Juniper Berries Regulate Diabetes and Obesity Markers Through Modulating PPAR, PPAR, and LXR: In Vitro and In Vivo Effects

The berries of Juniperus communis have been traditionally used for therapeutic purposes. They have been reported to possess various pharmacological effects such as anti-inflammatory, hypoglycemic and hypolipidemic activities. In this study, a methanolic extract of J. communis berries (JB) was evaluated for its effects on peroxisome proliferator-activated receptors alpha and gamma (PPAR alpha and PPAR gamma), liver X receptor (LXR), glucose uptake and lipid accumulation using various cellular systems. At a concentration of 25 mu g/mL, JB caused 3.77-fold activation of PPAR alpha, 10.90-fold activation of PPAR gamma, and 4.43-fold activation of LXR in hepatic cells. JB inhibited (11%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (90%) in muscle cells. In high-fat diet (HFD) fed mice, JB at a dose of 25 mg/kg body weight exhibited a 21% decrease in body weight. Fasting glucose levels in mice treated with 12.5 mg/kg of JB were significantly decreased (39%) indicating its efficacy in regulating hyperglycemia and obesity induced by HFD thus ameliorating the symptoms of type 2 diabetes. A series of energy metabolic genes, including Sirt1 (2.00-fold) and RAF1 (2.04-fold), were upregulated by JB, while rosiglitazone regulated the hepatic PPAR gamma only. Phytochemical analysis of JB indicated presence of a number of flavonoids and biflavonoids which seem to be responsible for the observed activity. It was concluded that JB acted as a multiple agonist of PPAR alpha, PPAR gamma and LXR without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. The regulation of PPAR alpha, PPAR gamma and LXR seems to be through Sirt1 and RAF1. In vivo results confirmed the antidiabetic and antiobesity potential of JB and indicated its utility in metabolic disorder and type 2 diabetes.