Studies On Anti-Inflammatory And Immunoregulatory Effects Of Myricetin And Its Mechanism

The inflammation is the most fundamental pathology process of infection and many diseases. Clinically,nonsteroidal anti-inflammatory drugs(NSAIDs) and steroidal anti-inflammatory drugs (SAIDs) are commonly used as anti-inflammatory agents.Their clinical curative effects are remarkable,but the side effects are reported frequently.Therefore,it is a very important research area of drug development to seek new low toxicity,high efficiency anti-inflammatory agent.Myrica rubra Sieb.et Zucc.,evergreen shrubs or the small arbor,belongs to the Myricaceae family,which is native to China and widespread in subtropical areas.Several flavonoids have been isolated from the leaves of Myrica rubra Sieb.et Zucc.,which are commonly used as an astringent, detoxicant and antidiarrheic in folk medicine.In the present study,the anti-inflammatory, analgesic,immunoregulatory activity and mechanism of myrciten(MYR),a major compound in Myrica rubra Sieb.et Zucc.leaves was evaluated with the purpose of providing some experimental evidence for developing new anti-inflammatory drugs.First,several kind of non-specific inflammatory models were used to evaluate anti-inflammatory effect of MYR comparatively.At doses of 50 and 200 mg/kg,MYR showed a significant inhibition on exudation and edema,migration of white cells and fibroplasticproliferation throughout the inflammation,which collectively demonstrated that MYR possessed potent anti-inflammatory activity on acute and chronic inflammation models.MYR showed a significant inhibition on xylene-induced ear edema in mice without the adrenal gland and the hind paw edema caused by carrageenin,but had no significant effects on the weight and level of VC of adrenal gland of rats with carrageenan-induced paw edema,which explained the anti-inflammatory activity of MYR was unrelated to hypothalamic-pituitary-adrenalaxis.MYR significantly decreased PGE₂ in inflamed tissue and MDA in the serum,and increased SOD in the serum,but had no significant effect on NO in the serum in carrageenan and egg white induced paw edema model.MYR dose-dependently inhibited RBC hemolysis by auto-oxidation and hemolysis of sheep erythrocyte oxidized by hydrogen peroxide,which showed positive anti-inflammatory effect of MYR through its influence on balance disturbances of the oxidation.Secondly,model of adjuvant arthritis(AA) rats,which is extremely similar to rheumatoid arthritis(R.A) of human in pathology and blood serum change,was used to evaluate immune inflammation effect of MYR.Result showed MYR alleviated the symptoms of primary and secondary adjuvant arthritis,improved pathomorphism of joint injury in AA rat,decreased level of MDA in the serum,and increased SOD activity,which indicated preventive and therapeutic effect of MYR may be connected to reduce lipid peroxidation and restore antioxidase activity and also provided the important theory basis and morphology material for treating RA.Thirdly,the analgesic effect of MYR was tested by a serial of models,such as chemical and hot stimulation.MYR showed a significant inhibition on chemical nociceptive models such as the acetic acid-induced writhing response and the licking time on the late phase in the formalin test in a dose-dependent manner,but did not manifest a significant effect in hot plate test and whip tail test. In addition,MYR inhibited the content of PGE₂ in the peritoneal fluid.These results collectively demonstrated that MYR possessed potent analgesic activity,which was related with peripheral analgesia,but,not with the opioid system.MYR may be a potent COX-1 inhibitor with anti-platelet activity,and its analgesic effect wasn't related toα(β) receptor.Inflammation and immunity be two aspect of a problem,and immunology study of MYR wasn't neglected when its anti-inflammatory effect was tested.Therefore,specific immunity function of MYR were investigated.The result indicated MYR had a significant inhibition on homogeneous(heterologous) passive cutaneous anaphylaxis(PCA),pruritus induced by dextran 40 and 2,4-dinitrochlorobenzol(DNCB)-induced delayed hypersensitivity reaction,which indicated MYR can inhibit typeâ… andâ…£allergic reaction.MYR also reduce serum hemolysin concentration induced by SRBC in mice,level of IL-2 and proliferation of T lymphocytes induced by ConA and proliferation of B lymphocytes induced by LPS in vitro,which indicated the inhibitory effcet of MYR on humoral immunity and cellular immunity in direct experimental proofs and laid the theoretical foundation for the prevention and treatment of RA.In summary,MYR possessed potent anti-inflammatory and immunoregulation activity,which indicated that MYR might be the valid target of playing positive anti-inflammation role in Myrica rubra Sieb.et Zucc leaves..