Antiarthritis Effect of Morin is Associated with Inhibition of Synovial Angiogensis

Abstract

Morin, a flavonoid isolated from Morus alba L. (Moraceae), possesses anti-inflammatory, antiangiogenic among other biological activities. This study investigated its effect on type II collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms in view of synovial angiogenesis. Morin administered po attenuated arthritic progression as indicated by reduction of arthritis scores and paw swelling. It also markedly reduced serum levels of the proinflammatory cytokines, tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but increased the level of anti-inflammatory cytokine interleukin-10, and ameliorated histopathological changes of joints. Morin markedly inhibited expression of CD31, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor in synovial membrane tissues, and decreased serum levels of VEGF in CIA rats. In vitro, morin markedly inhibited VEGF-induced migration and tube formation in human umbilical vein endothelial cells. These results indicate that morin had antirheumatoid potential, and its mechanism might be associated with inhibition of synovial angiogenesis.

The therapeutic potential of plant flavonoids on rheumatoid arthritis

“…Decreased T-bet mRNA was observed in the splenocytes of genistein treated CIA animals which were correlated to IL-4 levels (Wang et al 2008). (Zeng et al 2015). Ex vivo production of IL-4 was reduced from splenocytes isolated from sham operated CIA rats treated with genistein.…”

“…Proliferation of lymph node cells from CIA rats was inhibited by kaempferol-3-O--D-glucopyranoside in vitro (Dang et al 2009). Morin treatment inhibited angiogenesis in both an in vitro setting and in female CIA rats (Zeng et al 2015). Thus several flavonoids such as apigenin, luteolin, kaempferol, nobiletin, morin, baicalein, and naringin inhibited proinflammatory pathways, enhanced anti-inflammatory mechanisms, and improved clinical signs in cell lines and animal models of RA.…”

“…An improvement in several histopathological markers was also reported with morin and morin plus indomethacin treatment in AIA rats. In female CIA rats, treatment with morin was comparable to dexamethasone in terms of reducing paw edema, joint damage, clinical and histopathological scores (Sultana and Rasool 2015;Zeng et al 2015). Myricetin (Figure 4) improved clinical scores, decreased paw thickness in CIA mice.…”

“…Myricetin (Figure 4) improved clinical scores, decreased paw thickness in CIA mice. Histopathological changes associated with CIA were also reduced with myricetin treatment (Zeng et al 2015;Yuan et al 2015). Additionally, myricetin antagonised the production of IL-6 and MMP-1 in IL- stimulated synovial cells (Yuan et al, 2015;Lee et al 2007).…”

“…Increased GATA-3 mRNA was observed in the splenocytes of genistein treated CIA animals which were correlated to IL-4 levels (Wang et al 2008). Morin treatment increased IL-10 levels in the sera of female CIA rats (Zeng et al 2015). Expression of IL-4, Foxp3 and GATA-3 mRNA was enhanced in the ankle tissues of naringin treated AIA mice (Ahmad et al 2014).…”