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A number of plants used in folk medicine in Thailand and Eastern Asia are attracting interest due to the high bioactivities of their extracts. The aim of this study was to screen the edible leaf extracts of 20 plants found in Thailand and investigate the potential neuroprotective effects of the most bioactive sample. The total phenol and flavonoid content and 2,2-diphenyl-1-picrylhydrazyl radical-scavenging activity were determined for all 20 leaf extracts. Based on these assays, Glochidion littorale leaf extract (GLE), which showed a high value in all tested parameters, was used in further experiments to evaluate its effects on neurodegeneration in Caenorhabditis elegans . GLE treatment ameliorated H 2 O 2 -induced oxidative stress by attenuating the accumulation of reactive oxygen species and protected the worms against 1-methyl-4-phenylpyridinium-induced neurodegeneration. The neuroprotective effects observed may be associated with the activation of the transcription factor DAF-16. The characterization of this extract by LC-MS identified several phenolic compounds, including myricetin, coumestrin, chlorogenic acid, and hesperidin, which may play a key role in neuroprotection. This study reports the novel neuroprotective activity of GLE, which may be used to develop treatments for neurodegenerative diseases such as Parkinson's syndrome.

Emerging data support that plant food based isoflavones have ameliorating effects on a variety of neurodegenerative diseases including Parkinson's disease (PD). Our previous investigation revealed that dietary isoflavones including genistein (GEN), daidzein (DAI), and equol (EQL; a gut microbial metabolite of DAI) showed promising blood-brain barrier permeability and anti-neuroinflammatory activity in murine microglial BV2 cells. However, the neuroprotective effects of EQL against neurotoxins induced toxicity in PD related models remains unclear. Herein, EQL, along with GEN and DAI, were evaluated for their cytoprotective effect in a non-contact co-culture model with LPS-BV2-conditioned media and human neuroblastoma SH-SY5Y cells. In addition, their neuroprotective effects against PD related neurotoxins including 6-hydroxydopamine (6-OHDA) and 1-methyl-4-phenylpyridinium (MPP + ) induced cytotoxicity were evaluated in SH-SY5Y cells. Furthermore, EQL was evaluated for its neuroprotective effects against MPP + induced neurotoxicity using in vivo PD model including Caenorhabditis elegans lifespan assay. DAI (10 μM) and EQL (10 and 20 μM) showed cytoprotective effects by decreasing LPS-BV2-conditioned media induced cytotoxicity in SH-SY5Y cells by 29.2, 32.4 and 27.2%, respectively. EQL (10 and 20 μM) also showed neuroprotective effects by decreasing 6-OHDA and MPP + induced cytotoxicity in SH-SY5Y cells by 30.6-34.5 and 17.9-18.9%, respectively. Additionally, data from the in vivo assay supported EQL's neuroprotective effect as it increases survival of C. elegans exposed to MPP + from 72 to 108 h. Our findings support a growing body of evidence of the neuroprotective effects of dietary isoflavones and further studies are warranted to elucidate their mechanisms of action.

Mucuna pruriens (Mucuna) has been prescribed in Ayurveda for various brain ailments including 'kampavata' (tremors) or Parkinson's disease (PD). While Mucuna is a well-known natural source of levodopa (L-dopa), published studies suggest that other bioactive compounds may also be responsible for its anti-PD effects. To investigate this hypothesis, an L-dopa reduced (<0.1%) M. pruriens seeds extract (MPE) was prepared and evaluated for its anti-PD effects in cellular (murine BV-2 microglia and human SH-SY5Y neuroblastoma cells), Caenorhabditis elegans , and Drosophila melanogaster models. In BV-2 cells, MPE (12.5⁻50 μg/mL) reduced hydrogen peroxide-induced cytotoxicity (15.7-18.6%), decreased reactive oxygen species production (29.1-61.6%), and lowered lipopolysaccharide (LPS)-induced nitric oxide species release by 8.9⁻60%. MPE (12.5-50 μg/mL) mitigated SH-SY5Y cell apoptosis by 6.9-40.0% in a non-contact co-culture assay with cell-free supernatants from LPS-treated BV-2 cells. MPE (12.5-50 μg/mL) reduced 6-hydroxydopamine (6-OHDA)-induced cell death of SH-SY5Y cells by 11.85⁻38.5%. Furthermore, MPE (12.5-50 μg/mL) increased median (25%) and maximum survival (47.8%) of C. elegans exposed to the dopaminergic neurotoxin, methyl-4-phenylpyridinium. MPE (40 μg/mL) ameliorated dopaminergic neurotoxin (6-OHDA and rotenone) induced precipitation of innate negative geotaxis behavior of D. melanogaster by 35.3 and 32.8%, respectively. Therefore, MPE contains bioactive compounds, beyond L-dopa, which may impart neuroprotective effects against PD.

Published data supports the neuroprotective effects of several phenolic-containing natural products, including certain fruit, berries, spices, nuts, green tea, and olive oil. However, limited data are available for phenolic-containing plant-derived natural sweeteners including maple syrup. Herein, we investigated the neuroprotective effects of a chemically standardized phenolic-enriched maple syrup extract (MSX) using a combination of biophysical, in vitro, and in vivo studies. Based on biophysical data (Thioflavin T assay, transmission electron microscopy, circular dichroism, dynamic light scattering, and zeta potential), MSX reduced amyloid β 1-42 peptide (Aβ 1-42 ) fibrillation in a concentration-dependent manner (50-500 μg/mL) with similar effects as the neuroprotective polyphenol, resveratrol, at its highest test concentration (63.5 % at 500 μg/mL vs. 77.3 % at 50 μg/mL, respectively). MSX (100 μg/mL) decreased H 2 O 2 -induced oxidative stress (16.1 % decrease in ROS levels compared to control), and down-regulated the production of lipopolysaccharide (LPS)-stimulated inflammatory markers (22.1, 19.9, 74.8, and 87.6 % decrease in NOS, IL-6, PGE 2 , and TNFα levels, respectively, compared to control) in murine BV-2 microglial cells. Moreover, in a non-contact co-culture cell model, differentiated human SH-SY5Y neuronal cells were exposed to conditioned media from BV-2 cells treated with MSX (100 μg/mL) and LPS or LPS alone. MSX-BV-2 media increased SH-SY5Y cell viability by 13.8 % compared to media collected from LPS-BV-2 treated cells. Also, MSX (10 μg/mL) showed protective effects against Aβ 1-42 induced neurotoxicity and paralysis in Caenorhabditis elegans in vivo. These data support the potential neuroprotective effects of MSX warranting further studies on this natural product.

Pomegranate shows neuroprotective effects against Alzheimer's disease (AD) in several reported animal studies. However, whether its constituent ellagitannins and/or their physiologically relevant gut microbiota-derived metabolites, namely, urolithins (6H-dibenzo[b,d]pyran-6-one derivatives), are the responsible bioactive constituents is unknown. Therefore, from a pomegranate extract (PE), previously reported by our group to have anti-AD effects in vivo, 21 constituents, which were primarily ellagitannins, were isolated and identified (by HPLC, NMR, and HRESIMS). In silico computational studies, used to predict blood-brain barrier permeability, revealed that none of the PE constituents, but the urolithins, fulfilled criteria required for penetration. Urolithins prevented β-amyloid fibrillation in vitro and methyl-urolithin B (3-methoxy-6H-dibenzo[b,d]pyran-6-one), but not PE or its predominant ellagitannins, had a protective effect in Caenorhabditis elegans post induction of amyloid β(1-42) induced neurotoxicity and paralysis. Therefore, urolithins are the possible brain absorbable compounds which contribute to pomegranate's anti-AD effects warranting further in vivo studies on these compounds.

Introduction: Lamiaceae herbs have are well known for their immunomodulatory effects, however, the mechanism by which they effect innate immune system is not clearly understood., Objective: The effect of dietary supplementation with two Lamiaceae herbs (oregano and sage) modulation of on innate immunological parameters was investigated in Lumbricus terrestris., Materials and Methods: Animals were fed (ad libitum) on herbs supplemented diet [(0.1% (w/v) and 0.5% (w/v)] for 6 days. Changes in immune competent cell counts, viability, and relative neutrophil-like cell counts were determined in response to herb treatment. Changes in nitric oxide, phagocytic activity, and respiratory burst index were also determined in response to herb treatment relative to control. Additionally, effect of herb co-treatment cyclophosphamide (50 mg/kg-BW) induced immunosuppression was also evaluated., Results: Our results suggested abrogation of CP-induced immunosuppression in response to co-treatment with herbs. Significant increase in nitric oxide-mediated immune-competent cell counts, viability, and differentiation into neutrophil-like cells were observed in response to dietary supplementation with Lamiaceae herbs. Significantly higher phagocytic activity relative to control was also noted in response to dietary intake of oregano and sage. However, the respiratory burst index did not increase exponentially in response to herb treatments, suggesting a potential enhancement in pathogen recognition and antioxidant defenses., Conclusion: Lamiaceae herbs may have potential immune-modulatory properties important for human health and merits further investigation.

Members of the bacterial genus Salmonella are recognized worldwide as major zoonotic pathogens often found to persist in non-enteric environments including heterogeneous aquatic biofilms. In this study, Salmonella isolates that had been detected repeatedly over time in aquatic biofilms at different sites in Spring Lake, San Marcos, Texas, were identified as serovars Give, Thompson, Newport and -:z10:z39. Pathogenicity results from feeding studies with the nematode Caenorhabditis elegans as host confirmed that these strains were pathogenic, with Salmonella-fed C. elegans dying faster (mean survival time between 3 and 4 days) than controls, i.e., Escherichia coli-fed C. elegans (mean survival time of 9.5 days). Cells of these isolates inoculated into water at a density of up to 10(6) ml(-1) water declined numerically by 3 orders of magnitude within 2 days, reaching the detection limit of our quantitative polymerase chain reaction (qPCR)-based quantification technique (i.e., 10(3) cells ml(-1)). Similar patterns were obtained for cells in heterogeneous aquatic biofilms developed on tiles and originally free of Salmonella that were kept in the inoculated water. Cell numbers increased during the first days to more than 10(7) cells cm(-2), and then declined over time. Ten-fold higher cell numbers of Salmonella inoculated into water or into biofilm resulted in similar patterns of population dynamics, though cells in biofilms remained detectable with numbers around 10(4) cells cm(-2) after 4 weeks. Independent of detectability by qPCR, samples of all treatments harbored viable salmonellae that resembled the inoculated isolates after 4 weeks of incubation. These results demonstrate that pathogenic salmonellae were isolated from heterogeneous aquatic biofilms and that they could persist and stay viable in such biofilms in high numbers for some time.

In most bacteria, a global level of regulation exists involving intercellular communication via the production and response to cell density-dependent signal molecules. This cell density-dependent regulation has been termed quorum sensing (QS). QS is a global regulator, which has been associated with a number of important features in bacteria including virulence regulation and biofilm formation. Consequently, there is considerable interest in understanding, detecting, and inhibiting QS. Acyl homoserine lactones (acyl HSLs) are used as extracellular QS signals by a variety of Gram-negative bacteria. Chromobacterium violaceum, a Gram-negative bacterium commonly found in soil and water, produces the characteristic purple pigment violacein, the production of which is regulated by acyl HSL-mediated QS. Based on this readily observed pigmentation phenotype, C. violaceum strains can be used to detect various aspects of acyl HSL-mediated QS activity. In another commonly used bioassay organism, Agrobacterium tumefaciens, QS can be detected by the use of a reporter gene such as lacZ. Here, we describe several commonly used approaches incorporating C. violaceum and A. tumefaciens that can be used to detect acyl HSLs and QS inhibition.

Quorum sensing (QS) is a cell density dependent expression of species in bacteria mediated by hormone like compounds called autoinducers (AI). Several processes responsible for successful establishment of bacterial infection are mediated by QS. Inhibition of QS is therefore being considered as a new target for antimicrobial chemotherapy. Dietary phytochemicals are secondary metabolites in plants known to have several health benefits including antimicrobial activity. However, their ability to inhibit QS has never been studied. Our objective was to investigate the effect of sub-lethal concentrations (SLC) of bioactive dietary phytochemical extracts from common dietary fruit, herb and spice extracts on modulating QS mediated by AI in model bioassay test systems. QS inhibition was measured in violacein pigment producing Chromobacterium violaceum O26 (CVO26) and CV 31532 system, mediated by AI known as acylated homeserine lactone (AHL). We also investigated the effect of the sub-lethal concentrations of the extracts on swarming motility of pathogens Escherichia coli (EC)O157:H7 and Pseudomonas aeruginosa (PA-01). Our results indicate that all extracts significantly inhibited quorum sensing. The mechanism of inhibition appeared to be combination of interfering with AHL activity and modulating the synthesis of AHL's. Our results also indicated that various phytochemical extracts which inhibited QS also inhibited swarming of pathogenic bacteria, known to be modulated by QS. The observation that phytochemicals from foods can inhibit QS related processes opens up an exciting new strategy for antimicrobial chemotherapy and lead to the discovery of new category of antibiotics which can overcome the issues related to antimicrobial resistance.

In the current study, we screened 7 clonal lines from single seed phenotypes of Lamiaceae family for the inhibition of alpha-amylase, alpha-glucosidase and angiotensin converting enzyme (ACE) inhibitory activity. Water extracts of oregano had the highest alpha-glucosidase inhibition activity (93.7%), followed by chocolate mint (85.9%) and lemon balm (83.9%). Sage (78.4 %), and three different clonal lines of rosemary: rosemary LA (71.4%), rosemary 6 (68.4%) and rosemary K-2 (67.8%) also showed significant alpha-glucosidase inhibitory activity. The alpha-glucosidase inhibitory activity of the extracts was compared to selected specific phenolics detected in the extracts using HPLC. Catechin had the highest alpha-glucosidase inhibitiory activity (99.6 %) followed by caffeic acid (91.3 %), rosmarinic acid (85.1%) and resveratrol (71.1 %). Catechol (64.4%), protocatechuic acid (55.7%) and quercetin (36.9%) also exhibited significant alpha-glucosidase inhibitory activity. Results suggested that alpha-glucosidase inhibitory activity of the clonal extracts correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. The clonal extracts of the herbs and standard phenolics tested in this study did not have any effect on the alpha-amylase activity. We also investigated the ability of the clonal extracts to inhibit rabbit lung angiotensin I-converting enzyme (ACE). The water extracts of rosemary, rosemary LA had the highest ACE inhibitory activity (90.5%), followed by lemon balm (81.9%) and oregano (37.4 %). Lower levels of ACE inhibition were observed with ethanol extracts of oregano (18.5 %) and lemon balm (0.5 %). Among the standard phenolics only resveratrol (24.1 %), hydroxybenzoic acid (19.3 %) and coumaric acid (2.3 %) had ACE inhibitory activity.

Emerging epidemiological evidence is increasingly pointing to the beneficial effects of fruits and vegetables in managing chronic and infectious diseases. These beneficial effects are now suggested to be due to the constituent phenolic phytochemicals having antioxidant activity. Cranberry like other fruits is also rich in phenolic phytochemicals such as phenolic acids, flavonoids and ellagic acid. Consumption of cranberry has been historically been linked to lower incidences of urinary tract infections and has now been shown to have a capacity to inhibit peptic ulcer-associated bacterium, Helicobacter pylori. Isolated compounds from cranberry have also been shown to reduce the risk of cardiovascular diseases. Recent evidence suggests the ability of phytochemical components in whole foods in being more effective in protectively supporting human health than compared to isolated individual phenolic phytochemicals. This implies that the profile of phenolic phytochemicals determines the functionality of the whole food as a result of synergistic interaction of constituent phenolic phytochemicals. Solid state bioprocessing using food grade fungi common in Asian food cultures as well as cranberry phenolic synergies through the addition of functional biphenyls such as ellagic acid and rosmarinic acid along with processed fruit extracts have helped to advance these concepts. These strategies could be further explored to enrich cranberry and cranberry products with functional phytochemicals and further improve their functionality for enhancing health benefits.