) the hot plate test with naloxone (5 mg/kg) pretreatment to verify involvement of opioid receptors; (ii) the abdominal constriction test with 20 mg/kg l-arginine, N(G)-nitro-l-arginine methyl esters (l-NAME), methylene blue (MB), l-arginine plus l-NAME, or l-arginine plus MB or 10 mg/kg glibenclamide pretreatment to verify involvement of the l-arginine/nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) and K+-ATP pathways; and (iii) the paw-licking test using capsaicin (1.6 μg capsaicin/paw), glutamate (10 μmol glutamate/paw), or phorbol 12-myristate 13-acetate (PMA; 0.05 µg/paw) to verify involvement of vanilloid receptors, the glutamatergic system, and protein kinase C (PKC).. α-mangostin significantly inhibited nociception (p < .05) in all models. Only naloxone, l-arginine, methylene blue, PMA, and glibenclamide affected α-mangostin antinociception significantly (p < .05).. α-mangostin exhibits peripheral and central antinociception through modulation of opioid and vanilloid receptors, the glutamatergic system, and the l-arginine/NO/cGMP/PKC/K(+)-ATP pathways.

Topics: Analgesics; Animals; Arginine; Capsaicin; Disease Models, Animal; Glutamic Acid; Male; Mice; Mice, Inbred ICR; NG-Nitroarginine Methyl Ester; Rats; Xanthones

Based on the previously reported in vitro antiplasmodial activity of several xanthones from Garcinia mangostana, two xanthones, α-mangostin and a new compound, δ-mangostin, were isolated from mangosteen husk, and the in vitro antiplasmodial and cytotoxic effects were determined. α-Mangostin was more active against the resistant Plasmodium falciparum chloroquine-resistant (FCR3) strain (IC50  = 0.2 ± 0.01 μM) than δ-mangostin (IC50  = 121.2 ± 1.0 μM). Furthermore, the therapeutic response according to the administration route was evaluated in a Plasmodium berghei malarial murine model. The greatest therapeutic response was obtained with intraperitoneal administration; these xanthones reduced parasitemia by approximately 80% with a daily dose of 100 mg/kg administered twice a day for 7 days of treatment. Neither compound was effective by oral administration. Noticeable toxicological effects were not observed. In addition to the antimalarial effect of these xanthones isolated from G. mangostana husk, the availability of larger amounts of husk raw material to purify the bioactive xanthones is advantageous, permitting additional preclinical assays or chemical transformations to enhance the biological activity of these substances.

Topics: Animals; Antimalarials; Disease Models, Animal; Erythrocytes; Garcinia mangostana; Hemolysis; Humans; Injections, Intraperitoneal; Malaria; Mice; Mice, Inbred BALB C; Parasitemia; Plasmodium falciparum; U937 Cells; Xanthones

Pancreatic cancer (PC) is the most aggressive malignant disease, ranking as the fourth most leading cause of cancer-related death among men and women in the United States. In this study, we provide evidence of chemotherapeutic effects of α-mangostin, a dietary antioxidant isolated from the pericarp of Garcinia mangostana L. against human PC.. The chemotherapeutic effect of α-mangostin was determined using four human PC cells (PL-45, PANC1, BxPC3, and ASPC1). α-Mangostin resulted in a significant inhibition of PC cells viability without having any effects on normal human pancreatic duct epithelial cells. α-Mangostin showed a dose-dependent increase of apoptosis in PC cells. Also, α-mangostin inhibited the expression levels of pNF-κB/p65Ser552, pStat3Ser727, and pStat3Tyr705. α-Mangostin inhibited DNA binding activity of nuclear factor kappa B (NF-κB) and signal transducer and activator 3 (Stat3). α-Mangostin inhibited the expression levels of matrix metallopeptidase 9 (MMP9), cyclin D1, and gp130; however, increased expression of tissue inhibitor of metalloproteinase 1 (TIMP1) was observed in PC cells. In addition, i.p. administration of α-mangostin (6 mg/kg body weight, 5 days a week) resulted in a significant inhibition of both primary (PL-45) and secondary (ASPC1) human PC cell-derived orthotopic and ectopic xenograft tumors in athymic nude mice. No sign of toxicity was observed in any of the mice administered with α-mangostin. α-Mangostin treatment inhibited the biomarkers of cell proliferation (Ki-67 and proliferating cell nuclear antigen [PCNA]) in the xenograft tumor tissues.. We present, for the first time, that dietary antioxidant α-mangostin inhibits the growth of PC cells in vitro and in vivo.. These results suggest the potential therapeutic efficacy of α-mangostin against human PC.

Topics: Animals; Antineoplastic Agents, Phytogenic; Antioxidants; Cell Line; Cell Proliferation; Disease Models, Animal; Dose-Response Relationship, Drug; Garcinia mangostana; Humans; Injections, Intraperitoneal; Mice; Mice, Nude; Pancreatic Neoplasms; Structure-Activity Relationship; Xanthones; Xenograft Model Antitumor Assays

Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice.. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC.. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk.

Topics: Amyloid; Animals; Colitis, Ulcerative; Colon; Dextran Sulfate; Diet; Dietary Supplements; Disease Models, Animal; Dysbiosis; Female; Fruit; Garcinia mangostana; Interleukin-6; Mice; Mice, Inbred C57BL; Peroxidase; Proteobacteria; Xanthones

Classic galactosemia is a genetic disorder that results from profound loss of galactose-1P-uridylyltransferase (GALT). Affected infants experience a rapid escalation of potentially lethal acute symptoms following exposure to milk. Dietary restriction of galactose prevents or resolves the acute sequelae; however, many patients experience profound long-term complications. Despite decades of research, the mechanisms that underlie pathophysiology in classic galactosemia remain unclear. Recently, we developed a Drosophila melanogaster model of classic galactosemia and demonstrated that, like patients, GALT-null Drosophila succumb in development if exposed to galactose but live if maintained on a galactose-restricted diet. Prior models of experimental galactosemia have implicated a possible association between galactose exposure and oxidative stress. Here we describe application of our fly genetic model of galactosemia to the question of whether oxidative stress contributes to the acute galactose sensitivity of GALT-null animals. Our first approach tested the impact of pro- and antioxidant food supplements on the survival of GALT-null and control larvae. We observed a clear pattern: the oxidants paraquat and DMSO each had a negative impact on the survival of mutant but not control animals exposed to galactose, and the antioxidants vitamin C and α-mangostin each had the opposite effect. Biochemical markers also confirmed that galactose and paraquat synergistically increased oxidative stress on all cohorts tested but, interestingly, the mutant animals showed a decreased response relative to controls. Finally, we tested the expression levels of two transcripts responsive to oxidative stress, GSTD6 and GSTE7, in mutant and control larvae exposed to galactose and found that both genes were induced, one by more than 40-fold. Combined, these results implicate oxidative stress and response as contributing factors in the acute galactose sensitivity of GALT-null Drosophila and, by extension, suggest that reactive oxygen species might also contribute to the acute pathophysiology in classic galactosemia.

Topics: Animals; Antioxidants; Ascorbic Acid; Cysteine; Dimethyl Sulfoxide; Disease Models, Animal; Drosophila melanogaster; Drosophila Proteins; Galactose; Galactosemias; Galactosephosphates; Gene Expression; Gene Knockout Techniques; Genes, Insect; Glutathione; Glutathione Transferase; Humans; Mutation; Oxidative Stress; Paraquat; Reactive Oxygen Species; UDPglucose-Hexose-1-Phosphate Uridylyltransferase; Xanthones

α- and γ-Mangostin, which are the major xanthones purified from a Mangosteen, Garcinia mangostana Linn., exhibit a wide range of anticancer, antioxidant, and anti-inflammatory activities. Here, we assessed their therapeutic effects in a mouse model of ovalbumin (OVA)-induced allergic asthma. Animals were treated with α- and γ-mangostins orally for 3 days at doses of 10 and 30 mg/kg daily, 1h before the OVA challenge. Administration of α- and γ-mangostins significantly reduced the major pathophysiological features of allergic asthma, including inflammatory cell recruitment into the airway, airway hyperresponsiveness (AHR), and increased levels of Th2 cytokines. In addition, α- and γ-mangostins attenuated the increases in phosphoinositide 3-kinase (PI3K) activity, phosphorylation of Akt, and NF-κB in nuclear protein extracts after OVA challenge. In conclusion, α- and γ-mangostin may have therapeutic potential for the treatment of allergic asthma.

Topics: Administration, Oral; Animals; Anti-Asthmatic Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Female; Garcinia mangostana; Immunoglobulin E; Interleukins; Lung; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Transforming Growth Factor beta1; Xanthones

Stem bark of Allanblackia monticola has been used in association with others plant in the Cameroonian folk medicine for the treatment of various diseases such amoebic dysentery, diarrhoea, lung infections, and skin diseases. The methylene chloride fraction, its isolated compounds like alpha-mangostin, lupeol and acid betulinic were screened for antioxidant activity using free radical scavenging method. These isolated compounds were further tested for anti-inflammatory properties using carrageenan-induced model. Methylene chloride fraction, showed concentration-dependent radical scavenging activity, by inhibiting 1,1-diphenyl-1-picryl-hydrazyl radical (DPPH) with an IC(50) value of 14.60 microg/ml. alpha-Mangostin and betulinic acid (500 microg/ml), showed weak radical scavenging activity with a maximum inhibition reaching 38.07 microg/ml and 26.38 microg/ml, respectively. Betulinic acid, lupeol and alpha-mangostin (5 mg/kg and 9.37 mg/kg) showed anti-inflammatory activity with a maximum inhibition of 57.89%, 57.14% and 38.70%, respectively. Methylene chloride fraction of Allanblackia monticola and some derivatives, have antioxidant and anti-inflammatory activities.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Betulinic Acid; Carrageenan; Clusiaceae; Disease Models, Animal; Female; Free Radical Scavengers; Inflammation; Inhibitory Concentration 50; Male; Pentacyclic Triterpenes; Plant Bark; Plant Extracts; Rats; Rats, Wistar; Triterpenes; Xanthones