luteolin-7-glucoside and Inflammation

Toxoplasma gondii (T. gondii) infection can cause liver injury by inducing inflammation and oxidative stress. The Chinese herbal extract luteoloside (Lut) has considerable anti-inflammatory and antioxidant properties, but its effects on the liver injury during T. gondii infection have not been reported. This study investigated the hepatoprotective effects of Lut by treating T. gondii-infected mice with 0-200 mg/kg doses of Lut and further examined the expression of key proteins in the inflammation and oxidative stress-related pathways in the liver to investigate the potential mechanism of the hepatoprotective effects of Lut. Results showed that Lut remarkably reduced serum ALT and AST levels, considerably decreased inflammatory factors TNF-α, IL-6, and IL-1β, as well as oxidative products MDA, and greatly increased antioxidant enzymes SOD and GSH. The expression of key proteins TLR4, Myd88, TRAF6, p-NF-κB p65 in the TLR4/NF-κB pathway and P2X7R, NLRP3, caspase 1, IL-1β, IL-18 in the P2X7R/NLRP3 pathway were significantly decreased in the liver. And the expression of key proteins Nrf2, HO-1, NQO-1, and GCLC in the Nrf2/HO-1 antioxidant-related pathway was significantly upregulated. In conclusion, Lut attenuated T. gondii-induced liver injury by inhibiting the inflammatory response and enhancing antioxidant capacity. The hepatoprotective mechanisms of Lut are involved in inhibiting TLR4/NF-κB and P2X7R/NLRP3 inflammatory signaling pathways, as well as enhancing the Nrf2/HO-1 antioxidant pathway. These findings not only provide some reference for further exploring the specific hepatoprotective mechanism of Lut during T. gondii infection, but also provide some theoretical basis for the future clinical application of Lut as a hepatoprotective drug in T. gondii infection.

Topics: Animals; Antioxidants; Chemical and Drug Induced Liver Injury, Chronic; Inflammation; Liver; Mice; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Toll-Like Receptor 4; Toxoplasma

To investigate whether cynaroside protects human periodontal ligament (hPDL) cells from lipopolysaccharide (LPS)-induced damage and inflammation and to analyze the underlying mechanism.. LPS was used to stimulate hPDL and RAW264.7 cells. MTT assay was used to detect cell viability, and protein expression levels were measured via western blot analysis. Nitrite oxide and prostaglandin E. Cynaroside inhibited the expression of iNOS, COX-2, TNF-α, and IL-6 in LPS-stimulated hPDL and RAW264.7 cells without cytotoxicity. Furthermore, cynaroside significantly suppressed LPS-induced protein expression of matrix metalloproteinase 3. Additionally, cynaroside prevented LPS-induced NF-κB p65 subunit translocation to the nucleus by inhibiting the phosphorylation and degradation of IκB-α. Moreover, cynaroside could restore the mineralization ability of hPDL cells reduced by LPS.. Cynaroside protected hPDL cells from LPS-induced damage and inflammation via inhibition of NF-κB activation. These results suggest that cynaroside may be a potential therapeutic agent for the alleviation of periodontitis.

Topics: Animals; Cells, Cultured; Cyclooxygenase 2; Dinoprostone; Glucosides; Humans; Inflammation; Lipopolysaccharides; Luteolin; Matrix Metalloproteinase 3; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Periodontal Ligament; RAW 264.7 Cells; Transcription Factor RelA

Luteoloside is a flavonoid extracted from several natural herbs that exhibits anti-microbial and anti-inflammation properties. Our study mainly identified the anti-inflammatory mechanism of action of luteoloside in Staphylococcus aureus-induced endometritis. Histopathological observations and myeloperoxidase (MPO) activity showed that luteoloside could protect the uterus from S. aureus-induced damage and ameliorate the infiltration of inflammatory cells. Quantitative PCR (qPCR) and ELISA analysis also revealed that luteoloside could decrease the expression of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 and increase the expression of the anti-inflammatory cytokine IL-10 both in vivo and in vitro. However, western blot analysis revealed that luteoloside inhibited the expression of TLR2 and IL-8 and inhibited the phosphorylation of IκBα and NF-κB p65. Moreover, luteoloside inhibited the apoptosis of endometrial epithelial cells (EECs), suppressed the phosphorylation of p53, and decreased the expression of caspase-3 induced by S. aureus. Furthermore, this study showed that luteoloside inhibited the expression of Bax but increased the expression of Bcl-2. These results indicate that luteoloside has anti-inflammatory properties by inhibiting the TLR2 and NF-κB signaling pathways and plays an anti-apoptotic role in S. aureus-induced endometritis, which may be valuable for the clinical treatment of S. aureus-induced inflammation.

Topics: Animals; Apoptosis; Cytokines; Endometritis; Female; Glucosides; Humans; Inflammation; Luteolin; NF-kappa B; Protective Agents; Staphylococcus aureus; Toll-Like Receptor 2; Uterus

The epidermis is a dynamic tissue in which keratinocytes proliferate in the basal layer and undergo a tightly controlled differentiation while moving into the suprabasal layers. The balance between keratinocyte proliferation, differentiation, and death is essential, and its perturbation can result in pathological changes. Some common skin diseases, such as psoriasis, are characterized by hyperproliferation accompanied by inflammatory reactions, suggesting that molecules with topical anti-inflammatory and ROS scavenging abilities may be useful for their treatment. Here we investigate the potential of the flavone Luteolin-7-glucoside (LUT-7G) as a treatment for psoriasis. We show that LUT-7G leads to a modification of the cell cycle and the induction of keratinocyte differentiation, with modification of energy, fatty acid, and redox metabolism. LUT-7G treatment also neutralizes the proliferative stimulus induced by the proinflammatory cytokines IL-22 and IL-6 in HEKn. Moreover, in the Imiquimod (IMQ) mouse model of psoriasis, topical administration of LUT-7G leads to a marked reduction of acanthosis and re-expression of epidermal differentiation markers. Dissection of the IL-22 signalling pathway, activated by IMQ treatment, demonstrates that LUT-7G impairs the nuclear translocation of phosphorylated (activated) STAT3, blocking the IL-22 signalling cascade. Thus LUT-7G appears to be a promising compound for the treatment of hyperproliferative and inflammatory skin diseases, such as psoriasis.

Topics: Acanthosis Nigricans; Aminoquinolines; Animals; Cell Differentiation; Cell Nucleus; Cell Proliferation; Cells, Cultured; Cellular Senescence; Disease Models, Animal; Glucosides; Humans; Imiquimod; Immunohistochemistry; Inflammation; Interleukin-22; Interleukins; Keratinocytes; Lipids; Luteolin; Mice, Inbred C57BL; Oxidation-Reduction; Phenotype; Protein Transport; Psoriasis; Signal Transduction; STAT3 Transcription Factor

One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0μM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0μM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.

Topics: Anti-Inflammatory Agents; Cells, Cultured; Chrysanthemum; Cyclooxygenase 2; Flavonoids; Flowers; Inflammation; Lipopolysaccharides; Macrophages; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Phytotherapy; Plant Extracts; Spectrometry, Mass, Electrospray Ionization; Structure-Activity Relationship; Tumor Necrosis Factor-alpha

This protocol describes microsphere-based protease assays for use in flow cytometry and high-throughput screening. This platform measures a loss of fluorescence from the surface of a microsphere due to the cleavage of an attached fluorescent protease substrate by a suitable protease enzyme. The assay format can be adapted to any site or protein-specific protease of interest and results can be measured in both real time and as endpoint fluorescence assays on a flow cytometer. Endpoint assays are easily adapted to microplate format for flow cytometry high-throughput analysis and inhibitor screening.

Topics: Animals; Biotinylation; Flow Cytometry; Fluorescence Resonance Energy Transfer; Green Fluorescent Proteins; High-Throughput Screening Assays; Humans; Inflammation; Kinetics; Microspheres; Peptide Hydrolases; Peptides; Reproducibility of Results; Temperature