Signaling Pathways Research Articles

Vitamin D receptor and its antiproliferative effect in human pulmonary arterial hypertension

Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.

Extreme examples of reparative chondrogenesis: molecular mechanisms

Restoring hyaline cartilage integrity remains a significant challenge in regenerative medicine. When damaged, the defect is replaced by fibrosis connective tissue, resulting in a loss of the biomechanical properties of the cartilage. This review examines the intricate molecular mechanisms underlying reparative chondrogenesis and presents examples from a variety of animal species. It provides a comprehensive overview of the signaling pathways and cellular responses that promote cartilage repair, showcasing the regenerative abilities of fish and amphibians, including the little skate and axolotl, and surprising cases of chondrogenesis in mammals like the naked mole-rat and the Acomys mouse. Unraveling the dynamic interplay between growth factors, cytokines, and extracellular matrix components will shed light on the complex signaling pathways controlling reparative chondrogenesis. The comparative analysis presented in this review reveals both conserved and species-specific molecular pathways involved in cartilage regeneration. This provides valuable information for translational studies. By uncovering the genetic and epigenetic determinants governing extreme examples of reparative chondrogenesis, this review provides a comprehensive framework for developing therapeutic strategies to improve cartilage repair in humans.

Impact of high-fructose diet and metformin on histomorphological and molecular parameters of reproductive organs and vaginal microbiota of female rat

There are limited data on the effects of a high-fructose diet on the female reproductive system. Although metformin has some functional effects on female fertility, its reproductive outcome on high fructose diet-induced metabolic syndrome is unclear. The aim of the present study is to evaluate the impact of a high fructose diet on histomorphological and molecular parameters of the reproductive organs and vaginal microbiota as well as the treatment potential of metformin. Wistar albino rats were used in the study. The metabolic syndrome model was induced by a high-fructose diet in rats for 15 weeks. Metformin was orally administered once a day for the last 6 weeks. The high-fructose diet increased blood glucose, triglycerides, insulin, and ovarian testosterone levels; however, it reduced ovarian aromatase levels and follicle numbers and caused uterine inflammation. The high-fructose diet-induced molecular abnormalities on ovarian tissue were demonstrated by the downregulation of ovarian insulin signaling pathway proteins and dysregulation of ovarian mitogenic and apoptotic pathway proteins. A high-fructose diet caused vaginal dysbiosis, metformin increased probiotic bacteria in the vaginal microbiota. Our results revealed that metformin improves ovarian impairments by modulating hormonal balance, insulin level, mapk, and apoptotic signaling molecules, as well as regulating the vaginal microbiota.

Genetically modified E. Coli secreting melanin (E.melanin) activates the astrocytic PSAP-GPR37L1 pathway and mitigates the pathogenesis of Parkinson’s disease

The characteristic neuropathology of Parkinson’s disease (PD) involves the abnormal accumulation of phosphorylated α-synuclein (αSyn), as well as a significant decrease in neuromelanin (NM) levels within dopamine neurons (DaNs). Unlike αSyn aggregates, the relationship between NM levels and PD pathogenesis is not well understood. In this study, we engineered an E. coli MG1655 strain to produce exosomes containing melanin (E.melanin), and investigated its potential neuroprotective effects on DaNs in the context of PD. By employing a combination of cell cultures, biochemical studies, single nuclear RNA sequencing (snRNA seq), and various in vivo validations, we found that administration of E.melanin effectively alleviated DaNs loss and improved motor behavior impairments observed in both pharmacological and transgenic PD mouse models. Mechanistically, snRNA seq data suggested that E.melanin activated the PSAP-GPR37L1 signaling pathway specifically within astrocytes, leading to a reduction in astrocytic engulfment of synapses. Notably, activation of the GPR37L1 receptor using Tx14(A) peptide successfully rescued motor defects as well as protected against DaNs degeneration in mice with PD. Overall, our findings provide novel insights into understanding the molecular mechanisms underlying melanin’s protective effects on DaNs in PD while offering potential strategies for manipulating and treating its pathophysiological progression.

Exploration of Astragaloside IV in multiple organ dysfunction syndrome and hippocampus damage through network pharmacological analysis

Background: This study aims to investigate the potential therapeutic effect of Astragaloside IV on the hippocampus in multiple organ dysfunction syndrome (MODS) and its underlying mechanisms. Methods: Targets related to "Multiple Organ Dysfunction Syndrome," "Hippocampus," and "Astragaloside IV" were collected from the GeneCards database. Co-existing intersection targets were identified using a Venn diagram via the bioinformatics platform. A protein interaction network was constructed using the String database, and core targets were screened with the cytoHubba plug-in of Cytoscape software. GO functional enrichment and KEGG pathway enrichment analyses were performed using the DAVID database, and a "disease-site-drug-key target-KEGG pathway" network map was constructed to reveal the mechanisms of Astragaloside IV. Results: Two intersection targets were identified, and the protein interaction network showed their interactions. GO and KEGG analyses indicated that these targets are mainly involved in biological processes and pathways such as efferocytosis. The "disease-site-drug-key targets-KEGG pathway" network map further clarified that Astragaloside IV may treat MODS by affecting specific signaling pathways. Conclusion: Astragaloside IV may exert a therapeutic effect on the hippocampus in MODS by influencing pathways such as efferocytosis, offering new perspectives and potential targets for future research.

Decoding the Impact of a Bacterial Strain of Micrococcus luteus on Arabidopsis Growth and Stress Tolerance

Microbes produce various bioactive metabolites that can influence plant growth and stress tolerance. In this study, a plant growth-promoting rhizobacterium (PGPR), strain S14, was identified as Micrococcus luteus (designated as MlS14) using de novo whole-genome assembly. The MlS14 genome revealed major gene clusters for the synthesis of indole-3-acetic acid (IAA), terpenoids, and carotenoids. MlS14 produced significant amounts of IAA, and its volatile organic compounds (VOCs), specifically terpenoids, exhibited antifungal activity, suppressing the growth of pathogenic fungi. The presence of yellow pigment in the bacterial colony indicated carotenoid production. Treatment with MlS14 activated the expression of β-glucuronidase (GUS) driven by a promoter containing auxin-responsive elements. The application of MlS14 reshaped the root architecture of Arabidopsis seedlings, causing shorter primary roots, increased lateral root growth, and longer, denser root hairs; these characteristics are typically controlled by elevated exogenous IAA levels. MlS14 positively regulated seedling growth by enhancing photosynthesis, activating antioxidant enzymes, and promoting the production of secondary metabolites with reactive oxygen species (ROS) scavenging activity. Pretreatment with MlS14 reduced H2O2 and malondialdehyde (MDA) levels in seedlings under drought and heat stress, resulting in greater fresh weight during the post-stress period. Additionally, exposure to MlS14 stabilized chlorophyll content and growth rate in seedlings under salt stress. MlS14 transcriptionally upregulated genes involved in antioxidant defense and photosynthesis. Furthermore, genes linked to various hormone signaling pathways, such as abscisic acid (ABA), auxin, jasmonic acid (JA), and salicylic acid (SA), displayed increased expression levels, with those involved in ABA synthesis, using carotenoids as precursors, being the most highly induced. Furthermore, MlS14 treatment increased the expression of several transcription factors associated with stress responses, with DREB2A showing the highest level of induction. In conclusion, MlS14 played significant roles in promoting plant growth and stress tolerance. Metabolites such as IAA and carotenoids may function as positive regulators of plant metabolism and hormone signaling pathways essential for growth and adaptation to abiotic stress.

Immune Response and Transcriptome Analysis of the Head Kidney to Different Concentrations of Aeromonas veronii in Common Carp (Cyprinus carpio)

The common carp (Cyprinus carpio), a major economic freshwater fish, is suffering from a variety of bacterial infectious diseases because of its high-density, factory and intensive farming patterns. Aeromonas veronii is the causative agent of high mortality in common carp, causing severe economic losses in aquaculture. However, the regulatory mechanisms involved in the response of common carp to this bacterial infection remain poorly understood. In this study, we compared mortality, blood serum LZM (Lysozyme) and IgM (Immunoglobulin M) levels and transcriptome patterns of head kidney tissues after infection with different concentrations of Aeromonas veronii. We observed that mortality increased progressively with an increasing pathogen concentration. The concentrations of blood serum LZM and IgM significantly increased after infection. A total of 13 and 925 differentially expressed genes (DEGs) were identified after infection with low (T4) and high (T9) concentrations of bacterial suspension, respectively. KEGG and GO analyses of the DEGs highlighted multiple immune-related signaling pathways. Weighted gene co-expression network analysis (WGCNA) revealed that 136 and 83 hub genes were related to blood serum LZM and IgM, respectively. Finally, the gene expression in the head kidney was validated via RT–qPCR to be consistent with the transcriptome. These results provide insights into the mechanisms of the immune response to infection with different concentrations of Aeromonas veronii and offer useful information for further studies on immune defense mechanisms in common carp.

ZmCCD8 regulates sugar and amino acid accumulation in maize kernels via strigolactone signalling

SummaryHow carbon (sucrose) and nitrogen (amino acid) accumulation is coordinatively controlled in cereal grains remains largely enigmatic. We found that overexpression of the strigolactone (SL) biosynthesis gene CAROTENOID CLEAVAGE DIOXYGENASE 8 (CCD8) resulted in greater ear diameter and enhanced sucrose and amino acid accumulation in maize kernels. Loss of ZmCCD8 function reduced kernel growth with lower sugar and amino acid concentrations. Transcriptomic analysis showed down‐regulation of the transcription factors ZmMYB42 and ZmMYB63 in ZmCCD8 overexpression alleles and up‐regulation in zmccd8 null alleles. Importantly, ZmMYB42 and ZmMYB63 were negatively regulated by the SL signalling component UNBRANCHED 3, and repressed expression of the sucrose transporters ZmSWEET10 and ZmSWEET13c and the lysine/histidine transporter ZmLHT14. Consequently, null alleles of ZmMYB42 or ZmMYB63 promoted accumulation of soluble sugars and free amino acids in maize kernels, whereas ZmLHT14 overexpression enhanced amino acid accumulation in kernels. Moreover, overexpression of the SL receptor DWARF 14B resulted in more sucrose and amino acid accumulation in kernels, down‐regulation of ZmMYB42 and ZmMYB63 expression, and up‐regulation of ZmSWEETs and ZmLHT14 transcription. Together, we uncover a distinct SL signalling pathway that regulates sucrose and amino acid accumulation in kernels. Significant association of two SNPs in the 5′ upstream region of ZmCCD8 with ear and cob diameter implicates its potential in breeding toward higher yield and nitrogen efficiency.

Low molecular weight heparins promote migration and invasion of trophoblast cells through regulating the PI3K/AKT signaling pathway

Low molecular weight heparins promote migration and invasion of trophoblast cells through regulating the PI3K/AKT signaling pathway

Ketamine attenuates kidney damage and depression-like behaviors in mice with cisplatin-induced acute kidney injury

Acute kidney injury (AKI) is a serious condition characterized by decreased urine output, often accompanied by psychiatric symptoms like depression. However, there are limited pharmacological treatments available for AKI and its associated depressive symptoms. In this study, we investigated whether cisplatin-induced AKI in mice leads to depression-like behaviors and whether ketamine could alleviate both the kidney injury and these behaviors. Mice with cisplatin-induced AKI exhibited elevated levels of creatinine and urea, kidney damage, increased kidney injury molecule-1 protein, and pathological changes in the liver, colon, and spleen. They also showed depression-like behaviors and reduced expression of synaptic proteins in the prefrontal cortex. Remarkably, a single dose of ketamine significantly reduced these symptoms and pathological changes. Interestingly, the beneficial effects of ketamine on the kidneys, other organs, and depression-like behaviors, were reversed by the tropomyosin receptor kinase B (TrkB) inhibitor ANA-12. Western blot analysis revealed the involvement of the TrkB and ERK (extracellular signal-regulated kinase)-CREB (cAMP response element binding protein) signaling pathway. Additionally, metabolomics analysis indicated that blood metabolites, such as C16-ceramide, may contribute to the effects of ketamine in this model. These findings suggest that cisplatin-induced nephrotoxicity in AKI mice contributes to depression-like behaviors, and ketamine can alleviate both kidney damage and depression-like symptoms by modulating the TrkB and ERK-CREB signaling pathways, as well as altering blood metabolites. However, the role of the kidney-brain axis in these depression-like behaviors remains unclear. Furthermore, ketamine may have therapeutic potential for treating kidney diseases such as AKI, along with associated depressive symptoms.

Mesenchymal stem cells: a novel therapeutic approach for feline inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) poses a significant and growing global health challenge, affecting both humans and domestic cats. Research on feline IBD has not kept pace with its widespread prevalence in human populations. This study aimed to develop a model of feline IBD by incorporating dextran sulfate sodium (DSS) to evaluate the therapeutic potential of MSCs and to elucidate the mechanisms that enhance their action.MethodsWe conducted a comprehensive clinical assessment, including magnetic resonance imaging (MRI), endoscopy, and histopathological examination. Additionally, alterations in intestinal microbiota were characterized by 16 S rDNA sequencing, and the influence of MSCs on IBD-related gene expression was investigated through transcriptome analysis.ResultsAccording to our findings, MSC treatment significantly mitigated DSS-induced clinical manifestations, reduced inflammatory cell infiltration, decreased the production of inflammatory mediators, and promoted mucosal repair. Regarding the intestinal microbiota, MSC intervention effectively corrected the DSS-induced dysbiosis, increasing the presence of beneficial bacteria and suppressing the proliferation of harmful bacteria. Transcriptome analysis revealed the ability of MSCs to modulate various inflammatory and immune-related signaling pathways, including cytokine-cytokine receptor interactions, TLR signaling pathways, and NF-κB pathways.ConclusionThe collective findings indicate that MSCs exert multifaceted therapeutic effects on IBD, including the regulation of intestinal microbiota balance, suppression of inflammatory responses, enhancement of intestinal barrier repair, and modulation of immune responses. These insights provide a solid scientific foundation for employing MSCs as an innovative therapeutic strategy for IBD and pave the way for future clinical explorations.

Ligand‐Tethered Extracellular Vesicles Mediated RNA Therapy for Liver Fibrosis

AbstractLiver fibrosis poses a significant global health burden, in which hepatic stellate cells (HSCs) play a crucial role. Targeted nanomedicine delivery systems directed at HSCs have shown immense potential in the treatment of liver fibrosis. Herein, a bioinspired material, engineered therapeutic miR‐181a‐5p (a miRNA known to inhibit fibrotic signaling pathways) and targeted moiety hyaluronic acid (HA) co‐functionalized extracellular vesicles (EVs) are developed. HA is incorporated onto the surface of EVs using DSPE‐PEG as a linker, allowing preferential binding to CD44 receptors, which are overexpressed on activated HSCs. Our results confirmed enhanced cellular uptake and improved payload delivery, as evidenced by the increased intracellular abundance of miR‐181a‐5p in activated HSCs and fibrotic livers. HA‐equipped EVs loaded with miR‐181a‐5p (DPH‐EVs@miR) significantly reduce HSC activation and extracellular matrix (ECM) deposition by inhibiting the TGF‐β/Smad signaling pathway, thus alleviating the progression of liver fibrosis. Additionally, DPH‐EVs@miR improves liver function, ameliorates inflammatory infiltration, and mitigates hepatocyte apoptosis, demonstrating superior hepatic protective effects. Collectively, this study reports a prospective nanovesicle therapeutic platform loaded with therapeutic miRNA and targeting motifs for liver fibrosis. The biomarker‐guided EV‐engineering technology utilized in this study provides a promising tool for nanomedicine and precision medicine.

A Meta-analysis of the Risk of Adverse Cardiovascular Events in Patients with Cancer Treated with Inhibitors of the PI3K/AKT/mTOR Signaling Pathway

A Meta-analysis of the Risk of Adverse Cardiovascular Events in Patients with Cancer Treated with Inhibitors of the PI3K/AKT/mTOR Signaling Pathway

Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway

Decursin protects against DSS-induced experimental colitis in mice by inhibiting the cGAS-STING signaling pathway

Network Pharmacology and Molecular Dynamics Simulations Reveal the Mechanism of Total Alkaloid Components in Anisodus Tanguticus (Maxim.) Pascher in Treating Inflammation and Pain.

This study aimed to elucidate the mechanism that total alkaloids in Anisodus tanguticus (AT)(Maxim.) Pascher played anti-inflammatory and analgesic effects. In this paper, the anti-inflammatory effect in the total alkaloids of AT was confirmed via lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 cells and the main components of AT were immediately analyzed by UPLC/MS. Disease targets were obtained in GeneCards and DisGeNET. Targets of major compounds were searched in ETCM, TCMSP and other databases. The protein-protein interaction (PPI) network was constructed using STRING database, and Cytoscape was used for core targets screening. GO and KEGG enrichment analysis were performed using Daivid database. Sailvina was used for molecular docking. Molecular dynamics simulation analysis was performed using the Amber 20 program. The results showed that the main components in AT were anisodamine, atropine, fabiatrin, scopolamine, scopoletin and scopolin, possibly exerting anti-inflammatory and analgesic effects through pathways such as EGFR tyrosine kinase inhibitor resistance and IL-17 signaling pathway. Fabiatrin and scopolin could be potential drugs with good anti-inflammatory and analgesic effects.

Mycophenolate Mofetil, an Inhibitor of Inosine Monophosphate Dehydrogenase, and Tofacitinib, a Janus Kinase Inhibitor, Attenuate Airway Inflammation and Hyperresponsiveness in a Mouse Model of Allergic Asthma

Treatment-resistant asthma remains an unresolved clinical problem and a challenge for current medical science. Consequently, there is a growing and urgent need to develop novel or alternative therapeutic options for the treatment of asthma. The research problem raised in this study was to assess and compare mycophenolate mofetil (MMF), an inhibitor of inosine monophosphate dehydrogenase, and tofacitinib (TFB), a Janus kinase inhibitor, for anti-asthmatic properties, and consequently to determine whether these agents may have potential as alternative options for treatment of allergic asthma. For this purpose, we assessed the effect of administration of MMF and TFB on the development of a mouse model of allergic airway inflammation (AAI) and accompanying CD4+ (cluster of differentiation 4) T-cell immune response in the lung-draining mediastinal lymph nodes (MLNs) and lungs, i.e., in the inductive and effector sites, respectively, of the immune response underlying the development of allergic asthma. The results from a histopathological scoring system demonstrated that the administration of MMF and TFB did not prevent or abolish ovalbumin-induced AAI, but strongly attenuated its severity. The pulmonary function tests revealed that the treatment with MMF and TFB significantly reduced methacholine-induced bronchoconstriction. These results indicate that the treatment with TFB and MMF attenuated the development of ovalbumin-induced AAI. The magnitude of the anti-asthmatic effect was comparable between both agents. The study revealed that the impairment of the clonal expansion of effector CD4+ T cells in the MLNs is a critical event in the mechanism underlying the anti-asthmatic effect of MMF and TFB. Apart from this, the findings of the study strongly suggest that the suppression of the interleukin-33/suppression of tumorigenicity-2 signaling pathway may constitute an additional mechanism responsible for producing this effect. In turn, the results indicate that the anti-asthmatic action induced by the studied agents is not mediated by the generation of forkhead box protein 3-expressing CD4+ regulatory T cells. Clinical implication of the results: the results suggest that MMF and TFB may exert anti-asthmatic action, and thus they may be considered therapeutic options for the treatment of allergic asthma cases resistant to conventional/existing treatment.

Bio-characteristics, tissue expression of miR-375 in hypothalamic-pituitary-ovarian axis and its regulation in reproduction-related diseases

Our study concentrated on the expression of miRNA-375 in the hypothalamic-pituitary-gonadal axis of female Hu sheep. The investigation involved cloning the precursor sequence of miR-NA-375, followed by comparison with database entries and subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. In our approach, we obtained ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus, and pineal gland from fertile but nonpregnant Hu ewes. MiRNA extraction kit was used to extract miRNA from the above eight tissues. Real-time fluorescent quantitative polymerase chain reaction was used to evaluate the role of miR-375 in the hy-pothalamic-pituitary-gonadal axis. The results of miR-375 precursor sequence cloning were compared with those of Anopheles gambiae, Apis mellifera, Bos taurus, Drosophila melanogaster, Danio rerio, Fugu rubripes, Gallus gallus, Homo sapiens, Monodelphis domestica, Macaca mulatta, Mus musculus, Pan troglodytes, Rattus norvegicus, Tetraodon nigroviridis, Xenopus tropicalis miR-375 in miRBase database. It was found that oar-miR-375 was highly conserved. Notably, miR-375 expression in the pineal gland was significantly higher (p < 0.01) than that in the ovaries, thalamus, cerebellum, brain, uterus, pituitary gland, hypothalamus. The study also involved predicting miR-375 target genes. GO and KEGG enrichment analyses of these predicted target genes revealed that miR-375 is involved in 182 biological processes, affects 186 cellular components, and participates in 184 molecular functions. In terms of pathway enrichment, miR-375 was linked to nine pathways, including the Hippo, Wnt, and mTOR signaling pathways. This study has validated the interaction between miR-375 and its target gene FZD4, which can be recognized and bound to produce effects. These findings lead to the inference that miR-375 may play a crucial regulatory role in sheep reproduction through the Hippo pathway and Wnt pathway, laying a foundation for further exploration of miR-375’s role in this domain.

Cuproptosis: A Copper‐Mediated Programmed Cell Death

It has been found that various heavy metals can initiate different types of regulated cell deaths. Among these metals, copper, an essential trace micronutrient that plays a major role in a lot of physiological processes, also can initiate cell death. It can act as a constituent of metalloenzymes, and can act as a mediator for signaling pathways to regulate proliferation and metastasis of tumor. It is also an integral part of some metal‐based anticancer drugs. Recent studies have revealed that excessive intracellular copper accumulation leads to the aggregation of mitochondrial lipoylated proteins, causing proteotoxic stress and ultimately resulting in cell death. This newly discovered copper‐induced cell death is termed as cuproptosis. In the last few, a lot of research has been done to understand the mechanism of copper‐mediated cell death, and attempts have also been made to identify the relationship between cuproptosis and the development of cancer. In this review, we provide a comprehensive overview on the significance of copper, its regulation inside the body, the possible mechanism of cuproptosis, and how this cuproptosis can be employed as a therapeutic tool for cancer ablation.

Mass Spectrometry‐Based Platforms for Protein Lipoxidation Profiling

AbstractLipid peroxidation, occurring through enzymatic or non‐enzymatic processes, generates lipid‐derived electrophiles (LDEs), which can covalently modify nucleophilic amino acid residues in proteins, a process known as protein lipoxidation. This modification can alter protein structure and function, either causing damage or regulating signalling pathways. Identifying the protein targets and specific lipoxidation sites provide important clues for unveiling the oxidative stress‐related protein interaction network and molecular mechanisms of related diseases. In this review, we present a detailed overview of recent advances in protein LDE modification profiling, with a focus on mass spectrometry (MS)‐based chemoproteomic platforms for global protein lipoxidation profiling.

Design, Synthesis and Biological Activities Evaluation of Novel Pterostilbene-urea Derivatives as Potential Anti- inflammatory Agents.

1. The toxicity of derivatives was removed by the reasonable modification of bioactive skeleton. 2. As potential COX-2 inhibitor with IC50 values ranging from 39.42 to 179.84 nM/L, compounds (Q4-Q10, Q20) exhibited superior anti-inflammatory activity at low micromolar concentrations. 3. Q7 (IC50 (COX-2)=61.05 nM/L), Q10 (IC50 (COX-2)=54.68 nM/L) and Q20 (IC50 (COX-2)=39.42 nM/L) showed stronger COX-2 inhibitory abilities than Celecoxib (IC50 (COX-2)=67.89 nM/L). 4. The strongest anti-inflammatory agent, Q20 (IC50 NO= 9.96 μM/L, IC50 (COX-2)=39.42 nM/L) effectively inhibited the secretion of IL-1β and TNF-α, exhibited the IC50 values of 12.30 and 9.07 μM/L respectively. 5. Q20 exerted as anti-inflammatory actives via targeting COX-2, down-regulating iNOS and TLR4 protein, and inhibiting the activation of NLRP3 inflammasome and NF-κB signal pathway.