Micellar solubilization enhances the anti-inflammatory effect of xanthohumol.

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.

Protective effect of the herbal preparation, STW 5, against intestinal damage induced by gamma radiation in rats.

PURPOSE: STW 5 (marketed as Iberogast(®), Steigerwald Arzneimittelwerk GmbH, Darmstadt, Germany) is a herbal preparation reported to possess anti-inflammatory properties and antioxidant activity. We investigated the effect of STW 5 against intestinal injury induced after whole body exposure to ionizing radiation (IR). MATERIALS AND METHODS: Intestinal mucositis was induced in rats by irradiation at a level of 6 Gy. STW 5 (5 ml/kg) was delivered orally for 5 days before irradiation and 2 days after. Rats were sacrificed, jejunum homogenates were tested to assess biochemical parameters indicating intestinal injury and jejunum segments were exposed to semi-quantitative histological examination. RESULTS: IR led to an increase in overall damage severity (ODS) score associated with a significant rise in tumor necrosis factor (TNF-α) and thiobarbituric acid reactive substances (TBARS) by 46% and 50% (p ≤ 0.05), respectively, whereas the reduced glutathione (GSH), sucrase and alkaline phosphatase enzyme activities were significantly decreased by 68%, 76% and 25% (p ≤ 0.05), respectively, in intestinal homogenates. IR led to a reduction of plasma citrulline. Pre-treatment with STW 5 guarded against the changes in ODS score and in all parameters measured. CONCLUSION: Pre-treatment with STW 5 has the potential to decrease the severity of radiation-induced mucositis.

Effect of selective COX-2 inhibitor, celecoxib on adjuvant-induced arthritis model in irradiated rats.

PURPOSE: The potential value of celecoxib was compared to a standard non-steroidal anti-inflammatory drug (NSAID), diclofenac in the adjuvant-induced arthritis (AIA) model in rats as a model of chronic inflammation under the influence of ionising radiation. MATERIAL AND METHODS: Various inflammatory mediators and biochemical parameters were measured in the arthritic rats under the influence of ionising radiation. RESULTS: Exposure of the animals to a radiation dose of 2 Gy before inoculation of the adjuvant led to a marked increase in the paw volume reaching ca. 70% more than that in non-irradiated ones as well as a significant increase in the levels of interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumour necrosis factor-α (TNF-α), prostaglandin E2 (PGE2) as an index of cyclooxygenase-2 (COX-2) activity, thromboxane B2 (TXB2) as an index of cyclooxygenase-1 (COX-1) activity and plasma level of malondialdehyde (MDA). The blood glutathione (GSH) level was not affected by the dose of irradiation used while superoxidedismutase (SOD) activity was reduced. Treatment with celecoxib in a dose of 5 mg/kg was effective in decreasing the elevated levels of IL-6, IL-1ß, TNF-α, PGE2 whereas it lacked any effect on TXB2 level since it had hardly any effect on COX-1 enzyme. Both drugs at the selected dose levels showed no effect on level of MDA, GSH and SOD activity. CONCLUSION: Irradiation of animals caused a marked change in the inflammatory response in AIA model of inflammation. Both celecoxib and diclofenac were nearly equipotent in suppressing the inflammatory response in both normal and irradiated rats. Accordingly, since the inhibition of COX-1 by traditional NSAID is thought to have undesirable side-effects on proliferating tissues, it would seem preferable to use selective COX-2 inhibitors to limit such deleterious effect.