Thermoregulatory effects of alkaloids isolated from Wu-chu-yu in afebrile and febrile rats

Abstract

Dehydroevodiamine (DeHE) and evodiamine (EVO), alkaloids isolated from a Chinese medicinal herb, Wu-chu-yu, exhibit calcium antagonistic activity. Intraperitoneal injections of DeHE (5–20 mg/kg) and EVO (2.5–10 mg/kg) caused a dose-related hypothermia in afebrile rats at an ambient temperature (Ta) of 20 °C. Because the heat production of alkaloid-injected rats did not differ from that of the controls, the hypothermic effect likely resulted from increased peripheral heat loss. This suggestion is supported by the finding that both DeHE and EVO did not affect the thermoregulatory response of rats exposed to a Ta of 35 °C, at which heat loss was maximized. Injection of the same doses of DeHE and EVO attenuated the febrile response in a dose-related manner, induced by intrahypothalamic injection of exogenous pyrogen. The attenuation of the febrile response was associated with a reduction in heat production. Because DeHE and EVO did not affect HP in afebrile rats at a Ta of either 20 or 35 °C, but suppressed the metabolic rate of febrile rats at 20 °C, the thermoregulatory effect of DeHE and EVO could involve both a calcium-dependent increase in heat loss and a suppression in heat production; the latter may only be manifested when the set point for thermoregulation is elevated.