Carnosic acid, a new class of lipid absorption inhibitor from sage.
The methanolic extract from the leaves of Salvia officinalis L. (sage) showed significant inhibitory effect on serum triglyceride elevation in olive oil-loaded mice (500 and 1000 mg/kg, p.o.) and inhibitory activity (IC(50): 94 microg/mL) against pancreatic lipase, which is participated in digestion of lipids. Through bioassay-guided separation using the inhibitory activity against pancreatic lipase activity, 4 abietan-type diterpenes (carnosic acid, carnosol, royleanonic acid, 7-methoxyrosmanol) and a triterpene (oleanolic acid) were isolated from the active fraction. Among these compounds, carnosic acid and carnosol substantially inhibited pancreatic lipase activity with IC(50) values of 12 microg/mL (36 microM) and 4.4 microg/mL (13 microM), respectively. Carnosic acid significantly inhibited triglyceride elevation in olive oil-loaded mice at doses of 5-20 mg/kg (p.o.). However, other constituents (carnosol, royleanonic acid, oleanolic acid) did not show any effects at a dose of 200 mg/kg (p.o.). Furthermore, carnosic acid (20 mg/kg/day, p.o.) reduced the gain of body weight and the accumulation of epididymal fat weight in high fat diet-fed mice after 14 days.
Ninomiya
Kiyofumi
K
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8412, Japan.
Matsuda
Hisashi
H
Shimoda
Hiroshi
H
Nishida
Norihisa
N
Kasajima
Naoki
N
Yoshino
Tomoe
T
Morikawa
Toshio
T
Yoshikawa
Masayuki
M
D045784:Abietanes; D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004224:Diterpenes / Q000145:classification / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000145:classification / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008049:Lipase / Q000037:antagonists & inhibitors / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000201:enzymology; D010936:Plant Extracts / Q000145:classification / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D027543:Salvia officinalis / Q000737:chemistry*; D014280:Triglycerides / Q000097:blood
D045784:Abietanes; D004041:Dietary Fats; D004224:Diterpenes; D000960:Hypolipidemic Agents; D008055:Lipids; D010936:Plant Extracts; D014280:Triglycerides; D008049:Lipase; C018381:salvin