Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid, an α-hydroxy acid from rooibos (Aspalathus linearis) with hypoglycemic activity.
METHODS
The rare enolic phenylpyruvic acid-2-O-glucoside, (PPAG:Z-2-(β-D-glucopyranosyloxy)-3-phenylpropenoic acid), is one of the major constituents of fermented rooibos infusions. 3-Phenylpyruvic acid (2-oxo-3-phenylpropanoic acid), without the sugar moiety and with a keto form instead of an enolic arrangement, has been shown to enhance insulin release and glucose uptake in muscle cells. The purpose of this study was to assess if PPAG has similar activity on glucose metabolism.


RESULTS
Preliminary in vitro studies confirmed that PPAG, isolated from rooibos, enhanced glucose uptake. A dose-response study in Chang cells showed that PPAG enhanced glucose uptake in the concentration range 1.0-31.6 μM (EC50 = 3.6 μM). In obese insulin-resistant rats, oral administration of PPAG lowered fasting glucose concentrations and improved oral glucose tolerance values; messenger RNA expression of glucokinase, glucose transporter 1 and 2, insulin receptor, peroxisome proliferator-activated receptor alpha, and suppressor of cytokine signaling 3, were increased in the liver. This suggests that the liver is mainly responsible for PPAG bioactivity.


CONCLUSIONS
This study describes for the first time that PPAG increases in vitro glucose uptake and improves glucose tolerance in an obese insulin-resistant rat model, suggesting that it has potential as a new class of antidiabetic therapeutics that would contribute to the antidiabetic effect of rooibos.
Diabetes Discovery Platform, Medical Research Council (MRC), Tygerberg, South Africa.
Christo J F
CJ
Muller
Elizabeth
E
Joubert
Carmen
C
Pheiffer
Samira
S
Ghoor
Micheline
M
Sanderson
Nireshni
N
Chellan
Stephen J
SJ
Fey
Johan
J
Louw
D000818:Animals; D036903:Aspalathus / Q000737:chemistry*; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology; D009765:Obesity / Q000378:metabolism; D010666:Phenylpropionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C000591224:2-(glucopyranosyloxy)-3-phenylpropenoic acid; D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D010666:Phenylpropionates; D005947:Glucose
Antidiabetic; Aspalathus linearis; Enolic phenylpyruvic acid-2-O-glucoside