-
Frontiers in Immunology 2024Various gut bacteria, including , possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from...
The gut lactic acid bacteria metabolite, 10-oxo--6,-11-octadecadienoic acid, suppresses inflammatory bowel disease in mice by modulating the NRF2 pathway and GPCR-signaling.
Various gut bacteria, including , possess several enzymes that produce hydroxy fatty acids (FAs), oxo FAs, conjugated FAs, and partially saturated FAs from polyunsaturated FAs as secondary metabolites. Among these derivatives, we identified 10-oxo--6,-11-octadecadienoic acid (γKetoC), a γ-linolenic acid (GLA)-derived enon FA, as the most effective immunomodulator, which inhibited the antigen-induced immunoactivation and LPS-induced production of inflammatory cytokines. The treatment with γKetoC significantly suppressed proliferation of CD4 T cells, LPS-induced activation of bone marrow-derived dendritic cells (BMDCs), and LPS-induced IL-6 release from peritoneal cells, splenocytes, and CD11c cells isolated from the spleen. γKetoC also inhibited the release of inflammatory cytokines from BMDCs stimulated with poly-I:C, R-848, or CpG. Further experiments using an agonist of GPR40/120 suggested the involvement of these GPCRs in the effects of γKetoC on DCs. We also found that γKetoC stimulated the NRF2 pathway in DCs, and the suppressive effects of γKetoC and agonist of GPR40/120 on the release of IL-6 and IL-12 were reduced in BMDCs. We evaluated the role of NRF2 in the anti-inflammatory effects of γKetoC in a dextran sodium sulfate-induced colitis model. The oral administration of γKetoC significantly reduced body weight loss, improved stool scores, and attenuated atrophy of the colon, in wild-type C57BL/6 and mice with colitis. In contrast, the pathology of colitis was deteriorated in mice even with the administration of γKetoC. Collectively, the present results demonstrated the involvement of the NRF2 pathway and GPCRs in γKetoC-mediated anti-inflammatory responses.
Topics: Animals; NF-E2-Related Factor 2; Mice; Receptors, G-Protein-Coupled; Signal Transduction; Gastrointestinal Microbiome; Mice, Inbred C57BL; Inflammatory Bowel Diseases; Mice, Knockout; Cytokines; Disease Models, Animal; Dextran Sulfate; Oleic Acids; Lactobacillus plantarum; Colitis; Dendritic Cells; Male
PubMed: 38745644
DOI: 10.3389/fimmu.2024.1374425 -
Genes Mar 2024Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of...
Extensive genome structure variations, such as copy number variations (CNVs) and presence/absence variations, are the basis for the remarkable genetic diversity of maize; however, the effect of CNVs on maize herbivory defense remains largely underexplored. Here, we report that the naturally occurring duplication of the maize 9-lipoxygenase gene leads to increased resistance of maize to herbivory by fall armyworms (FAWs). Previously, we showed that ZmLOX5-derived oxylipins are required for defense against chewing insect herbivores and identified several inbred lines, including Yu796, that contained duplicated CNVs of , referred to as . To test whether introgression of the locus into a herbivore-susceptible B73 background that contains a single gene is a feasible approach to increase resistance, we generated a series of near-isogenic lines that contained either two, one, or zero copies of the locus in the B73 background via six backcrosses (BC6). Droplet digital PCR (ddPCR) confirmed the successful introgression of the locus in B73. The resulting B73-2× inbred line displayed increased resistance against FAW, associated with increased expression of , increased wound-induced production of its primary oxylipin product, the α-ketol, 9-hydroxy-10-oxo-12(Z),15(Z)-octadecadienoic acid (9,10-KODA), and the downstream defense hormones regulated by this molecule, 12-oxo-phytodienoic acid (12-OPDA) and abscisic acid (ABA). Surprisingly, wound-induced JA-Ile production was not increased in B73-2×, resulting from the increased JA catabolism. Furthermore, B73-2× displayed reduced water loss in response to drought stress, likely due to increased ABA and 12-OPDA content. Taken together, this study revealed that the duplicated CNV of quantitively contributes to maize antiherbivore defense and presents proof-of-concept evidence that the introgression of naturally occurring duplicated CNVs of a defensive gene into productive but susceptible crop varieties is a feasible breeding approach for enhancing plant resistance to herbivory and tolerance to abiotic stress.
Topics: Zea mays; Animals; DNA Copy Number Variations; Plant Proteins; Lipoxygenase; Herbivory; Oxylipins; Plant Diseases
PubMed: 38674336
DOI: 10.3390/genes15040401 -
The Journal of Biological Chemistry May 2024Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise...
Unsaturated fatty acid ketones with αβ,γδ conjugation are susceptible to Michael addition of thiols, with unresolved issues on the site of adduction and precise structures of the conjugates. Herein we reacted 13-keto-octadecadienoic acid (13-oxo-ODE or 13-KODE) with glutathione (GSH), N-acetyl-cysteine, and β-mercaptoethanol and identified the adducts. HPLC-UV analyses indicated none of the products exhibit a conjugated enone UV chromophore, a result that conflicts with the literature and is relevant to the mass spectral interpretation of 1,4 versus 1,6 thiol adduction. Aided by the development of an HPLC solvent system that separates the GSH diastereomers and thus avoids overlap of signals in proton NMR experiments, we established the two major conjugates are formed by 1,6 addition of GSH at the 9-carbon of 13-oxo-ODE with the remaining double bond α to the thiol in the 10,11 position. N-acetyl cysteine reacts similarly, while β-mercaptoethanol gives equal amounts of 1,4 and 1,6 addition products. Equine glutathione transferase catalyzed 1,6 addition of GSH to the two major diastereomers in 44:56 proportions. LC-MS in positive ion mode gives a product ion interpreted before as evidence of 1,4-thiol adduction, whereas here we find this ion using the authentic 1,6 adduct. LC-MS with negative ion APCI gave a fragment selective for 1,4 adduction. These results clarify the structures of thiol conjugates of a prototypical unsaturated keto-fatty acid and have relevance to the application of LC-MS for the structural analysis of keto-fatty acid glutathione conjugation.
Topics: Glutathione; Sulfhydryl Compounds; Mass Spectrometry; Chromatography, High Pressure Liquid; Chromatography, Liquid; Mercaptoethanol; Liquid Chromatography-Mass Spectrometry
PubMed: 38636660
DOI: 10.1016/j.jbc.2024.107293 -
Foods (Basel, Switzerland) Mar 2024The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by...
The volatile composition of (Fortunei × Tomentosa) essential oil isolated by steam distillation (yielding 0.013% /) from flowers (forestry wastes) was investigated by gas chromatography-mass spectrometry. Thirty-one components were identified, with 3-acetoxy-7, 8-epoxylanostan-11-ol (38.16%), β-monoolein (14.4%), lycopene, 1,2-dihydro-1-hydroxy- (10.21%), and 9,12-octadecadienoic acid, 2-phenyl-1,3-dioxan-5-yl ester (9.21%) as main compounds. In addition, molecular docking was employed to identify potential protein targets for the 31 quantified essential oil components. Inhibition of these targets is typically associated with antibacterial or antioxidant properties. Molecular docking revealed that six of these components, namely, 13-heptadecyn-1-ol, ascabiol, geranylgeraniol, anethole, and quinol dimethyl ether, outperformed the native ligand (hypoxanthine) of xanthine oxidase in terms of theoretical binding affinity, therefore implying a significant in silico inhibitory potential against xanthine oxidase. These findings suggest that the essential oil extracted from flowers could be valuable for developing protein-targeted antioxidant compounds with applications in the food, pharmaceutical, and cosmetic industries.
PubMed: 38611313
DOI: 10.3390/foods13071007 -
World Journal of Experimental Medicine Mar 2024The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques...
BACKGROUND
The investigation of plant-based therapeutic agents in medicinal plants has revealed their presence in the extracts and provides the vision to formulate novel techniques for drug therapy. (), a perennial herb belonging to the family is extensively used in conventional medication.
AIM
To determine the existence of therapeutic components in leaf and callus extracts from wild plants using gas chromatography-mass spectrometry (GC-MS).
METHODS
In this study, we conducted GC-MS on wild plant leaf extracts and correlated the presence of constituents with those in callus extracts. Various growth regulators such as 6-benzylaminopurine (BAP), 2,4-dichlorophenoxyacetic acid (2,4-D), α-naphthylacetic acid (NAA), and di-phenylurea (DPU) were added to plant leaves and callus and grown on MS medium.
RESULTS
The results clearly indicated that the addition of BAP (2.0 mg/L), 2,4-D (0.2 mg/mL), DPU (2.0 mg/L) and 2,4-D (0.2 mg/mL) in MS medium resulted in rapid callus development. The plant profile of extracts by GC-MS analysis showed that 24, 10, and 14 bioactive constituents were detected in the methanolic extract of leaf, green callus and the methanolic extract of white loose callus, respectively.
CONCLUSION
Octadecadienoic acid, hexadecanoic acid and methyl ester were the major constituents in the leaf and callus methanolic extract. Octadecadienoic acid was the most common constituent in all samples. The maximum concentration of octadecadienoic acid in leaves, green callus and white loose callus was 21.93%, 47.79% and 40.38%, respectively. These findings demonstrate that the concentration of octadecadienoic acid doubles compared to . In addition to octadecadienoic acid; butyric acid, benzene, 1-methoxy-4-(1-propenyl), dospan, tridecanedialdehyde, methylcyclohexenylbutanol, chlorpyrifos, n-secondary terpene diester, anflunine and other important active compounds were also detected. All these components were only available in callus formed . This study showed that the callus contained additional botanical characteristics compared with wild plants. Due to the presence of numerous bioactive compounds, the medical use of for various diseases has been accepted and the plant is considered an important source of therapeutics for research and development.
PubMed: 38590309
DOI: 10.5493/wjem.v14.i1.88064 -
ACS Omega Apr 2024This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the...
This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of . Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (,), methyl ester, and others. The addition of methanolic extract to an AgNO solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.
PubMed: 38585127
DOI: 10.1021/acsomega.3c10119 -
Frontiers in Cellular and Infection... 2024Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune...
BACKGROUND
Combination antiretroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection in people with HIV (PWH). However, a chronic state of immune activation and inflammation is maintained despite achieving HIV suppression and satisfactory immunological recovery. We aimed to determine whether the plasma metabolomic profile of PWH on long-term suppressive ART and immunologically recovered approximates the normality by comparison with healthy controls with similar age and gender.
METHODS
We carried out a cross-sectional study in 17 PWH on long-term ART (HIV-RNA <50 copies/mL, CD4 ≥500 cells/mm, and CD4/CD8 ≥1) and 19 healthy controls with similar age and gender. Metabolomics analysis was performed by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS). The statistical association analysis was performed by principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and Generalized Linear Models (GLM) with a gamma distribution (log-link). Significance levels (p-value) were corrected for multiple testing (q-value).
RESULTS
PCA and PLS-DA analyses found no relevant differences between groups. Adjusted GLM showed 14 significant features (q-value<0.20), of which only three could be identified: lysophosphatidylcholine (LysoPC) (22:6) (q-value=0.148), lysophosphatidylethanolamine (LysoPE) (22:6) (q-value=0.050) and hydroperoxy-octadecatrienoic acid (HpOTrE)/dihydroperoxy-octadecatrienoic acid (DiHOTrE)/epoxy-octadecadienoic acid (EpODE) (q-value=0.136). These significant identified metabolites were directly correlated to plasma inflammatory biomarkers in PWH and negatively correlated in healthy controls.
CONCLUSION
PWH on long-term ART have a metabolomic profile that is almost normal compared to healthy controls. Nevertheless, residual metabolic alterations linked to inflammatory biomarkers persist, which could favor the development of age-related comorbidities among this population.
Topics: Humans; Cross-Sectional Studies; Metabolomics; Biomarkers; Inflammation; HIV Infections
PubMed: 38550617
DOI: 10.3389/fcimb.2024.1340610 -
BMC Microbiology Mar 2024Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross...
BACKGROUND
Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively.
RESULTS
The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection.
CONCLUSION
The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.
Topics: Female; Humans; Papillomavirus Infections; Vagina; RNA, Ribosomal, 16S; Tandem Mass Spectrometry; Metabolome; Microbiota; Biomarkers
PubMed: 38519882
DOI: 10.1186/s12866-024-03244-1 -
Heliyon Mar 2024Barley scientifically known as is a major grain crop. Over the course of time, great interest has been developed in the usage of barley, because of its various...
Barley scientifically known as is a major grain crop. Over the course of time, great interest has been developed in the usage of barley, because of its various pharmacological activities. Current study is designed to determine the chemical constituents of seed extract by GC-MS technique, and antioxidant assays i.e. 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) and 2-azino-bis(3-ethyl benzthiazoline-6-sulfonic acid) (ABTS) methods. GC-MS identified 16 non-polar compounds in the hexane extract of plant, which includes carboxylic acid (6.25%), fatty acid (37.5%), carboxylic acid amide derivative of fatty acid (6.25%), triterpinoids (18.75%), fat soluble vitamin (6.25%), phytosterol (6.25%), stigmastanes (6.25%), beta diketones (6.25%), and cycloartenol (6.25%) respectively. The major compound includes Hexadecanoic acid, methyl ester (6.84%), n-Hexadecanoic acid (8.58%), 9,12-Octadecanoic acid (Z,Z)-, Methyl Ester (8.04%), 9,12-Octadecadienoic acid (Z,Z) (57.01%), Lup-20(29)-en-3-one (3.57%), γ-Sitosterol (3.31%). Some constituents such as Lup-20(29)-en-3-one, campesterol and squalene were observed and were not previously reported. Total phenolic and total flavonoid content were determined using spectrophotometric technique and calculated as gallic acid equivalents GAE/g dry weight and rutin equivalent RE/g of dry weight respectively.The highest phenolic content exhibited by the acetone extract of seedsi.e. 0.0597 mg GAE/g while the highest flavonoid content exhibited by dichloromethane extract i.e. 0.09 mg RE/g and 0.25 mg QE/g of dry weight respectively. All the extracts showed significant antioxidant activity in DPPH and ABTS cation decolorization assays. Methanol and dichloromethane extract showed the highest DPPH radical scavenging activity i.e. 52.41% and 42.07% at the concentration of 100 mg/ml respectively. Moreover, the IC has been determined by the acetone and methanol extract of seeds. The high antioxidant activity of its seed extracts has made this plant pharmacologically important. Conclusively, there is a vast scope to further explore the active principals of barley so that more of its pharmacological properties can be identified.
PubMed: 38509904
DOI: 10.1016/j.heliyon.2024.e27297 -
ACS Omega Mar 2024Medicinally valuable components derived from natural resources are highly desirable as prospective alternatives to synthetic drugs to treat fatal diseases, such as...
Medicinally valuable components derived from natural resources are highly desirable as prospective alternatives to synthetic drugs to treat fatal diseases, such as cancer and diabetes mellitus. (L.) Dumort () () is a halophyte plant that can thrive in saline environments and possesses excellent medicinal properties. Hence, for the present investigation, has been chosen, and its phytochemical constituents have been extracted utilizing various solvents, including hexane, acetone, and methanol, and identified by GC-MS, LC-MS, and HPLC analyses. The antioxidant activity of the compounds using DPPH, ABTS, and reducing power assays demonstrated that all three extracts of possessed significant radical scavenging activity comparable to standard ascorbic acid with lower IC values (69.20-95.58 μg/mL). In addition, the evaluation of antidiabetic activity by α-amylase inhibition and α-glucosidase inhibition methods revealed that the acetone extract of (SMAE) displayed equipotent activity of standard acarbose with an IC of 32.6 μg/mL. Advantageously, SMAE also exhibited better inhibition activity against the growth of lung cancer cells with an IC of 78.19. μg/mL and less toxicity on the noncancerous HUVEC cells with a high IC of 300 μg/mL. In addition, the cancer cell death mechanism via the apoptotic pathway induced by SMAE was confirmed by DAPI staining and ROS analysis. The analysis of ADME properties, including absorption, distribution, metabolism, and excretion, witnessed that the physicochemical and druglikeness factors were best catered by stigmasterol, γ-sitosterol, and vitamin E. Further, the key phytochemicals identified from SMAE were docked with CtBP1 and SOX2 bound to importin-α target proteins associated with carcinogenic pathways using Schrodinger software. The results showed that the phytochemicals, scilicet, stigmasterol, γ-sitosterol, octadecadienoic acid, and vitamin E, showed a good binding affinity with Glide scores in the range -2.845-4.018 kcal/mol. Overall, the findings support that the least investigated traditional edible medicinal mangrove-related is high in pharmacologically active constituents and might be one of the finest sources of naturally derived molecules for drug development and delivery systems.
PubMed: 38496978
DOI: 10.1021/acsomega.3c05591