Extract isolated from Angelica hirsutiflora with insulin secretagogue activity.
BACKGROUND
Angelica genus (Umbelliferae) has traditionally been used as the medicine and health food considered alleviating several disorders including diabetes mellitus. Angelica hirsutiflora Liu Chao & Chuang is an endemic species and a folk medicine in Taiwan.


OBJECTIVE
The scientific evidence of anti-diabetic effect for Angelica hirsutiflora remains unknown. The methanolic extracts isolated from Angelica hirsutiflora were studied for its insulin secretagogue and hypoglycemic activities.


METHODS
The in vitro effects and possible mechanisms of Angelica hirsutiflora extract on the insulin secretion in isolated mouse and human islets and pancreatic beta-cell line HIT-T15 were determined; and tested the regulation of blood glucose in fasted mice and high-fat diet-induced diabetic mice.


RESULTS
Angelica hirsutiflora extract potently stimulated the release of insulin from cultured HIT-T15 cells and isolated mouse and human islets. The intracellular calcium levels were also increased in HIT-T15 cells and isolated human islets treated with Angelica hirsutiflora extract. Angelica hirsutiflora extract was capable of enhancing the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2 protein in HIT-T15 cells. Specific ERK inhibitor PD98059 inhibited the increase of insulin secretion by Angelica hirsutiflora extract in HIT-T15 cells and isolated mouse islets. When Angelica hirsutiflora extract was administered to the fasted mice, it decreased the rise in blood glucose level after starch loading. The plasma insulin level was also increased by Angelica hirsutiflora extract treatment. In high-fat diet-induced diabetic mice, Angelica hirsutiflora extract markedly improved the oral glucose intolerance as compared with the vehicle control.


CONCLUSIONS
These findings support that Angelica hirsutiflora extract may be useful in the control of hyperglycemia in non-insulin-dependent diabetes mellitus by acting as an insulin secretagogue.
Graduate Institute of Natural Products, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Yann Lii
YL
Leu
Ya Wen
YW
Chen
Ching Yao
CY
Yang
Chun Fa
CF
Huang
Guan Hong
GH
Lin
Keh Sung
KS
Tsai
Rong Sen
RS
Yang
Shing Hwa
SH
Liu
D029969:Angelica / Q000737:chemistry*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D010936:Plant Extracts / Q000494:pharmacology*; D013624:Taiwan
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D010936:Plant Extracts; D002118:Calcium