Antidiabetic effect of orally administered conophylline-containing plant extract on streptozotocin-treated and Goto-Kakizaki rats.
Conophylline, a vinca alkaloid from Ervatamia microphylla, is known to induce the differentiation of pancreatic precursor cells to insulin-producing cells. In the present research we examined the antidiabetic effects of this alkaloid in vivo by oral administration. Crude conophylline preparations were prepared from the leaves of Tabernaemontana divaricata collected in Okinawa Prefecture, Japan. Conophylline was orally absorbed and showed an increase in its plasma level in both normal and streptozotocin-induced diabetic Sprague-Dawley rats. The plasma conophylline concentration reached its maximum from 1.5 to 3h after a single oral administration and gradually decreased in 24h. The alkaloid decreased the blood glucose level and increased the plasma insulin level in streptozotocin-induced diabetic rats after repetitive administration for 15 days. Fasting blood glucose levels in rats treated orally with conophylline at 0.11 and 0.46 mg/kg/day were 411+/-47 and 381+/-65 mg/dl, respectively; whereas the glucose level of the control rats was 435+/-46 mg/dl. Conophylline also decreased the fasting blood glucose level in Goto-Kakizaki rats in a dose-dependent manner after repetitive administration for 42 days. These results suggest that the extract from conophylline-containing leaves may be useful as a functional food for the treatment of type 2 diabetes mellitus.
Fujii
Mikio
M
Food R&D Center, Japan Tobacco Inc., 5-14 Haneda-asahi-cho, Ota-ku, Tokyo 144-0042, Japan.
Takei
Izumi
I
Umezawa
Kazuo
K
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007564:Japan; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology; D018515:Plant Leaves; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin; D030014:Tabernaemontana / Q000737:chemistry*; D014748:Vinca Alkaloids / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D014748:Vinca Alkaloids; C099167:conophylline; D013311:Streptozocin