Silymarin Attenuates Arthritis and Myositis in a Murine Model of Acute Infection by Chikungunya and Mayaro Viruses.

Abstract

The alphaviruses chikungunya (CHIKV) and Mayaro (MAYV) are responsible for acute febrile illnesses often accompanied by severe and persistent joint and muscle pain. Due to the lack of specific treatment, research into antivirals against these emerging viruses is seen as an urgent need. Previous studies demonstrated that silymarin exhibits potent antiviral activity against CHIKV and MAYV. Then, given the promising antiviral profile of silymarin, and the prominent joint and muscle pain caused by these viruses, we evaluated whether silymarin could reverse these damages in a murine model of alphavirus-induced arthritis and myositis. BALB/c mice were infected with CHIKV or MAYV in the right hind paw pad, and treated groups received silymarin orally (200 mg/kg/day). Clinical observation revealed reduced paw edema in silymarin-treated animals. At 7 and 12 days postinfection (dpi), animals were euthanized and various tissues collected. In infected and treated animals, a greater than 90% reduction in CHIKV viral load was observed in the spleen (7 and 12 dpi), paw (7 dpi), soleus muscle, and liver (12 dpi). Similarly, for MAYV, a greater than 90% reduction in viral load was detected in the spleen (7 and 12 dpi), liver, quadriceps, soleus muscle (7 dpi), and paw (12 dpi). Histological analysis revealed reduced inflammatory infiltrates in the liver, paw, and muscles as well as a decrease in both the number and area of lymphoid nodules in the spleen (12 dpi). Furthermore, silymarin treatment reduced TNF-α levels by at least 2-fold in the paw (7 and 12 dpi) and quadriceps (12 dpi). These findings suggest that silymarin not only limits viral replication in key target tissues, including the spleen, liver, muscle, and paw, but also mitigates inflammation by reducing paw edema, inflammatory infiltrates in hepatic, musculoskeletal, and paw tissues, the number and area of lymphoid nodules in the spleen, and TNF-α levels in the quadriceps muscle and paw, thereby supporting its therapeutic potential against CHIKV and MAYV infections.