Effect of puerarin supplementation on cardiovascular disease risk factors: a randomized, double-blind, placebo-controlled, 2-way crossover trial
These factors promote the transcription of the MMP-13 gene by activating the MAPK and NF-B signaling pathways.342,343,344 The GLP-1R signaling pathway may also affect the expression of MMP-13 and ADAMTS5, by reducing the signal transduction caused by IL-1, thus decreasing their synthesis.345,346 GLP-1 may also reduce the expression of cartilage-degrading enzymes by inhibiting the MAPK pathway or activating anti-inflammatory pathways such as PI3K/Akt, thereby alleviating cartilage damage.206,347 In another study, treatment of primary mouse chondrocytes with liraglutide reduced the mRNA expression levels of iNOS, MMP-13, and ADAMTS5, leading to a decrease in the secretion of inflammatory markers, including NO, prostaglandin E, and IL-6.348 Similarly, in human chondrocytes stimulated by TNF, GLP-1 analogs (such as liraglutide) showed an anti-catabolic effect, reducing the mRNA expression of MMP-3, MMP-13, and ADAMTS5.349,350 At the same time, the levels of two important components of the cartilage matrix, proteoglycans (a large molecule and a major component of the cartilage matrix) and type II collagen (the main structural protein of cartilage), increased.349,350 This change suggests that liraglutide not only inhibits inflammation and cartilage degradation but may also promote the synthesis and accumulation of cartilage matrix, thereby helping to protect and repair joint cartilage.273 Furthermore, a study using the anterior cruciate ligament transection (ACLT) rat model further confirmed that subcutaneous injection of liraglutide at 50 g/kg/day, whether for 3 weeks or 6 weeks, could reduce OARSI scores, highlighting the potential of liraglutide in treating joint degeneration.273 GLP-1RAs and RA The role of GLP-1RA was also investigated in RA, which is characterized by chronic inflammation of the synovium and joint destruction
GlutaNAC is a compound of L-Glutathione & NAC (N-Acetyl Cysteine)
We also applied a series of complementary proximity-based techniques based on both BRET and FRET to monitor GLP-1R redistribution between the plasma membrane and different endosomal compartments
