Effects of water-soluble mangosteen extract on cognitive function and neuropsychiatric symptoms in patients with mild to moderate Alzheimer's disease (WECAN-AD): A randomized controlled trial.

Introduction: The water-soluble mangosteen pericarp extract's (WME) effect was investigated in Alzheimer's disease (AD). Methods: The participants received 4 mg/kg/day of WME for 24 weeks (low dose, n = 33), 4 mg/kg/day for 12 weeks and then 8 mg/kg/day for 12 weeks (high dose, n = 33); or a placebo (n = 42). The outcomes were neuropsychiatric test scores, safety, tolerability, and the blood 4-hydroxynonenal level. Results: The proportion of participants who achieved the minimum clinically important difference for the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog; -2.6 points) at 24 weeks was significantly higher in the low-dose group (and a trend in the high-dose group) than in the placebo group. WME appeared safe and well tolerated. At 24 weeks, the 4-hydroxynonenal level declined in both intervention groups. The participants with a 5% reduction in this level showed greater ADAS-Cog improvements. Conclusion: WME is a safe and well-tolerated cognitive enhancer in AD with varying benefits across individuals based on antioxidative response.

Antioxidant-Enhancing Property of the Polar Fraction of Mangosteen Pericarp Extract and Evaluation of Its Safety in Humans.

Crude extract from the pericarp of the mangosteen (mangosteen extract [ME]) has exhibited several medicinal properties in both animal models and human cell lines. Interestingly, the cytotoxic activities were always observed in nonpolar fraction of the extract whereas the potent antioxidant was often found in polar fraction. Although it has been demonstrated that the polar fraction of ME exhibited the antioxidant activity, the safety of the polar fraction of ME has never been thoroughly investigated in humans. In this study, we investigated the safety of oral administration of the polar fraction of ME in 11 healthy Thai volunteers. During a 24-week period of the study, only minor and tolerable side effects were reported; no serious side effects were documented. Blood chemistry studies also showed no liver damage or kidney dysfunction in all subjects. We also demonstrated antioxidant property of the polar fraction of ME both in vitro and in vivo. Interestingly, oral administration of the polar fraction of ME enhanced the antioxidant capability of red blood cells and decreased oxidative damage to proteins within red blood cells and whole blood.

The platelet amyloid precursor protein ratio as a diagnostic marker for Alzheimer's disease in Thai patients.

The platelet amyloid precursor protein (APP) ratio has recently been shown to be a promising diagnostic marker for Alzheimer's disease (AD). To evaluate its usefulness in Thai patients, platelet APP was analyzed by immunoblotting. The APP ratio was calculated as the ratio of the combined band density of the 120-kD and 130-kD isoforms compared to that of the 110-kD isoform. The mean ages (and ranges) of 27 normal and 13 AD-affected subjects were 68.3 (60-84) and 79.3 (70-97) years, respectively. The Thai Mental State Examination (TMSE) scores demonstrated that the AD patients had significantly poorer cognitive functions than the normal subjects, with mean TMSE scores of 20.3 and 27.6 (maximum score of 30 points), respectively (p<0.05). The platelet APP ratios of the AD patients were significantly lower than those of normal subjects: values (mean ± standard deviation) were 7.32 ± 1.29 and 9.13 ± 3.00, respectively (p<0.05) for AD patients and normal subjects. However, the ranges of the APP ratios from both groups markedly overlapped, which precluded the establishment of a cutoff level to differentiate between the AD and normal subjects. In addition, no significant correlations were observed between the platelet APP ratio and the TMSE score or between the APP ratio and the serum cholesterol in this study, in contrast to previous reports.

Protective effects of mangosteen extract on H2O2-induced cytotoxicity in SK-N-SH cells and scopolamine-induced memory impairment in mice.

Mangosteen extracts (ME) contain high levels of polyphenolic compounds and antioxidant activity. Protective effects of ME against ß-amyloid peptide (Aß), induced cytotoxicity have been reported. Here, we further studied the protective effects of ME against oxidative stress induced by hydrogen peroxide (H2O2) and polychlorinated biphenyls (PCBs), and demonstrated the protection against memory impairment in mice. The cytoprotective effects of ME were measured as cell viability and the reduction in ROS activity. In SK-N-SH cell cultures, 200 µg/ml ME could partially antagonize the effects of 150 or 300 µM H2O2 on cell viability, ROS level and caspase-3 activity. At 200, 400 or 800 µg/ml, ME reduced AChE activity of SK-N-SH cells to about 60% of the control. In vivo study, Morris water maze and passive avoidance tests were used to assess the memory of the animals. ME, especially at 100 mg/kg body weight, could improve the animal's memory and also antagonize the effect of scopolamine on memory. The increase in ROS level and caspase-3 activity in the brain of scopolamine-treated mice were antagonized by the ME treatment. The study demonstrated cytoprotective effects of ME against H2O2 and PCB-52 toxicity and having AChE inhibitory effect in cell culture. ME treatment in mice could attenuate scopolamine-induced memory deficit and oxidative stress in brain.

Protective effect of mangosteen extract against beta-amyloid-induced cytotoxicity, oxidative stress and altered proteome in SK-N-SH cells.

Beta-amyloid (A beta) plays a key role in the pathogenesis of Alzheimer's disease (AD) by inducing neurotoxicity and cell death mainly through production of reactive oxygen species (ROS). Garcinia mangostana L. (mangosteen) has been recognized as a major source of natural antioxidants that could decrease ROS. However, its role in protection of A beta-induced cytotoxicity and apoptosis in neuronal cells remains unclear. We therefore examined such a protective effect of mangosteen extract (ME) by evaluating cell viability using MTT test, ROS level, caspase-3 activity, and cellular proteome. Treating SK-N-SH cells with 5-20 microM A beta((1-42)) for 24 h caused morphologically cytotoxic changes, decreased cell viability and increased ROS level, whereas preincubation with 50-400 microg/mL ME 30 min before the induction by A beta((1-42)) successfully prevented such cytotoxic effects in a dose-dependent manner (completely at 400 microg/mL). The A beta-induced increase in caspase-3 activity was also preventable by 400 microg/mL ME. Proteomic analysis using 2-D gel electrophoresis (n = 5 gels/group) followed by mass spectrometry revealed 63 proteins whose levels were significantly altered by A beta((1-42)) induction. Interestingly, changes in 10 proteins were successfully prevented by the ME pretreatment. In summary, we report herein the significant protective effects of ME against A beta-induced cytotoxicity, increased ROS, and increased caspase activity in SK-N-SH cells. Moreover, proteomic analysis revealed some proteins that might be responsible for these protective effects by ME. Further characterizations of these proteins may lead to identification of novel therapeutic targets for successful prevention and/or decreasing the severity of AD.

Utility of plasma fluorometric emission scanning for diagnosis of the first 2 cases reports of variegate porphyria: a very rare type of porphyrias in Thai.

Two Thai women who are siblings presented with a history of recurrent pruritic vesicles on dorsum of both hands and extensor surface of forearms where the sun-exposed areas are. The excoriated vesicles were healed with depressed scars. They had no previous history of intense abdominal pain, seizure, or psychiatric disorder Urinary porphyrins were analyzed by High Performance Liquid Chromatography (HPLC). The level of coproporphyrin III was detected to be higher than the uroporphyrin level. Fluorescence emission scanning of both patients' plasma was performed and demonstrated typical emission peak at 626 nm, that confirmed the diagnosis of variegate porphyria.

Antiproliferation, antioxidation and induction of apoptosis by Garcinia mangostana (mangosteen) on SKBR3 human breast cancer cell line.

This study was designed to determine the antiproliferative, apoptotic and antioxidative properties of crude methanolic extract (CME) from the pericarp of Garcinia mangostana (family Guttiferae) using human breast cancer (SKBR3) cell line as a model system. SKBR3 cells were cultured in the presence of CME at various concentrations (0-50 microg/ml) for 48 h and the percentage of cell viability was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-di phenyl tetrazolium bromide (MTT) assay. CME showed a dose-dependent inhibition of cell proliferation with ED(50) of 9.25+/-0.64 microg/ml. We found that antiproliferative effect of CME was associated with apoptosis on breast cancer cell line by determinations of morphological changes and oligonucleosomal DNA fragments. In addition, CME at various concentrations and incubation times were also found to inhibit ROS production. These investigations suggested that the methanolic extract from the pericarp of Garcinia mangostana had strong antiproliferation, potent antioxidation and induction of apoptosis. Thus, it indicates that this substance can show different activities and has potential for cancer chemoprevention which were dose dependent as well as exposure time dependent.

Cytotoxicity and apoptosis of ovarian and breast cancer cell lines induced by OVS1 monoclonal antibody and paclitaxel.

OVS1 monoclonal antibody (MAb) produced against ovarian cancer is currently used to identify mucinous cystadenocarcinoma antigen as a tumor marker secreted in serum. The potential of OVS1 MAb in ovarian cancer treatment was studied by evaluating the induction of cytotoxicity and apoptosis of SKOV3 ovarian cancer and BT549 breast cancer cell lines induced by OVS1. Paclitaxel, an antitumor drug, was used as positive control and applied as a combined drug together with OVS1 MAb. OVS1 MAb and paclitaxel were found by MTT assay to induce cytotoxicity against both cell lines. The ED50 of OVS1 MAb were 26.25 and 25.00 microg/ml and of paclitaxel were 21.88 and 9.20 nM against SKOV3 and BT549 cell lines, respectively. The quantitative amount of cells determined by fluorimetric assay was correlated to the results of the MTT assay. The combined application of OVS1 MAb and paclitaxel on these two cell lines resulted in a greater cytotoxicity than observed by either agent alone. OVS1 MAb and paclitaxel applied against both cell lines induced the morphological changes of apoptotic cell death at 24 hours visualized by two color fluorescence dyes, Ho33342 and propidium iodide. Combination of the two substances enhanced the rate of apoptosis compared to either OVS1 MAb or paclitaxel given alone. DNA fragmentation was detected in an agarose gel electrophoresis after treating cells with OVS1 MAb and paclitaxel at 24 hours. These findings on the induction of cytotoxicity and apoptosis by OVS1 MAb on cancer cell lines have implications on the potential application of OVS1 MAb for clinical therapy.

p53 tumor suppressor gene mutation in ovarian cancer in Thai patients.

OBJECTIVES: To characterize molecular mutations of p53 gene in Thai ovarian cancer and compare the mutations with their pathological and clinical findings. MATERIAL AND METHOD: Direct DNA sequencing of hot spot region of p53 gene (exons 5 to 8) from 28 primary ovarian cancer tissues, 2 metastatic tumors and their paired blood samples was performed. The detected mutations were compared to the pathological and clinical findings and responsiveness to treatments after 36 months of follow-up. RESULTS: One insertion and 4 point mutations in exon 5 of p53 gene were found in 5 out of 28 (18%) ovarian cancer patients. There was no mutation in the paired blood samples. The histological types of the detected tumors were 3 endometrioids and 2 serous cystadenocarcinomas. All 5 patients were in stage I to IV disease and showed overall 4 out of 5 (80%) complete response until 36 months after surgery followed by chemotherapy, compared to 14 out of 28 (50%) of complete response in all cases of ovarian cancer. CONCLUSION: The authors found 5 cases of ovarian cancer patients with p53 gene mutations giving the same response to complete standard treatment as all cases. Significant factors affecting responsiveness of these patients depended more on stages, grades and histological cell types of the cancer.