7 research outputs found
Hydroxylated Bisabolol Oxides: Evidence for Secondary Oxidative Metabolism in <i>Matricaria chamomilla</i>
German chamomile (<i>Matricaria
chamomilla</i>) is one
of the most popular medicinal plants used in Western herbal medicine.
Among the various phytochemicals present in the essential oil of the
flowers of German chamomile, bisabolol and its oxidized metabolites
are considered as marker compounds for distinguishing different chemotypes.
These compounds are influential in mediating the aroma of the essential
oil of <i>M. chamomilla</i> and contribute to the therapeutic
properties (anti-inflammatory, antibacterial, insecticidal, and antiulcer)
of this species. In order to find other possible bisabolol derivatives
as marker compounds for authentication of German chamomile in botanical
and commercial products, an in-depth investigation using a GC-assisted
fractionation procedure was performed on nonpolar fractions. As a
result of this approach, three new hydroxylated derivatives of bisabolol
oxides A and B (<b>1</b>â<b>3</b>) have been isolated
from <i>M. chamomilla</i>. Plausible biogenetic pathways
are presented
Inhibition of CYP3A4 and CYP1A2 by <i>Aegle marmelos</i> and its constituents
<p>1.â<i>Aegle marmelos</i> (bael) is a popular tree in India and other Southeast Asian countries. The fruit is usually consumed as dried, fresh or juice, and is reported to have a high nutritional value and many perceived health benefits. Despite its edible nature and therapeutic properties, no studies are reported regarding its effects on major drug metabolizing enzymes.</p> <p>2.âThis study was aimed to evaluate the inhibitory potential of methanolic extract of <i>A. marmelos</i> fruit and its constituents (three furanocoumarins, namely marmelosin, marmesinin and 8-hydroxypsoralen, and 1 alkaloid, aegeline) towards major Cytochrome P450 enzymes (CYP3A4, 2D6, 1A2, 2C9 and 2C19) using human liver microsomes and recombinant CYPs.</p> <p>3.âThe methanolic extract and marmelosin was found to be competitive and time-dependant inhibitor of CYP3A4. While reversible and non-competitive inhibition was observed for CYP1A2. Time-dependent inhibition of CYP3A4 was not affected by the addition of reduced glutathione. Marmesinin showed moderate inhibition of CYP3A4 and 1A2, while aegeline was a very weak inhibitor of CYP3A4 and showed no inhibition for CYP1A2 isoform. No significant inhibition of recombinant CYP2D6, 2C9, and 2C19 was seen with the extract or its constituents.</p> <p>4.âThis is the first report of CYP3A4 and CYP1A2 inhibition by <i>A. marmelos</i> extract and one of its furanocoumarins, marmelosin. Further studies are warranted to determine if acute or prolonged use of bael fruit could affect the pharmacokinetics of drugs that are substrates of CYP3A4 or CYP1A2.</p
Quality Evaluation of Terpinen-4-ol-Type Australian Tea Tree Oils and Commercial Products: An Integrated Approach Using Conventional and Chiral GC/MS Combined with Chemometrics
GC/MS,
chiral GC/MS, and chemometric techniques were used to evaluate
a large set (<i>n</i> = 104) of tea tree oils (TTO) and
commercial products purported to contain TTO. Twenty terpenoids were
determined in each sample and compared with the standards specified
by ISO-4730-2004. Several of the oil samples that were ISO compliant
when distilled did not meet the ISO standards in this study primarily
due to the presence of excessive <i>p</i>-cymene and/or
depletion of terpinenes. Forty-nine percent of the commercial products
did not meet the ISO specifications. Four terpenes, viz., α-pinene,
limonene, terpinen-4-ol, and α-terpineol, present in TTOs with
the (+)-isomer predominant were measured by chiral GC/MS. The results
clearly indicated that 28 commercial products contained excessive
(+)-isomer or contained the (+)-isomer in concentrations below the
norm. Of the 28 outliers, 7 met the ISO standards. There was a substantial
subset of commercial products that met ISO standards but displayed
unusual enantiomeric +/â ratios. A class predictive model based
on the oils that met ISO standards was constructed. The outliers identified
by the class predictive model coincided with the samples that displayed
an abnormal chiral ratio. Thus, chiral and chemometric analyses could
be used to confirm the identification of abnormal commercial products
including those that met all of the ISO standards
Streptomyces distallicus, a Potential Microbial Biolarvicide
Infected mosquitos from the genus Aedes have become
one of the worldâs most influential contributors to human morbidity
and death. To explore new biopesticides with activity against Aedes aegypti, Streptomyces distallicus, a species related to the subspecies group of Streptomyces
netropsis, was investigated. Six metabolites, aureothin,
allo-aureothin, deoxyaureothin, 4âČ,7-dihydroxy isoflavone,
2-methyl-5-(3-indolyl)oxazole, and 2-ethyl-5-(3-indolyl)oxazole were
isolated, and chemical structures, were elucidated based on one- and
two-dimensional NMR spectroscopy analyses and HRMS. The A. aegypti larvicidal activity of these compounds
was evaluated. Only two isomeric compounds, aureothin and allo-aureothin,
showed larvicidal activity against A. aegypti with LC50 values of 1.5 and 3.1 ppm for 24 h post-treatment,
respectively, and 3.8 and 7.4 ppm for 48 h post-treatment, respectively.
The crude extract of S. distallicus also demonstrated potent larvicidal activity with LC50 values of 1.46 and 1.2 ppm for 24 and 48 h post-treatment, respectively.
Deoxyaureothin, a furan ring reduced form of aureothin, showed no
activity against A. aegypti. The hybrid
imported fire ants activity of aureothin was also evaluated, but it
did not show any activity at the highest dose of 62.5 ÎŒg/g.
Described here is the first report on a bioassay-directed investigation
of the secondary metabolites of S. distallicus and biological evaluation of isolated compounds aureothin and its
isomer and intermediates as potential microbial larvicides. S. distallicus and crude extracts thereof are a promising
source of potential microbial biolarvicides
Proteoform-Specific Protein Binding of Small Molecules in Complex Matrices
Characterizing the specific binding
between protein targets and small molecules is critically important
for drug discovery. Conventional assays require isolation and purification
of small molecules from complex matrices through multistep chromatographic
fractionation, which may alter their original bioactivity. Most proteins
undergo posttranslational modification, and only certain proteoforms
have the right conformation with accessible domains and available
residues for small molecule binding. We developed a top-down mass
spectrometry (MS) centric workflow for rapid evaluation of the bioactivity
of crude botanical extracts after a one-step reaction. Our assay distinguished
covalent from noncovalent binding and mapped the residue for covalent
binding between bioactive constituents and specific proteoforms of
the target protein. We augmented our approach with a nanoflow liquid
chromatography-selected reaction monitoring (SRM)-MS assay for simultaneous
identification and label-free multiplex quantitation of small molecules
in the crude botanical extracts. Our assay was validated for various
proteoforms of human serum albumin, which plays a key role in pharmacokinetics
of small molecules <i>in vivo</i>. We demonstrated the utility
of our proteoform-specific assay for evaluating thymoquinone in crude
botanical extracts, studying its pharmacokinetics in human blood,
and interpreting its toxicity to human breast cancer cells in tissue
culture
Octulosonic Acid Derivatives from Roman Chamomile (<i>Chamaemelum nobile</i>) with Activities against Inflammation and Metabolic Disorder
Six new octulosonic acid derivatives
(<b>1</b>â<b>6</b>) were isolated from the flower
heads of Roman chamomile
(<i>Chamaemelum nobile</i>). Their structures were elucidated
by means of spectroscopic interpretation. The biological activity
of the isolated compounds was evaluated toward multiple targets related
to inflammation and metabolic disorder such as NAG-1, NF-ÎșB,
iNOS, ROS, PPARα, PPARγ, and LXR. Similar to the action
of NSAIDs, all the six compounds (<b>1</b>â<b>6</b>) increased NAG-1 activity 2â3-fold. They also decreased cellular
oxidative stress by inhibiting ROS generation. Compounds <b>3</b>, <b>5</b>, and <b>6</b> activated PPARÎł 1.6â2.1-fold,
while PPARα was activated 1.4-fold by compounds <b>5</b> and <b>6</b> only. None of the compounds showed significant
activity against iNOS or NF-ÎșB. This is the first report of
biological activity of octulosonic acid derivatives toward multiple
pathways related to inflammation and metabolic disorder. The reported
anti-inflammatory, hypoglycemic, antiedemic, and antioxidant activities
of Roman chamomile could be partly explained as due to the presence
of these constituents
Flavones isolated from <i>Pseudognaphalium liebmannii</i> with tracheal smooth muscle relaxant properties
The inflorescences of Pseudognaphalium liebmannii are used as folk medicine to treat various respiratory diseases. In this work, we report the isolation of seven known flavones: 5-hydroxy-3,7-dimethoxyflavone 1, 5,8-dihydroxy-3,7-dimethoxyflavone 2, 5,7-dihydroxy-3,8-dimethoxyflavone 3 (gnaphaliin A), 3,5-dihydroxy-7,8-dimethoxyflavone 4 (gnaphaliin B), 3,5-dihydroxy-6,7,8-trimethoxyflavone 5, 3,5,7-trimethoxyflavone 6 and 3-O-methylquercetin 7. All these flavones except 1 and 6 showed a relaxant effect on guinea pig tracheal preparation with EC50 between 69.91â±â15.32 and 118.72â±â7.06â”M. Aminophylline (EC50â=â122.03â±â7.05â”M) was used as a relaxant reference drug. The active flavones shifted the concentration-response curves of forskolin and nitroprusside leftward, and significantly reduced the EC50 values of these drugs. Furthermore, these flavones dose-dependently inhibited phosphodiesterase (PDE) in an in vitro assay. This reveals that the inflorescences of P. liebmannii contain several flavones with relaxant effect on airway smooth muscle and with PDEs inhibition that contribute to supporting the anti-asthmatic traditional use.</p