Chronopharmacological study of KE-SI-TO components in mice.
Influence of dosing time on pharmacological effects and toxicity of KE-SI-TO (KST) components, as well as the role of each component in the circadian rhythms of KST, was investigated in ICR male mice under an LD (12:12) cycle. The mice given Cinnamomi Cortex (258 mg/kg, i.p.) or Paeoniae Radix (258 mg/kg, i.p.) showed a significant circadian rhythm in the time spent on the hot plate with the shortest latency at 0900 and the longest one at 0100 (p<0.01, respectively). The mice given Cinnamomi Cortex or Glycyrrhizae Radix (129 mg/kg, i.p.) showed a significant circadian rhythm with the lowest rectal temperature (RT) at 1700 and the highest one at 0500 (p<0.01, respectively). Cinnamomi Cortex (850 mg/kg, i.p.)- or Glycyrrhizae Radix (2500 mg/kg, i.p.)-induced toxicity showed a significant circadian rhythm with the highest mortality at 1700 and the lowest one at 0500 (p<0.05, respectively). The rhythmic patterns of the drug-induced analgesia, hypothermia and toxicity resembled the overall rhythms occurring after KST (1000 or 6000 mg/kg, i.p.) injection. These results suggest that the circadian rhythms in actions of Cinnamomi Cortex, Paeoniae Radix and Glycyrrhizae Radix are mainly responsible for the rhythm in the effects and toxicity of KST.
Ohdo
S
S
Department of Clinical Pharmacokinetics, Kyushu University, Fukuoka, Japan.
Ogawa
N
N
Song
J G
JG
Higuchi
S
S
D000700:Analgesics / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002909:Chronobiology Phenomena; D002940:Circadian Rhythm / Q000187:drug effects*; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000633:toxicity; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D013997:Time Factors
D000700:Analgesics; D004365:Drugs, Chinese Herbal; C089053:keishi-ni-eppi-ichi-to