AIM OF STUDY: Although anticancer activity has been reported for the plant, the goal of the study was designed to isolate and characterize the active metabolites from G. mangostana and measure their cytotoxic properties. In this research, the mechanism of antiproliferative/cytotoxic effects of the tested compounds was investigated.
MATERIALS AND METHODS: The CHCl3 fraction of the air-dried fruit hulls was repeatedly chromatographed on SiO2, RP18, Diaion HP-20, and polyamide columns to furnish fourteen compounds. The structures of these metabolites were proven by UV, IR, 1D, and 2D NMR measurements and HRESIMS. Additionally, the cytotoxic potential of all compounds was assessed against MCF-7, HCT-116, and HepG2 cell lines using SRB-U assay. Antiproliferative and cell cycle interference effects of potentially potent compounds were tested using DNA content flow cytometry. The mechanism of cell death induction was also studied using annexin-V/PI differential staining coupled with flow cytometry.
RESULTS: The CHCl3 soluble fraction afforded two new xanthones: mangostanaxanthones V (1) and VI (2), along with twelve known compounds: mangostanaxanthone IV (3), β-mangostin (4), garcinone E (5), α-mangostin (6), nor-mangostin (7), garcimangosone D (8), aromadendrin-8-C-β-D-glucopyranoside (9), 1,2,4,5-tetrahydroxybenzene (10), 2,4,3`-trihydroxybenzophenone-6-O-β-glucopyranoside (11), maclurin-6-O-β-D-glucopyranoside (rhodanthenone) (12), epicatechin (13), and 2,4,6,3`,5`-pentahydroxybenzophenone (14). Only compound 5 showed considerable antiproliferative/cytotoxic effects with IC50's ranging from 15.8 to 16.7µM. Compounds 3, 4, and 6 showed moderate to weak cytotoxic effects (IC50's ranged from 45.7 to 116.4µM). Using DNA content flow cytometry, it was found that only 5 induced significant cell cycle arrest at G0/G1-phase which is indicative of its antiproliferative properties. Additionally, by using annexin V-FITC/PI differential staining, 5 induced cells killing effect via the induction of apoptosis and necrosis in both HepG2 and HCT116 cells. Compound 3 produce necrosis and apoptosis only in HCT116 cells. On contrary, 6 induced apoptosis and necrosis in HepG2 cells and moderate necrosis in HCT116 cells.
CONCLUSION: Fourteen compounds were isolated from chloroform fraction of G. mangostana fruit hulls. Cytotoxic properties exhibited by the isolated xanthones from G. mangostana reinforce the avail of it as a natural cytotoxic agent against various cancers. These evidences could provide relevant bases for the scientific rationale of using G. mangostana in anti-cancer treatment.
METHODS: Study samples were collected from 22 participants; 9 from patients with AKU, 9 from individuals who were AKU carriers, and 4 people served as control. Confirmation of AKU diagnosis was established by the ferric chloride test and quantitative determination of urinary homogentisic acid (HGA) levels.
RESULTS: In the ferric chloride test, the urine samples of AKU patients showed a characteristic black ring upon addition of few drops of ferric chloride solution. During urinary HGA determination, patients with AKU had increased levels of urinary HGA as compared to carriers and controls. The following 10 bacterial species were isolated from the urinary tract of AKU patients, carriers and controls: Sphingomonas paucimobilis, Escherichia coli, Francisella tularensis, Staphylococcus hominis, Staphylococcus haemolyticus, Leuconostoc mesenteroides, Dermacoccus nishinomiyaensis, Kytococcus sedentarius, Serratia fonticola and Granulicatella adiacens. The presence of S. paucimobilis was found in three male patients, and one female each from the carrier and control groups. Almost all study samples were positive for D. nishinomiyaensis and K. sedentarius. S. fonticola and G. adiacens were found only in AKU carrier females.
CONCLUSIONS: The results deduced that males show symptoms of arthritis early and more severely than females and by this it appears that there is an association between these symptoms and the percentage of bacterial infection in males that requires more accurate diagnosis and treatment to clarify such relationship. In the current study, males (patients, carriers, and controls) were more likely to have bacterial infections than females (64% vs. 36%). The 16 and 2 bacterial isolates, detected in 7 males and 2 females AKU patients, respectively, revealed that male AKU patients had a 2.3-fold greater rate of bacterial infection than female AKU patients. Therefore, further studies are warranted to investigate if there's any relationship between higher incidence of bacterial infections and development of AKU-related clinical symptoms in the male population.
METHODS: K562 CML cells were treated with resveratrol, and their effects were analyzed through CCK-8 assay for cell viability, TUNEL assay for DNA fragmentation, and real-time PCR for gene expression. Key apoptotic genes (BCL-2, AIF, BAX) were assessed alongside survival-related genes (CASP3, PGC1α, Cyclin-D1, p53) to evaluate resveratrol's anti-proliferative and pro-apoptotic potential.
RESULT: Resveratrol exhibited a time-dependent reduction in K562 cell viability, with IC₅₀ values decreasing from 282.2 µM at 24 hours to 107.1 µM and 102.4 µM at 48 and 72 hours, respectively. Apoptotic activity, assessed via the TUNEL assay, revealed significant DNA fragmentation in 55 ± 5% of treated cells, while control cells showed no fragmentation. Gene expression analysis demonstrated upregulation of pro-apoptotic genes, including BCL-2, AIF (p < 0.05), BAX (p < 0.01), and VDAC1 (4.5-fold, p < 0.001). Conversely, genes linked to cell survival and metabolism, such as CASP3, PGC1α, NDUFA9, Cyclin-D1, and p53, were slightly downregulated (p < 0.05), highlighting resveratrol's dual role in promoting apoptosis and inhibiting cell survival.
CONCLUSION: These findings suggest that resveratrol exerts anti-proliferative and pro-apoptotic effects in CML cells by modulating key genes and induction of DNA fragmentation, highlighting its potential as a therapeutic agent for CML treatment.
METHODS: The modified SPEED or M-SPEED is a sequence prediction algorithm, which modified the previous SPEED algorithm by using time duration of appliance's ON-OFF states to decide the next state. M-SPEED discovered periodic episodes of inhabitant behavior, trained it with learned episodes, and made decisions based on the obtained knowledge.
RESULTS: The results showed that M-SPEED achieves 96.8% prediction accuracy, which is better than other time prediction algorithms like PUBS, ALZ with temporal rules and the previous SPEED.
CONCLUSIONS: Since human behavior shows natural temporal patterns, duration times can be used to predict future events more accurately. This inhabitant activity prediction system will certainly improve the smart homes by ensuring safety and better care for elderly and handicapped people.