PubMed

bioRxiv. 2023 Oct 24:2023.10.23.563601. doi: 10.1101/2023.10.23.563601. Preprint.ABSTRACTAdenosine triphosphate (ATP) serves as an extracellular messenger that mediates diverse cell-to-cell communication. Compelling evidence supports that ATP is released from cells through pannexins, a family of heptameric large pore-forming channels. However, the activation mechanisms that trigger ATP release by pannexins remain poorly understood. Here, we discover lysophospholipids as endogenous pannexin activators, using activity-guided fractionation of mouse tissue extracts combined with untargeted metabolomics and electrophysiology. We show that lysophospholipids directly and reversibly activate pannexins in the absence of other proteins. Molecular docking, mutagenesis, and single-particle cryo-EM reconstructions suggest that lysophospholipids open pannexin channels by altering the conformation of the N-terminal domain. Our results provide a connection between lipid metabolism and ATP signaling, both of which play major roles in inflammation and neurotransmission.ONE-SENTENCE SUMMARY: Untargeted metabolomics discovers a class of messenger lipids as endogenous activators of membrane channels important for inflammation and neurotransmission.PMID:37961151 | PMC:PMC10634739 | DOI:10.1101/2023.10.23.563601

J Food Sci. 2023 Nov 13. doi: 10.1111/1750-3841.16828. Online ahead of print.ABSTRACTIn this study, we analyzed the differences in metabolites between semiwaxy japonica rice (Yangnongxiang 28 [YNX28]) and conventional japonica rice (Hongyang 5 [HY5]) before and after brown rice milling. The metabolites of brown and milled rice grains from the two rice varieties were analyzed by LC-MS-based nontargeted metabolomics. A total of 266 differentially abundant metabolites (DMs) were tentatively identified in brown rice grains of YNX28 (YNX28B) compared with milled rice grains of YNX28 (YNX28H), and these included 248 upregulated and 12 downregulated DMs. A total of 273 (234 upregulated and 39 downregulated) DMs were tentatively identified in brown rice grains of HY5 (HY5B) compared with milled rice grains of this variety (HY5H). Kyoto Encyclopedia of Genes and Genomes pathway involved and enrichment analyses revealed that 53 and 7 metabolite pathways were enriched and significantly enriched (p < 0.05), respectively, in the DMs identified in YNX28B compared with YNX28H, and the main enriched pathways were related to starch and sucrose metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and glycine, serine and threonine metabolism. Forty-six metabolite pathways were enriched in DMs identified in HY5B compared with HY5H, and these included 16 pathways that were significantly enriched (p < 0.05); in addition, the main enriched pathways were related to starch and sucrose metabolism, glycerol phospholipid metabolism, arginine and proline metabolism, and glycine, serine and threonine metabolism. This study provides a theoretical reference for further on the changes in metabolites during rice processing and provides a basis for improving the nutritional quality in rice. PRACTICAL APPLICATION: Original data were obtained regarding the changes of different metabolites in semiwaxy japonica rice and conventional japonica rice before and after processing. The purpose of this study was to investigate the difference of metabolite loss in two rice varieties before and after processing. This paper reports on the differences of metabolites between the two types of japonica rice before and after processing, as well as the changes of key metabolites before and after processing, it also provides important theoretical basis for developing new rice varieties with good nutritional quality.PMID:37960988 | DOI:10.1111/1750-3841.16828

Aging Cell. 2023 Nov 13:e14009. doi: 10.1111/acel.14009. Online ahead of print.ABSTRACTDuring aging, muscle gradually undergoes sarcopenia, the loss of function associated with loss of mass, strength, endurance, and oxidative capacity. However, the 3D structural alterations of mitochondria associated with aging in skeletal muscle and cardiac tissues are not well described. Although mitochondrial aging is associated with decreased mitochondrial capacity, the genes responsible for the morphological changes in mitochondria during aging are poorly characterized. We measured changes in mitochondrial morphology in aged murine gastrocnemius, soleus, and cardiac tissues using serial block-face scanning electron microscopy and 3D reconstructions. We also used reverse transcriptase-quantitative PCR, transmission electron microscopy quantification, Seahorse analysis, and metabolomics and lipidomics to measure changes in mitochondrial morphology and function after loss of mitochondria contact site and cristae organizing system (MICOS) complex genes, Chchd3, Chchd6, and Mitofilin. We identified significant changes in mitochondrial size in aged murine gastrocnemius, soleus, and cardiac tissues. We found that both age-related loss of the MICOS complex and knockouts of MICOS genes in mice altered mitochondrial morphology. Given the critical role of mitochondria in maintaining cellular metabolism, we characterized the metabolomes and lipidomes of young and aged mouse tissues, which showed profound alterations consistent with changes in membrane integrity, supporting our observations of age-related changes in muscle tissues. We found a relationship between changes in the MICOS complex and aging. Thus, it is important to understand the mechanisms that underlie the tissue-dependent 3D mitochondrial phenotypic changes that occur in aging and the evolutionary conservation of these mechanisms between Drosophila and mammals.PMID:37960952 | DOI:10.1111/acel.14009

Nutrients. 2023 Nov 2;15(21):4651. doi: 10.3390/nu15214651.ABSTRACTBackground: Kashin-Beck disease (KBD) is a distinct osteoarthropathy in China with an unclear pathogenesis. This study aims to explore whether perturbations in the intestine metabolome could be linked to KBD individuals. Methods: An investigation was conducted in KBD endemic villages and fecal samples were collected. After applying inclusion and exclusion criteria, a total of 75 subjects were enrolled for this study, including 46 KBD (including 19 Grade I KBD and 27 Grade II KBD) and 29 controls. Untargeted metabolomics analysis was performed on the platform of UHPLC-MS. PLS-DA and OPLS-DA were conducted to compare the groups and identify the differential metabolites (DMs). Pathway analysis was conducted on MPaLA platform to explore the functional implication of the DMs. Results: Metabolomics analysis showed that compared with the control group, KBD individuals have a total of 584 differential metabolites with dysregulated levels such as adrenic acid (log2FC = -1.87, VIP = 4.84, p = 7.63 × 10-7), hydrogen phosphate (log2FC = -2.57, VIP = 1.27, p = 1.02 × 10-3), taurochenodeoxycholic acid (VIP = 1.16, log2FC = -3.24, p = 0.03), prostaglandin E3 (VIP = 1.17, log2FC = 2.67, p = 5.61 × 10-4), etc. Pathway analysis revealed several significantly perturbed pathways associated with KBD such as selenium micronutrient network (Q value = 3.11 × 10-3, Wikipathways), metabolism of lipids (Q value = 8.43 × 10-4, Reactome), free fatty acid receptors (Q value = 3.99 × 10-3, Reactome), and recycling of bile acids and salts (Q value = 2.98 × 10-3, Reactome). Subgroup comparisons found a total of 267 differential metabolites were shared by KBD vs. control, KBD II vs. control, and KBD I vs. control, while little difference was found between KBD II and KBD I (only one differential metabolite detected). Conclusions: KBD individuals showed distinct metabolic features characterized by perturbations in lipid metabolism and selenium-related bioprocesses. Our findings suggest that the loss of nutrients metabolism balance in intestine was involved in KBD pathogenesis. Linking the nutrients metabolism (especially selenium and lipid) to KBD cartilage damage should be a future direction of KBD study.PMID:37960304 | DOI:10.3390/nu15214651

Nutrients. 2023 Nov 1;15(21):4639. doi: 10.3390/nu15214639.ABSTRACTTaste disorders are common among cancer patients undergoing chemotherapy, with a prevalence ranging from 20% to 86%, persisting throughout treatment. This condition leads to reduced food consumption, increasing the risk of malnutrition. Malnutrition is associated not only with worse treatment efficacy and poor disease prognosis but also with reduced functional status and quality of life. The fruit of Synsepalum dulcificum (Daniell), commonly known as miracle berry or miracle fruit, contains miraculin, a taste-modifying protein with profound effects on taste perception. The CLINMIR Protocol is a triple-blind, randomized, placebo-controlled clinical trial designed to evaluate the regular consumption of a food supplement containing a miraculin-based novel food, dried miracle berry (DMB), on the taste perception (measured through electrogustometry) and nutritional status (evaluated through the GLIM Criteria) of malnourished cancer patients under active antineoplastic treatment. To this end, a pilot study was designed with 30 randomized patients divided into three study arms (150 mg DMB + 150 mg freeze-dried strawberries, 300 mg DMB, or placebo) for three months. Throughout the five main visits, an exhaustive assessment of different parameters susceptible to improvement through regular consumption of the miraculin-based food supplement will be conducted, including electrical and chemical taste perception, smell perception, nutritional and morphofunctional assessment, diet, quality of life, the fatty acid profile of erythrocytes, levels of inflammatory and cancer-associated cytokines, oxidative stress, antioxidant defense system, plasma metabolomics, and saliva and stool microbiota. The primary anticipated result is that malnourished cancer patients with taste distortion who consume the miraculin-based food supplement will report an improvement in food taste perception. This improvement translates into increased food intake, thereby ameliorating their nutritional status and mitigating associated risks. Additionally, the study aims to pinpoint the optimal dosage that provides maximal benefits. The protocol adheres to the SPIRIT 2013 Statement, which provides evidence-based recommendations and is widely endorsed as an international standard for trial protocols. The clinical trial protocol has been registered at the platform for Clinical Trials (NCT05486260).PMID:37960292 | DOI:10.3390/nu15214639

Nutrients. 2023 Oct 31;15(21):4625. doi: 10.3390/nu15214625.ABSTRACTCerebrotendinous xanthomatosis (CTX) is a rare inherited disease characterized by sterol 27-hydroxylase (CYP27A1) deficiency and, thus, a lack of bile acid synthesis with a marked accumulation of 7α-hydroxylated bile acid precursors. In addition to their renowned lipid-emulgating role, bile acids have been shown to stimulate secretion of the glucose-lowering and satiety-promoting gut hormone glucagon-like peptide 1 (GLP-1). In this paper, we examined postprandial bile acid, glucose, insulin, GLP-1 and fibroblast growth factor 19 (FGF19) plasma profiles in patients with CTX and matched healthy controls. Seven patients and seven age, gender and body mass index matched controls were included and subjected to a 4 h mixed meal test with regular blood sampling. CTX patients withdrew from chenodeoxycholic acid (CDCA) and statin therapy three weeks prior to the test. Postprandial levels of total bile acids were significantly lower in CTX patients and consisted of residual CDCA with low amounts of ursodeoxycholic acid (UDCA). The postprandial plasma glucose peak concentration occurred later in CTX patients compared to controls, and patients' insulin levels remained elevated for a longer time. Postprandial GLP-1 levels were slightly higher in CTX subjects whereas postprandial FGF19 levels were lower in CTX subjects. This novel characterization of CTX patients reveals very low circulating bile acid levels and FGF19 levels, aberrant postprandial glucose and insulin profiles, and elevated postprandial GLP-1 responses.PMID:37960277 | DOI:10.3390/nu15214625

Nutrients. 2023 Oct 29;15(21):4597. doi: 10.3390/nu15214597.ABSTRACT5-Heptadecylresorcinol (AR-C17), a primary biomarker of whole grain (WG) consumption, has been demonstrated to improve the thermogenic activity of aging mice. However, the intricate regulatory mechanism is not fully understood. This study conducted metabolomics analysis on young and aging mice with or without AR-C17 administration after cold exposure. The results showed that the aging mice displayed lower levels of acylcarnitine (ACar) in their plasma compared with the young mice during cold exposure, and 150 mg/kg/day of AR-C17 administration for 8 weeks could increase the plasma ACar levels of aging mice. ACar has been reported to be an essential metabolic fuel for the thermogenesis of brown adipose tissue (BAT). AR-C17 had similar effects on the ACar levels in the BAT as on the plasma of the aging mice during cold exposure. Furthermore, the aging mice had reduced ACar metabolism in the BAT, and AR-C17 could improve the ACar metabolism in the BAT of aging mice, thereby promoting the metabolic utilization of ACar by BAT. Moreover, the glucose and lipid levels of aging mice could be improved by AR-C17. This study revealed a deeper metabolic mechanism involved in the AR-C17-mediated thermogenic regulation of BAT, providing a new theoretical basis for the nutrition and health benefits of WG.PMID:37960251 | DOI:10.3390/nu15214597

Nutrients. 2023 Oct 27;15(21):4574. doi: 10.3390/nu15214574.ABSTRACTAn intermittent fasting (IF) regimen has been shown to protect against metabolic dysfunction-associated steatohepatitis (MASH). However, the precise mechanism remains unclear. Here, we explored how IF reduced hepatic lipid accumulation, inflammation, and fibrosis in mice with MASH. The mice were fed a high-fat diet (HFD) for 30 weeks and either continued on the HFD or were subjected to IF for the final 22 weeks. IF reduced body weight, insulin resistance, and hepatic lipid accumulation in HFD-fed mice. Lipidome analysis revealed that IF modified HFD-induced hepatic lipid composition. In particular, HFD-induced impaired autophagic flux was reversed by IF. The decreased hepatic lysosome-associated membrane protein 1 level in HFD-fed mice was upregulated in HFD+IF-fed mice. However, increased hepatic lysosomal acid lipase protein levels in HFD-fed mice were reduced by IF. IF attenuated HFD-induced hepatic inflammation and galectin-3-positive Kupffer cells. In addition to the increases in hepatic hydroxyproline and lumican levels, lipocalin-2-mediated signaling was reversed in HFD-fed mice by IF. Taken together, our findings indicate that the enhancement of the autophagy-lysosomal pathway may be a critical mechanism of MASH reduction by IF.PMID:37960230 | DOI:10.3390/nu15214574

Nutrients. 2023 Oct 27;15(21):4554. doi: 10.3390/nu15214554.ABSTRACT(1) Background: Probiotics in the form of nutritional supplements are safe and potentially useful for strategic application among endurance athletes. Bifidobacterium animalis lactis BL-99 (BL-99) was isolated from the intestines of healthy Chinese infants. We combined plasma-targeted metabolomics and fecal metagenomics to explore the effect of 8 weeks of BL-99 supplementation on cross-country skiers' metabolism and sports performance. (2) Methods: Sixteen national top-level male cross-country skiers were recruited and randomly divided into a placebo group (C) and a BL-99 group (E). The participants took the supplements four times/day (with each of three meals and at 21:00) consistently for 8 weeks. The experiment was conducted in a single-blind randomized fashion. The subject's dietary intake and total daily energy consumption were recorded. Blood and stool samples were collected before and after the 8-week intervention, and body composition, muscle strength, blood biochemical parameters, plasma-targeted metabolomic data, and fecal metagenomic data were then analyzed. (3) Results: The following changes occurred after 8 weeks of BL-99 supplementation: (a) There was no significant difference in the average total daily energy consumption and body composition between the C and E groups. (b) The VO2max and 60°/s and 180°/s knee joint extensor strength significantly increased in both the C and E groups. By the eighth week, the VO2max and 60 s knee-joint extensor strength were significantly higher in the E group than in the C group. (c) The triglyceride levels significantly decreased in both the C and E groups. In addition, the LDL-C levels significantly decreased in the E group. (d) The abundance of Bifidobacterium animalis increased two-fold in the C group and forty-fold in the E group. (e) Plasma-targeted metabolomic analysis showed that, after eight weeks of BL-99 supplementation, the increases in DHA, adrenic acid, linoleic acid, and acetic acid and decreases in glycocholic acid and glycodeoxycholic acid in the E group were significantly higher than those in the C group. (f) Spearman correlation analysis showed that there was a significant positive correlation between Bifidobacterium animalis' abundance and SCFAs, PUFAs, and bile acids. (g) There was a significant correlation between the most significantly regulated metabolites and indicators related to sports performance and lipid metabolism. (4) Conclusions: Eight weeks of BL-99 supplementation combined with training may help to improve lipid metabolism and sports performance by increasing the abundance of Bifidobacterium, which can promote the generation of short-chain fatty acids and unsaturated fatty acids, and inhibit the synthesis of bile acids.PMID:37960207 | DOI:10.3390/nu15214554

Nutrients. 2023 Oct 25;15(21):4520. doi: 10.3390/nu15214520.ABSTRACT(1) Background: Muscle loss is associated with frailty and a reduction in physical strength and performance, which is caused by increased oxidative stress. Ginger (Zingiber officinale Roscoe) is a potential herb that can be used to reduce the level of oxidative stress. This study aimed to determine the effect of ginger on the expression of metabolites and their metabolic pathways in the myoblast cells to elucidate the mechanism involved and its pharmacological properties in promoting myoblast differentiation. (2) Methods: The myoblast cells were cultured into three stages (young, pre-senescent and senescent). At each stage, the myoblasts were treated with different concentrations of ginger extract. Then, metabolomic analysis was performed using liquid chromatography-tandem mass spectrometry (LCMS/MS). (3) Results: Nine metabolites were decreased in both the pre-senescent and senescent control groups as compared to the young control group. For the young ginger-treated group, 8-shogaol and valine were upregulated, whereas adipic acid and bis (4-ethyl benzylidene) sorbitol were decreased. In the pre-senescent ginger-treated group, the niacinamide was upregulated, while carnitine and creatine were downregulated. Ginger treatment in the senescent group caused a significant upregulation in 8-shogaol, octadecanamide and uracil. (4) Conclusions: Ginger extract has the potential as a pharmacological agent to reduce muscle loss in skeletal muscle by triggering changes in some metabolites and their pathways that could promote muscle regeneration in ageing.PMID:37960173 | DOI:10.3390/nu15214520

Nutrients. 2023 Oct 25;15(21):4512. doi: 10.3390/nu15214512.ABSTRACTColorectal cancer (CRC) is a significant health concern and is the third most commonly diagnosed and second deadliest cancer worldwide. CRC has been steadily increasing in developing countries owing to factors such as aging and epidemics. Despite extensive research, the exact pathogenesis of CRC remains unclear, and its causes are complex and variable. Numerous in vitro, animal, and clinical trials have demonstrated the efficacy of probiotics such as Lactobacillus plantarum in reversing the adverse outcomes of CRC. These findings suggest that probiotics play vital roles in the prevention, adjuvant treatment, and prognosis of CRC. In this study, we constructed a mouse model of CRC using an intraperitoneal injection of azomethane combined with dextran sodium sulfate, while administering 5-fluorouracil as well as high- and low-doses of L. plantarum Zhang-LL live or heat-killed strains. Weight changes and disease activity indices were recorded during feeding, and the number of polyps and colon length were measured after euthanasia. HE staining was used to observe the histopathological changes in the colons of mice, and ELISA was used to detect the expression levels of IL-1β, TNF-α, and IFN-γ in serum. To investigate the specific mechanisms involved in alleviating CRC progression, gut microbial alterations were investigated using 16S rRNA amplicon sequencing and non-targeted metabolomics, and changes in genes related to CRC were assessed using eukaryotic transcriptomics. The results showed that both viable and heat-killed strains of L. plantarum Zhang-LL in high doses significantly inhibited tumorigenesis, colon shortening, adverse inflammatory reactions, intestinal tissue damage, and pro-inflammatory factor expression upregulation. Specifically, in the gut microbiota, the abundance of the dominant flora Acutalibacter muris and Lactobacillus johnsonii was regulated, PGE2 expression was significantly reduced, the arachidonic acid metabolism pathway was inhibited, and CD22-mediated B-cell receptor regulation-related gene expression was upregulated. This study showed that L. plantarum Zhang-LL live or heat-inactivated strains alleviated CRC progression by reducing the abundance of potentially pathogenic bacteria, increasing the abundance of beneficial commensal bacteria, mediating the arachidonic acid metabolism pathway, and improving host immunogenicity.PMID:37960165 | DOI:10.3390/nu15214512

Nutrients. 2023 Oct 24;15(21):4502. doi: 10.3390/nu15214502.ABSTRACTStructural changes in the gut microbiota are closely related to the development of functional constipation, and regulating the gut microbiota can improve constipation. Rifaximin is a poorly absorbed antibiotic beneficial for regulating gut microbiota, but few studies have reported its effects on constipation. The purpose of this study was to investigate the effect of rifaximin on loperamide-induced constipation in SD rats. The results showed that rifaximin improved constipation by increasing serum 5-HT, SP, and the mRNA expression of AQP3, AQP8, and reducing the mRNA expression of TLR2 and TLR4. In addition, rifaximin could regulate the gut microbiota of constipated rats, such as increasing the potentially beneficial bacteria Akkermansia muciniphila and Lactobacillus murinus, reducing the Bifidobacterium pseudolongum. According to metabolomics analysis, many serum metabolites, including bile acids and steroids, were changed in constipated rats and were recovered via rifaximin intervention. In conclusion, rifaximin might improve loperamide-induced constipation in rats by increasing serum excitatory neurotransmitters and neuropeptides, modulating water metabolism, and facilitating intestinal inflammation. Muti-Omics analysis results showed that rifaximin has beneficial regulatory effects on the gut microbiota and serum metabolites in constipated rats, which might play critical roles in alleviating constipation. This study suggests that rifaximin might be a potential strategy for treating constipation.PMID:37960154 | DOI:10.3390/nu15214502

Plants (Basel). 2023 Nov 4;12(21):3772. doi: 10.3390/plants12213772.ABSTRACTMung bean (Vigna radiata (L.) Wilczek) sprouts are popular over the world because of their taste, nutritional value, well-balanced biochemical composition, and other properties beneficial for human health. Germination conditions affect the composition of metabolites in mung bean sprouts, so a detailed study into its variability is required. This article presents the results of a comparison of the metabolite composition in the leaves of mung bean sprouts germinated first in the dark (DS) and then in the light (LS). Gas chromatography with mass spectrometry (GC-MS) made it possible to identify more than 100 compounds representing various groups of phytochemicals. Alcohols, amino acids, and saccharides predominated in the total amount of compounds. The analysis of metabolomic profiles exposed a fairly high intra- and intervarietal variability in the metabolite content. DS and LS differed in the qualitative and quantitative content of the identified compounds. The intravarietal variability was more pronounced in DS than in LS. DS demonstrated higher levels of saccharides, fatty acids, acylglycerols, and phenolic compounds, while amino acids were higher in LS. Changes were recorded in the quantitative content of metabolites participating in the response of plants to stressors-ornithine, proline, GABA, inositol derivatives, etc. The changes were probably induced by the stress experienced by the sprouts when they were transferred from shade to light. The analysis of variance and principal factor analysis showed the statistically significant effect of germination conditions on the content of individual compounds in leaves. The identified features of metabolite variability in mung bean genotypes grown under different conditions will contribute to more accurate selection of an illumination pattern to obtain sprouts with desirable biochemical compositions for use in various diets and products with high nutritional value.PMID:37960128 | DOI:10.3390/plants12213772

Plants (Basel). 2023 Nov 3;12(21):3766. doi: 10.3390/plants12213766.ABSTRACTAlpinia plants are widely cherished for their vibrant and captivating flowers. The unique feature of this genus lies in their labellum, a specialized floral structure resulting from the fusion of two non-fertile staminodes. However, the intricate process of pigment formation, leading to distinct color patterns in the various labellum segments of Alpinia, remains a subject of limited understanding. In this study, labellum tissues of two Alpinia species, A. zerumbet (yellow-orange flowers) and A. oxyphylla (white-purple flowers), were sampled and analyzed through morphological structure observation, metabolite analysis, and transcriptome analyses. We found that hemispherical/spherical epidermal cells and undulate cell population morphology usually display darker flower colors, while flat epidermal cells and cell populations usually exhibit lighter flower colors. Metabolomic analysis identified a high concentration of anthocyanins, particularly peonidin derivatives, in segments with orange and purple pigments. Additionally, segments with yellow pigments showed significant accumulations of flavones, flavanols, flavanones, and xanthophylls. Furthermore, our investigation into gene expression levels through qRT-PCR revealed notable differences in several genes that participated in anthocyanin and carotenoid biosynthesis among the four pigmented segments. Collectively, these findings offer a comprehensive understanding of pigmentation in Alpinia flowers and serve as a valuable resource for guiding future breeding efforts aimed at developing Alpinia varieties with novel flower colors.PMID:37960122 | DOI:10.3390/plants12213766

Plants (Basel). 2023 Nov 2;12(21):3753. doi: 10.3390/plants12213753.ABSTRACTHuanglongbing (HLB; also known as citrus greening) is the most destructive bacterial disease of citrus worldwide with no known sustainable cure yet. Herein, we used non-targeted metabolomics and transcriptomics to prove that γ-aminobutyric acid (GABA) accumulation might influence the homeostasis of several metabolic pathways, as well as antioxidant defense machinery, and their metabolism-related genes. Overall, 41 metabolites were detected in 'Valencia' sweet orange (Citrus sinensis) leaf extract including 19 proteinogenic amino acids (PAA), 10 organic acids, 5 fatty acids, and 9 other amines (four phenolic amines and three non-PAA). Exogenous GABA application increased most PAA in healthy (except L-threonine, L-glutamine, L-glutamic acid, and L-methionine) and 'Candidatus L. asiaticus'-infected citrus plants (with no exception). Moreover, GABA accumulation significantly induced L-tryptophan, L-phenylalanine, and α-linolenic acid, the main precursors of auxins, salicylic acid (SA), and jasmonic acid (JA), respectively. Furthermore, GABA supplementation upregulated most, if not all, of amino acids, phenolic amines, phytohormone metabolism-related, and GABA shunt-associated genes in both healthy and 'Ca. L. asiaticus'-infected leaves. Moreover, although 'Ca. L. asiaticus' induced the accumulation of H2O2 and O2•- and generated strong oxidative stress in infected leaves, GABA possibly stimulates the activation of a multilayered antioxidative system to neutralize the deleterious effect of reactive oxygen species (ROS) and maintain redox status within infected leaves. This complex system comprises two major components: (i) the enzymatic antioxidant defense machinery (six POXs, four SODs, and CAT) that serves as the front line in antioxidant defenses, and (ii) the non-enzymatic antioxidant defense machinery (phenolic acids and phenolic amines) that works as a second defense line against 'Ca. L. asiaticus'-induced ROS in citrus infected leaves. Collectively, our findings suggest that GABA might be a promising alternative eco-friendly strategy that helps citrus trees battle HLB particularly, and other diseases in general.PMID:37960112 | DOI:10.3390/plants12213753

Plants (Basel). 2023 Oct 30;12(21):3722. doi: 10.3390/plants12213722.ABSTRACTNeolamarckia cadamba (Roxb.) Bosser, a member of the Rubiaceae family, is a botanical species with recognized therapeutic properties. It is commonly used in traditional medicine to treat cardiac ailments and other disorders. However, the precise active constituents and the potential mechanisms by which they manage cardiovascular disorders remain unclear. Therefore, this study aimed to ascertain the bioactive components and investigate their underlying mechanisms of action. N. cadamba is used to treat cardiovascular disorders using the integrated metabolomic methodology. An HPLC-QTOF-MS/MS analysis determined the potential chemicals in the N. cadamba leaf ethanol extract (NCEE). A thorough investigation of the NCEE samples used in this study led to the identification of 32 phytoconstituents. Of the 32 compounds, 19 obeyed Lipinski's rule of five (RO5). A molecular docking study directed towards HMG-CoA reductase used 19 molecules. The reference drug atorvastatin indicated a binding energy of -3.9 kcal/mol, while the other substances, Cinchonain Ib and Dukunolide B, revealed binding energies of -5.7 and -5.3 kcal/mol, respectively. Both phytocompounds showed no toxicity and exhibited favorable pharmacokinetic properties. In vivo study results concluded that treatment with NCEE significantly reduced the cardiac myocardial infarction (MI) marker CK-MB and atherogenic risk indices, such as the atherogenic index plasma (AIP), cardiac risk ratio (CRR), and atherogenic coefficient (AC) in isoproterenol-induced MI rats. In MI rats, NCEE therapy significantly improved the antioxidant system of the heart tissue, as evidenced by the increased levels of GSH and SOD, lower levels of the oxidative stress marker MDA, and significantly decreased HMG-CoA activity. Additionally, electrocardiogram (ECG) signals from rats treated with NCEE resembled those treated with traditional atorvastatin to treat myocardial infarction. This study used H&E staining to show that administering NCEE before treatment reduced cardiac myocyte degeneration in rats with myocardial infarction, increased the presence of intact nuclei, and increased myocardial fiber strength. The potential cardioprotective effect observed in myocardial infarction (MI) rats treated with NCEE can be extrapolated from computational data to be caused by Cinchonain Ib.PMID:37960078 | DOI:10.3390/plants12213722

Plants (Basel). 2023 Oct 25;12(21):3669. doi: 10.3390/plants12213669.ABSTRACTAs a subtropical and tropical tree, bayberry (Myrica rubra) is an important fruit tree grown commercially in southern China. Interestingly, our studies found that the fruit quality of bayberry with accompanying ryegrass was significantly improved, but its mechanism remains unclear. The aim of this study was to explore the mechanism of accompanying ryegrass on the beneficial effect of the fruit quality of bayberry by measuring the vegetative growth parameters, fruit parameters with economic impact, physical and chemical properties of rhizosphere soil, microbial community structure, and metabolites of the bayberry with/without ryegrass. Notably, the results revealed a significant difference between bayberry trees with and without accompanying ryegrass in fruit quality parameters, soil physical and chemical properties, microbial community structure, and metabolites. Compared with the control without accompanying ryegrass, the planting of ryegrass increased the titratable sugar, vitamin C, and titratable flavonoid contents of bayberry fruits by 2.26%, 28.45%, and 25.00%, respectively, and decreased the titratable acid contents by 9.04%. Furthermore, based on 16S and ITS amplicon sequencing of soil microflora, the accompanying ryegrass caused a 12.47% increment in Acidobacteriota while a 30.04% reduction in Actinobacteria was recorded, respectively, when compared with the bayberry trees without ryegrass. Redundancy discriminant analysis of microbial communities and soil properties indicated that the main variables of the bacterial community included available nitrogen, available phosphorus, exchangeable aluminum, and available kalium, while the main variables of the fungal community included exchangeable aluminum, available phosphorus, available kalium, and pH. In addition, the change in microbial community structure was justified by the high correlation analysis between microorganisms and secondary metabolites. Indeed, GC-MS metabolomics analysis showed that planting ryegrass caused a 3.83%-144.36% increase in 19 metabolites such as 1,3-Dipentyl-heptabarbital and carbonic acid 1, respectively, and a 23.78%-51.79% reduction of 5 metabolites compared to the bayberry trees without the accompanying ryegrass. Overall, the results revealed the significant change caused by the planting of ryegrass in the physical and chemical properties, microbiota, and secondary metabolites of the bayberry rhizosphere soils, which provides a new insight for the ecological improvement of bayberry.PMID:37960028 | DOI:10.3390/plants12213669

Molecules. 2023 Nov 6;28(21):7447. doi: 10.3390/molecules28217447.ABSTRACTThe processing of tea leaves plays a crucial role in the formation of the taste of the resulting tea. In order to study the compositions of and changes in taste-related substances during the processing of Rizhao green tea, non-targeted metabolomics was used, based on UHPLC-Q Exactive MS. Totals of 529, 349, and 206 non-volatile metabolites were identified using three different detection modes, of which 112 secondary metabolites were significantly changed. Significant variations in secondary metabolites were observed during processing, especially during the drying stage, and the conversion intensity levels of non-volatile metabolites were consistent with the law of "Drying > Fixation > Rolling". The DOT method was used to screen tea-quality-related compounds that contributed significantly to the taste of Rizhao green tea, including (-)-epicatechin gallate, (-)-epicatechin gallate, gallic acid, L-theanine, and L-leucine, which make important contributions to taste profiles, such as umami and bitterness. Metabolic pathway analysis revealed that purine metabolism, caffeine metabolism, and tyrosine metabolism perform key roles in the processing of Rizhao green tea in different processing stages. The results of this study provide a theoretical basis for tea processing and practical advice for the food industry.PMID:37959866 | DOI:10.3390/molecules28217447

Molecules. 2023 Nov 4;28(21):7430. doi: 10.3390/molecules28217430.ABSTRACTMajor depressive disorder (MDD) is a serious mental illness with a heavy social burden, but its underlying molecular mechanisms remain unclear. Mass spectrometry (MS)-based metabolomics is providing new insights into the heterogeneous pathophysiology, diagnosis, treatment, and prognosis of MDD by revealing multi-parametric biomarker signatures at the metabolite level. In this comprehensive review, recent developments of MS-based metabolomics in MDD research are summarized from the perspective of analytical platforms (liquid chromatography-MS, gas chromatography-MS, supercritical fluid chromatography-MS, etc.), strategies (untargeted, targeted, and pseudotargeted metabolomics), key metabolite changes (monoamine neurotransmitters, amino acids, lipids, etc.), and antidepressant treatments (both western and traditional Chinese medicines). Depression sub-phenotypes, comorbid depression, and multi-omics approaches are also highlighted to stimulate further advances in MS-based metabolomics in the field of MDD research.PMID:37959849 | DOI:10.3390/molecules28217430

Molecules. 2023 Oct 30;28(21):7340. doi: 10.3390/molecules28217340.ABSTRACTThe aim of this study was to conduct a screening of potential therapeutic compounds found in the Atractylodes macrocephala rhizoma essential oil (AO) and explore its mechanism of action in the treatment of ulcerative colitis (UC). An inflammation cell model was employed in conjunction with phospho-antibody array technology to explore potential therapeutic compounds of AO and their anti-inflammatory and antioxidant effects. Furthermore, we assessed their efficacy and mechanisms of action in treating dextran sulfate sodium (DSS)-induced colitis in mice. Via the screening process, we identified atractylone (ATR) as the primary active compound in AO. It has been demonstrated that ATR can both decrease the levels of tumor necrosis factor (TNF)-α and reactive oxygen species (ROS) and increase the expression of adhesion proteins such as claudin, ZO-1, and occludin in vitro. Moreover, ATR has been shown to improve UC symptoms in vivo. Via a non-targeted metabolomics analysis of colon tissue, we identified 57 distinct metabolites that responded to ATR treatment. Subsequent analysis of the metabolic pathways revealed that the action of ATR was primarily focused on the amino acid metabolism pathway. In summary, ATR may alleviate the symptoms of UC by regulating multiple signaling pathways. Additionally, ATR has a comprehensive function in anti-inflammation, antioxidative stress, and intestinal injury reduction.PMID:37959758 | DOI:10.3390/molecules28217340