Z-2-(β-d-glucopyranosyloxy)-3-phenylpropenoic acid, an α-hydroxy acid from rooibos (Aspalathus linearis) with hypoglycemic activity

• Published in: Molecular nutrition & food research 2013-12, Vol.57 (12), p.2216-2222
• Main Authors: Muller, Christo J. F., Joubert, Elizabeth, Pheiffer, Carmen, Ghoor, Samira, Sanderson, Micheline, Chellan, Nireshni, Fey, Stephen J., Louw, Johan
• Format: Article
• Language: English
• Subjects: Animals; Antidiabetic; Aspalathus - chemistry; Aspalathus linearis; Biological and medical sciences; Blood Glucose - metabolism; Cell Line - drug effects; Diabetes Mellitus, Experimental - drug therapy; Dose-Response Relationship, Drug; Enolic phenylpyruvic acid-2-O-glucoside; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Glucose - metabolism; Glucose Tolerance Test; Glucosides - pharmacology; Hypoglycemic Agents - pharmacology; Insulin Resistance; Liver - drug effects; Liver - physiology; Male; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; Obesity - metabolism; Phenylpropionates - pharmacology; Rats; Rats, Wistar; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201300294

Scope 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. Methods and 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. Conclusion 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.