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Molecules (Basel, Switzerland) Jun 2024Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Aiton,...
Ulcerative colitis (UC) is difficult to cure and easy to relapse, leading to poor quality of life for patients. Oxymatrine (OMT) is one of the main alkaloids of Aiton, which has many effects, such as anti-inflammation, anti-oxidative stress, and immunosuppression. This study aimed to investigate whether OMT could attenuate ulcerative colitis by inhibiting the NOD-like receptor family pyrin domain containing three (NLRP3) inflammasome-mediated pyroptosis. In this study, the UC rat models were established by 2,4,6-Trinitrobenzenesulfonic acid (TNBS) in vivo, while RAW264.7 cells and peritoneal macrophages were stimulated with Lipopolysaccharides/Adenosine Triphosphate (LPS/ATP) in vitro to simulate pyroptosis models, and Western blotting (WB) and other detection techniques were applied to analyze proteins involved in the NLRP3 inflammasome pathway. Our results showed that OMT alleviated colitis ulcers and pathological damage in the TNBS-induced UC rats and exhibited an inhibitory effect on pyroptosis at the early stage of UC. In the model group, the pyroptosis reached the peak at 24 h after modeling with the contents of active-cysteine-aspartic proteases-1 (caspase-1), Gasdermin D (GSDMD)-N, and cleaved-interleukin-1 beta (IL-1β) to the highest expression level. Meanwhile, we found that OMT (80 mg kg) remarkably decreased the expression levels of NLRP3, active-caspase-1, and cleaved-IL-1β at 24 h in the lesion tissue from UC rats. Further experiments on cells demonstrated that OMT at concentrations of 100 and 250 μM significantly inhibited cell death caused by NLRP3 inflammasome activation ( < 0.05), downregulated caspase-1, GSDMD, and decreased the levels of active-caspase-1, GSDMD-N, cleaved-IL-1β in RAW326.7 cells, and peritoneal macrophages. In summary, these results indicated that OMT could attenuate ulcerative colitis through inhibiting pyroptosis mediated by the NLRP3 inflammasome. The inhibition of the NLRP3 inflammasome may be a potential strategy for UC.
Topics: Animals; Quinolizines; Colitis, Ulcerative; Alkaloids; Pyroptosis; NLR Family, Pyrin Domain-Containing 3 Protein; Mice; Rats; Inflammasomes; RAW 264.7 Cells; Male; Disease Models, Animal; Rats, Sprague-Dawley; Trinitrobenzenesulfonic Acid; Lipopolysaccharides; Matrines
PubMed: 38930963
DOI: 10.3390/molecules29122897 -
Molecules (Basel, Switzerland) Jun 2024Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses were conducted on essential oil extracted from Saudi Arabian L. () aerial parts,...
Gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) analyses were conducted on essential oil extracted from Saudi Arabian L. () aerial parts, resulting in the identification of 58 constituents, representing 93.0% of the total oil composition. The oil primarily consisted of monoterpenes (38.6%), sesquiterpenes (14.1%), and other compounds such as ethyl esters and cyclic ketones (40.3%). The main components identified were piperitone (16.5%), ethyl cinnamate (12.9%), and camphor (9.7%). Multivariate statistical analyses (MVAs), including principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) analysis, were employed to compare the chemical makeup of this oil with 20 other oils from various regions. The study revealed distinct clusters, highlighting unique chemotypes and geographic variations. Particularly, the oil from the current study demonstrated a specialized chemical profile with significant concentrations of specific compounds, contributing significantly to its distinctiveness. Further cytotoxicity testing on RAW264.7 macrophages suggested that concentrations below 20 μg/mL of oil are suitable for future pharmacological investigations. This study provides valuable insights into the chemical diversity, geographic variations, and potential biomedical applications of these essential oils.
Topics: Oils, Volatile; Artemisia; Saudi Arabia; Mice; Animals; RAW 264.7 Cells; Gas Chromatography-Mass Spectrometry; Principal Component Analysis; Plant Oils
PubMed: 38930948
DOI: 10.3390/molecules29122882 -
Molecules (Basel, Switzerland) Jun 2024This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of leaf oil. A yellow oil was obtained...
This study is the first to investigate the chemical composition and antioxidant, anti-inflammatory, and cytotoxic activities of leaf oil. A yellow oil was obtained through hydro-distillation, with a yield of 0.1% (/). The GC-MS analysis revealed 66 compounds, constituting 99.6% of the oil. Sesquiterpene hydrocarbons predominated (70.4%), followed by monoterpene hydrocarbons (13.2%), oxygenated sesquiterpenes (12.4%), non-terpenic compounds (2.0%), and oxygenated monoterpenes (1.6%). Major constituents included germacrene D (25.1%), ()-caryophyllene (17.4%), bicyclogermacrene (6.6%), -pinene (6.2%), and -pinene (4.7%). The assessment of antioxidant capacity via 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging assay yielded a weak effect, with an IC value > 100 µg/mL. The inhibition of lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells was quantified using the MTT assay, showing an IC value of 15.15 ± 0.68 µg/mL. Furthermore, cytotoxic effects on SK-LU-1 cell line growth were evaluated using the sulforhodamine B assay, resulting in an IC value of 37.45 ± 2.43 μg/mL. The anti-inflammatory activity was notable among the analyzed bioactivities of this oil. By employing a computational model, the predominant secondary metabolites in the essential oil were selected as candidates for interaction analysis with cyclooxygenase-2, an enzyme implicated in the inflammatory response. Our findings suggest that leaf oil could serve as a potential source of natural compounds with prospective therapeutic effects in treating inflammatory conditions.
Topics: Oils, Volatile; Anti-Inflammatory Agents; Antioxidants; Mice; Animals; RAW 264.7 Cells; Peperomia; Nitric Oxide; Plant Leaves; Gas Chromatography-Mass Spectrometry; Computer Simulation; Southeast Asian People
PubMed: 38930872
DOI: 10.3390/molecules29122808 -
Medicina (Kaunas, Lithuania) Jun 2024: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in...
: As modulators of the tumor microenvironment, macrophages have been extensively studied for their potential in developing anticancer strategies, particularly in regulating macrophage polarization towards an antitumorigenic (M1) phenotype rather than a protumorigenic (M2) one in various experimental models. Here, we evaluated the effect of PD98059, a mitogen-activated protein kinase kinase MAPKK MEK1-linked pathway inhibitor, on the differentiation and polarization of THP-1 monocytes in response to phorbol-12-myristate-13-acetate (PMA) under various culture conditions for tumor microenvironmental application. : Differentiation and polarization of THP-1 were analyzed by flow cytometry and RT-PCR. Polarized THP-1 subsets with different treatment were compared by motility, phagocytosis, and so on. : Clearly, PMA induced THP-1 differentiation occurs in adherent culture conditions more than nonadherent culture conditions by increasing CD11b expression up to 90%, which was not affected by PD98059 when cells were exposed to PMA first (post-PD) but inhibited when PD98059 was treated prior to PMA treatment (pre-PD). CD11b THP-1 cells treated with PMA and PMA-post-PD were categorized into M0 (HLA-DR and CD206), M1 (HLA-DR and CD206), and M2 (HLA-DR and CD206), resulting in an increased population of M1 macrophages. The transcription levels of markers of macrophage differentiation and polarization confirmed the increased M1 polarization of THP-1 cells with post-PD treatment rather than with PMA-only treatment. The motility and cytotoxicity of THP-1 cells with post-PD treatment were higher than THP-1 cells with PMA, suggesting that post-PD treatment enhanced the anti-tumorigenicity of THP-1 cells. Confocal microscopy and flow cytometry showed the effect of post-PD treatment on phagocytosis by THP-1 cells. : We have developed an experimental model of macrophage polarization with THP-1 cells which will be useful for further studies related to the tumor microenvironment.
Topics: Humans; Macrophages; Tetradecanoylphorbol Acetate; Flavonoids; THP-1 Cells; Cell Differentiation; Monocytes; Flow Cytometry; Phagocytosis
PubMed: 38929626
DOI: 10.3390/medicina60061009 -
International Journal of Molecular... Jun 2024Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins...
Arterial macrophage cholesterol accumulation and impaired cholesterol efflux lead to foam cell formation and the development of atherosclerosis. Modified lipoproteins interact with toll-like receptors (TLR), causing an increased inflammatory response and altered cholesterol homeostasis. We aimed to determine the effects of TLR antagonists on cholesterol efflux and foam cell formation in human macrophages. Stimulated monocytes were treated with TLR antagonists (MIP2), and the cholesterol efflux transporter expression and foam cell formation were analyzed. The administration of MIP2 attenuated the foam cell formation induced by lipopolysaccharides (LPS) and oxidized low-density lipoproteins (ox-LDL) in stimulated THP-1 cells ( < 0.001). The expression of ATP-binding cassette transporters A (ABCA)-1, ABCG-1, scavenger receptor (SR)-B1, liver X receptor (LXR)-α, and peroxisome proliferator-activated receptor (PPAR)-γ mRNA and proteins were increased ( < 0.001) following MIP2 administration. A concentration-dependent decrease in the phosphorylation of p65, p38, and JNK was also observed following MIP2 administration. Moreover, an inhibition of p65 phosphorylation enhanced the expression of ABCA1, ABCG1, SR-B1, and LXR-α. TLR inhibition promoted the cholesterol efflux pathway by increasing the expression of ABCA-1, ABCG-1, and SR-B1, thereby reducing foam cell formation. Our results suggest a potential role of the p65/NF-kB/LXR-α/ABCA1 axis in TLR-mediated cholesterol homeostasis.
Topics: Humans; Foam Cells; Cholesterol; Liver X Receptors; Toll-Like Receptors; ATP Binding Cassette Transporter 1; Lipoproteins, LDL; PPAR gamma; THP-1 Cells; Macrophages; ATP Binding Cassette Transporter, Subfamily G, Member 1; Lipopolysaccharides; Scavenger Receptors, Class B
PubMed: 38928513
DOI: 10.3390/ijms25126808 -
International Journal of Molecular... Jun 2024Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables,...
Onion ( L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.
Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Topics: Animals; Osteoblasts; RANK Ligand; Osteoporosis; Flavonoids; Mice; Onions; Cell Differentiation; Plant Extracts; Rats; Cell Proliferation; RAW 264.7 Cells; Osteogenesis; Humans; Female; Osteoclasts; Bone Density; Ovariectomy; Rats, Sprague-Dawley; Osteoprotegerin
PubMed: 38928460
DOI: 10.3390/ijms25126754 -
International Journal of Molecular... Jun 2024Renal cell carcinoma (RCC) is one of the most common malignant tumors of the kidney, presenting significant challenges for clinical diagnosis and treatment. Macrophages...
Renal cell carcinoma (RCC) is one of the most common malignant tumors of the kidney, presenting significant challenges for clinical diagnosis and treatment. Macrophages play crucial roles in RCC, promoting tumor progression and warranting further investigation. Previous studies have identified as a transmembrane protein associated with reproduction, but its relationship with tumors or macrophages has not been discussed. This study utilized transcriptomic sequencing data from 609 KIRC patients in the TCGA database and single-cell sequencing data from 34,326 renal carcinoma cells for subsequent analysis. We comprehensively evaluated the expression of and its relationship with clinical features, tumor prognosis, immune infiltration, and mutations. Additionally, we further assessed the correlation between and macrophage M2 polarization using single-cell data and explored its potential as a cancer therapeutic target through molecular docking. The results demonstrated that is upregulated in RCC and associated with poor survival rates. In clinical staging, the proportion of malignant and high-metastasis patients was higher in the high- group than in the low- group. Furthermore, we found that influences RCC immune infiltration, with its expression positively correlated with various immune checkpoint and M2-related gene expressions, positively associated with M2 macrophage infiltration, and negatively correlated with activated NK cells. Moreover, showed specific expression in macrophages, with the high-expression subgroup exhibiting higher M2 polarization, hypoxia, immune evasion, and angiogenesis scores, promoting tumor progression. Finally, we predicted several potential drugs targeting , such as conivaptan and nilotinib. Our analysis elaborately delineates the immune characteristics of in the tumor microenvironment and its positive correlation with macrophage M2 polarization, providing new insights into tumor immunotherapy. We also propose potential FDA-approved drugs targeting this gene, which should be tested for their binding effects with in future studies.
Topics: Carcinoma, Renal Cell; Humans; Kidney Neoplasms; Biomarkers, Tumor; Macrophages; Prognosis; Gene Expression Regulation, Neoplastic; Female; Male; Tumor Microenvironment; Molecular Docking Simulation
PubMed: 38928412
DOI: 10.3390/ijms25126707 -
International Journal of Molecular... Jun 2024The ability of tumor-derived extracellular vesicles (EVs) to modulate the function of myeloid cells is widely recognized. Hence, a comprehensive understanding of the...
The ability of tumor-derived extracellular vesicles (EVs) to modulate the function of myeloid cells is widely recognized. Hence, a comprehensive understanding of the distinct components associated with EVs and the signals that they deliver to myeloid cells could provide potential approaches to impede the immunosuppression by myeloid-derived suppressor cells (MDSCs). We investigated melanoma EV-associated microRNAs (miRs) using the RET transgenic melanoma mouse model and simulated their transfer to normal myeloid cells by transfecting immature mouse myeloid cells and human monocytes. We observed elevated levels of miR-125a-5p, -125b-5p, and let-7e-5p in mouse melanoma-infiltrating MDSCs. In addition, miR-125a-5p levels in the tumor microenvironment correlated with mouse melanoma progression. The delivery of miR-125a-5p, alone or in combination with let-7e-5p and miR-99b-5p from the same genomic cluster, to normal myeloid cells resulted in their conversion to MDSC-like cells. Our findings indicate that miR-125a-5p could modulate myeloid cell activation in the melanoma microenvironment via a NF-κB-dependent mechanism.
Topics: MicroRNAs; Myeloid-Derived Suppressor Cells; Animals; Humans; Mice; Tumor Microenvironment; Melanoma; Mice, Transgenic; NF-kappa B; Extracellular Vesicles; Cell Line, Tumor; Gene Expression Regulation, Neoplastic; Mice, Inbred C57BL; Monocytes
PubMed: 38928399
DOI: 10.3390/ijms25126693 -
International Journal of Molecular... Jun 2024Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A-D (-) and an isopimarane diterpenoid talaromarane A () were isolated...
Five new diterpenes including four diterpenes with 1,2,3,4,4a,5,6,8a-octalin skeleton talaroacids A-D (-) and an isopimarane diterpenoid talaromarane A () were isolated from the mangrove endophytic fungus sp. JNQQJ-4. Their structures and absolute configurations were determined by analysis of high-resolution electrospray ionization mass spectroscopy (HRESIMS), 1D/2D Nuclear Magnetic Resonance (NMR) spectra, single-crystal X-ray diffraction, quantum chemical calculation, and electronic circular dichroism (ECD). Talaromarane A () contains a rare 2-oxabicyclo [3.2.1] octan moiety in isopimarane diterpenoids. In bioassays, compounds , , , and displayed significant anti-inflammatory activities with the IC value from 4.59 to 21.60 μM.
Topics: Talaromyces; Diterpenes; Anti-Inflammatory Agents; Animals; Mice; Molecular Structure; RAW 264.7 Cells; Magnetic Resonance Spectroscopy
PubMed: 38928398
DOI: 10.3390/ijms25126691 -
International Journal of Molecular... Jun 2024The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand,...
The aryl hydrocarbon receptor (AhR) is a transcription factor that regulates the immune system through complicated transcriptional programs. Genistein, an AhR ligand, exhibits anti-inflammatory properties. However, its role in modulating immune responses via the AhR signaling pathway remains unclear. In this study, 360 male Arbor Acre broilers (1-day-old) were fed a basal diet supplemented with 40 or 80 mg/kg genistein and infected with or without (). Our results demonstrated that genistein ameliorated -induced intestinal damage, as reflected by the reduced intestinal lesion scores and improved intestinal morphology and feed-to-gain ratio. Moreover, genistein increased intestinal sIgA, TGF-β, and IL-10, along with elevated serum IgG, IgA, and lysozyme levels. Genistein improved intestinal AhR and cytochrome P450 family 1 subfamily A member 1 (CYP1A1) protein levels and AhR cell numbers in -challenged broilers. The increased number of AhRCD163 cells in the jejunum suggested a potential association between genistein-induced AhR activation and anti-inflammatory effects mediated through M2 macrophage polarization. In IL-4-treated RAW264.7 cells, genistein increased the levels of AhR, CYP1A1, CD163, and arginase (Arg)-1 proteins, as well as IL-10 mRNA levels. This increase was attenuated by the AhR antagonist CH223191. In summary, genistein activated the AhR signaling pathway in M2 macrophages, which enhanced the secretion of anti-inflammatory cytokines and attenuated intestinal damage in -infected broilers .
Topics: Animals; Receptors, Aryl Hydrocarbon; Genistein; Chickens; Macrophages; Mice; Enteritis; Male; RAW 264.7 Cells; Poultry Diseases; Intestines; Clostridium perfringens; Clostridium Infections; Necrosis; Macrophage Activation; Inflammation; Signal Transduction
PubMed: 38928362
DOI: 10.3390/ijms25126656