Walnut leaf extract inhibits PTP1B and enhances glucose-uptake in vitro

Ethnopharmacological relevance Walnut, Juglans regia L. (Juglandaceae), is one of the medicinal plants used to treat diabetic symptoms in Austrian folk medicine. The air-dried green leaves are either used as aqueous decoctions or liquor preparations and are consumed on a daily basis. We investigated the hypoglycemic effect of a methanolic Juglans regia leaf extract on glucose uptake, protein tyrosine phosphatase 1B (PTP1B) inhibition and peroxisome proliferator-activated receptor gamma (PPARγ) activation. Material and methods Hypoglycemic activity was assessed by glucose-uptake in C2C12 myocytes, inhibition of PTP1B and activation of PPARγ. Phytochemical characterization of the extract was carried out by LC-MS and GC-MS. Results Methanolic Juglans regia leaf extract enhanced the glucose uptake rate in C2C12 myocytes at concentrations of 25 μg/mL compared to untreated cells. This activity may partly be explained by the inhibition of PTP1B but not PPARγ agonism. LC-MS analyses revealed chlorogenic acid (1), 3-p-coumaroylquinic acid (2), a trihydroxynaphthalene-hexoside (3), as well as eight flavonoids (4-11) as main phenolic constituents in the active extract. Conclusions The finding that Juglans regia leaf extract enhances glucose uptake and inhibits PTP1B provides an in vitro-based rationale for the traditional use of walnut leaf preparations against elevated blood-glucose levels.