Synergistic effect of α-mangostin on antibacterial activity of tetracycline, erythromycin, and clindamycin against acne involved bacteria / 中草药·英文版

Objective: To evaluate the synergistic effect of α-mangostin with tetracycline, erythromycin, and clindamycin against bacteria involved in acne production. Methods: A broth microdilution method was used to determine the minimum inhibitory concentration (MIC) of α-mangostin and a range of antibiotics. Synergistic effects on antibacterial activity were determined based on their own MIC, and then using a checkerboard method and a time-kill assay at 37 °C for 24 h. Results: α-Mangostin exhibited antibacterial activity against Propionibacterium acnes, Staphylococcus aureus, S. epidermidis and S. pyogenes with MIC values of 0.78, 3.13, 0.78, and 6.25 µg/mL, respectively. The results of the checkerboard assay showed that α-mangostin produced synergistic effects with tetracycline, erythromycin, and clindamycin against all tested bacteria, with a fractional inhibitory concentration index (FICI) between 0.09 and 0.32. Moreover, time-kill curve data indicated that α-mangostin increased the antibacterial activity of tetracycline, erythromycin, and clindamycin. Conclusion: These findings suggested that α-mangostin may be used to enhance the antibacterial activity of some antibiotics against bacteria involved in acne production.

α-Mangostin and apigenin induced the necrotic death of BT474 breast cancer cellswith autophagy and inflammation

Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin Ⅴ and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, α-mangostin and apigenin arrested the cell-cycle at the G1-phase, but at the G2/M-phase by doxorubicin. All three compounds induced a change in transcript expression levels of inflammation-associated, proto-oncogene, autophagy-associated and apoptosis-associated genes. Conclusions: α-Mangostin and apigenin are worth investigating as potential new sources of chemotherapeutic agents for breast cancer treatment.

Alpha-mangostin affects the proliferation and apoptosis of gastric cancer cells by increasing autophagy / 西安交通大学学报(医学版)

Objective To investigate the possible molecular mechanism for alpha(α)-mangostin's inhibition of the proliferation and apoptosis of human gastric cancer cells.Methods Human gastric adenocarcinoma SGC7901 cell line was treated with α-mangostin.CCK8 method was used to measure the viability of SGC7901 cells.The effect of α-mangostin on apoptosis and cell cycle was determined by immune fluorescence and flow cytometry.The expression of the relevant proteins was detected using Western blot.The shapiro-wilk test was performed for evaluation of deviation from normality.Normally distributed data was analyzed with one-way ANOVA.Welch test was used in data with heterogeneity of variance and multiple compared by Games-Howell test after that.Results CCK8 results showed that cell viability differed significantly among groups treated with different concentrations of α-mangostin(10,15,20,25,and 30 μmol/L)(P＜0.05).QPCR data showed that the concentration of α-mangostin was positively correlated with mRNA level of LC 3 but not caspase protein(r=0.976,P＜0.05).In 15 μmol/L but not 10 μmol/L α-mangostin treatment system,the autophagy inhibitors 3-MA(10 μmol/L),bafilomycin A(10 μmol/L)and LY294002(10 μmol/L)could significantly alleviate α-mangostin's killing effect on SGC7901 cells(P＜0.05).Conclusion The anti-tumor effects of α-mangostin against human gastric adenocarcinoma cells in vitro can be partly attributed to apoptosis,autophagy and arresting cell phase.

α-Mangostin regulates the proliferation and apoptosis of osteoarthritis chondrocytes / 中成药

AIM To analyze the effects of α-mangostin on the proliferation and apoptosis of osteoarthritis (OA) chondrocytes.METHODS Human OA chondrocytes were isolated and then treated with 5,10 or 20 μmol/L α-mangostin.24,48 or 72 h after the treatment,the cell proliferation was measured by MTT assay,and the cell apoptosis was detected by flow cytometry.The expression check on MMP-1,MMP-3,MMP-13,PPARγ,PPARδ,PGC-lα and TNF-α was accomplished by Western blot.The contents of collagen-Ⅱ,PG,IL-1β and IL-6 were tested by ELISA.RESULTS α-Mangostin significantly induced cell proliferation and suppressed cell apoptosis,and it significantly increased the production of collagen-Ⅱ and PG,decreased the expressions of MMP-1,MMP-3 and MMP-13,induced the expressions of PPARγ,PPARδ and PGC-1α,and decreased the expression of TNF-α.Furthermore,α-mangostin significantly inhibited the production of IL-1β and IL-6.CONCLUSION α-Mangostin attenuates the destruction and degradation of cartilago articularis by inducing OA chondrocytes proliferation,inhibiting cell apoptosis and inflammation,and increasing expressions of PPARγand PPARδ.

α-Mangostin and apigenin induced the necrotic death of BT474 breast cancer cells with autophagy and inflammation

Objective: To find new compounds in order to overcome the mainstay of metastatic breast cancer due to the adverse side effects from, and increasing resistance to, current chemotherapeutic agents. Methods: α-Mangostin and apigenin were reported in comparison to doxorubicin, a chemotherapeutic drug. Ductal carcinoma (BT474) cell line and non-tumorigenic epithelial tissue from mammary gland (MCF-10A) were used. Cell viability assessment was calculated by the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Cell morphology was investigated by light microscopy. By flow cytometry analysis, programmed cell death was observed using annexin V and propidium iodide staining while cell-cycle arrest was observed using propidium iodide staining. Change in transcriptional expression was evaluated by real-time quantitative reverse transcription PCR. Results: In 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the result revealed α-mangostin and apigenin were more cytotoxic to BT474 cells. Longer exposure times to α-mangostin and apigenin caused more floating cells and a lower density of adhered cells with more vacuoles present in the colonies in BT474 only. α-Mangostin and apigenin caused necrosis in BT474 cells in a 24 h exposure, but a small amount of early apoptotic cells could also be detected at 24, 48 and 72 h exposure, whereas doxorubicin caused early apoptosis to BT474 cells at 24 h. Transcript expression and activity analysis supported caspase-3 was involved in the death of BT474 cells treated by all compounds. Moreover, α-mangostin and apigenin arrested the cell-cycle at the G

Antibiofilm activity of α-mangostin extracted from Garcinia mangostana L. against Staphylococcus aureus

Objective To isolate α-mangostin (AMG) from the peels of mangosteen (Garcinia mangostana L.), grown in Vietnam, and to investigate antibiofilm activity of this compound against three Staphylococcus aureus (S. aureus) strains, one of which was methicillin-resistant S. aureus (MRSA) and the other two strains were methicillin-sensitive S. aureus (MSSA). Methods AMG in n-hexane fraction was isolated on a silica gel column and chemically analyzed by HPLC and NMR. The antibiofilm activity of this compound was investigated by using a 96-well plate model for the formation of biofilms. Biofilm biomass was quantified using crystal violet. The viability of cells was observed under confocal microscopy using LIVE/DEAD BacLight stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membrane-damaging activity was assayed by measuring the hemolysis of human red blood cells in presence of AMG. Results The results indicated that the isolated AMG, with a purity that exceeded 98%, had minimal inhibitory concentrations in the range of 4.6–9.2 μmol/L for the three strains tested. Interestingly, the MSSA strains were more sensitive to AMG than the MRSA strain. Minimal bactericidal concentrations were 2-fold higher than the minimal inhibitory concentration values for the three strains, indicating that AMG was a bactericidal compound. AMG also prevented biofilm formation effectively, albeit that again the MRSA strain was the most resistant. Interestingly, biofilms of the MRSA strain contained protein as a main component of the extracellular matrix, whereas this was polysaccharide in the MSSA strains. This might relate to the resistance of the MRSA 252 strain to AMG. Assays using human red blood cells indicated that AMG caused significant membrane damage with 50% of cell lysis occurred at concentration of about 36 μmol/L. Conclusions Our results provide evidence that the isolated AMG has inhibitory activity against biofilm formation by S. aureus, including MRSA. Thus, isolated AMG proposes a high potential to develop a novel phytopharmaceutical for the treatment of MRSA.

Antibiofilm activity of α-mangostin extracted from Garcinia mangostana L. against Staphylococcus aureus

OBJECTIVE@#To isolate α-mangostin (AMG) from the peels of mangosteen (Garcinia mangostana L.), grown in Vietnam, and to investigate antibiofilm activity of this compound against three Staphylococcus aureus (S. aureus) strains, one of which was methicillin-resistant S. aureus (MRSA) and the other two strains were methicillin-sensitive S. aureus (MSSA).@*METHODS@#AMG in n-hexane fraction was isolated on a silica gel column and chemically analyzed by HPLC and NMR. The antibiofilm activity of this compound was investigated by using a 96-well plate model for the formation of biofilms. Biofilm biomass was quantified using crystal violet. The viability of cells was observed under confocal microscopy using LIVE/DEAD BacLight stains. Biofilm composition was determined using specific chemical and enzyme tests for polysaccharide, protein and DNA. Membrane-damaging activity was assayed by measuring the hemolysis of human red blood cells in presence of AMG.@*RESULTS@#The results indicated that the isolated AMG, with a purity that exceeded 98%, had minimal inhibitory concentrations in the range of 4.6-9.2 μmol/L for the three strains tested. Interestingly, the MSSA strains were more sensitive to AMG than the MRSA strain. Minimal bactericidal concentrations were 2-fold higher than the minimal inhibitory concentration values for the three strains, indicating that AMG was a bactericidal compound. AMG also prevented biofilm formation effectively, albeit that again the MRSA strain was the most resistant. Interestingly, biofilms of the MRSA strain contained protein as a main component of the extracellular matrix, whereas this was polysaccharide in the MSSA strains. This might relate to the resistance of the MRSA 252 strain to AMG. Assays using human red blood cells indicated that AMG caused significant membrane damage with 50% of cell lysis occurred at concentration of about 36 μmol/L.@*CONCLUSIONS@#Our results provide evidence that the isolated AMG has inhibitory activity against biofilm formation by S. aureus, including MRSA. Thus, isolated AMG proposes a high potential to develop a novel phytopharmaceutical for the treatment of MRSA.

Sensitization of 5-Fluorouracil-Resistant SNUC5 Colon Cancer Cells to Apoptosis by α-Mangostin

5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis. Exposure of α-mangostin induced significant DNA damages and increased the intracellular 8-hydroxyguanosine (8-OH-G) and 4-hydroxynonenal (4-HNE) levels in SNUC5 and SNUC5/5-FUR cells. Western blot analysis illustrated that α-mangostin-induced apoptosis was mediated by the activation of the extrinsic and intrinsic pathways in SNUC5/5-FUR cells. In particular, we observed that Fas receptor (FasR) level was lower in SNUC5/5-FUR cells, compared with SNUC5 cells and that silencing FasR attenuated α-mangostin-mediated apoptosis in SNUC5/5-FUR cells. Together, our study illustrates that α-mangostin might be an efficient apoptosis sensitizer that can overcome chemoresistance against 5-FU by activating apoptosis pathway.

Anti-inflammatory Effect of Mangosteen (Garcinia mangostana L.) Peel Extract and its Compounds in LPS-induced RAW264.7 Cells

Inflammation plays an important role in host defense against external stimuli such as infection by pathogen, endotoxin or chemical exposure by the production of the inflammatory mediators that produced by macrophage. Anti-inflammatory factor is important to treat the dangers of chronic inflammation associated with chronic disease. This research aims to analyze the anti-inflammatory effects of Garcinia mangostana L. peel extract (GMPE), α-mangostin, and γ-mangostin in LPS-induced murine macrophage cell line (RAW 264.7) by inhibiting the production of inflammatory mediators. The cytotoxic assay of G. mangostana L. extract, α-mangostin, and γ-mangostin were performed by MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) to determine the safe and non-toxic concentration in RAW 264.7 for the further assay. The concentration of inflammatory mediators (COX-2, IL-6, and IL-1β) were measured by the ELISA-based assay and NO by the nitrate/nitrite colorimetric assay in treated LPS-induced RAW 264.7 cells. The inhibitory activity was determined by the reducing concentration of inflammatory mediators in treated LPS-induced RAW 264.7 over the untreated cells. This research revealed that GMPE, α-mangostin, and γ-mangostin possess the anti-inflammatory effect by reducing COX-2, IL-6, IL-1β, and NO production in LPS-induces RAW 264.7 cells.

Antioxidant and tyrosinase inhibition activities of α- mangostin and Garcinia mangostana Linn. pericarp extracts.

The methanol, ethyl acetate and petroleum ether crude extracts of mangosteen pericarp and α- mangostin were evaluated for the antioxidant capacity and tyrosinase inhibition properties. The ferric reducing antioxidant power (FRAP) assay was used to investigate their antioxidant capacity. Tyrosinase inhibition effect was evaluated using mushroom tyrosinase inhibition assay. Methanol extract has higher antioxidant reducing capacity (m= 1.621), compared to the rest of the extracts. Meanwhile, ethyl acetate extract and α- mangostin showed potent tyrosinase inhibition activities as compared to Kojic acid, a well- known tyrosinase inhibitor. It is observed that tyrosinase inhibition effect is antioxidant independent as ethyl acetate extract possessed low antioxidant capacity. This study suggests direct tyrosinase inhibition by ethyl acetate extract of Garcinia mangostana.

Sunscreen Activity of α -mangostin from the Pericarps of Garcinia mangostana.

A sunscreen active compound has been isolated from the ethanol extract of Garcinia mangostana Linn (Clusiaceae). The ethanol extract was fractionated by liquid liquid extraction with n-hexane, methylene chloride and ethyl acetate, followed by further fractionation and purification using column chromatography on silica gel and gradient elution with combinations of n-hexane and ethyl acetate. Isolation and fractionation was guided by sunscreen activity assay. One of the active compounds was identified as αmangostin based on LC-MS and NMR Spectroscopy. The SPF value of the isolated α –mangostin at 50 and 100 ppm were 21.76 and 37.18, respectively and were much higher than the SPF values of the fractions obtained by liquid-liquid extraction.