Effect of Angelica dahurica extract and imperatorin on gouty arthritis / 中国药理学通报

Aim To investigate the effects of Angelica dahurica extract and imperatorin on gouty arthritis induced by monosodium urate(MSU)crystal.Methods The model of gouty arthritis was established by injecting MSU crystals into the left ankle of rats.The degree of ankle swelling was measured at 0-24 h in rats.The histopathological changes of synovial tissues were observed.Meanwhile the mRNA and protein expression levels of Nod-like receptor protein 3(NLRP3), interleukin-1β(IL-1β), cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1 receptor type 1(IL-1R1), interleukin-6(IL-6), tumor necrosis factor-α(TNF-α)were detected by Western blot and RT-PCR in synovial tissues.Results Angelica dahurica extract and imperatorin significantly reduced MSU induced left ankle swelling in rats, and improved inflammatory infiltration in synovial tissues.The expression of NLRP3, IL-1β, caspase-1, IL-1R1, IL-6, TNF-α protein or mRNA in synovial tissues decreased significantly.Conclusion Angelica dahurica extract and its active component imperatorin could ameliorate gouty arthritis, which supplys basic data support for its clinical application.

Betulin Targets Lipin1/2-Meidated P2X7 Receptor as a Therapeutic Approach to Attenuate Lipid Accumulation and Metaflammation

The present study focused on the potential mechanism of betulin (BT), a pentacyclic triterpenoid isolated from the bark of white birch (Betula pubescens), against chronic alcohol-induced lipid accumulation and metaflammation. AML-12 and RAW 264.7 cells were administered ethanol (EtOH), lipopolysaccharide (LPS) or BT. Male C57BL/6 mice were fed Lieber-DeCarli liquid diets containing 5% EtOH for 4 weeks, followed by single EtOH gavage on the last day and simultaneous treatment with BT (20 or 50 mg/ kg) by oral gavage once per day. In vitro, MTT showed that 0-25 mM EtOH and 0-25 μM BT had no toxic effect on AML-12 cells. BT could regulate sterolregulatory-element-binding protein 1 (SREBP1), lipin1/2, P2X7 receptor (P2X7r) and NOD-like receptor family, pyrin domains-containing protein 3 (NLRP3) expressions again EtOH-stimulation. Oil Red O staining also indicated that BT significantly reduced lipid accumulation in EtOH-stimulated AML-12 cells. Lipin1/2 deficiency indicated that BT might mediate lipin1/2 to regulate SREBP1 and P2X7r expression and further alleviate lipid accumulation and inflammation. In vivo, BT significantly alleviated histopathological changes, reduced serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and triglyceride (TG) levels, and regulated lipin1/2, SREBP1, peroxisome proliferator activated receptor α/γ (PPARα/γ) and PGC-1α expression compared with the EtOH group. BT reduced the secretion of inflammatory factors and blocked the P2X7rNLRP3 signaling pathway. Collectively, BT attenuated lipid accumulation and metaflammation by regulating the lipin1/2-mediated P2X7r signaling pathway.