Juniper berry (Juniperus communis L.) extract regulates obesity markers through modulating PPAR-alpha, PPAR-gamma, and LXR: in vitro and in vivo effects

Authors: CHAE, HEE-SUNG - University Of Mississippi; DALE, OLIVIA - University Of Mississippi; MIR, TAHIR - University Of Mississippi; ASHFAQ, MOHAMMAD - University Of Mississippi; AVULA, BHARATHI - University Of Mississippi; WALKER, LARRY - University Of Mississippi; KHAN, IKHLAS - University Of Mississippi; KHAN, SHABANA - University Of Mississippi

Submitted to: Journal of Medicinal Food
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/15/2023
Publication Date: 5/15/2023
Citation: Chae, H., Dale, O., Mir, T.M., Ashfaq, M.K., Avula, B., Walker, L.A., Khan, I.A., Khan, S.I. 2023. Juniper berry (Juniperus communis L.) extract regulates obesity markers through modulating PPAR-alpha, PPAR-gamma, and LXR: in vitro and in vivo effects. Journal of Medicinal Food. https://doi.org/10.1089/jmf.2022.0146.
DOI: https://doi.org/10.1089/jmf.2022.0146

Interpretive Summary: This study was carried out to determine the antidiabetic effects of juniper berries through in vitro target based methods in mammaliam cells. The mechanism of action was evaluated in terms of PPAR and LXR activation. The effect of juniper berries was also determined on glucose uptake as well as lipid accumulation that would further support its effectiveness in diabetes and obesity which are the two important components of metabolic disorder. Furthermore, the in vivo efficacy of juniper berries was studied in obese mice that were fed on high fat diet. The results indicated that juniper berries could be effective in ameliorating the condition of diabetes and obesity by working through multiple pathways.

Technical Abstract: Purpose: This study was carried out to investigate the anti-diabetic and anti-obesity effects of Juniperus communis berries through a series of in vitro and in vivo methods. Study design and Methods: A methanolic extract of J. communis berries (JB) was evaluated for its effects on peroxisome proliferator-activated receptors alpha and gamma (PPARa and PPAR'), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARa, PPAR' and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG. Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. Furthermore, the hypoglycemic and anti-obesity effects were determined in high fat diet (HFD) induced diabetic mice. Results: At a concentration of 25 µg/mL, JB caused 3.1-fold activation of PPARa and 10.9-fold activation of PPAR', while the activation of LXR was 4.4-fold. JB inhibited (11%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (90%) in muscle cells at 50 µg/mL. In 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 JB (at doses of 50, 25 and 12.5 mg/kg) were significantly decreased indicating that JB may regulate hyperglycemia and obesity induced by HFD thus ameliorating the symptoms of type2 diabetes. In addition, qRT-PCR revealed that genes relevant to lipid and cholesterol metabolic process responded to JB treatment in human hepatocytes. A series of energy metabolic genes, including Sirt1 and RAF1 were upregulated. Rosiglitazone regulated the hepatic PPAR' mRNA expression only. Phytochemical analysis of JB indicated presence of a number of flavonoids and biflavonoids which seem to be responsible for the observed activity. Conclusion: It was concluded that JB acted as a PPARa/' dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. The regulation of PPARa, PPAR' and LXR seems to be through Sirt1 and RAF1. In vivo results confirmed the antidiabetic and anti-obesity potential of JB and indicated its utility in metabolic disorder and type2 diabetes.