Next Article in Journal
MiR-34b-5p Mediates the Proliferation and Differentiation of Myoblasts by Targeting IGFBP2
Next Article in Special Issue
Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro
Previous Article in Journal
Myricetin Suppresses the Propagation of Hepatocellular Carcinoma via Down-Regulating Expression of YAP
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

Therapeutic Application of Micellar Solubilized Xanthohumol in a Western-Type Diet-Induced Mouse Model of Obesity, Diabetes and Non-Alcoholic Fatty Liver Disease

1
Institute of Biochemistry (Emil-Fischer Zentrum), Friedrich-Alexander University Erlangen-Nürnberg, Fahrstr. 17, D-91054 Erlangen, Germany
2
Institute of Nutritional Sciences, University of Hohenheim, Garbenstr. 28, D-70599 Stuttgart, Germany
3
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany
4
Central Laboratory of German Pharmacists, Carl-Mannich-Str. 20, D-65760 Eschborn, Germany
5
AQUANOVA AG, Birkenweg 8-10, D-64295 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Cells 2019, 8(4), 359; https://doi.org/10.3390/cells8040359
Received: 5 April 2019 / Revised: 15 April 2019 / Accepted: 16 April 2019 / Published: 17 April 2019
  |  
PDF [2919 KB, uploaded 25 April 2019]
  |  

Abstract

Xanthohumol (XN), a prenylated chalcone from hops, has been reported to exhibit a variety of health-beneficial effects. However, poor bioavailability may limit its application in the prevention and therapy of diseases. The objective of this study was to determine whether a micellar solubilization of xanthohumol could enhance the bioavailability and biological efficacy of xanthohumol in a Western-type diet (WTD) induced model of obesity, diabetes and non-alcoholic fatty liver disease (NAFLD). After 3 weeks feeding with WTD, XN was additionally applied per oral gavage as micellar solubilizate (s-XN) or native extract (n-XN) at a daily dose of 2.5 mg/kg body weight for a further 8 weeks. Control mice received vehicle only in addition to the WTD. WTD-induced body weight-gain and glucose intolerance were significantly inhibited by s-XN application. Furthermore, WTD-induced hepatic steatosis, pro-inflammatory gene expression (MCP-1 and CXCL1) and immune cell infiltration as well as activation of hepatic stellate cells (HSC) and expression of collagen alpha I were significantly reduced in the livers of s-XN-treated mice compared to WTD controls. In contrast, application of n-XN had no or only slight effects on the WTD-induced pathological effects. In line with this, plasma XN concentration ranged between 100–330 nmol/L in the s-XN group while XN was not detectable in the serum samples of n-XN-treated mice. In conclusion, micellar solubilization enhanced the bioavailability and beneficial effects of xanthohumol on different components of the metabolic syndrome including all pathological steps of NAFLD. Notably, this was achieved in a dose more than 10-fold lower than effective beneficial doses of native xanthohumol reported in previous in vivo studies. View Full-Text
Keywords: xanthohumol; micellar solubilisation; obesity; diabetes; non-alcoholic fatty liver disease xanthohumol; micellar solubilisation; obesity; diabetes; non-alcoholic fatty liver disease
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Mahli, A.; Seitz, T.; Freese, K.; Frank, J.; Weiskirchen, R.; Abdel-Tawab, M.; Behnam, D.; Hellerbrand, C. Therapeutic Application of Micellar Solubilized Xanthohumol in a Western-Type Diet-Induced Mouse Model of Obesity, Diabetes and Non-Alcoholic Fatty Liver Disease. Cells 2019, 8, 359.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Cells EISSN 2073-4409 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top