| Inflammation is an adaptive immune response, which is closely related with many diseases, including hypertension, diabetes, dermatitis, arthritis and cancer. Non-steroidal anti-inflammatory drugs (NSAIDs) play a very important role in the prevention of diseases and possess analgesic and antipyretic properties. However, long term use of NSAIDs would result in many adverse effects, such as diarrhea, gastrointestinal damage, liver toxicity, kidney toxicity, cardiovascular adverse reactions, etc., therefore, their applications are limited. In order to obtain new drugs with high biological activity and low side effects, inspired by Curcumin which is an active constituent from the rhizomes of Curcuma longa (turmeric), with Wide range of physiological activity, the primary goals of this study were to compare the anti-inflammatory activity of different compositions of concomitant use Curcumin and various NSAIDs, and to investigate their mechanism and side effects, thus laying a foundation for the development of new anti-inflammatory drugs.To investigate whether Curcumin and the 12 NSAIDs combinations have any anti-inflammatory activity, their effects on TPA-induced mouse ear edema were determined. The results showed that the combination of Curcumin PVP dispersion and tolfenamic acid (Cur-PVP+T) has stronger activities, the inhibitory effect is up to 85.9%. That is 10 times,3 times and 2 times relative to Curcumin, Curcumin PVP dispersion and tolfenamic acid alone respectively.HE staining, western blot and IHC were utlized to investigate the antiiinflammatory mechanism of Cur-PVP+T. Cur-PVP+T markedly suppressed TPA-induced pro-inflammatory cytokines and COX-2 expressions, inhibited NF-κB activity, downregulated IκB kinase (IKK) activities, and inhibited PI3K/Akt and PI3K/PKC signaling pathways.For mouse hepatic and gastric damage model, PEG400, tolfenamic acid (T), Curcumin and the combination of Curcumin and tolfenamic acid were oral administered once daily for 6 days to female BALB/c mice. The changes of body weight were recorded everyday, and all mice were sacrificed and dissected to viscerate the liver, stomach and spleen 24h after the last treatment. The results are as follows:(1) The body weight of T group decrease significantly, that of Cur-PVP+T group is weak;(2) Spleen index of T group is higher than other group, thus proving that Curcumin PVP dispersion can relieve the harm to body;(3) Fetching liver stomach tissue, making paraffin section, and observing, T group appears a large number of inflammatory lesions, Cur-PVP+T group has more obvious improvement relative T group;(4) Finally, the expression of NF-κB was been determined by western blot, we also get a similar trend. The expression of NF-κB in T group markly increased, Cur-PVP+T group has more obvious improvement relative T group;In summary, the anti-inflammatory activities, pathology and toxicology of the new formulation (Cur-PVP+T) have been conducted adequate research, hoping to provide a good foundation for the development of such drugs. |
