Protective Effect of Mangosteen Extract against beta-Amyloid-Induced Cytotoxicity, Oxidative Stress and Altered Proteome in SK-N-SH Cells

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Low effects on cytotoxicity against neuroblastoma cancer cell line (SK-N-SH) and free-radical scavenging activity of Stemona alkaloids

Stemona plants contain alkaloids with different skeletal types. They are well-characterized and are commonly used for insecticide, killing head lice, treating skin diseases, antitussive, and anticancer treatment. Eleven Stemona alkaloids of three skeletal types, protestemonine-, croomine-, and stichoneurine-type, i.e. protostemonine-type (didehydrostemofoline, stemofoline, stemocurtisine, stemocurtisinol, stemokerrine, oxystemokerrine), croomine-type (croomine), and stichoneurine-type (tuberostemonine, tuberostemonine A, tuberostemonine N, neotuberostemonine) were isolated from various Stemona roots and investigated for their cytotoxicity and free radical scavenging activity, which have not yet been reported. Cytotoxicity on neuroblastoma cancer cell (SK-N-SH) was determined by MTT assay, while free radical scavenging activity was investigated using the DPPH radical scavenging method. Protostemonine type alkaloids possessed insignificant effect on the cytotoxicity and free radical scavenging activity, while croomine and stichoneurine type alkaloids showed weak to moderate effect

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

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

Abstract 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

Effects of ME on oxidative stress and apoptosis <i>in</i><i>vitro</i>.

<p>(<b>A</b>, <b>B</b>) Intracellular levels of ROS in SK-N-SH cells treated with H₂O₂ (<b>A</b>) or PCB-52 (<b>B</b>) for 24 h with or without prior ME incubation. ROS levels were determined using DCFH-DA assay. The fluorescence was measured and expressed as percentage compared to untreated cells (n=3 independent experiments for each bar). (<b>C</b>, <b>D</b>) Caspase-3 activity in SK-N-SH cells treated with H₂O₂ (<b>C</b>) or PCB-52 (<b>D</b>) with or without ME preincubation. Caspase-3 activity was measured using colorimetric assay. Data were expressed as percentage of the activity compared to untreated cells (n=5 independent experiments for each bar). *<i>P</i> < 0.05, ** <i>P</i> < 0.01, *** <i>P</i> < 0.001 compared to untreated control; ^#<i>P</i> < 0.05, ^##<i>P</i> < 0.01 compared to cells treated with corresponding chemicals concentration with no ME preincubation.</p

Cytotoxicity screening of mangosteen extract in SK-N-SH cells.

<p>SK-N-SH cells were treated with mangosteen extract at the concentrations of 25-800 µg/ml. After 24-hour incubation, cytotoxicity was determined by MTT assay. Data were presented as mean ± SEM (n=8 for each group). ***<i>P</i> < 0.001 compared to control.</p

Western blot analysis of karyopherin β1 (KPNB1) in mouse brain homogenates.

<p>Scopolamine-treated mice with or without prior ME treatment were obtained from passive avoidance test. At the end of the test, whole brain from the mice was subjected to protein extraction. A total 30 µg proteins derived from brain extracts (n=3) were resolved by 12% SDS-PAGE and transferred onto a nitrocellulose membrane. After blocking non-specific bindings, the membrane was incubated with mouse monoclonal anti-KPNB1 (1:1,000 in 1% skim milk/PBS) and then incubated with rabbit anti-mouse IgG conjugated with horseradish peroxidase (1:2,000 in 1% skim milk/PBS). β-actin served as the loading control. The immunoreactive bands were visualized by chemiluminescence and autoradiography. Data was presented as KPNB1 band intensity relative to β-actin band. KPNB1 (97 kDa) level was significantly decreased after treatment with scopolamine but could be successfully preserved at its basal level by mangosteen extract. Data were reported as Mean ± SEM (n=3). * <i>P</i> < 0.05 compared to the control. </p