Sepsis is characterized by the host's dysregulated immune response to an infection followed by a potentially fatal organ dysfunction. Although there have been some advances in the treatment of sepsis, mainly focused on broad-spectrum antibiotics, mortality rates remain high, urging for the search of new therapies. Oxidative stress is one of the main features of septic patients, so antioxidants can be a good alternative treatment.
Agaricus brasiliensis
is a nutraceutical rich in bioactive compounds such as polyphenols and polysaccharides, exhibiting antioxidant, antitumor, and immunomodulatory activities. Here, we investigated the immunomodulatory and antioxidant effects of
A. brasilensis
aqueous extract in the cecal ligation and puncture (CLP) sepsis model. Our data showed that aqueous extract of
A. brasiliensis
reduced systemic inflammatory response and improved bacteria clearance and mice survival. In addition,
A brasiliensis
decreased the oxidative stress markers in serum, peritoneal cavity, heart and liver of septic animals, as well as ROS production (
in vitro
and
in vivo
) and
tert
-Butyl hydroperoxide-induced DNA damage in peripheral blood mononuclear cells from healthy donors
in vitro
. In conclusion, the aqueous extract of
A. brasiliensis
was able to increase the survival of septic animals by a mechanism involving immunomodulatory and antioxidant protective effects.