Studies On The Anti-inflammatory Activities Of AP And Its Possible Mechanisms

Apple polyphenols (AP) is the general term that multicomponent polyphenol extract from apple. AP has strong antioxidant activity and a variety of physiological functions. Studies has found that AP has free radical scavenging,antioxidation,anti-allergy,anti-mutagenize,anti-cancer, depressurization. The preliminary results indicate that apple polyphenols have strong in vitro antioxidant activity and on ethanol-induced liver injury in mice play a role in protection.Domestic and international researches about AP mainly focused on antioxidant activity, but anti-inflammatory activity of AP and its mechanisms has not been reported at home and abroad. In the present study we investigated the anti-inflammatory activity and its possible mechanisms of AP in order to providing experimental basis for clinical application of AP.Firstly, the anti-inflammatory doses of AP were determined as 25,50,100 and 200 mg/kg and oral administration period of AP was determined as 7 days according to the time response curve and the dose response curve of anti-inflammatory activity of AP on xylene induced mouse ear swelling. Secondly, anti-inflammatory of AP was investigated systematically through several kinds of acute phase, sub-acute phase and chronic phase of inflammation animal models. The results showed that AP(50,100 and 200 mg/kg) inhibited ear edema induced by xylene in mice in a dose-dependent manner. AP (35,70 and 140 mg/kg) inhibited the angle carrageenan-induced hind paw swelling in rats, and AP (50,100 and 200 mg/kg) suppressed significantly acetic acid-induced peritoneal capillary permeability,the white blood cells of carboxymethyl cellulose capsule and the weight of cotton-pellet grahuloma in mice in mice. Ours results suggested that AP had significant anti-inflammatory effects acute phase, sub-acute and chronic inflammation.In order to explore the anti-inflammatory mechanisms of AP, we investigated the relatinonship between anti-inflammatory activity of AP and endogenous anti-inflammatory system. The result showed that AP (50,100 and 200 mg/kg) still significantly inhibited ear edema induced by xylene in adrenalectomized mice and had no effect on content of vitamin C in adrenal of normal mice. It suggested that the anti-inflammatory mechanism of AP was different from that of steroid hormones, may not dependent on endogenous anti-inflammatory system. However, we found that AP(35,70 and 140 mg/kg) significantly reduced the contents PGE2 and histamine and AP(140 mg/kg) also significantly reduced 5-HT content in the exudate of inflammed food pad of rats. Our results also showed that AP(35,70 and 140 mg/kg) significantly inhibited the increase of serum MDA content and AP (70 and 140 mg/kg) significantly inhibited the reduction of SOD activity and GSH depletion in pleurisy rats. Moreover, AP(17.5,35,70 and 140 mg/kg) showed significant protective effect on DNA damage and AP (140 mg/kg) reduced the release of reactive oxygen species in lung cells of acute lung injury rats.In conclusion, AP has significant anti-inflammatory effects, not only for the first acute phase, but also for the sub-acute and chronic inflammation. The anti-inflammatory activity of AP may be related to the inhibition on the synthesis and release of classical inflammatory mediators. Moreover, reduction reactive oxygen species release, inhibition lipid peroxidation, enhancement antioxidant capacity and protection on DNA damage of AP may be one of the important anti-inflammatory mechanisms. This paper provided experimental basis and useful reference for the clinical application of AP as anti-inflammatory agent.