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. 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. 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. 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. 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.

A novel series of thiadiazole derivatives were designed and synthesized for evaluation as selective COX-2 inhibitors in vitro and were investigated in vivo as anti-inflammatory and analgesic agents against carrageenan-induced rat paw oedema model in irradiated rats, since it is well-known that ionizing radiation plays an important role in exaggerating the inflammatory responses in experimental animals. Ulcerogenic activity and acute toxicity were evaluated for the most potent compounds. In order to understand the binding mode of the synthesized compounds into the active site of the COX-2 enzyme, a docking study was performed. Most of the tested compounds showed high inhibitory ability against COX-2. Among them, thiadiazole derivatives bearing sulfonamide moieties, 7b, c and 13c, e, were the most potent COX-2 inhibitors, with extremely high selectivity indices (SI) compared to celecoxib; they showed high safety margins on gastric mucosa with no ulceration effects, and they were found to be non-toxic in experimental rats. The docking study showed a similar orientation of these compounds to that of celecoxib within the active site of the COX-2 enzyme, and a similar ability to immerge deeply into the additional pocket and bind with Arg513 and His90, the key amino acids responsible for selectivity.