21 research outputs found
Effect of a Labile Methyl Donor on the Transformation of 5‑Demethyltangeretin and the Related Implication on Bioactivity
Polymethoxyflavones
(PMFs) belong to a subgroup of flavonoids that
particularly exist in the peels of citrus fruits. Despite their many
health-beneficial biofunctionalities, the lipophilic nature of PMFs
limits their water solubility and oral bioavailability. To investigate
the effect of the delivery system on the improvement of PMF bioavailibility,
a lecithin-based emulsion was formulated for the delivery of two PMF
compounds, tangeretin and 5-demethyltangeretin. While the emulsion
system improved the digestion kinetics and the total solubilized PMF
concentrations in in vitro lipolysis studies, the concentration of
5-demethyltangeretin decreased due to chemical transformation to its
permethoxylated counterpart, tangeretin. The emulsifier lecithin used
in this emulsion formulation contained a choline headgroup as a labile
methyl group donor. The presence of a methyl donor potentially caused
the transformation of 5-demethyltangeretin and reduced its anti-cancer-cell-proliferation
activities. Moreover, this is the first report in the literature of
the transformation from 5-demethyltangeretin to tangeretin in a lecithin-based
emulsion during lipolysis, and the mechanism underlying this phenomenon
has also been proposed for the first time
Identification of Indicative Gut Microbial Guilds in a Natural Aging Mouse Model
Gut microbial dysbiosis during later life may contribute
to health
conditions, possibly due to an increase in intestinal permeability,
immune changes, and systemic inflammation. Mouse models have been
employed to determine the influence of gut microbes on aging; however,
suitable gut microbial indicators are currently lacking. Therefore,
this study aimed to determine the gut microbial indicators and their
potential guilds in a natural aging mouse model. In agreement with
previous studies, alpha diversity indicesincluding observed
OTUs, ACE, Chao1, and Simpsonwere significantly lower in aged
mice than in younger mice. The results of beta diversity analysis
revealed the compositional differences between young and aged mice,
and the MRPP, ANOSIM, and Adonis tests indicated that the results
were representative. By employing ANCOM and LEfSe analyses, Bacteroides thetaiotaomicron (Bacteroides) and Anaeroplasma were identified
as the indicators of young and aged mice, respectively. Notably, these
indicators were still present after 3 months. The result of network
analysis confirmed the negative correlation of these genera in mice,
and the potential guild members were identified based on the increased
abundance of Anaeroplasma in aged mice.
The gut microbes of aged mice tend to correspond to those involved
in human diseases, selenocompound metabolism, and glycolysis/gluconeogenesis
in functional predictions. In this study, the gut microbial indicators
in aged mice have been identified, and it is envisaged that these
findings could provide a new approach for future studies of antiaging
Identification of Indicative Gut Microbial Guilds in a Natural Aging Mouse Model
Gut microbial dysbiosis during later life may contribute
to health
conditions, possibly due to an increase in intestinal permeability,
immune changes, and systemic inflammation. Mouse models have been
employed to determine the influence of gut microbes on aging; however,
suitable gut microbial indicators are currently lacking. Therefore,
this study aimed to determine the gut microbial indicators and their
potential guilds in a natural aging mouse model. In agreement with
previous studies, alpha diversity indicesincluding observed
OTUs, ACE, Chao1, and Simpsonwere significantly lower in aged
mice than in younger mice. The results of beta diversity analysis
revealed the compositional differences between young and aged mice,
and the MRPP, ANOSIM, and Adonis tests indicated that the results
were representative. By employing ANCOM and LEfSe analyses, Bacteroides thetaiotaomicron (Bacteroides) and Anaeroplasma were identified
as the indicators of young and aged mice, respectively. Notably, these
indicators were still present after 3 months. The result of network
analysis confirmed the negative correlation of these genera in mice,
and the potential guild members were identified based on the increased
abundance of Anaeroplasma in aged mice.
The gut microbes of aged mice tend to correspond to those involved
in human diseases, selenocompound metabolism, and glycolysis/gluconeogenesis
in functional predictions. In this study, the gut microbial indicators
in aged mice have been identified, and it is envisaged that these
findings could provide a new approach for future studies of antiaging
Peracetylated (−)-Epigallocatechin-3-gallate (AcEGCG) Potently Suppresses Dextran Sulfate Sodium-Induced Colitis and Colon Tumorigenesis in Mice
Previous studies reported that peracetylated (-)-epigallocatechin-3-gallate
(AcEGCG) has antiproliferative and anti-inflammatory activities. Here,
we evaluated the chemopreventive effects and underlying molecular
mechanisms of dietary administration of AcEGCG and EGCG in dextran
sulfate sodium (DSS)-induced colitis in mice. The mice were fed a
diet supplemented with either AcEGCG or EGCG prior to DSS induction.
Our results indicated that AcEGCG administration was more effective
than EGCG in preventing the shortening of colon length and the formation
of aberrant crypt foci (ACF) and lymphoid nodules (LN) in mouse colon
stimulated by DSS. Our study observes that AcEGCG treatment inhibited
histone 3 lysine 9 (H3K9) acetylation but did not affect histone acetyltransferase
(HAT) activity and acetyl- CREB-binding protein (CBP)/p300 levels.
In addition, pretreatment with AcEGCG decreased the proinflammatory
mediator levels by down-regulating of PI3K/Akt/NFκB phosphorylation
and p65 acetylation. We also found that treatment with AcEGCG increased
heme oxygenase-1Â(HO-1) expression via activation of extracellular
signal-regulated protein kinase (ERK)Â1/2 signaling and acetylation
of NF-E2-related factor 2 (Nrf2), thereby abating DSS-induced colitis.
Moreover, dietary feeding with AcEGCG markedly reduced colitis-driven
colon cancer in mice. Taken together, these results demonstrated for
the first time the in vivo chemopreventive efficacy and molecular
mechanisms of dietary AcEGCG against inflammatory bowel disease (IBD)
and potentially colon cancer associated with colitis. These findings
provide insight into the biological actions of AcEGCG and might establish
a molecular basis for the development of new cancer chemopreventive
agents
Autophagy inhibitor sensitized pterostilbene and 3′-hydroxypterostilbene-induced apoptosis in COLO 205 cancer cells.
<p>Cells were pretreated with 25 µM CQ for 1 h before treatment with 50 µM of pterostilbene or 3′-hydroxypterostilbene for 24 h. (A) Cell viability was determined by MTT assay. (B, C) Sub-G1 cell population (%) was analyzed and quantification after PI staining followed by flow cytometry. Data were presented as mean ±SD of triplicate experiments. <sup>*</sup><i>P</i><0.05 and <sup>**</sup><i>P</i><0.01 indicates statistically significant difference from the pterostilbene-treated group.</p
5‑Demethylnobiletin and 5‑Acetoxy-6,7,8,3′,4′-pentamethoxyflavone Suppress Lipid Accumulation by Activating the LKB1-AMPK Pathway in 3T3-L1 Preadipocytes and High Fat Diet-Fed C57BL/6 Mice
Polymethoxyflavones (PMFs) and
hydroxylated polymethoxyflavones
(HPMFs), such as nobiletin (Nob) and 5-demethylnobiletin (5-OH-Nob),
are unique flavonoids that are found exclusively in citrus peels.
Nobiletin has been shown to suppress adipogenesis in vitro, but the
antiadipogenic activity of 5-OH-Nob has not been investigated. Both
nobiletin and 5-OH-Nob have poor aqueous solubility and low oral bioavailability.
We employed chemical modification to produce the acetyl derivative
of 5-OH-Nob, that is, 5-acetyloxy-6,7,8,3′,4′-pentamethoxyflavone
(5-Ac-Nob), to improve its bioavailability and bioactive efficiency.
We found that 5-Ac-Nob reduced triacylglycerol (TG) content to a greater
extent than 5-OH-Nob in 3T3-L1 preadipocytes. Orally administered
5-Ac-Nob resulted in a significant reduction in body weight, intra-abdominal
fat, plasma and liver TG levels, and plasma cholesterol level in high
fat diet-induced obese male C57BL/6J mice. The 5-Ac-Nob treatment
decreased lipid accumulation by triggering the adenosine 5′-monophosphate-activated
protein kinase (AMPK) pathway to alter transcriptional factors or
lipogenesis-related enzymes in vivo and in vitro
3′-Hydroxypterostilbene down-regulated mTOR, PI3K/Akt and MAPKs signaling in COLO 205 cancer cells.
<p>COLO 205 cells were treated with 50 µM 3′-hydroxypterostilbene at different times. Cell lyates were prepared and the protein levels of (A) p-mTOR, p-P70S6K, (B) p-PI3K, p-Akt and (C) p-ERK1/2, p-JNK1/2, p-p38 were analyzed by Western blotting analysis. All analyses were representative of at least three independent experiments. The values under each lane indicate relative density of the band normalized to β-actin using a densitometer.</p
Autophagy induction by pterostilbene and 3′-hydroxypterostilbene in COLO 205 cancer cells.
<p>Cells were treated with 50 µM pterostilbene or 3′-hydroxypterostilbene for 24 h and stained with acridine orange. (A) Green and red fluorescence in acridine orange-stained cells were observed under fluorescence microscope. (B, C) Detection and quantification of autophagy in COLO 205 cells. Cells were treated with 25 and 50 µM of pterostilbene or 3′-hydroxypterostilbene for 24 h and stained with acridine orange. The measurement of green and red fluorescence in acridine orange-stained cells was performed using flow cytometry. (D) Cell lysates were prepared after 24 h treatment and the protein expression of LC3 I/II were analyzed by Western blotting. Data were presented as mean ±SD of triplicate experiments. *<i>P</i><0.05 indicates statistically significant difference from the pterostilbene-treated group.</p
Effects of pterostilbene and 3′-hydroxypterostilbene administration on the body weight and organ weight in a COLO 205 xenograft model<sup>a</sup>.
a<p>COLO 205 cells were injected into 3–4 week old BALB/c nude mice (5×10<sup>6</sup> cells per mouse). After tumors grew to about 100–200 mm<sup>3</sup>, mice were <i>i.p.</i> treated with pterostilbene or 3′-hydroxypterostilbene for 15 days. All mice of each group were sacrificed by CO<sub>2</sub> asphyxiation at the end of experiment. Comparisons were analyzed using ANOVA followed by Fisher's least significant difference test.</p><p>Effects of pterostilbene and 3′-hydroxypterostilbene administration on the body weight and organ weight in a COLO 205 xenograft model<sup><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111814#nt102" target="_blank">a</a></sup>.</p
Chemical structure of pterostilbene and 3′-hydroxypterostilbene.
<p>Chemical structure of pterostilbene and 3′-hydroxypterostilbene.</p