8 research outputs found
Metabolic Fate of Tea Polyphenols in Humans
Polyphenols, a ubiquitous group of secondary plant metabolites
sharing at least one aromatic ring structure with one or more hydroxyl
groups, represent a large group of natural antioxidants abundant in
fruits, vegetables, and beverages, such as grape juice, wine, and
tea, and are widely considered to contribute to health benefits in
humans. However, little is yet known concerning their bioactive forms <i>in vivo</i> and the mechanisms by which they may alter our metabolome,
which ultimately contribute toward disease prevention. Here we report
a study to determine the metabolic fate of polyphenolic components
in a Chinese tea (Pu-erh) in human subjects using a metabonomic profiling
approach coupled with multivariate and univariate statistical analysis.
Urine samples were collected at 0 h, 1 h, 3 h, 6 h, 9 h, 12 h, and
24 h within the first 24 h and once a day during a 6 week period including
a 2 week baseline phase, a 2 week daily Pu-erh tea ingestion phase,
and a 2 week “wash-out” phase, and they were analyzed
by gas chromatography mass spectrometry and liquid chromatography
mass spectrometry. The dynamic concentration profile of bioavailable
plant molecules (due to <i>in vivo</i> absorption and the
hepatic and gut bacterial metabolism) and the human metabolic response
profile were measured and correlated with each other. This study demonstrates
that the metabonomic strategy will enable us to integrate the overwhelming
amount of metabolic end points as a systems' response to the absorption,
metabolism, and disposition of a multicomponent botanical intervention
system, leading to a direct elucidation of their mechanisms of action
Global and Targeted Metabolomics Evidence of the Protective Effect of Chinese Patent Medicine <i>Jinkui Shenqi</i> Pill on Adrenal Insufficiency after Acute Glucocorticoid Withdrawal in Rats
Glucocorticoids
are commonly used in anti-inflammatory and immunomodulatory
therapies, but glucocorticoid withdrawal can result in life-threatening
risk of adrenal insufficiency. Chinese patented pharmaceutical product <i>Jinkui Shenqi</i> pill (JKSQ) has potent efficacy on clinical
adrenal insufficiency resulting from glucocorticoid withdrawal. However,
the underlying molecular mechanism remains unclear. We used an animal
model to study JKSQ-induced metabolic changes under adrenal insufficiency
and healthy conditions. Sprague–Dawley rats were treated with
hydrocortisone for 7 days with or without 15 days of JKSQ pretreatment.
Sera were collected after 72 h hydrocortisone withdrawal and used
for global and free fatty acids (FFAs)-targeted metabolomics analyses
using gas chromatography/time-of-flight mass spectrometry and ultraperformance
liquid chromatography/quadruple time-of-flight mass spectrometry.
Rats without hydrocortisone treatment were used as controls. JKSQ
pretreatment normalized the significant changes of 13 serum metabolites
in hydrocortisone-withdrawal rats, involving carbohydrates, lipids,
and amino acids. The most prominent effect of JKSQ was on the changes
of FFAs and some [product FFA]/[precursor FFA] ratios, which represent
estimated desaturase and elongase activities. The opposite metabolic
responses of JKSQ in adrenal insufficiency rats and normal rats highlighted
the “<i>Bian Zheng Lun Zhi</i>” (treatment
based on ZHENG differentiation) guideline of TCM and suggested that
altered fatty acid metabolism was associated with adrenal insufficiency
after glucocorticoid withdrawal and the protective effects of JKSQ
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner
Transcriptomic and Metabonomic Profiling Reveal Synergistic Effects of Quercetin and Resveratrol Supplementation in High Fat Diet Fed Mice
Dietary quercetin and resveratrol have been frequently
used in treating various diseases, but the underlying mechanisms are
not entirely clear. Here, we report combined transcriptomic and metabonomic
profiling that showed that the combined supplementation with quercetin
and resveratrol produced synergistic effects on a high-fat diet-induced
metabolic phenotype in mice. Histological and phenotypic improvements
in serum and hepatic total cholesterol, insulin, fasting blood glucose,
and HbA1c were also observed in mice receiving combined quercetin
and resveratrol supplementation. This combined quercetin and resveratrol
supplementation resulted in significant restoration of gene sets in
functional pathways of glucose/lipid metabolism, liver function, cardiovascular
system, and inflammation/immunity, which were altered by high fat
diet feeding. The integration of transcriptomic and metabonomic data
indicated quercetin and resveratrol supplementation enhanced processes
of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis.
These alterations discovered at both the transcriptional and metabolic
levels highlight the significance of combined “omics”
platforms for elucidating mechanistic pathways altered by dietary
polyphenols, such as quercetin and resveratrol, in a synergistic manner
Distinct Urinary Metabolic Profile of Human Colorectal Cancer
A full spectrum of metabolic aberrations that are directly
linked
to colorectal cancer (CRC) at early curable stages is critical for
developing and deploying molecular diagnostic and therapeutic approaches
that will significantly improve patient survival. We have recently
reported a urinary metabonomic profiling study on CRC subjects (<i>n</i> = 60) and health controls (<i>n</i> = 63), in
which a panel of urinary metabolite markers was identified. Here,
we report a second urinary metabonomic study on a larger cohort of
CRC (<i>n</i> = 101) and healthy subjects (<i>n</i> = 103), using gas chromatography time-of-flight mass spectrometry
and ultra performance liquid chromatography quadrupole time-of-flight
mass spectrometry. Consistent with our previous findings, we observed
a number of dysregulated metabolic pathways, such as glycolysis, TCA
cycle, urea cycle, pyrimidine metabolism, tryptophan metabolism, polyamine
metabolism, as well as gut microbial–host co-metabolism in
CRC subjects. Our findings confirm distinct urinary metabolic footprints
of CRC patients characterized by altered levels of metabolites derived
from gut microbial–host co-metabolism. A panel of metabolite
markers composed of citrate, hippurate, <i>p</i>-cresol,
2-aminobutyrate, myristate, putrescine, and kynurenate was selected,
which was able to discriminate CRC subjects from their healthy counterparts.
A receiver operating characteristic curve (ROC) analysis of these
markers resulted in an area under the receiver operating characteristic
curve (AUC) of 0.993 and 0.998 for the training set and the testing
set, respectively. These potential metabolite markers provide a novel
and promising molecular diagnostic approach for the early detection
of CRC
Metabonomics Identifies Serum Metabolite Markers of Colorectal Cancer
Recent studies suggest that biofluid-based
metabonomics may identify
metabolite markers promising for colorectal cancer (CRC) diagnosis.
We report here a follow-up replication study, after a previous CRC
metabonomics study, aiming to identify a distinct serum metabolic
signature of CRC with diagnostic potential. Serum metabolites from
newly diagnosed CRC patients (<i>N</i> = 101) and healthy
subjects (<i>N</i> = 102) were profiled using gas chromatography
time-of-flight mass spectrometry (GC–TOFMS) and ultraperformance
liquid chromatography quadrupole time-of-flight mass spectrometry
(UPLC–QTOFMS). Differential metabolites were identified with
statistical tests of orthogonal partial least-squares-discriminant
analysis (VIP > 1) and the Mann–Whitney <i>U</i> test
(<i>p</i> < 0.05). With a total of 249 annotated serum
metabolites, we were able to differentiate CRC patients from the healthy
controls using an orthogonal partial least-squares-discriminant analysis
(OPLS-DA) in a learning sample set of 62 CRC patients and 62 matched
healthy controls. This established model was able to correctly assign
the rest of the samples to the CRC or control groups in a validation
set of 39 CRC patients and 40 healthy controls. Consistent with our
findings from the previous study, we observed a distinct metabolic
signature in CRC patients including tricarboxylic acid (TCA) cycle,
urea cycle, glutamine, fatty acids, and gut flora metabolism. Our
results demonstrated that a panel of serum metabolite markers is of
great potential as a noninvasive diagnostic method for the detection
of CRC