Osteoarthritis (OA) is a common and debilitating joint disease worldwide without interventions available to reverse its progression. Artesunate (ART), an anti-malaria agent, possesses diverse biological activities, including the inhibition of osteoclastogenesis and angiogenesis in various cells, but its role in subchondral bone during OA progression is not known. Here, we explored the curative effects of ART on the pathogenesis of OA in anterior cruciate ligament transection (ACLT) mice models. We found that ART attenuated articular cartilage degeneration, defined by lowered histologic scoring of OA and retarded calcification of the cartilage zone. Moreover, ART improved the expression of lubricin and aggrecan and reduced the expression of collagen X (Col X) and matrix metalloproteinase-13 (MMP-13). In parallel, ART normalized abnormal subchondral bone remodeling by maintaining bone volume fraction (BV/TV) and subchondral bone plate thickness (SBP Th) and reducing trabecular pattern factor (Tb.pf) compared to the vehicle-treated mice. Our results indicated that ART suppressed osteoclastic bone resorption through regulating RANKL-OPG system, restored coupled bone remodeling by indirectly inhibiting TGF-β/Smad2/3 signaling. Additionally, ART abrogated CD31 hi Emcn hi vessel formation via downregulating the expression of vascular endothelial growth factor (VEGF) and angiogenin-1 in subchondral bone. In conclusion, ART attenuates ACLT-induced OA by blocking bone resorption and CD31 hi Emcn hi vessel formation in subchondral bone, indicating that this may be a new therapeutic alternative for OA.

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Osteoarthritis (OA) is a progressive and degenerative joint disorder that is highly prevalent worldwide and for which there is currently no effective medical therapy. Artesunate (ART), a natural compound used to treat malaria, possesses diverse biological properties, including the regulation of inflammation and apoptosis in various cells; however, its role in OA remains unclear. The aim of the present study was to investigate the effects of ART on interleukin (IL)-1β-induced chondrocyte-like ATdc5 cells and in an OA mouse model. The results revealed that ART dose-dependently relieved the inhibitory effect of IL-1β on cell viability. Moreover, ART significantly reduced the overexpression of matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs-5 and cyclooxygenase-2 at both the gene and protein levels in chondrocyte-like ATdc5 cells stimulated by IL-1β. Furthermore, ART decreased the expression of pro-apoptotic Bax, cleaved caspase-3 and cleaved caspase-7 in a dose-dependent manner, and increased the expression of the anti-apoptotic factor Bcl-2. These changes were mediated by the inhibitory effect of ART on the nuclear factor-κB signaling pathway, defined as repression of the phosphorylation of IκBα and p65, and improved redistribution of p65. Additionally, ART blocked the advancement of the calcified cartilage zone and the loss of proteoglycan, and lowered histological scoring of OA in a mouse model. Taken together, these results indicate that ART may be of value as a therapeutic agent for OA.

Background: The previous studies have demonstrated that the polysaccharide isolated from Tarphochlamys affinis (PTA) exhibits anti-tumor effect on S₁₈₀ tumor-bearing mice and protective effects against hepatic injury. Methods: In this study, we investigated the anti-tumor activity and possible underlying mechanism of PTA on liver cancer using a murine H22 hepatocarcinoma model. Results: PTA was capable of repressing transplanted H22 solid hepatic tumor cell growth in vivo. The relative weight of immune organs (spleen and thymus) and lymphocyte proliferation induced by ConA or LPS were improved after PTA treatment. Furthermore, treatment with PTA promoted immune-stimulating serum cytokine secretion in H22 tumor-bearing mice. Additionally, the percentage of CD4⁺ T lymphocytes, CD8⁺ T lymphocytes and NK cells was increased in tumor-bearing mice following PTA administration. In tumor tissue, PTA significantly up-regulated the expression of Bax and p53 proteins and down-regulated the expression of Bcl-2 protein. In addition, at the therapeutic dose, PTA displayed very few toxic effects to major organs, such as the liver and kidney, in tumor-bearing mice. Conclusion: In H22 tumor-bearing mice, PTA exhibited prominent anti-tumor activity in vivo. The possible mechanism of action might be related to enhanced host immune system function and induction of H22 tumor cell apoptosis.

A new rhodol-hemicyanine based ratiometric and reversible fluorescent probe has been developed for real-time monitoring of glutathione dynamics in living cells.