calycosin-7-o-beta-d-glucopyranoside and Inflammation

Osteoarthritis (OA) treatment aims to improve inflammation and delay cartilage degeneration. However, there is no effective strategy presently available. Ononin, a representative isoflavone glycoside component extracted from natural Chinese herbs, exerts anti-inflammatory and proliferative effects. However, the therapeutic effect of ononin on chondrocyte inflammation remains unclear.. In this study, we explored the therapeutic effect and potential mechanism of ononin in OA by establishing an interleukin-1 beta (IL-1β)-induced chondrocyte inflammation model.. Our results verified that ononin alleviated the IL-1β-induced decrease in chondrocyte viability, attenuated the overexpression of the inflammatory factors tumour necrosis factor α (TNF-α) and interleukin 6 (IL-6), and simultaneously inhibited the expression of cartilage extracellular matrix (ECM)-degrading enzymes such as matrix metalloproteinase-13 (MMP-13). Furthermore, the decomposition of Collagen II protein could be alleviated in the OA model by ononin. Finally, ononin improved chondrocyte inflammation by downregulating the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signalling pathways.. Our findings suggested that ononin could inhibit the IL-1β-induced proinflammatory response and ECM degradation in chondrocytes by interfering with the abnormal activation of the MAPK and NF-κB pathways, indicating its protective effect against OA.

Topics: Animals; Anti-Inflammatory Agents; Cartilage; Chondrocytes; Down-Regulation; Glucosides; Inflammation; Interleukin-1beta; Isoflavones; Male; MAP Kinase Signaling System; Matrix Metalloproteinase 13; Mitogen-Activated Protein Kinases; NF-kappa B; Osteoarthritis; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; Signal Transduction; Tumor Necrosis Factor-alpha

As a kind of chronic inflammatory diseases, Rheumatoid arthritis (RA) has a low cure rate and easy recurrence. It has widely reported that abnormal activation of mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways are associated with the development of RA inflammation. Blocking the inflammatory signaling pathways of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) can delay the development of RA. Ononin is a natural isoflavone glycoside and plays a key role in modulating inflammation related signaling pathways. However, whether Ononin exerts anti-inflammatory effects on RA inflammation remains unknown. In this study, we evaluated the therapeutic effect of Ononin on RA by establishing a tumor necrosis factor α (TNF-α)-induced RA-FLS cell model. Our data confirmed that Ononin could alleviate TNF-α-induced RA-FLS and MH7A cells viability, increase cell apoptosis, decrease the production of pro-inflammatory cytokines like interleukin-1β (IL-1β) and interleukin 6 (IL-6), and further inhibit the abnormal activation of NF-κB and MAPK pathways. Our results suggested that Ononin could be a potential therapeutic agent for RA.

Topics: Apoptosis; Arthritis, Rheumatoid; Cell Line; Cell Survival; Cytokines; Fibroblasts; Glucosides; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Isoflavones; Mitogen-Activated Protein Kinases; NF-kappa B; Signal Transduction; Synoviocytes; Tumor Necrosis Factor-alpha

Formononetin (MBHS) and its glycosylated derivative ononin (MBHG), as the major isoflavones, have exhibited the anti-inflammatory impacts on the lipopolysaccharide (LPS)-induced inflammation. Although various researches have focused on interpreting the pharmaceutical activities of MBHG and MBHS, the molecular mechanisms in zebrafish models are still unclear.. The purpose of the present work is to investigate the molecular mechanisms of the anti-inflammatory effects of MGHG and MBHS based on lipidomics and targeted transcriptomics.. UHPLC-MS was applied for the lipid analyses and RT-PCR was adopted for the mRNA analyses, and the results of different groups were compared for exploring the significantly changed lipids and mRNAs.. The results of lipidomics revealed that phosphatidylcholines (PCs) were drastically down-regulated in the MBHG or MBHS treated LPS-induced inflammatory zebrafish models. Besides, MBHS can also decrease the levels of triacylglycerols (TAGs). For the targeted transcriptomics analyses, 4 cytokines (TNF-α, IL-1β, IL-6 and IFN-γ) and 3 mRNA (JNK1, ERK1 and p38a) involved in the MAPK pathway were down-regulated and IL-10 was up-regulated under the treatment of MBHG or MBHS.. Combining the results of lipidomics and targeted transcriptomics, we indicated that MBHG and MBHS exerted potent anti-inflammatory effects on the LPS-induced zebrafish models through the MyD88 or TRIF MAPK/ERK and MAPK/JNK pathways and the glycerophospholipid, glycosylphosphatidylinositol (GPI)-anchor biosynthesis and glycerolipid metabolisms. Our results provided new insights into the anti-inflammatory mechanisms of MBHG or MBHS and supplied an effective method to interpret the pharmacological mechanisms of drugs.

Topics: Animals; Anti-Inflammatory Agents; Gene Expression Profiling; Glucosides; Inflammation; Isoflavones; Lipidomics; Lipopolysaccharides; MAP Kinase Signaling System; Transcriptome; Tumor Necrosis Factor-alpha; Zebrafish; Zebrafish Proteins

Increasing evidence has shown that ononin, a major isoflavone, has anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. However, the molecular mechanisms underlying the anti-inflammatory effects of ononin are still unclear. In the present study, we investigated these effects and the underlying mechanisms of ononin on LPS-induced inflammatory responses. Mouse RAW 264.7 cells were treated with 1μg/mL LPS and 5, 25, 50, 100 or 150μM ononin for 18h. Cell viability was assessed using MTT assays, and the production of nitric oxide (NO), prostaglandin E

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Survival; Enzyme-Linked Immunosorbent Assay; Glucosides; Inflammation; Isoflavones; Lipopolysaccharides; MAP Kinase Signaling System; Mice; NF-kappa B; RAW 264.7 Cells; Signal Transduction