Kangen-karyu raises surface body temperature through oxidative stress modification

Kangen-karyu, a prescription containing six herbs, has been shown to achieve its pharmacological effect through oxidative stress-dependent pathways in animal models. The aim of this study is to investigate the relationship between the antioxidative effect and pharmacological mechanisms of Kangen-karyu, specifically its body temperature elevating effect in humans. Healthy human volunteers, age 35 ± 15 years old, were enrolled in this study. Surface body temperature, serum nitrite, reactive oxygen species (ROS) scavenging activities, and inflammatory cytokines were investigated before and 120 min after Kangen-karyu oral intake. Kangen-karyu significantly increased the surface-body temperature of the entire body; this effect was more remarkable in the upper body and continued for more than 120 min. Accompanying this therapeutic effect, serum nitrite levels were increased 120 min after oral administration. Serum ROS scavenging activities were enhanced against singlet oxygen and were concomitantly decreased against the alkoxyl radical. Serum nitrite levels and superoxide scavenging activities were positively correlated, suggesting that Kangen-karyu affects the O(2)(•−)-NO balance in vivo. Kangen-karyu had no effect on IL-6, TNF-α and adiponectin levels. These results indicate that the therapeutic effect of Kangen-karyu is achieved through NO- and ROS-dependent mechanisms. Further, this mechanism is not limited to ROS production, but includes ROS-ROS or ROS-NO interactions.