Gene Expression and Metabolome Analysis Reveals Anti-Inflammatory Impacts of 11,17diHDoPE on PM10-Induced Mouse Lung Inflammation.

Oxylipins, the metabolites of polyunsaturated fatty acids, are vital in regulating cell proliferation and inflammation. Among these oxylipins, specialized pro-resolving mediators notably contribute to inflammation resolution. Previously, we showed that the specialized pro-resolving mediators isomer 11,17dihydroxy docosapentaenoic acid (11,17diHDoPE) can be synthesized in bacterial cells and exhibits anti-inflammatory effects in mammalian cells. This study investigates the in vivo impact of 11,17diHDoPE in mice exposed to particulate matter 10 (PM10). Our results indicate that 11,17diHDoPE significantly mitigates PM10-induced lung inflammation in mice, as evidenced by reduced pro-inflammatory cytokines and pulmonary inflammation-related gene expression. Metabolomic analysis reveals that 11,17diHDoPE modulates inflammation-related metabolites such as threonine, 2-keto gluconic acid, butanoic acid, and methyl oleate in lung tissues. In addition, 11,17diHDoPE upregulates the LA-derived oxylipin pathway and downregulates arachidonic acid- and docosahexaenoic acid-derived oxylipin pathways in serum. Correlation analyses between gene expression and metabolite changes suggest that 11,17diHDoPE alleviates inflammation by interfering with macrophage differentiation. These findings underscore the in vivo role of 11,17diHDoPE in reducing pulmonary inflammation, highlighting its potential as a therapeutic agent for respiratory diseases.

Metabolomic Comparison of Guava (Psidium guajava L.) Leaf Extracts Fermented by Limosilactobacillus fermentum and Lactiplantibacillus plantarum and Their Antioxidant and Antiglycation Activities.

Probiotic fermentation of plant-based materials can lead to the generation of various bioactive substances via bacterial metabolites and the biotransformation of phenolic compounds. We compared the metabolic differences between fermentation by Limosilactobacillus fermentum KCTC15072BP (LFG) and fermentation by Lactiplantibacillus plantarum KGMB00831 (LPG) in guava leaf extract (0%, 0.5%, and 2% (w/v))-supplemented medium via non-targeted metabolite profiling. By performing multivariate statistical analysis and comparing the different guava leaf extract groups, 21 guava-derived and 30 bacterial metabolites were identified. The contents of guava-derived glucogallin, gallic acid, and sugar alcohols were significantly higher in LFG than they were in LPG. Similarly, significantly higher contents of guava-derived pyrogallol, vanillic acid, naringenin, phloretin, and aromatic amino acid catabolites were obtained with LPG than with LFG. LFG led to significantly higher antioxidant activities than LPG, while LPG led to significantly higher antiglycation activity than LFG. Interestingly, the fermentation-induced increase in the guava-leaf-extract-supplemented group was significantly higher than that in the control group. Thus, the increased bioactivity induced by guava fermentation with the Lactobacillaceae strain may be influenced by the synergistic effects between microbial metabolites and plant-derived compounds. Overall, examining the metabolic changes in plant-based food fermentation by differentiating the origin of metabolites provides a better understanding of food fermentation.

Qualitative and Quantitative Metabolite Comparison of Korean Traditional Alcoholic Beverages: Takju, Yakju, and Traditional-Soju.

With increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.

Metabolomics Reveals the Effects of Nitrogen/Phosphorus/Potassium (NPK) Fertilizer Levels on Cucumber Fruit Raised in Different Nutrient Soils.

Fertilizers are widely used to improve the quality of fruits and vegetables. However, the overuse of fertilizers has become an issue because it causes environmental problems and negatively affects productivity and fruit quality. In this study, we examined the effects of nitrogen, phosphorus, and potassium (NPK) fertilizer levels on the metabolism of cucumber fruit in low- and high-nutrient soils using mass-spectrometry-based metabolomics approaches. Cucumber metabolite content was notably different depending on the initial soil nutrient status. Most amino acids and phenylpropanoids were abundant in the cucumbers raised in low-nutrient soil, whereas organic acids, some amino acids (aspartate, glutamate, and ornithine), and carbohydrates were comparatively higher in fruits from high-nutrient soil. The fertilizer supply resulted in an alteration in the metabolite profile, while no change in fruit yield was observed in either low- or high-nutrient soils. Fertilizer treatment perturbed the metabolite contents in cucumbers from low-nutrient soil. In contrast, treatment with higher concentrations of fertilizer in high-nutrient soil increased phenylpropanoid content in the cucumbers, while most metabolites decreased. In conclusion, fertilization levels should be carefully determined, considering culture conditions such as the original soil status, to increase product yield and fruit quality and avoid environmental problems.

Combination of Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 attenuates fat accumulation and alters the metabolome and gut microbiota in mice with high-fat diet-induced obesity.

This study evaluated the effects of formulations with Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 on adiposity, the alteration of microbiota, and the metabolome in high-fat diet-fed mice. The strains were selected based on their fat and glucose absorption inhibitory activities and potential metabolic interactions. The optimal ratio of the two strains in the probiotic formulation was determined based on their adipocyte differentiation inhibitory activities. Treatment of formulations with BEPC22 and BELP53 for 10 weeks decreased body weight gain at 6 weeks; it also decreased the food efficiency ratio, white adipose tissue volume, and adipocyte size. Moreover, it decreased the expression of the lipogenic gene Ppar-γ in the liver, while significantly increasing the expression of the fat oxidation gene Ppar-α in the white adipose tissue. Notably, treatment with a combination of the two strains significantly reduced the plasma levels of the obesity hormone leptin and altered the microbiota and metabolome. The omics data also indicated the alteration of anti-obesity microbes and metabolites such as Akkermansia and indolelactic acid, respectively. These findings suggest that treatment with a combination of BEPC22 and BELP53 exerts synergistic beneficial effects against obesity.

Strain-specific metabolomic diversity of Lactiplantibacillus plantarum under aerobic and anaerobic conditions.

The chemotaxonomic diversity of 20 Lactiplantibacillus plantarum strains was investigated using non-targeted metabolite profiling under different culture conditions. Multivariate and metabolic pathway analyses based on GC-MS and LC-MS/MS datasets showed that amino acid metabolism, especially 2-hydroxy acids, was enriched under aerobic conditions (AE), whereas fatty acid & sugar metabolism was increased under anaerobic conditions (AN). Based on the metabolite profiles, L. plantarum strains were clustered into three main groups (A, B, and C). Overall, 79 and 83 significantly discriminant metabolites were characterized as chemical markers of AE and AN growth conditions, respectively. Notably, alcohols were more abundant in group A whereas amino acids, peptides, purines, and pyrimidines were significantly higher in group C. 2-hydroxy acids and oxylipins biosynthesized through amino acid and fatty acid metabolism, respectively, were more abundant in groups A and B. Furthermore, we observed a strong correlation between the chemical diversity of L. plantarum groups and their antioxidant activity from metabolite extracts. We propose a non-targeted metabolomic workflow to comprehensively characterize the chemodiversity of L. plantarum strain under different culture conditions, which may help reveal specific biomarkers of individual strains depending on the culture conditions.

Peripheral metabolic alterations associated with pathological manifestations of Parkinson's disease in gut-brain axis-based mouse model.

Introduction: Parkinson's disease (PD) is a representative neurodegenerative disease, and its diagnosis relies on the evaluation of clinical manifestations or brain neuroimaging in the absence of a crucial noninvasive biomarker. Here, we used non-targeted metabolomics profiling to identify metabolic alterations in the colon and plasma samples of Proteus mirabilis (P. mirabilis)-treated mice, which is a possible animal model for investigating the microbiota-gut-brain axis. Methods: We performed gas chromatography-mass spectrometry to analyze the samples and detected metabolites that could reflect P. mirabilis-induced disease progression and pathology. Results and discussion: Pattern, correlation and pathway enrichment analyses showed significant alterations in sugar metabolism such as galactose metabolism and fructose and mannose metabolism, which are closely associated with energy metabolism and lipid metabolism. This study indicates possible metabolic factors for P. mirabilis-induced pathological progression and provides evidence of metabolic alterations associated with P. mirabilis-mediated pathology of brain neurodegeneration.

Antiinflammatory effect of the ethanolic extract of Korean native herb Potentilla rugulosa Nakai in Bisphenol-a-stimulated A549 cells.

Potentilla rugulosa Nakai (P. rugulosa) is a perennial herb in the Rosaceae family and found in the Korean mountains. Previously, our findings demonstrated that P. rugulosa contains numerous polyphenols and flavonoids exhibiting important antioxidant and anti-obesity bioactivities. Bisphenol A (BPA) is a xenoestrogen that was shown to produce pulmonary inflammation in humans. However, the mechanisms underlying BPA-induced inflammation remain to be determined. The aim of this study was to examine whether ethanolic extract of P. rugulosa exerted an inhibitory effect on BPA-induced inflammation utilizing an adenocarcinoma human alveolar basal epithelial cell line A549. The P. rugulosa extract inhibited BPA-mediated cytotoxicity by reducing levels of reactive oxygen species (ROS). Further, P. rugulosa extract suppressed the upregulation of various pro-inflammatory mediators induced by activation of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, inhibition of the NF-κB and MAPK signaling pathways by P. rugulosa extract was found to occur via decrease in the transcriptional activity of NF-κB. Further, blockade of phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and stress-activated protein kinase/Jun N-terminal kinase (SAPK/JNK) was noted. Thus, our findings suggest that the ethanolic extract of P. rugulosa may act as a natural anti-inflammatory therapeutic agent.

Bidirectional Interactions between Green Tea (GT) Polyphenols and Human Gut Bacteria.

Green tea (GT) polyphenols undergo extensive metabolism within gastrointestinal tract (GIT), where their derivatives compounds potentially modulate the gut microbiome. This biotransformation process involves a cascade of exclusive gut microbial enzymes which chemically modify the GT polyphenols influencing both their bioactivity and bioavailability in host. Herein, we examined the in vitro interactions between 37 different human gut microbiota and the GT polyphenols. UHPLC-LTQ-Orbitrap-MS/MS analysis of the culture broth extracts unravel that genera Adlercreutzia, Eggerthella and Lactiplantibacillus plantarum KACC11451 promoted C-ring opening reaction in GT catechins. In addition, L. plantarum also hydrolyzed catechin galloyl esters to produce gallic acid and pyrogallol, and also converted flavonoid glycosides to their aglycone derivatives. Biotransformation of GT polyphenols into derivative compounds enhanced their antioxidant bioactivities in culture broth extracts. Considering the effects of GT polyphenols on specific growth rates of gut bacteria, we noted that GT polyphenols and their derivate compounds inhibited most species in phylum Actinobacteria, Bacteroides, and Firmicutes except genus Lactobacillus. The present study delineates the likely mechanisms involved in the metabolism and bioavailability of GT polyphenols upon exposure to gut microbiota. Further, widening this workflow to understand the metabolism of various other dietary polyphenols can unravel their biotransformation mechanisms and associated functions in human GIT.

Effects of Fermented Artemisia annua L. and Salicornia herbacea L. on Inhibition of Obesity In Vitro and In Mice.

Plant extracts including secondary metabolites have anti-inflammatory and anti-obesity activities. This study was conducted to investigate the anti-obesity properties of fermented Artemisia annua (AW) and Salicornia herbacea (GW) in vitro and in mice. The metabolite profiling of AW and GW extracts was performed using UHPLC-LTQ-Orbitrap-MS/MS, and gene expression was analyzed using real-time PCR for adipocyte difference factors. The anti-obesity effects in mice were measured using serum AST, ALT, glucose, TG, and cholesterol levels. Metabolites of the plant extracts after fermentation showed distinct differences with increasing anti-obesity active substances. The efficacy of inhibitory differentiation adipogenesis of 3T3-L1 adipocytes was better for GW than AW in a concentration-dependent manner. RT-PCR showed that the GW extract significantly reduced the expression of genes involved in adipocyte differentiation and fat accumulation (C/EBPα, PPARγ, and Fas). In C57BL/6 mice fed the HFD, the group supplemented with AW and GW showed reduced liver weight, NAS value, and fatty liver by suppressing liver fat accumulation. The GW group significantly reduced ALT, blood glucose, TG, total cholesterol, and LDL-cholesterol. This study displayed significant metabolite changes through biotransformation in vitro and the increasing anti-obesity effects of GW and AW in mice. GW may be applicable as functional additives for the prevention and treatment of obesity.

Genome-scale metabolic modeling and in silico analysis of opportunistic skin pathogen Cutibacterium acnes.

Cutibacterium acnes, one of the most abundant skin microbes found in the sebaceous gland, is known to contribute to the development of acne vulgaris when its strains become imbalanced. The current limitations of acne treatment using antibiotics have caused an urgent need to develop a systematic strategy for selectively targeting C. acnes, which can be achieved by characterizing their cellular behaviors under various skin environments. To this end, we developed a genome-scale metabolic model (GEM) of virulent C. acnes, iCA843, based on the genome information of a relevant strain from ribotype 5 to comprehensively understand the pathogenic traits of C. acnes in the skin environment. We validated the model qualitatively by demonstrating its accuracy prediction of propionate and acetate production patterns, which were consistent with experimental observations. Additionally, we identified unique biosynthetic pathways for short-chain fatty acids in C. acnes compared to other GEMs of acne-inducing skin pathogens. By conducting constraint-based flux analysis under endogenous carbon sources in human skin, we discovered that the Wood-Werkman cycle is highly activated under acnes-associated skin condition for the regeneration of NAD, resulting in enhanced propionate production. Finally, we proposed potential anti-C. acnes targets by using the model-guided systematic framework based on gene essentiality analysis and protein sequence similarity search with abundant skin microbiome taxa.

Anti-inflammatory effects of Athyrium yokoscense extract via inhibition of the Erk1/2 and NF-κB pathways in bisphenol A-stimulated A549 cells.

Bisphenol A is an environmental endocrine disruptor that has similar functions to estrogen in humans. However, few studies have investigated pulmonary inflammation induced by BPA, and the effect of Athyrium yokoscense extract on this inflammatory response is unknown. In this study, we investigated this effect in A549 human alveolar epithelial cells. BPA at concentrations higher than 100 µM were cytotoxic to A549 cells at 24 and 48 h after treatment; however, AYE (100 µg/mL) had a protective effect against BPA-induced cytotoxicity. AYE also inhibited the generation of intracellular reactive oxygen species, expressions of cyclooxygenase-2 and extracellular signal-regulated kinase1/2 proteins, activities of phospholipase A2, COX-2, nuclear factor kappa-light-chain-enhancer of activated B cells, and proinflammatory mediators including prostaglandin E2, tumor necrosis factor-α, and interleukin-6 induced by BPA in A549 cells. This study demonstrated that BPA, which induces chronic lung disease, causes oxidative stress and inflammatory response in lung epithelial cell line, and found that AYE reduces BPA-induced oxidative stress and inflammatory response by down-regulating the Erk1/2 and NF-κB pathways.

Protective effects of CCL01 against Aß-induced neurotoxicity in 5xFAD transgenic mouse model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common dementia characterized by the excessive accumulation of amyloid-beta (Aß) and tau aggregates, as well as neuronal damage and neuroinflammation. Metabolic disruption in AD has been noticed because metabolite alterations closely correlate with Aß neuropathology and behavioral phenotypes. Accordingly, controlling various neuropathological processes and metabolic disruption is an efficient therapeutic strategy for AD treatment. In this study, we evaluated the effects of a combination of Cuscuta seeds and Lactobacillus paracasei NK112 (CCL01) on AD neuropathology and altered metabolism in five familial AD (5xFAD) transgenic mice and neuronal cell cultures. First, we observed that CCL01 exerted neuroprotective effects in HT22 hippocampal neurons and primary cultured neurons. CCL01 ameliorated memory decline and protected synapses and neuronal survival in 5xFAD mice. These effects were related to the inhibition of tau phosphorylation. CCL01 also inhibited the activation of mitogen-activated protein kinase (MAPK) signaling and neuroinflammatory processes. Moreover, the metabolite profile-particularly characterized by altered phospholipid metabolism-was significantly changed in the 5xFAD group, while CCL01 partly restored the alteration. Lysophosphatidylcholine (lysoPC), the levels of which were higher in the brains of 5xFAD mice, exerted neurotoxicity in vitro, whereas CCL01 protected neurons from lysoPC-induced toxicity by regulating MAPK signaling. Additionally, CCL01 administration reduced gut inflammation in the 5xFAD mice. In summary, we demonstrated that CCL01 improved the memory function of 5xFAD mice by protecting neurons against Aß- and lysoPC-induced toxicity through the regulation of MAPK signaling, neuroinflammation, tau phosphorylation, and gut inflammation, suggesting the potential of CCL01 as treatment for AD.

Sophora flavescens Aiton methanol extract exerts anti-inflammatory effects via reduction of Src kinase phosphorylation.

ETHNOPHARMACOLOGICAL RELEVANCE: Sophora flavescens Aiton (Family: Leguminosae), an herbal plant, has been used in East Asian home remedies for centuries for treating ulcers, skin burns, fevers, and inflammatory disorders. In addition, the dried root of S. flavescens was also applied for antipyretic, analgesic, antihelmintic, and stomachic uses. AIM OF STUDY: Nonetheless, how this plant can show various pharmacological activities including anti-inflammatory responses was not fully elucidated. In this study, therefore, we aimed to investigate the curative effects of S. flavescens on inflammation and its molecular mechanism. MATERIALS AND METHODS: For reaching this aim, various in vitro and in vivo experimental models with LPS-treated RAW264.7 cells, HCl/EtOH-induced gastric ulcer, and LPS-triggered lung injury conditions were employed and anti-inflammatory activity of S. flavescens methanol extract (Sf-ME) was also tested. Fingerprinting profile of Sf-ME was identified via LC-MS analysis. Its anti-inflammatory molecular mechanism was also examined by immunoblotting analysis. RESULTS: Nitric oxide production and mRNA expression levels of iNOS, COX-2, IL-1ß, and TNF-α were decreased. Additionally, phosphorylation of Src in the signaling cascade was decreased, and activities of the transcriptional factor NF-κB were reduced as determined by a luciferase reporter assay. Moreover, in vivo, gastritis and lung injury lesions were attenuated by Sf-ME. CONCLUSION: Taken together, these findings suggest that Sf-ME could be a potential anti-inflammatory therapeutic agent via suppression of Src kinase activity and regulation of IL-1ß secretion.

Psychophysiological Responses of Humans during Seed-Sowing Activity Using Soil Inoculated with Streptomyces rimosus.

Electroencephalogram (EEG) responses and serum metabolite levels were used to investigate the effects of horticultural activities (seed-sowing) on the psychophysiological aspects of adults based on the presence or absence of the soil microorganism Streptomyces rimosus. In this case, 31 adults were subjected to seed-sowing activities using S. rimosus inoculated (experimental group) and medium (control group) soils. EEG was measured to analyze the resulting psychophysiological response, and blood samples (5 mL) were collected. The relative gamma power (RG), relative high beta (RHB), and SEF 50 and SEF 90 were significantly higher in the right than in the left occipital lobe (p < 0.05). In both occipital lobes, ratios of SMR to theta (RST), mid beta to theta (RMT), and SMR-mid beta to theta (RSMT) were high (p < 0.05). GC-TOF-MS-based serum metabolite analysis detected 33 metabolites. Compared to the control group, the experimental group showed a lower content of amino acids (except aspartic acid), lipids, and C6 sugar monomers after the activity (p < 0.05). Aminomalonic acid was decreased, and aspartic acid was increased (p < 0.05). This study confirmed a positive effect on improving the concentration and attention of adults when seed-sowing activity was performed using S. rimosus-inoculated soil.

Comprehensive Metabolite Profiling of Four Different Beans Fermented by Aspergillus oryzae.

Fermented bean products are used worldwide; most of the products are made using only a few kinds of beans. However, the metabolite changes and contents in the beans generally used during fermentation are unrevealed. Therefore, we selected four different beans (soybean, Glycine max, GM; wild soybean, Glycine soja, GS; common bean, Phaseolus vulgaris, PV; and hyacinth bean, Lablab purpureus, LP) that are the most widely consumed and fermented with Aspergillus oryzae. Then, metabolome and multivariate statistical analysis were performed to figure out metabolite changes during fermentation. In the four beans, carbohydrates were decreased, but amino acids and fatty acids were increased in the four beans as they fermented. The relative amounts of amino acids were relatively abundant in fermented PV and LP as compared to other beans. In contrast, isoflavone aglycones (e.g., daidzein, glycitein, and genistein) and DDMP-conjugated soyasaponins (e.g., soyasaponins ßa and γg) were increased in GM and GS during fermentation. Notably, these metabolite changes were more significant in GS than GM. In addition, the increase of antioxidant activity in fermented GS was significant compared to other beans. We expect our research provides a basis to extend choice for bean fermentation for consumers and food producers.

Psychophysiological and Metabolomics Responses of Adults during Horticultural Activities Using Soil Inoculated with Streptomyces rimosus: A Pilot Study.

This study compared the physiological effects at a metabolomics level with autonomic nervous system responses in adults during soil mixing activities, based on the presence or absence of Streptomyces rimosus in the soil. Thirty adult participants performed soil mixing activities for 5 min using sterilized soil with culture media and Streptomyces rimosus, respectively. Blood samples were drawn twice from each participant after each activity. Electroencephalograms were measured during the activity. Serum metabolites underwent metabolite profiling by gas chromatography, followed by multivariate analyses. Serum brain-derived neurotrophic factor and C-reactive protein levels were measured by Enzyme-Linked Immunosorbent Assay. Soil-emitted volatile organic compounds were identified via solid-phase microextraction and gas chromatography-mass spectroscopy, followed by multivariate analyses. The volatile compound analysis revealed that the terpenoid and benzoid compounds, geosmin, and 2-methylisoborneol were greater in soil with Streptomyces rimosus. Serum metabolomics revealed that the treatment group (soil inoculated with Streptomyces rimosus) possessed relatively higher levels of serotonin compared to the control group (soil mixed with culture media), and serum C-reactive protein levels were significantly lower in the treatment group. In the treatment group, the electroencephalogram revealed that alpha band activity of the occipital lobe increased. This study concludes that Streptomyces rimosus soil contact can positively affect human metabolic and autonomic reactions. Therefore, this pilot study confirmed the possible role of soil microorganisms in horticultural activities for psychophysiological effects in humans.

Non-targeted metabolomic analysis for the comparative evaluation of volatile organic compounds in 20 globally representative cucumber lines.

Volatile organic compounds (VOCs) are one of the main fruit-quality determinants in cucumber. Here, we investigated the differences in the VOC and primary metabolite composition among 20 representative cucumber lines. Results of non-targeted metabolomics revealed that the cucumber breeding line of the Korean group showed a unique VOC composition in the fruit peel compared to the other groups. Fruit-flesh VOCs significantly differed among Korean, European, and Thai fruits. The main cucumber flavor components, 2-hexenal, hexanal, 6-nonenal, 2,4-nonadienal, and 2,6-nonadienal, were lower in the Korean cucumber lines than in the others. Conversely, linoleic acid derivatives and α-linolenic acid, which are precursors of these VOCs, were abundant in Korean cucumber line. This suggests that the metabolism related to the characteristic flavor of cucumber are downregulated in Korean cucumber line. This study provides novel insights into the fruit flavor-associated metabolome in various cucumber lines.

Effects of limited water supply on metabolite composition in tomato fruits (Solanum lycopersicum L.) in two soils with different nutrient conditions.

Effect of water supply to metabolites in tomato fruit was compared in two soils with different nutrient conditions, i.e., either limited or excess. Two types of soil nutrient condition, type A: nutrient-limited and type B: nutrient-excess, were prepared as follows; type A is a low nutrient-containing soil without a replenishment of starved nitrogen and phosphorous, type B is a high nutrient-containing soil exceeding the recommended fertilization. Soil water was adjusted either at -30 kPa (sufficient) or -80 kPa (limited). For harvested tomato fruits, we examined primary and secondary metabolites using non-targeted mass spectrometry based metabolomics. The fruit production and leaf SPAD were greatly dependent on soil nutrient levels, by contrast, the level of lycopene remained unchanged by different levels of water and nutrient supply. The perturbation of metabolites by water supply was clear in the nutrient-excess soil. In particular, limited water supply strongly decreased primary metabolites including sugars and amino acids. We demonstrated that water stress differently shifted primary metabolites of tomato fruits in two soils with different nutrient conditions via non-targeted mass spectrometry-based metabolomics. In conclusion, we suggest that the limited water supply in soils with surplus nutrient is not a recommendable way for tomato 'cv. Super Dotaerang' production if fruit nutritional quality such as sugars and amino acids is in the consideration, although there was no disadvantage in fruit yield.

Inhibition of α-synuclein aggregation by MT101-5 is neuroprotective in mouse models of Parkinson's disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease, and becomes increasingly prevalent with age. α-Synuclein (α-syn) forms the major filamentous component of Lewy bodies, which are pathological hallmarks of α-synucleinopathies such as PD. We evaluated the neuroprotective effects of MT101-5, a standardized herbal formula that consists of an ethanolic extract of Genkwae Flos, Clematidis Radix, and Gastrodiae Rhizoma, against α-synuclein-induced cytotoxicity in vivo. MT101-5 protected against behavioral deficits and loss of dopaminergic neurons in human α-syn-overexpressing transgenic mice after treatment with 30 mg/kg/day for 5 months. We investigated transcriptomic changes within MT101-5 mechanisms of action (MOA) suppressing α-syn aggregation in an α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic PD. We found that inhibition of α-syn fibril formation was associated with changes in transcripts in mitochondrial biogenesis, electron transport, chaperones, and proteasomes following treatment with MT101-5. These results suggest that the mixed herbal formula MT101-5 may be used as a pharmaceutical agent for preventing or improving PD.