A5089596123- Silymarin and Mushroom Poisoning
- Microbial Natural Products and Biosynthesis
- Drug-Induced Hepatotoxicity and Protection
- Berberine and alkaloids research
- Fungal Biology and Applications
- Synthesis and bioactivity of alkaloids
- Selenium in Biological Systems
- Pharmacogenetics and Drug Metabolism
- Heavy Metals in Plants
- Drug Transport and Resistance Mechanisms
- Metalloenzymes and iron-sulfur proteins
- Plant Toxicity and Pharmacological Properties
- Chemical synthesis and alkaloids
- Tea Polyphenols and Effects
- Herbal Medicine Research Studies
- Traditional and Medicinal Uses of Annonaceae
- Essential Oils and Antimicrobial Activity
- Natural product bioactivities and synthesis
- Alkaloids: synthesis and pharmacology
- Ginseng Biological Effects and Applications
- Hepatitis C virus research
- Metabolomics and Mass Spectrometry Studies
- Bioactive Compounds and Antitumor Agents
- Oral and gingival health research
- Phytochemicals and Antioxidant Activities
University of North Carolina at Greensboro
2015-2024
Rensselaer Polytechnic Institute
2016-2018
Greensboro College
2017
Washington State University Spokane
2014-2015
RTI International
2003-2014
University of North Carolina at Chapel Hill
2013
Research Triangle Park Foundation
2003-2008
North Carolina State University
2007
Bristol-Myers Squibb (United States)
2007
North Carolina Central University
2007
Silymarin, also known as milk thistle extract, inhibits hepatitis C virus (HCV) infection and displays antioxidant, anti-inflammatory, immunomodulatory actions that contribute to its hepatoprotective effects. In the current study, we evaluated of seven major flavonolignans one flavonoid comprise silymarin. Activities tested included inhibition of: HCV cell culture infection, NS5B polymerase activity, TNF-α-induced NF-κB transcription, virus-induced oxidative stress, T-cell proliferation. All...
Complete separation, isolation, and structural characterization of four diastereoisomeric flavonolignans, silybins A (1) B (2), isosilybins (3) (4) from the seeds milk thistle (Silybum marianum) were achieved for first time using a preparative reversed-phase HPLC method. In addition, three other silychristin (5) isosilychristin (6) silydianin (7), flavonoid, taxifolin (8) isolated. Structures, including absolute stereochemistries 1-4, confirmed 2D NMR CD spectroscopy.
Silymarin, an extract from milk thistle (Silybum marianum), and its purified flavonolignans have been recently shown to inhibit hepatitis C virus (HCV) infection, both in vitro vivo. In the current study, we further characterized silymarin's antiviral actions. Silymarin had effects against cell culture (HCVcc) infection that included inhibition of entry, RNA protein expression, infectious production. did not block HCVcc binding cells but inhibited entry several viral pseudoparticles (pp),...
Abstract Extracts from the seeds of milk thistle, Silybum marianum, are known commonly as silibinin and silymarin possess anticancer actions on human prostate carcinoma in vitro vivo. Seven distinct flavonolignan compounds a flavonoid have been isolated commercial extracts. Most notably, two pairs diastereomers, silybin A B isosilybin B, among these compounds. In contrast, is composed only 1:1 mixture B. With isomers now quantities sufficient for biological studies, each pure compound was...
It is often argued that the efficacy of herbal medicines a result combined action multiple constituents work synergistically or additively. Determining bioactive in these mixtures poses significant challenge. We have developed an approach to address this challenge, synergy-directed fractionation, which combines comprehensive mass spectrometry profiling with synergy assays and natural products isolation. The applicability fractionation was demonstrated using botanical medicine goldenseal...
Abstract The safety and efficacy of kratom (Mitragyna speciosa ) for treatment pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two these, mitragynine 7-hydroxymitragynine. Here, we profiled 53 commercial products using untargeted LC–MS metabolomics, revealing distinct chemotypes that contain different levels the alkaloid speciofoline. Both were confirmed with DNA barcoding to be M. speciosa. To evaluate...
Two separate commercial products of kratom [Mitragyna speciosa (Korth.) Havil. Rubiaceae] were used to generate reference standards its indole and oxindole alkaloids. While has been studied for over a century, the characterization data in literature many alkaloids are either incomplete or inconsistent with modern standards. As such, full 1H 13C NMR spectra, along HRESIMS ECD data, reported 1–19. Of these, four new (7, 11, 17, 18) characterized using 2D absolute configurations 7, 18...
Silybin A (1), silybin B (2), and isosilybin (3), three of the seven flavonolignans that constitute silymarin, an extract fruits milk thistle (Silybum marianum), were detected for first time from a fungal endophyte, Aspergillus iizukae, isolated surface-sterilized leaves S. marianum. The identified using UPLC-PDA-HRMS-MS/MS method by matching retention times, HRMS, MS/MS data with authentic reference compounds. Attenuation flavonolignan production was observed following successive...
This study demonstrates how regio- and diastereo-isomers with near-identical NMR spectra can be distinguished unambiguously assigned using quantum mechanical driven 1H iterative Full Spin Analysis (HiFSA). The method is illustrated four natural products, the flavonolignans silybin A, B, isosilybin which exhibit extremely similar coupling patterns chemical shift differences well below commonly reported level of accuracy 0.01 ppm. HiFSA approach generated highly reproducible fingerprints that...
As part of our ongoing investigation filamentous fungi for anticancer leads, an active fungal extract was identified from the Mycosynthetix library (MSX 63935; related to Phoma sp.). The initial exhibited cytotoxic activity against H460 (human non-small cell lung carcinoma) and SF268 astrocytoma) lines selected further study. Bioactivity-directed fractionation yielded resorcylic acid lactones (RALs) 1 (a new natural product) 3 compound) known RALs zeaenol (2), (5E)-7-oxozeaenol (4),...
Sulfite oxidase catalyzes the terminal reaction in degradation of sulfur amino acids. Genetic deficiency sulfite results neurological abnormalities and often leads to death at an early age. The mutation gene responsible for a 5-year-old girl was identified by sequence analysis cDNA obtained from fibroblast mRNA be guanine adenine transition nucleotide 479 resulting acid substitution Arg-160 Gln. Recombinant protein containing R160Q expressed Escherichia coli , purified, characterized. mutant...
Bioactivity-directed fractionation of extracts two Diospyros maritima bark samples from Indonesia, one collected at sea level in a beach forest Java and the other slight elevation away shore on island Lombok, yielded diverse set secondary metabolites. The naphthoquinone plumbagin (1), although found both specimens, constituted much larger percentage former sample, which also series dimers, maritinone (2), chitranone (3), zeylanone (4). latter sample new derivative, (4S)-shinanolone (5),...
Silymarin prevents liver disease in many experimental rodent models, and is the most popular botanical medicine consumed by patients with hepatitis C. Silibinin a major component of silymarin, consisting flavonolignans silybin A B, which are insoluble aqueous solution. chemically modified soluble version silibinin, SIL, has been shown to potently reduce C virus (HCV) RNA levels vivo when administered intravenously. silibinin inhibit HCV infection cell culture targeting multiple steps...
Abstract Sixteen polyketides belonging to diverse structural classes, including monomeric/dimeric tetrahydroxanthones and resorcylic acid lactones, were isolated from an organic extract of a fungal culture Setophoma terrestris (MSX45109) by bioactivity‐directed fractionation as part search for anticancer leads filamentous fungi. Of these, six new: penicillixanthone B ( 5 ), blennolide H 6 11‐deoxyblennolide D 7 I 9 J 10 pyrenomycin 16 ). The known compounds were: secalonic A 1 E 2 G 3 4...
Echinacea preparations, which are used for the prevention and treatment of upper respiratory infections, account 10% dietary supplement market in U.S., with sales totaling more than $100 million annually. In an attempt to shed light on Echinacea's mechanism action, we evaluated effects a 75% ethanolic root extract purpurea, prepared accord industry methods, cytokine chemokine production from RAW 264.7 macrophage-like cells. We found that displayed dual activities; could itself stimulate...
Bacterial efflux pumps are active transport proteins responsible for resistance to selected biocides and antibiotics. It has been shown that production of is up-regulated in a number highly pathogenic bacteria, including methicillin resistant Staphylococcus aureus. Thus, the identification new bacterial pump inhibitors topic great interest. Existing assays evaluate inhibitory activity rely on fluorescence by an substrate. When employing these plant extracts some purified compounds, we...
A challenge that must be addressed when conducting studies with complex natural products is how to evaluate their complexity and variability. Traditional methods of quantifying a single or small range metabolites may not capture the full chemical multiple samples. Different metabolomics approaches were evaluated discern they facilitated comparison composition commercial green tea [Camellia sinensis (L.) Kuntze] products, goal capturing variability commercially used selecting representative...
Sulfite oxidase deficiency is a lethal genetic disease that results from defects either in the genes encoding proteins involved molybdenum cofactor biosynthesis or sulfite gene itself. Several point mutations have been identified patients suffering this worldwide. Although detailed biochemical analyses carried out on these mutations, no structural data could be obtained because of problems crystallizing recombinant human and rat oxidases failure to clone chicken gene. We synthesized for de...
Extracts of milk thistle (Silybum marianum, Asteraceae), termed "silymarin," are used worldwide, primarily for hepatoprotective applications and recently prostate cancer chemoprevention. Silymarin is a mixture at least eight compounds, four major constituents group structurally related flavonolignans: silybin A, B, isosilybin B. The initiation in vivo studies to compare the respective preclinical activities each compound required that gram quantities these diastereoisomers be prepared....
Bioactivity-guided fractionation of the stem bark Mitrephora glabra yielded nine compounds, comprising three ent-kaurenoids (1−3), five polyacetylenic acids/esters (4−8), and one aporphine alkaloid, liriodenine (9). The structures six new compounds (1−3, 5, 7, 8) were determined by spectroscopic data interpretation. All evaluated for their inhibitory activities against a panel cancer cell lines battery microorganisms.
Three bioactive compounds were isolated from an organic extract of ascomycete fungus the order Chaetothyriales (MSX 47445) using bioactivity-directed fractionation as part a search for anticancer leads filamentous fungi. Of these, two benzoquinones [betulinan A (1) and betulinan C (3)], third was terphenyl compound, BTH-II0204-207:A (2). The structures elucidated set spectroscopic spectrometric techniques; structure new compound (3) confirmed via single-crystal X-ray diffraction. Compounds...