A citrus flavonoid hesperidin suppresses infection-induced endotoxin shock in mice.

Administration of a citrus flavonoid hesperidin (HES) to mice before LPS challenge significantly reduced tumor necrosis factor (TNF)-alpha production in a dose-dependent manner. Treatment of HES 3 h before intraperitoneal (i.p.) infection with 10(8) CFU Salmonella typhimurium aroA resulted in rescue from lethal shock as similar to LPS-nonresponder mice. Not only bacterial numbers in livers and spleens but also plasma LPS levels significantly decreased by pretreatment with HES. In addition, HES markedly suppressed plasma levels of TNF-alpha and high mobility group box chromosomal protein 1 (HMGB-1), decreased the number of apoptotic cells in livers and normalized the activated states of blood coagulation factors such as prothrombin time and platelet numbers caused by infection. Pretreatment of LPS with HES suppressed the chromogenic Limulus reaction.