Cinchonain Ib isolated from Eriobotrya japonica induces insulin secretion in vitro and in vivo.
OBJECTIVE
Eriobotrya japonica leaves had been used traditionally for the treatment of diabetes mellitus by immersing the dried leaves in a hot water drink. Few studies have shown the hypoglycemic effect of Eriobotrya japonica using crude alcoholic extract and isolated methanolic compounds. These studies proposed that the mechanism of action could be by stimulating the beta-islets of Langerhans to secrete insulin, however with no scientific evidence.


METHODS
Eriobotrya japonica water extract (EJWE) and the compounds derived from it: cinchonain Ib, procyanidin B-2, chlorogenic acid and epicatechin, were tested for their effects on insulin secretion from INS-1 cells and following oral administration in rats.


RESULTS
The present study showed that EJWE increased significantly (p<0.05) insulin secretion from INS-1 cells in dose-dependent manner. Oral administration of EJWE at 230 mg/kg to rats, however, decreased plasma insulin level for as long as 240 min post-administration and caused a transient drop of blood glucose at 15 and 30 min post-administration. On the other hand, cinchonain Ib enhanced significantly (p<0.05) insulin secretion from INS-1 cells, whereas epicatechin inhibited significantly (p<0.05) insulin secretion from INS-1 cells. In addition, cinchonain Ib enhanced significantly (150%: p<0.05) plasma insulin level in rats for as long as 240 min after 108 mg/kg oral administration but did not induce any change in blood glucose level.


CONCLUSIONS
These data indicate that cinchonain Ib has an insulinotropic effect and suggest the possible use of cinchonain Ib for managing type 2 diabetes.
Qa'dan
Fadi
F
Department of Medicinal Pharmaceutical Chemistry and Pharmacognosy, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan. f_qadan@yahoo.com
Verspohl
Eugen J
EJ
Nahrstedt
Adolf
A
Petereit
Frank
F
Matalka
Khalid Z
KZ
D000284:Administration, Oral; D000818:Animals; D044946:Biflavonoids / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D002392:Catechin / Q000494:pharmacology*; D002396:Catechols / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line; D002726:Chlorogenic Acid / Q000494:pharmacology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D031983:Eriobotrya / Q000737:chemistry*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D018515:Plant Leaves; D044945:Proanthocyanidins / Q000494:pharmacology*; D011753:Pyrones / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D044946:Biflavonoids; D001786:Blood Glucose; D002396:Catechols; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D044945:Proanthocyanidins; D011753:Pyrones; C513224:cinchonain Ib; C479580:procyanidin B2; D002726:Chlorogenic Acid; D002392:Catechin; D005905:Glyburide