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

## TL;DR

Silymarin reduces joint and muscle inflammation and lowers virus levels in mice infected with chikungunya or Mayaro viruses.

## Contribution

Silymarin's therapeutic potential against alphavirus-induced arthritis and myositis is demonstrated in a murine model.

## Key findings

- Silymarin reduced viral load by over 90% in multiple tissues of infected mice.
- Treatment decreased inflammation and TNF-α levels in affected tissues.
- Histological improvements were observed in liver, paw, and muscle tissues.

## 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.