Mohamed T Khayyal1, Rania M El-Hazek2, Walaa A El-Sabbagh3, Jan Frank4, Dariush Behnam5, Mona Abdel-Tawab6. 1. Pharmacology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt. Electronic address: mtkhayyal@gmail.com. 2. National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt. Electronic address: mrsisisiso@gmail.com. 3. National Centre for Radiation Research and Technology, Atomic Energy Authority, Cairo, Egypt. Electronic address: walaaelsabbagh5@gmail.com. 4. Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany. Electronic address: jan.frank@nutres.de. 5. AQUANOVA AG, Darmstadt, Germany. Electronic address: dariush.behnam@aquanova.de. 6. Zentrallaboratorium Deutscher Apotheker, Eschborn, Germany. Electronic address: m.tawab@zentrallabor.com.
Abstract
BACKGROUND: Xanthohumol is known to exert anti-inflammatory properties but has poor oral bioavailability. Using advanced micellization technology, it has been possible to markedly enhance its bioavailability. PURPOSE: In the present study, we compared the chronic anti-inflammatory activities of native and micellar xanthohumol in the rat adjuvant arthritis model, using diclofenac as a reference drug. METHODS: Adjuvant arthritis was induced by injecting Freund's complete adjuvant into the right hind paw of rats and monitoring paw volume over 3 weeks. The drugs were given daily for 3 weeks, starting from the day of adjuvant inoculation. Serum was collected at the end of the experiment to measure inflammatory and oxidative stress parameters. Statistical comparisons between different groups were carried out by one-way analysis of variance followed by Tukey-Kramer multiple comparison test. RESULTS: Micellar solubilized xanthohumol showed a better anti-inflammatory activity than its native form. The reduction in paw volume was reflected in corresponding changes in relevant mediators of inflammation like tumor necrosis factor-α, interleukin-6 and C-reactive protein, myloperoxidase and lipid peroxidation markers. CONCLUSION: The findings confirm that micellar solubilization of xanthohumol enhances its anti-inflammatory activity, probably as a result of improving its bioavailabilty. The solubilized xanthohumol may prove to be a promising adjuvant tool for anti-inflammatory treatment and a potential anti-inflammatory alternative to synthetic drugs.
BACKGROUND:Xanthohumol is known to exert anti-inflammatory properties but has poor oral bioavailability. Using advanced micellization technology, it has been possible to markedly enhance its bioavailability. PURPOSE: In the present study, we compared the chronic anti-inflammatory activities of native and micellar xanthohumol in the rat adjuvant arthritis model, using diclofenac as a reference drug. METHODS: Adjuvant arthritis was induced by injecting Freund's complete adjuvant into the right hind paw of rats and monitoring paw volume over 3 weeks. The drugs were given daily for 3 weeks, starting from the day of adjuvant inoculation. Serum was collected at the end of the experiment to measure inflammatory and oxidative stress parameters. Statistical comparisons between different groups were carried out by one-way analysis of variance followed by Tukey-Kramer multiple comparison test. RESULTS: Micellar solubilized xanthohumol showed a better anti-inflammatory activity than its native form. The reduction in paw volume was reflected in corresponding changes in relevant mediators of inflammation like tumor necrosis factor-α, interleukin-6 and C-reactive protein, myloperoxidase and lipid peroxidation markers. CONCLUSION: The findings confirm that micellar solubilization of xanthohumol enhances its anti-inflammatory activity, probably as a result of improving its bioavailabilty. The solubilized xanthohumol may prove to be a promising adjuvant tool for anti-inflammatory treatment and a potential anti-inflammatory alternative to synthetic drugs.
Authors: Ines L Paraiso; Luce M Mattio; Armando Alcázar Magaña; Jaewoo Choi; Layhna S Plagmann; Margaret A Redick; Cristobal L Miranda; Claudia S Maier; Sabrina Dallavalle; Chrissa Kioussi; Paul R Blakemore; Jan F Stevens Journal: ACS Pharmacol Transl Sci Date: 2021-11-04