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Irritable bowel syndrome (IBS) is a female predominant functional gastrointestinal disorder, underpinned by microbial dysbiosis and microinflammation. We suggest that changes in trace amine (TA) load and metabolism may link together diet, inflammation and sex in this context.The effect of E2 treatment on microbial growth and TA generation was assessed using liquid chromatography and tandem mass spectrometry methodology. To investigate the effects of TAs on the gut, WST-1, prostaglandin E2 and tight junction protein dynamics were investigated in TA treated (HT-29) colon epithelial monolayer cultures.Differential E2-dependent alterations of the TA production capabilities of microbes were observed. Significantly, E2 treatment resulted in a 50% increase in tryptamine secretion from a probiotic microbe (p 0.0001). Moreover, in vitro experiments indicated that TA treatment exerted type-specific effects in the gut, e.g., reducing mitochondrial functionality, even at low doses of tryptamine (p 0.0001) and ρ-tyramine (p 0.001). Additionally, prostaglandin E2 levels were significantly increased following ρ-tyramine and agmatine treatment (p 0.05). In terms of functionality, all investigated TAs resulted in occludin redistribution and loss of zona occludens-1 and occludin co-localization.Increases in the gastrointestinal TA load may contribute to a relatively pro-inflammatory outcome in the intestine, along with tight junction protein disruption. Additionally, fluctuating levels of endogenous E2 may modulate microbially-derived TA levels, potentially explaining exaggerating gastrointestinal symptomology in females during low E2 phases. Thus, current data warrants subsequent investigations in appropriate in vivo models to fully elucidate the role of the trace aminergic system in the sex bias observed in IBS.

South African rooibos (Aspalathus linearis) tea is globally consumed for its health benefits and caffeine free nature, but no information is available on the neuroprotective capacity of (unfermented) green rooibos. Our aim was to investigate the cytoprotective activity of green rooibos in neuronal cells, including probing antioxidant and enzyme inhibitory properties that could explain observed effects in these cells. We also investigated the anxiolytic potential of green rooibos using zebrafish larval models. Green rooibos extract (Green oxithin (TM)) was assessed for its neuroprotective potential in Neuro-2a cells treated with different concentrations of the extract (12.5-25-50-100 mu g mL(-1)) and different concentrations of hydrogen peroxide (250 or 125 mu M) as oxidizing agent. Cell viability (MTT) and redox status (intracellular ROS) were also quantified in these cells. Antioxidant properties of the extract were quantified using cell-free systems (DPPH, ORAC and xanthine/xanthine oxidase), and potential neuroprotection evaluated in terms of its potential to inhibit key enzymes of the CNS (monoamine oxidase A (MOA-A), acetylcholinesterase (AChE) and tyrosinase (TYR)). Results demonstrated that green rooibos extract exerted significant cytoprotective properties in Neuro-2a cells, particularly when exposed to lethal 250 mu M hydrogen peroxide, increasing cell survival by more than 100%. This may be ascribed (at least partially) to its capacity to limit intracellular ROS accumulation in these cells. Data from cell-free systems confirmed that green rooibos was able to scavenge free radicals (synthetic and physiological) in a dose dependent manner with a similar profile activity to vitamins C and E. Green rooibos also acted as a moderate MAO-A inhibitor, but had no significant effect on AChE or TYR. Finally, zebrafish larvae treated with lower doses of green rooibos demonstrated a significant anxiolytic effect in the light-dark anxiety model. Using the PTZ excitotoxicity model, green rooibos was shown to rescue GABA receptor signalling, which together with its demonstrated inhibition of MAO-A, may account for the anxiolytic outcome. Current data confirms that green rooibos could be considered a functional brain food and may be a good option as starting ingredient in the development of new nutraceuticals.

In order to promote gastrointestinal health, significant increases in the prevalence of gastrointestinal disorders should be paralleled by similar surges in therapeutics research. Nutraceutical interventions may play a significant role in patient management. The current study aimed to determine the potential of Aspalathus linearis (rooibos) to prevent gastrointestinal dysregulation resulting from high-dose trace-amine (TA) exposure. Considering the substantial female bias in functional gastrointestinal disorders, and the suggested phytoestrogenicity of rooibos, the study design allowed for a comparison between the effects of an ethanol extract of green rooibos and 17β-estradiol (E2). High levels of ρ-tyramine (TYR) and agmatine (AGM), but not β-phenethylamine (PEA) or tryptamine (TRP), resulted in prostaglandin E2 (PGE2) hypersecretion, increased tight-junction protein (TJP; occludin and ZO-1) secretion and (dissimilarly) disrupted the TJP cellular distribution profile. Modulating benefits of rooibos and E2 were TA-specific. Rooibos pre-treatment generally reduced IL-8 secretion across all TA conditions and prevented PGE2 hypersecretion after exposure to both TYR and AGM, but was only able to normalise TJP levels and the distribution profile in AGM-exposed cells. In contrast, E2 pre-treatment prevented only TYR-associated PGE2 hypersecretion and TJP dysregulation. Together, the data suggest that the antioxidant and anti-inflammatory effects of rooibos, rather than phytoestrogenicity, affect benefits illustrated for rooibos.

Rheumatoid arthritis is prevalent in more than 1% of the global population, with the highest occurrence between ages 35 and 50, which places a huge burden on the economy. Drug discovery for the prevention of this chronic disease is; therefore, a priority. It is known that subclinical progression of many chronic non-communicable diseases is exacerbated via accelerated ageing, a pro-inflammatory phenotype shift. However, rheumatoid arthritis additionally has significant humoral immune activation, inflammatory signalling-and thus the accelerated ageing profile-may differ from other chronic inflammatory diseases. The current study simulated inflammatory arthritis onset in a collagen-induced arthritis (CIA) rodent model, to characterise the redox and inflammatory profile at the onset of clinical symptoms, in different tissues, in the presence and absence of preventative antioxidant treatment. The data illustrate that an increased free radical level are evident already very early on in RA disease progression. Furthermore, oxidative stress seems to somewhat precede a significant pro-inflammatory state, perhaps due to humoral immune activation. Our data across different compartments further suggest that the compensatory increase in endogenous antioxidant activity is gradually exhausted at a different pace, with the liver showing the first signs of oxidant damage, even before significant evidence exist in circulation. The current data further suggest that preventative antioxidant intervention may have a sparing effect on endogenous antioxidant mechanisms and preserve telomere length to delay disease progression-or at least the accelerated ageing known to exacerbate RA symptoms-although it did not seem to have a significant direct effect on the autoimmune activity.

South African rooibos (

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides, with several having antimicrobial activity. The biosynthetic machinery responsible for modification of the cla...

Changes in the in utero environment result in generational transfer of maladapted physiology in the context of conditions such as stress, obesity, and anxiety. Given the significant contribution of noncommunicable diseases—which are characterised by chronic inflammation—to population mortality, the potential for chronic maternal inflammation mediating foetal programming is a growing concern. The extent of generational transfer in terms of immune functionality and leukocyte glucocorticoid sensitivity was investigated over two generations of offspring (F1 and F2) in a model of chronic LPS-induced maternal inflammation in C57/BL/6 mice. Maternal inflammation resulted in glucocorticoid hypersensitivity (increased glucocorticoid receptor expression levels) in the majority of leukocyte subpopulations in both F1 and F2 offspring. Furthermore, splenocytes stimulated with LPS in vitro exhibited exacerbated inflammatory cytokine responses, which were even more prominent in F2 than F1; this effect could be ascribed to NLRP3 inflammasome hyperactivity in F1 but not F2. Current data illustrates that parental chronic inflammation may mediate the inflammatory profile in offspring, potentially propagating a maladapted proinflammatory phenotype in subsequent generations.

Lanthipeptides are ribosomally synthesized and posttranslationally modified peptides, with modifications that are incorporated during biosynthesis by dedicated enzymes. Various modifications of the peptides are possible, resulting in a highly diverse group of bioactive peptides that offer a potential reservoir for use in the fight against a plethora of diseases. Their activities range from the antimicrobial properties of lantibiotics, especially against antibiotic-resistant strains, to antiviral activity, immunomodulatory properties, antiallodynic effects, and the potential to alleviate cystic fibrosis symptoms. Lanthipeptide biosynthetic genes are widespread within bacterial genomes, providing a substantial repository for novel bioactive peptides. Using genome mining tools, novel bioactive lanthipeptides can be identified, and coupled with rapid screening and heterologous expression technologies, the lanthipeptide drug discovery pipeline can be significantly sped up. Lanthipeptides represent a group of bioactive peptides that hold great potential as biotherapeutics, especially at a time when novel and more effective therapies are required. With this review, we provide insight into the latest developments made toward the therapeutic applications and production of lanthipeptides, specifically looking at heterologous expression systems.

Mesenchymal stem cell (MSC) dysfunction is a serious complication in ageing and age-related inflammatory diseases such as type 2 diabetes mellitus. Inflammation and oxidative stress-induced cellular senescence alter the immunomodulatory ability of MSCs and hamper their pro-regenerative function, which in turn leads to an increase in disease severity, maladaptive tissue damage and the development of comorbidities. Targeting stem/progenitor cells to restore their function and/or protect them against impairment could thus improve healing outcomes and significantly enhance the quality of life for diabetic patients. This review discusses the dysregulation of MSCs' immunomodulatory capacity in the context of diabetes mellitus and focuses on intervention strategies aimed at MSC rejuvenation. Research pertaining to the potential therapeutic use of either pharmacological agents (NFкB antagonists), natural products (phytomedicine) or biological agents (exosomes, probiotics) to improve MSC function is discussed and an overview of the most pertinent methodological considerations given. Based on in vitro studies, numerous anti-inflammatory agents, antioxidants and biological agents show tremendous potential to revitalise MSCs. An integrated systems approach and a thorough understanding of complete disease pathology are however required to identify feasible candidates for in vivo targeting of MSCs.

Although rheumatoid arthritis affects 1% of the global population, the role of rheumatoid cachexia, which occurs in up to a third of patients, is relatively neglected as research focus, despite its significant contribution to decreased quality of life in patients. A better understanding of the cellular and molecular processes involved in rheumatoid cachexia, as well as its potential treatment, is dependent on elucidation of the intricate interactions of the cells involved, such as myoblasts, fibroblasts and macrophages. Persistent RA-associated inflammation results in a relative depletion of the capacity for regeneration and repair in the satellite cell niche. The repair that does proceed is suboptimal due to dysregulated communication from the other cellular role players in this multi-cellular environment. This includes the incomplete switch in macrophage phenotype resulting in a lingering pro-inflammatory state within the tissues, as well as fibroblast-associated dysregulation of the dynamic control of the extracellular matrix. Additional to this endogenous dysregulation, some treatment strategies for RA may exacerbate muscle wasting and no multi-cell investigation has been done in this context. This review summarizes the most recent literature characterising clinical RA cachexia and links these features to the roles of and complex communication between multiple cellular contributors in the muscle niche, highlighting the importance of a targeted approach to therapeutic intervention.

Mesenchymal stem cell (MSC) dysfunction is a serious complication in ageing and age-related inflammatory diseases such as type 2 diabetes mellitus. Inflammation and oxidative stress-induced cellular senescence alter the immunomodulatory ability of MSCs and hamper their pro-regenerative function, which in turn leads to an increase in disease severity, maladaptive tissue damage and the development of comorbidities. Targeting stem/progenitor cells to restore their function and/or protect them against impairment could thus improve healing outcomes and significantly enhance the quality of life for diabetic patients. This review discusses the dysregulation of MSCs' immunomodulatory capacity in the context of diabetes mellitus and focuses on intervention strategies aimed at MSC rejuvenation. Research pertaining to the potential therapeutic use of either pharmacological agents (NFкB antagonists), natural products (phytomedicine) or biological agents (exosomes, probiotics) to improve MSC function is discussed and an overview of the most pertinent methodological considerations given. Based on in vitro studies, numerous anti-inflammatory agents, antioxidants and biological agents show tremendous potential to revitalise MSCs. An integrated systems approach and a thorough understanding of complete disease pathology are however required to identify feasible candidates for in vivo targeting of MSCs.

Due to atrophy, muscle weakness is a common occurrence in rheumatoid arthritis (RA). The majority of human studies are conducted on the vastus lateralis muscle—a muscle with mixed fiber type—but little comparative data between multiple muscles in either rodent or human models are available. The current study therefore assessed both muscle ultrastructure and selected redox indicators across various muscles in a model of collagen-induced rheumatoid arthritis in female Sprague-Dawley rats. Only three muscles, the gastrocnemius, extensor digitorum longus (EDL), and soleus, had lower muscle mass (38%, 27%, and 25% loss of muscle mass, respectively; all at least P<0.01), while the vastus lateralis muscle mass was increased by 35% (P<0.01) in RA animals when compared to non-RA controls. However, all four muscles exhibited signs of deterioration indicative of rheumatoid cachexia. Cross-sectional area was similarly reduced in gastrocnemius, EDL, and soleus (60%, 58%, and 64%, respectively; all P<0.001), but vastus lateralis (22% smaller, P<0.05) was less affected, while collagen deposition was significantly increased in muscles. This pathology was associated with significant increases in tissue levels of reactive oxygen species (ROS) in all muscles except the vastus lateralis, while only the gastrocnemius had significantly increased levels of lipid peroxidation (TBARS) and antioxidant activity (FRAP). Current data illustrates the differential responses of different skeletal muscles of the hindlimb to a chronic inflammatory challenge both in terms of redox changes and resistance to cachexia.

Due to a lack of specific or sensitive biomarkers, drug discovery advances have been limited for individuals suffering from irritable bowel syndrome (IBS). While current therapies provide symptomatic relief, inflammation itself is relatively neglected, despite the presence of chronic immune activation and innate immune system dysfunction. Moreover, considering the microgenderome concept, gender is a significant aetiological risk factor. We believe that we have pinpointed a “missing link” that connects gender, dysbiosis, diet, and inflammation in the context of IBS, which may be manipulated as therapeutic target. The trace aminergic system is conveniently positioned at the interface of the gut microbiome, dietary nutrients and by-products, and mucosal immunity. Almost all leukocyte populations express trace amine associated receptors and significant amounts of trace amines originate from both food and the gut microbiota. Additionally, although IBS-specific data are sparse, existing data supports an interpretation in favour of a gender dependence in trace aminergic signalling. As such, trace aminergic signalling may be altered by fluctuations of especially female reproductive hormones. Utilizing a multidisciplinary approach, this review discusses potential mechanisms of actions, which include hyperreactivity of the immune system and aberrant serotonin signalling, and links outcomes to the symptomology clinically prevalent in IBS. Taken together, it is feasible that the additional level of regulation by the trace aminergic system in IBS has been overlooked, until now. As such, we suggest that components of the trace aminergic system be considered targets for future therapeutic action, with the specific focus of reducing oxidative stress and inflammation.

Considering that the phenomenon of accelerated ageing contributes to early onset of various chronic diseases, modelling of the relevant dysregulated systems or responses is vital for research aimed at identification of potential therapeutic targets. Here, we aimed to establish a model capable of simulating the redox and inflammatory changes of accelerated ageing—specifically, the aim was early phase accelerated ageing, which would allow therapeutic intervention in a preventative approach prior to clinical disease manifestation. A secondary aim was to evaluate the sensitivity of the model to reflect preventative treatment efficacy. Daily d-galactose injections (250 mg/kg body mass/day) for 8 weeks in 9-week-old male Wistar rats induced a model of early accelerated ageing (decreased plasma FRAP; P

It is a well-known fact that DHEA declines on ageing and that it is linked to ageing-related neurodegeneration, which is characterised by gradual cognitive decline. Although DHEA is also associated with inflammation in the periphery, the link between DHEA and neuroinflammation in this context is less clear. This review drew from different bodies of literature to provide a more comprehensive picture of peripheral vs central endocrine shifts with advanced age—specifically in terms of DHEA. From this, we have formulated the hypothesis that DHEA decline is also linked to neuroinflammation and that increased localised availability of DHEA may have both therapeutic and preventative benefit to limit neurodegeneration. We provide a comprehensive discussion of literature on the potential for extragonadal DHEA synthesis by neuroglial cells and reflect on the feasibility of therapeutic manipulation of localised, central DHEA synthesis.

Oxidative stress and inflammation are intricately interlinked as aetiological factors in the context of ageing and chronic disease-related accelerated ageing. Previous research by our group has highlighted the anti-oxidant and anti-inflammatory potential of grape-derived polyphenols in the context of acute inflammation and oxidative stress. The aim here was to add to this by assessing efficacy of the treatment (acutely) to address ageing-associated cumulative pro-oxidant and pro-inflammatory changes in an in vitro model. Blood from young and aged humans was analysed for baseline oxidative stress and inflammatory status. Isolated neutrophils were acutely exposed to the polyphenol treatment in vitro. The chemokinetic capacity of treated and control neutrophils in response to fMLP was subsequently determined in a Dunn chamber, using live cell imaging. Neutrophils were also analysed for the expression of selected molecular markers associated with functional capacity and oxidative stress. Results indicate that the aged population had significantly worse oxidative stress and inflammatory profiles (higher plasma conjugated dienes and MPO) than young controls. Neutrophils isolated from both young and aged individuals had improved chemokinetic accuracy and capacity after in vitro polyphenol treatment. Additionally, increased shedding of CD16 and expression of CD66b suggested sites via which the polyphenol achieved improved neutrophil motility. We conclude that grape seed-derived polyphenols facilitated improved neutrophil functionality by acting on the molecular targets elucidated here.

Increasing consumer bias toward natural products and the considerable wealth of indigenous knowledge has precipitated an upturn in market-driven research into potentially beneficial medicinal plants. In this context, Aspalathus linearis (Rooibos) has been identified to be a promising candidate which may impact cardiovascular disease (CVD), which is one of the most widely studied chronic diseases of modern times. Despite these efforts, ischemic heart disease remains the number one cause of mortality globally. Apart from genetic predisposition and other aetiological mechanisms specific to particular types of CVD, co-factors from interlinked systems contribute significantly to disease development and the severity of its clinical manifestation. The bioactivity of Rooibos is directed towards multiple therapeutic targets. Experimental data to date include antioxidant, anti-inflammatory and anti-diabetic effects, as well as modulatory effects in terms of the immune system, adrenal steroidogenesis and lipid metabolism. This review integrates relevant literature on the therapeutic potential of Rooibos in the context of CVD, which is currently the most common of non-communicable diseases. The therapeutic value of whole plant extracts versus isolated active ingredients are addressed, together with the potential for overdose or herb-drug interaction. The body of research undertaken to date clearly underlines the benefits of Rooibos as both preventative and complementary therapeutic functional food in the context of CVD.

One of the limiting factors in tissue regeneration, particularly in the context of chronic disease such as myodystrophy, motor neuron disease, sarcopenia, and cardiovascular disease, is limited availability of stem cells. We propose employing autologous macrophages to deliver stem cells, thereby facilitating tissue regeneration, by a novel and relatively non-invasive therapeutic intervention. Circulatory monocytic cells of M1 phenotype have capacity for transendothelial migration to infiltrate damaged tissue, making them ideal delivery vehicles. However, in order to deliver viable stem cells, these macrophages must undergo phagosome maturation arrest. Our aim was to induce phagosome maturation arrest in prepolarised M1 macrophages, whilst maintaining capacity for phagocytic engulfment (including phagosome formation) and transendothelial migration. Primary human M1 macrophages were treated with a wortmannin-concanamycin A-chloroquine cocktail to induce arrest. Modified cells were allowed to ingest 4.5 μm protein-coated fluorescent latex beads (simulated stem cells), before migratory capacity in response to MCP-1 was assessed over a 2-hr period in a Transwell co-culture system. Data indicate that phagosome acidification (as indicated by pHrodo®) was prevented in treated cells, effectively limiting digestion of ingested "cargo" (1.23 ± 0.26% vs. 7.52 ± 0.98% in controls; p

Newly hatched broiler chickens are the most susceptible to Salmonella infections, especially during the first 24 h. At this age, the gut microbiome is not fully developed and offers little protection in the form of competitive exclusion. In this study, one group of newly hatched, Salmonella-free broilers were colonised with a multi-species probiotic (2.0 × 1010 to 8.9 × 1010 CFU per kg feed) for 28 days, consisting of Lactobacillus crispatus, Lactobacillus salivarius, Lactobacillus gallinarum, Lactobacillus johnsonii, Enterococcus faecalis and Bacillus amyloliquefaciens. Broilers in another group received oxytetracycline (200 mg/kg feed), instead of the probiotic, for 28 days. On days 9 and 10, broilers in both groups were gavaged with 9 × 107 CFU Salmonella Enteritidis A9, a pathogenic strain isolated from infected broilers. On day 14, Salmonella was detected in the ceca of 95% of broilers treated with the multi-species probiotic, but 2 weeks later, almost half of the birds (45%) had no Salmonella in their ceca. Similar results were recorded after 28 days of treatment with oxytetracycline. Only 10% of Salmonella-infected birds not treated were Salmonella-free on day 28. Growth performance, immune organ weight (spleen and bursa of Fabricius) and whole blood cell counts of birds treated with the multi-species probiotic and oxytetracycline, respectively, were similar to untreated and uninfected birds throughout the 28-day trial (p > 0.05). On day 14, serum lysozyme levels of broilers exposed to the probiotic were lower (8.0 μg/mL) compared with those of broilers treated with oxytetracycline (11.0 μg/mL). Although the multi-species probiotic and oxytetracycline stimulated the immune system, probiotics are safer to use than antibiotics and should be the preferred choice of treatment.

Lanthipeptides are ribosomally synthesized and post-translationally modified peptides, with several having antimicrobial activity. The biosynthetic machinery responsible for modification of the class I lanthipeptide nisin provides a means for modification of a diverse range of lanthipeptides. However, literature regarding expression of class I lanthipeptides in a malleable Gram-negative host such as

Little is known about the migration of bacteriocins across human cells. In this study, we report on migration of three bacteriocins nisin, plantaricin 423 and bacST4SA across colonic adenocarcinoma (Caco-2) cells and human umbilical vein endothelial cells (HUVECs). Bacteriocins were fluorescently labelled while still maintaining antimicrobial activity. Migration of fluorescently labelled bacteriocins across monolayers was assessed in vitro using transmigration well inserts. After 3 h, 75% of nisin, 85% of plantaricin 423 and 82% of bacST4SA migrated across the Caco-2 cell monolayer. Over the same time span, 88% nisin, 93% plantaricin 423 and 91% bacST4SA migrated across the HUVEC monolayer. The viability of both cell types remained unchanged when exposed to 50 µM of nisin, plantaricin 423 or bacST4SA. The effect of human plasma on bacteriocin activity was also assessed. Activity loss was dependent on bacteriocin type and concentration, with the class-IIa bacteriocins retaining more activity compared to nisin. This is the first report of bacteriocins migrating across simulated gastrointestinal- and vascular-barriers. This study provides some of the first evidence that bacteriocins are capable of crossing the gut-blood-barrier. However, in vivo studies need to be performed to confirm these findings and expand on the role of bacteriocin migration across cell barriers.

Staphylococcus aureus is a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, including S. aureus . It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options for skin and soft tissue infections. A select few lantibiotics, a group of natural defense peptides produced by bacteria, inhibit the growth of numerous clinical S. aureus isolates, including methicillin-resistant strains. In this study, the antimicrobial activities of nisin, clausin, and amyloliquecidin, separately administered, were compared to that of a mupirocin-based ointment, which is commonly used as treatment for S. aureus- induced skin infections. Full-thickness excisional wounds, generated on the dorsal surfaces of mice, were infected with a bioluminescent strain of S. aureus (strain Xen 36). The infections were monitored in real time using in vivo bioluminescent imaging. Lantibiotic treatments significantly reduced the bioluminescence of S. aureus Xen 36 to a level similar to that recorded with mupirocin treatment. Wound closure, however, was more pronounced during lantibiotic treatment. Lantibiotics thus have the potential to be used as an alternative treatment option for S. aureus- induced skin infections.

International audience; The root cap releases cells that produce massive amounts of mucilage containing polysaccharides, proteoglycans, extracellular DNA (exDNA) and a variety of antimicrobial compounds. The released cells – known as border cells or border‐like cells – and mucilage secretions form networks that are defined as root extracellular traps (RETs). RETs are important players in root immunity. In animals, phagocytes are some of the most abundant white blood cells in circulation and are very important for immunity. These cells combat pathogens through multiple defence mechanisms, including the release of exDNA‐containing extracellular traps (ETs). Traps of neutrophil origin are abbreviated herein as NETs. Similar to phagocytes, plant root cap‐originating cells actively contribute to frontline defence against pathogens. RETs and NETs are thus components of the plant and animal immune systems, respectively, that exhibit similar compositional and functional properties. Herein, we describe and discuss the formation, molecular composition and functional similarities of these similar but different extracellular traps.

Cyanidin and chlorogenic acid are polyphenols from plant origin that are present in many common fruits, particularly in berries. To corroborate the protective or detrimental effects of both compounds from a neuro-inflammatory perspective, in vitro experiments were carried out in human astrocytes (U-373). Astrocytes were pre-treated with a range of concentrations of either cyanidin, chlorogenic acid or a combined treatment for a period of 30 min, before exposure to Escherichia coli lipopolysaccharide (LPS) challenge for 23.5 h, after which cytotoxicity (propidium iodide exclusion assay), cytoprotective effects (XTT assay) and effects on functional capacity (secretion of pro-inflammatory cytokines IL-6 and MCP-1) were evaluated. No treatment resulted in cytotoxicity, but high dose (20 µg/mL) LPS significantly reduced mitochondrial reductive capacity (p

Cyanidin-3-O-glucoside, also known as kuromanin, is one of the most important anthocyanins in nature. The scope of this paper is to discuss the potential role of this anthocyanin as therapeutic agent to prevent or treat chronic diseases in which oxidative stress may be involved through a modulation of certain enzymes. The inhibitory potential of cyanidin-3-O-glucoside against enzymatic targets of neurodegenerative or metabolic diseases was tested using monoamine oxidase A (MAO-A), acetylcholinesterase (AChE), tyrosinase (TYR), fatty acid amide hydrolase (FAAH), α-glucosidase (α-GLU) and dipeptidyl peptidase-4 (DPP-4). The antioxidant activity was evaluated through the xanthine/xanthine oxidase system. Cyanidin-3-O-glucoside inhibited MAO-A, TYR and FAAH enzymes whereas it could not inhibit AChE activity. IC50 values for these assays were 7.6 μM, 18.1 μM and 152.1 μM, respectively. Additionally, cyanidin-3-O-glucoside was able to inhibit α-GLU (IC50 = 479.8 μM) and DPP-4 (IC50 = 125.1 μM). Finally, the antioxidant activity of cyanidin-3-O-glucoside was confirmed by the xanthine/xanthine oxidase method, being more efficient than gallic acid as superoxide radical scavenger. In conclusion, cyanidin-3-O-glucoside has demonstrated to be a candidate as enzyme inhibitor with neuroprotective, antioxidant and antidiabetic potential.

CITATION: Smith, C. & Myburgh, K. H. 2005. Assessment of endocrine stress status in athletes – new twists to the tale. South African Journal of Sports Medicine, 17(3):19-29, doi:10.17159/5124.

Stress-related illnesses rate among the most prevalent non-fatal diseases globally. With the global trend for consumer bias towards natural medicine, the Sceletium plant has become more prominent in the field of natural products. Although potentially useful effects of Sceletium tortuosum on the central nervous system have been reported, limited data is available on effects of the plant in the peripheral compartment.The current study aimed to elucidate the effect(s) of a Sceletium extract (TRI) rich in mesembrine (1% of plant extract w/w), on adrenal steroid biosynthesis.Steroidogenesis was assessed basally and in response to stimuli (forskolin, angiotensin II, KCl), in human adrenocortical carcinoma cells (H295R). Steroid hormone levels were assessed using UPLC-MS/MS. UPLC-MS analyses of TRI identified major alkaloids Δ7-mesembrenone, mesembrenone and mesembrine.Highest dose TRI treatment (1 mg/ml, 34.5 μM mesembrine) increased pregnenolone and decreased 16-hydroxyprogesterone levels (both P0.00001) in forskolin-stimulated conditions only, suggesting CYP17 enzyme inhibition. This led to significant inhibition of forskolin-associated increases in cortisol levels at the highest dose (P0.001) and basal cortisol levels across all doses (P0.0001). Independently of forskolin, TRI inhibited androstenedione and testosterone production across all doses (both P0.00001), suggesting inhibition of 3βHSD and 17βHSD respectively. TRI decreased both the angiotensin II- (P0.05) and forskolin-induced (P0.0001) increases in aldosterone production.Our data suggest potentially beneficial effects of TRI in the context of stress and hypertension. These should be further investigated in a whole organism model, while the effects on the androgenic pathway should also be further elucidated.