Differential remodeling in small and large murine airways revealed by novel whole lung airway analysis.

Airway remodeling occurs in chronic asthma leading to increased airway smooth muscle (ASM) mass and extracellular matrix (ECM) deposition. Although extensively studied in murine airways, studies report only selected larger airways at one time-point meaning the spatial distribution and resolution of remodeling are poorly understood. Here we use a new method allowing comprehensive assessment of the spatial and temporal changes in ASM, ECM, and epithelium in large numbers of murine airways after allergen challenge. Using image processing to analyze 20-50 airways per mouse from a whole lung section revealed increases in ASM and ECM after allergen challenge were greater in small and large rather than intermediate airways. ASM predominantly accumulated adjacent to the basement membrane, whereas ECM was distributed across the airway wall. Epithelial hyperplasia was most marked in small and intermediate airways. After challenge, ASM changes resolved over 7 days, whereas ECM and epithelial changes persisted. The new method suggests large and small airways remodel differently, and the long-term consequences of airway inflammation may depend more on ECM and epithelial changes than ASM. The improved quantity and quality of unbiased data provided by the method reveals important spatial differences in remodeling and could set new analysis standards for murine asthma models.

Oxidised IL-33 drives COPD epithelial pathogenesis via ST2-independent RAGE/EGFR signalling complex.

BACKGROUND: Epithelial damage, repair and remodelling are critical features of chronic airway diseases including chronic obstructive pulmonary disease (COPD). Interleukin (IL)-33 released from damaged airway epithelia causes inflammation via its receptor, serum stimulation-2 (ST2). Oxidation of IL-33 to a non-ST2-binding form (IL-33ox) is thought to limit its activity. We investigated whether IL-33ox has functional activities that are independent of ST2 in the airway epithelium. METHODS: In vitro epithelial damage assays and three-dimensional, air-liquid interface (ALI) cell culture models of healthy and COPD epithelia were used to elucidate the functional role of IL-33ox. Transcriptomic changes occurring in healthy ALI cultures treated with IL-33ox and COPD ALI cultures treated with an IL-33-neutralising antibody were assessed with bulk and single-cell RNA sequencing analysis. RESULTS: We demonstrate that IL-33ox forms a complex with receptor for advanced glycation end products (RAGE) and epidermal growth factor receptor (EGFR) expressed on airway epithelium. Activation of this alternative, ST2-independent pathway impaired epithelial wound closure and induced airway epithelial remodelling in vitro. IL-33ox increased the proportion of mucus-producing cells and reduced epithelial defence functions, mimicking pathogenic traits of COPD. Neutralisation of the IL-33ox pathway reversed these deleterious traits in COPD epithelia. Gene signatures defining the pathogenic effects of IL-33ox were enriched in airway epithelia from patients with severe COPD. CONCLUSIONS: Our study reveals for the first time that IL-33, RAGE and EGFR act together in an ST2-independent pathway in the airway epithelium and govern abnormal epithelial remodelling and muco-obstructive features in COPD.

The IL-33:ST2 axis is unlikely to play a central fibrogenic role in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating interstitial lung disease (ILD) with limited treatment options. Interleukin-33 (IL-33) is proposed to play a role in the development of IPF however the exclusive use of prophylactic dosing regimens means that the therapeutic benefit of targeting this cytokine in IPF is unclear. METHODS: IL-33 expression was assessed in ILD lung sections and human lung fibroblasts (HLFs) by immunohistochemistry and gene/protein expression and responses of HLFs to IL-33 stimulation measured by qPCR. In vivo, the fibrotic potential of IL-33:ST2 signalling was assessed using a murine model of bleomycin (BLM)-induced pulmonary fibrosis and therapeutic dosing with an ST2-Fc fusion protein. Lung and bronchoalveolar lavage fluid were collected for measurement of inflammatory and fibrotic endpoints. Human precision-cut lung slices (PCLS) were stimulated with transforming growth factor-ß (TGFß) or IL-33 and fibrotic readouts assessed. RESULTS: IL-33 was expressed by fibrotic fibroblasts in situ and was increased by TGFß treatment in vitro. IL-33 treatment of HLFs did not induce IL6, CXCL8, ACTA2 and COL1A1 mRNA expression with these cells found to lack the IL-33 receptor ST2. Similarly, IL-33 stimulation had no effect on ACTA2, COL1A1, FN1 and fibronectin expression by PCLS. Despite having effects on inflammation suggestive of target engagement, therapeutic dosing with the ST2-Fc fusion protein failed to reduce BLM-induced fibrosis measured by hydroxyproline content or Ashcroft score. CONCLUSIONS: Together these findings suggest the IL-33:ST2 axis does not play a central fibrogenic role in the lungs with therapeutic blockade of this pathway unlikely to surpass the current standard of care for IPF.

IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD.

BACKGROUND: Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. METHODS: The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. RESULTS: We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. CONCLUSIONS: Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.

Biomechanical and clinical correlates of swing-phase knee flexion in individuals with spastic cerebral palsy who walk with flexed-knee gait.

OBJECTIVE: To identify clinical and biomechanical parameters that influence swing-phase knee flexion and contribute to stiff-knee gait in individuals with spastic cerebral palsy (CP) and flexed-knee gait. DESIGN: Retrospective analysis of clinical data and gait kinematics collected from 2010 to 2013. SETTING: Motion and gait analysis laboratory at a children's hospital. PARTICIPANTS: Individuals with spastic CP (N=34; 20 boys, 14 girls; mean age ± SD, 10.1±4.1y [range, 5-20y]; Gross Motor Function Classification System I-III) who walked with flexed-knee gait ≥20° at initial contact and had no prior surgery were included; the more-involved limb was analyzed. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: The magnitude and timing of peak knee flexion (PKF) during swing were analyzed with respect to clinical data, including passive range of motion and Selective Control Assessment of the Lower Extremity, and biomechanical data, including joint kinematics and hamstring, rectus femoris, and gastrocnemius muscle-tendon length during gait. RESULTS: Data from participants demonstrated that achieving a higher magnitude of PKF during swing correlated with a higher maximum knee flexion velocity in swing (ρ=.582, P<0.001) and a longer maximum length of the rectus femoris (ρ=.491, P=.003). In contrast, attaining earlier timing of PKF during swing correlated with a higher knee flexion velocity at toe-off (ρ=-.576, P<.001), a longer maximum length of the gastrocnemius (ρ=-.355, P=.039), and a greater peak knee extension during single-limb support phase (ρ=-.354, P=.040). CONCLUSIONS: Results indicate that the magnitude and timing of PKF during swing were independent, and their biomechanical correlates differed, suggesting important treatment implications for both stiff-knee and flexed-knee gait.

Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.

Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 260-320 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections.

Structure-activity analysis of flavonoids: direct and indirect antioxidant, and antiinflammatory potencies and toxicities.

Flavonoids are secondary plant products that are well represented in healthy diets because of ingestion of fruit, vegetables, herbs, and teas. Increased consumption is correlated with decreased risks of cardiovascular disease, cancer, and other chronic diseases. Certain flavonoids confer direct antioxidant protection to cells, others induce enzymes that protect cells against oxidative and other insults ("indirect antioxidants"), and others appear to be protective by both mechanisms. Hydroxylated flavones manifest substantial direct antioxidant activity but do not effectively induce cytoprotective enzymes. Methoxylated flavones that potently induce cytoprotective enzymes were evaluated to elucidate the structural prerequisites for effective chemoprotective agents: protecting healthy cells with minimal collateral toxicity. Flavones and flavanones methoxylated at the 5-position of the A-ring were among the most potent inducers of the cytoprotective NAD(P)H:quinone-oxidoreductase 1 (NQO1) in 3 different cell lines. Other flavones were equally potent inducers, but more toxic. Flavanones contain no Michael reaction center, yet some are potent inducers of NQO1, have low cytotoxicity, and inhibit LPS-stimulated iNOS activity, which suggests a redox mechanism of action rather than the Keap1/Nrf2/ARE mechanism by which so many of the classic inducers operate. Evaluation in vivo will reveal whether differential protective advantages support their possible evaluation in a cancer prevention setting.

Electrophilic tuning of the chemoprotective natural product sulforaphane.

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)butane], a naturally occurring isothiocyanate derived from cruciferous vegetables, is a highly potent inducer of phase 2 cytoprotective enzymes and can protect against electrophiles including carcinogens, oxidative stress, and inflammation. The mechanism of action of sulforaphane is believed to involve modifications of critical cysteine residues of Keap1, which lead to stabilization of Nrf2 to activate the antioxidant response element of phase 2 enzymes. However, the dithiocarbamate functional group formed by a reversible reaction between isothiocyanate of sulforaphane and sulfhydryl nucleophiles of Keap1 is kinetically labile, and such modification in intact cells has not yet been demonstrated. Here we designed sulforaphane analogs with replacement of the reactive isothiocyanate by the more gentle electrophilic sulfoxythiocarbamate group that also selectively targets cysteine residues in proteins but forms stable thiocarbamate adducts. Twenty-four sulfoxythiocarbamate analogs were synthesized that retain the structural features important for high potency in sulforaphane analogs: the sulfoxide or keto group and its appropriate distance to electrophilic functional group. Evaluation in various cell lines including hepatoma cells, retinal pigment epithelial cells, and keratinocytes as well as in mouse skin shows that these analogs maintain high potency and efficacy for phase 2 enzyme induction as well as the inhibitory effect on lipopolysaccharide-induced nitric oxide formation like sulforaphane. We further show in living cells that a sulfoxythiocarbamate analog can label Keap1 on several key cysteine residues as well as other cellular proteins offering new insights into the mechanism of chemoprotection.

Biomarker Exploration in Human Peripheral Blood Mononuclear Cells for Monitoring Sulforaphane Treatment Responses in Autism Spectrum Disorder.

Autism Spectrum Disorder (ASD) is one of the most common neurodevelopmental disorders with no drugs treating the core symptoms and no validated biomarkers for clinical use. The multi-functional phytochemical sulforaphane affects many of the biochemical abnormalities associated with ASD. We investigated potential molecular markers from three ASD-associated physiological pathways that can be affected by sulforaphane: redox metabolism/oxidative stress; heat shock response; and immune dysregulation/inflammation, in peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with ASD. We first analyzed the mRNA levels of selected molecular markers in response to sulforaphane ex vivo treatment in PBMCs from healthy donors by real-time quantitative PCR. All of the tested markers showed quantifiability, accuracy and reproducibility. We then compared the expression levels of those markers in PBMCs taken from ASD patients in response to orally-delivered sulforaphane. The mRNA levels of cytoprotective enzymes (NQO1, HO-1, AKR1C1), and heat shock proteins (HSP27 and HSP70), increased. Conversely, mRNA levels of pro-inflammatory markers (IL-6, IL-1ß, COX-2 and TNF-α) decreased. Individually none is sufficiently specific or sensitive, but when grouped by function as two panels, these biomarkers show promise for monitoring pharmacodynamic responses to sulforaphane in both healthy and autistic humans, and providing guidance for biomedical interventions.

Induction of chemoprotective phase 2 enzymes by ginseng and its components.

Phase 2 detoxification enzymes protect against carcinogenesis and oxidative stress. Ginseng ( PANAX spp.) extracts and components were assayed for inducer activity of NQO1 (quinone reductase), a phase 2 enzyme, in Hepa1c1c7 cells. Ginseng extracts were analyzed for ginsenosides and panaxytriol. Korean red PANAX GINSENG extracts demonstrated the most potent phase 2 enzyme induction activity (76,900 U/g dried rhizome powder and 27,800 U/g for two similar preparations). The ginsenoside-enriched HT-1001 American ginseng ( PANAX QUINQUEFOLIUS) extract was the next most potent inducer, with activity of 15,900 U/g, followed by raw American ginseng root with activity of 8700 U/g. Neither a polysaccharide-enriched extract of American ginseng nor a commercial white PANAX GINSENG preparation showed any inducer activity. Pure ginsenosides showed no inducer activity. Protopanaxadiol and protopanaxatriol, deglycosylated ginsenoside metabolic derivatives, showed potent induction activity (approximately 500,000 U/g each). Synthetic panaxytriol was over 10-fold more potent (induction potency 5,760,000 U/g). There was no correlation between ginsenoside content and phase 2 enzyme induction. The most potent inducing red ginseng extract also had the highest panaxytriol content, 120.8 microg/g. We found that ginseng induced NQO1 and that polyacetylenes are the most active components.

Anxiety sensitivity and posttrauma stress symptoms in female undergraduates following a campus shooting.

Participants were recruited from female undergraduate students participating in an ongoing longitudinal study at the time of a campus shooting. Eighty-five percent (N = 691) of the 812 students who were invited to participate in the current study completed questionnaires an average of 27 days following a campus shooting. In a mixed cross-sectional and longitudinal design, the cognitive and the physical concerns dimensions of postshooting anxiety sensitivity accounted for unique variance in posttrauma stress symptom severity (cross-sectional), after controlling for preshooting psychological symptoms (longitudinal). The cognitive concerns dimension showed the strongest relationship. Anxiety sensitivity also appeared to moderate the relationships of hyperarousal symptoms with reexperiencing and numbing symptoms.

Discovery and development of clofarabine: a nucleoside analogue for treating cancer.

The treatment of acute leukaemias, which are the most common paediatric cancers, has improved considerably in recent decades, with complete response rates approaching approximately 90% in some cases. However, there remains a major need for treatments for patients who do not achieve or maintain complete remission, for whom the prognosis is very poor. In this article, we describe the challenges involved in the discovery and development of clofarabine, a second-generation nucleoside analogue that received accelerated approval from the US FDA at the end of 2004 for the treatment of paediatric patients 1-21 years old with relapsed or refractory acute lymphoblastic leukaemia after at least two prior regimens. It is the first such drug to be approved for paediatric leukaemia in more than a decade, and the first to receive approval for paediatric use before adult use.

Sarcopenia--mechanisms and treatments.

BACKGROUND: Sarcopenia is a consequence of aging. This atrophic event is responsible for decrease in strength and associated functional deficits seen in the aging adult. PURPOSE: This paper reviews: (1) the mechanisms contributing to sarcopenia, (2) the impact of age-related changes in muscle composition on 3 processes integral to muscle function, (3) the efficacy of pharmaceuticals and over-the-counter nutritional supplements in the management of sarcopenia, (4) experimental use of pharmaceutical regulation of myostatin to increase muscle mass and strength in animal models, and (5) efficacy of resistance training as a means of maintaining or recovering muscle mass and strength. METHODS: PubMed was searched for relevant research articles using the following descriptors: sarcopenia, aging, muscle mass, muscle performance, muscle strength, myostatin, testosterone, growth hormone, dehydroepiandrosterone, hormone replacement, nutrition, resistance training, and endurance training. RESULTS: Sarcopenia is mediated by multiple mechanisms, including alpha-motor neuron death, altered hormone concentrations, increased inflammation, and altered nutritional status. Age-related changes within muscle likely affect processes integral to muscle function. These changes negatively influence muscle performance directly or by contributing to sarcopenia. Pharmaceutical or supplement interventions to treat sarcopenia have not proved encouraging to date, either lacking or providing limited efficacy, along with the potential for negative health consequences. In contrast, resistance training has proven safe and highly effective for increasing muscle mass and strength in aging adults. CONCLUSION: Sarcopenia is a multifactorial consequence of aging that will affect many adults. Resistance training is the most effective and safe intervention to attenuate or recover some of the loss of muscle mass and strength that accompanies aging.

Cultivar effect on Moringa oleifera glucosinolate content and taste: a pilot study.

Leaves of the tropical tree Moringa oleifera are widely promoted in areas of chronic malnutrition as nutritional supplements for weaning infants and nursing mothers. Adoption, in these circumstances may hinge upon taste, which can vary greatly amongst cultivars. It is widely assumed that this taste variation is primarily germplasm-dependent, and results from the breakdown of glucosinolates to isothiocyanates. Leaves of 30 accessions, grown at a single field plot, were sampled 3 times over the course of a year. Taste, assessed in a masked protocol, was not related to glucosinolate content of the leaves.

Bioavailability of Sulforaphane Following Ingestion of Glucoraphanin-Rich Broccoli Sprout and Seed Extracts with Active Myrosinase: A Pilot Study of the Effects of Proton Pump Inhibitor Administration.

We examined whether gastric acidity would affect the activity of myrosinase, co-delivered with glucoraphanin (GR), to convert GR to sulforaphane (SF). A broccoli seed and sprout extract (BSE) rich in GR and active myrosinase was delivered before and after participants began taking the anti-acid omeprazole, a potent proton pump inhibitor. Gastric acidity appears to attenuate GR bioavailability, as evidenced by more SF and its metabolites being excreted after participants started taking omeprazole. Enteric coating enhanced conversion of GR to SF, perhaps by sparing myrosinase from the acidity of the stomach. There were negligible effects of age, sex, ethnicity, BMI, vegetable consumption, and bowel movement frequency and quality. Greater body mass correlated with reduced conversion efficiency. Changes in the expression of 20 genes in peripheral blood mononuclear cells were evaluated as possible pharmacodynamic indicators. When grouped by their primary functions based on a priori knowledge, expression of genes associated with inflammation decreased non-significantly, and those genes associated with cytoprotection, detoxification and antioxidant functions increased significantly with bioavailability. Using principal components analysis, component loadings of the changes in gene expression confirmed these groupings in a sensitivity analysis.

A Strategy to Deliver Precise Oral Doses of the Glucosinolates or Isothiocyanates from Moringa oleifera Leaves for Use in Clinical Studies.

The tropical tree Moringa oleifera produces high yields of protein-rich leaf biomass, is widely used as a food source, contains an abundance of phytochemicals, and thus has great potential for chronic disease prevention and perhaps, treatment. We have developed and characterized standardized ways of preparing aqueous "teas" from moringa leaves to deliver precisely calibrated levels of phytochemicals for use in clinical trials. These phytochemicals, especially the glucosinolate glucomoringin and the isothiocyanate moringin, produced from it following hydrolysis by the enzyme myrosinase, provide potent anti-inflammatory and cytoprotective indirect antioxidant activity. The taste of both hot and cold teas is palatable without the need for flavor masking. These teas can be easily and reproducibly prepared in underserved tropical regions of the world where moringa is cultivated. Isothiocyanate yield from a cold extraction was rapid and essentially complete after 30 min and its anti-inflammatory potential is comparable to that of equimolar purified moringin. A preparation similar to this may be safe to consume with respect to its bacterial titer even after 48 h without refrigeration. Thus, facile delivery of moringa tea to both adults and children for clinical evaluation of their effects on such conditions as autism, diabetes, and hypertension, is now possible.

A dicyanotriterpenoid induces cytoprotective enzymes and reduces multiplicity of skin tumors in UV-irradiated mice.

Inducible phase 2 enzymes constitute a primary line of cellular defense. The oleanane dicyanotriterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-onitrile (TP-225) is a very potent inducer of these systems. Topical application of TP-225 to SKH-1 hairless mice increases the levels of NAD(P)H-quinone acceptor oxidoreductase 1 (NQO1) and heme oxygenase 1 (HO-1) and protects against UV radiation-induced dermal thickening. Daily topical treatments of 10 nmol of TP-225 to the backs of mice that were previously subjected to low-level chronic UVB radiation (30 mJ/cm(2)/session, twice a week for 17 weeks), led to 50% reduction in multiplicity of skin tumors. In addition, the total tumor burden of squamous cell carcinomas was reduced by 5.5-fold. The identification of new agents for protection against UV radiation-induced skin cancer and understanding of their mechanism(s) of action is especially important in view of the fact that human skin cancers represent a significant source of increasing morbidity and mortality.

(3R, 9R, 10R)-Panaxytriol: A molecular-based nutraceutical with possible application to cancer prevention and treatment.

Panaxytriol is a nutraceutical-based active constituent of Korean red ginseng and is reported to exhibit potent anti-tumor properties. Its activity may be in part due to its induction of phase 2 chemoprotective enzymes. Its unique properties may have important implications in cancer therapeutics.

Novel semisynthetic analogues of betulinic acid with diverse cytoprotective, antiproliferative, and proapoptotic activities.

Betulinic acid (BA), a pentacyclic triterpene isolated from birch bark and other plants, selectively inhibits the growth of human cancer cell lines. However, the poor potency of BA hinders its clinical development, despite a lack of toxicity in animal studies even at high concentrations. Here, we describe six BA derivatives that are markedly more potent than BA for inhibiting inducible nitric oxide synthase, activating phase 2 cytoprotective enzymes, and inducing apoptosis in cancer cells and in Bax/Bak(-/-) fibroblasts, which lack two key proteins involved in the intrinsic, mitochondrial-dependent apoptotic pathway. Notably, adding a cyano-enone functionality in the A ring of BA enhanced its cytoprotective properties, but replacing the cyano group with a methoxycarbonyl strikingly increased potency in the apoptosis assays. Higher plasma and tissue levels were obtained with the new BA analogues, especially CBA-Im [1-(2-cyano-3-oxolupa-1,20(29)-dien-28-oyl)imidazole], compared with BA itself and at concentrations that were active in vitro. These results suggest that BA is a useful platform for drug development, and the enhanced potency and varied biological activities of CBA-Im make it a promising candidate for further chemoprevention or chemotherapeutic studies.

Wild and domesticated Moringa oleifera differ in taste, glucosinolate composition, and antioxidant potential, but not myrosinase activity or protein content.

Taste drives consumption of foods. The tropical tree Moringa oleifera is grown worldwide as a protein-rich leafy vegetable and for the medicinal value of its phytochemicals, in particular its glucosinolates, which can lead to a pronounced harsh taste. All studies to date have examined only cultivated, domestic variants, meaning that potentially useful variation in wild type plants has been overlooked. We examine whether domesticated and wild type M. oleifera differ in myrosinase or glucosinolate levels, and whether these different levels impact taste in ways that could affect consumption. We assessed taste and measured levels of protein, glucosinolate, myrosinase content, and direct antioxidant activity of the leaves of 36 M. oleifera accessions grown in a common garden. Taste tests readily highlighted differences between wild type and domesticated M. oleifera. There were differences in direct antioxidant potential, but not in myrosinase activity or protein quantity. However, these two populations were readily separated based solely upon their proportions of the two predominant glucosinolates (glucomoringin and glucosoonjnain). This study demonstrates substantial variation in glucosinolate composition within M. oleifera. The domestication of M. oleifera appears to have involved increases in levels of glucomoringin and substantial reduction of glucosoonjnain, with marked changes in taste.