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- Hsu, Yu-Ming, et al.
(author)
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Zoanthamine-Type Alkaloids from the Zoanthid Zoanthus kuroshio Collected in Taiwan and Their Effects on Inflammation
- 2016
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In: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:10, s. 2674-2680
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Journal article (peer-reviewed)abstract
- Zoanthus kuroshio is a colorful zoanthid with a fluorescent pink oral disc and brown tentacles, which dominates certain parts of the Taiwanese and Japanese coasts. This sea anemone is a rich source of biologically active alkaloids. In the current investigation, two novel halogenated zoanthamines [5 alpha-iodozoanthenamine (1) and 11 beta-chloro-11-deoxykuroshine A (2)], along with four new zoanthamines [18-epi-kuroshine A (3), 7 alpha-hydroxykuroshine E (4), 5 alpha-methoxykuroshine E (5), and 18-epi-kuroshine E (6)], and six known compounds were isolated from Z. kuroshio. Compounds 1 and 2 are the first examples of halogenated zoanthamine-type alkaloids isolated from nature. Compounds 3 and 6 are the first zoanthamine stereoisomers with a cis-junction of the A/B rings. All isolated compounds were evaluated for their anti-inflammatory activities by measuring their effects on superoxide anion generation and elastase release by human neutrophils in response to fMLP.
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- Lai, Kuei-Hung, et al.
(author)
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Cytotoxic Lanostanoids from Poria cocos
- 2016
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In: Journal of natural products (Print). - : American Chemical Society (ACS). - 0163-3864 .- 1520-6025. ; 79:11, s. 2805-2813
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Journal article (peer-reviewed)abstract
- Six new and 16 known lanostanoids were isolated from the sclerotia of Poria cocos. The structures of the new isolates were elucidated to be 16α-hydroxy-3-oxo-24-methyllanosta-5,7,9(11),24(31)-tetraen-21-oic acid (1), 3β,16α,29-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (2), 3β,16α,30-trihydroxy-24-methyllanosta-7,9(11),24(31)-trien-21-oic acid (3), 3β-acetoxy-16α,24β-dihydroxylanosta-7,9(11),25-trien-21-oic acid (4), 3β,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (5), and 3α,16α-dihydroxy-7-oxo-24-methyllanosta-8,24(31)-dien-21-oic acid (6), based on extensive spectroscopic analyses. The absolute configuration of 4 was determined using Mosher's method. The antiproliferative activity of the isolated compounds (except 3 and 4) was evaluated against four leukemic cell lines (Molt 4, CCRF-CEM, HL 60, and K562). Dehydropachymic acid (9), dehydroeburicoic acid (12), pachymic acid (14), and lanosta-7,9(11),24-trien-21-oic acid (20) exhibited an antiproliferative effect on the CCRF-CEM cancer cell line with IC50 values of 2.7, 6.3, 4.9, and 13.1 μM, respectively. Both dehydropachymic acid (9) and dehydroeburicoic acid (12) showed antiproliferative effects against Molt 4 (IC50 13.8 and 14.3 μM) and HL 60 (IC50 7.3 and 6.0 μM) leukemic cell lines. Primary computational analysis using a chemical global positioning system for natural products (ChemGPS-NP) on the active lanostanoids from P. cocos suggested that targets other than topoisomerases may be involved in the antiproliferative activity.
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- Lai, Kuei-Hung, et al.
(author)
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Antileukemic Scalarane Sesterterpenoids and Meroditerpenoid from Carteriospongia (Phyllospongia) sp., Induce Apoptosis via Dual Inhibitory Effects on Topoisomerase II and Hsp90
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Two new scalarane sesterterpenoids, 12 beta-(3'beta-hydroxybutanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (1) and 12 beta-(3'beta-hydroxypentanoyloxy)-20,24-dimethyl-24-oxo-scalara-16-en-25-al (2), along with one known tetraprenyltoluquinol-related metabolite (3), were isolated from the sponge Carteriospongia sp. In leukemia Molt 4 cells, 1 at 0.0625 mu g/mL (125 nM) triggered mitochondrial membrane potential (MMP) disruption and apoptosis showing more potent effect than 2 and 3. The isolates inhibited topoisomerase II alpha expression. The apoptotic-inducing effect of 3 was supported by the in vivo experiment through suppressing the volume of xenograft tumor growth (47.58%) compared with the control. Compound 1 apoptotic mechanism of action in Molt 4 cells was further elucidated through inducing ROS generation, calcium release and ER stress. Using the molecular docking analysis, 1 exhibited more binding affinity to N-terminal ATP-binding pocket of Hsp90 protein than 17-AAG, a standard Hsp90 inhibitor. The expression of Hsp90 client proteins, Akt, p70(S6k), NF kappa B, Raf-1, p-GSK3 beta, and XIAP, MDM 2 and Rb2, and CDK4 and Cyclin D3, HIF1 and HSF1 were suppressed by the use of 1. However, the expression of Hsp70, acetylated tubulin, and activated caspase 3 were induced after 1 treatment. Our results suggested that the proapoptotic effect of the isolates is mediated through the inhibition of Hsp90 and topoisomerase activities.
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- Yu, Bowei, et al.
(author)
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Age-specific and sex-specific associations of visceral adipose tissue mass and fat-to-muscle mass ratio with risk of mortality
- 2023
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In: Journal of Cachexia, Sarcopenia and Muscle. - : John Wiley & Sons. - 2190-5991 .- 2190-6009. ; 14:1, s. 406-417
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Journal article (peer-reviewed)abstract
- BackgroundLimited studies have explored the association between visceral adipose tissue (VAT) mass and fat-to-muscle mass ratio (FMR) and mortality. We aimed to evaluate the sex-specific association of VAT and FMR with all-cause and cause-specific mortality by age. MethodsA total of 438 896 participants (49.8% men, mean age +/- standard deviation: 57 +/- 8 years for men; 56 +/- 8 years for women) were included from the UK Biobank cohort. The nature of VAT was predictive, as obtained by sex-stratified, non-linear prediction models. Fat and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as the fat mass divided by the muscle mass in the whole body. VAT and FMRs were divided into quintiles in ascending order, and the 3rd quintile was used as the reference. Cox regression analyses were used to estimate the associations between VAT, FMR and mortality. ResultsDuring a median of 12.4 years of follow-up, we documented 29 903 deaths. After adjusting for various covariates, the individuals in the highest quintiles of VAT and FMR had the highest hazard ratios (HRs) of all-cause mortality [1.24 (95% confidence interval: 1.17-1.33) for VAT and 1.24 (1.17-1.31) for FMR in men; and 1.11 (1.03-1.21) for VAT in women], except that the 1st quintile of FMR in women had the greatest HR [1.18 (1.09-1.27)]. Significant interactions were observed in both sexes according to age category (P for interaction < 0.05). Among men <50 years, participants in the 1st and 5th quintiles of VAT and FMR had significantly higher risks of mortality [1.30 (1.02-1.66) and 1.67 (1.27-2.19) in VAT; 1.25 (0.99-1.56) and 1.41 (1.11-1.79) in FMR, respectively]; in women, this phenomenon was observed in the >= 60 age group [1.16 (1.06-1.27) and 1.19 (1.08-1.31) in VAT; 1.18 (1.08-1.29) and 1.11 (1.01-1.22) in FMR, respectively]. VAT showed a linear positive association with mortality in women <60 years and a J-shaped association from respiratory disease in both sexes >= 60 years. FMR showed a linear positive association with mortality from cancer in men <60 years and a J-shaped association with mortality from cause-specific mortality in both sexes >= 60 years, except for mortality from cardiovascular disease in men. ConclusionsMost associations of VAT and FMR with all-cause mortality were J-shaped and were significantly modified by age status (<50, 50-59 and >= 60 years). The clinical implication is that regarding body composition and VAT mass, different health strategies may be adopted for people of different sexes and ages.
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