The Artemisia annua Compound experimental study of the treatment of rheumatoid arthritis
|School||China Academy of Traditional Chinese Medicine|
|Course||Chinese and Western medicine combined with the basis|
|Keywords||Rheumatoid arthritis Compound Power of Artemisiae annuae(CPA) adjuvant-induced arthritis ( AA) type II collagen-induced arthritis(CIA) immunoregulation anti-inflammatory|
Objectives:Rheumatoid arthritis (RA) is a chronic and symmetric polyarthritis, which belongs to an autoimmune disease and is characterized by mainly inflammation of synovial membranes at early stage and destructions of articular cartilage and bone at late stage.No therapy that can prevent completely bone-erosion and can ultimately cure the disease is available so far. Traditional Chinese medicine (TCM) has accumulated a wealth of experience in the treatments of rheumatic and rheumatoid diseases. RA can be effectively treated by TCM in our country. According to theories of TCM, RA at active stage falls under arthralgia due to damp-heat, and arthralgia due to damp-heat is frequently accompanied by yin-deficiency. Therefore, the therapeutic principles of clearing away heat and removing dampness in combination with nourishing yin should be adopted in the treatment of arthralgia due to damp-heat. Compound Powder of Artemisiae annuae (CPA) has been shown to treat effectively arthralgia due to damp-heat in long-term clinical practice. In the light of the pathogenesis and clinical manifestations of RA, and the characteristics of Artemisiae annuae in treating immunological diseases, three series of experiments were carried out in order to judge the therapeutic effect of CPA on RA and its pharmacological actions, and delve into the mechanisms governing its actions.Methods:1 Effects of CPA on experimental arthritis. Two models of arthritis were developed respectively by Freund’s complete adjuvant and type II collagen in the rats. The inhibitory effect of CPA on the rat’s foot swelling induced by Freund’s complete adjuvant and the therapeutic effect of CPA on the rat’s foot swelling induced by type II collagen were observed, and autoantibody IgG, IL-1 β , and TNF- α levels in serum, and number of CD4~+ and CD8~+ T-lymphocyte, and pathologic changes in ankle joints were determined in the rats with arthritis induced by type II collagen.2 Immunoregulatory effects of CPA. The effect of CPA on pyagocytic function of reticuloendothelial system was observed by the test of carbonparticle clearance in mice and the inhibitory effect of CPA on humoral immune reaction was observed by determining antibody level in splenocytes homogenate of the mice sensitized by sheep erythrocytes, and the inhibitory effect of CPA on delayed allergy was observed in the mice with delayed allergy caused by dinitrofluorobenzene (DNFB).3 Anti-inflammatory effects of CPA. OD value in abdominal cavity fluid from the mice injected with Evans blue intravenously and with intraperitoneal injection of acetic acid was measured for observing suppressed effect of CPA on the increase in capillary permeability, and granulomas stripped from sterilized and weighed buttons imbedded in back of the rats was weighed to observe the effect of CPA on generation of granulomas in the rats.Results:1 The inhibitory effect of CPA on foot swelling of rats.Different dosages of CPA could produce a decrease in swelling degree of rat’s foot injected with the adjuvant. The differences in decrease in swelling degree of rat’s foot between groups of various dosages of CPA and model group at different time steps were significant or very significant statistically (/?<().01-0.05). The large dose group of CPA had the best effect, which was similar to the effects of prednisone group and shirebi (Granulae for treating arthralgia due to damp-heat) group in effect strength and duration of effect.Different dosages of CPA could produce a decrease in swelling degree of rat’s foot injected without the adjuvant. The differences in decrease in swelling degree of rat’s foot between group of large dosage of CPA and model group at different time steps were significant or very significant statistically (P<0.01-0.05). The effect of large dose group of CPA was similar to that of prednisone group and superior to that of shirebi group. No obvious erythema on aural region and inflammatory nodule on tail were found in the rats of groups of different dosages of CPA.2 The therapeutic effect of CPA on rat’s arthritis induced type B collagen.CPA could significantly relieve the foot swelling in rats with arthritis induced type II collagen. As compared with model group, the differences were significant (P<0.0l-0.05). The large dose group of CPA had the best effect, which was similar to prednisone group and shirebi group.IgG level in serum was significantly decreased in the rats of large dose group of CPA. The very significant difference was shown (P-cO.Ol) as compared with model group (P<0.01). This effect of CPA was similar to that of prednisone group, and better than that of shirebi group.Number of CD4+ T lymphocyte was decreased significantly in groups of different dosages of CPA. As compared with model group, the significant differences were shown (P<0.01-0.05). The small dose group of CPA had the best effect among the groups of large, middle, and small dose. CPA could produce an increase in number of CD8+ T lymphocyte, but no significant differences were shown as compared with model group. CD4+/CD8+ T lymphocyte ratios in various groups of taking the drugs were lower than that model group, which showed the significant differences (P<0.01-0.001).TNF- a level in serum was markedly decreased in rats of groups of large and middle dose of CPA, which showed the significant differences (P<0.01) as compared with model group. The effects in large and middle dose groups were similar to that in prednisone group. There were no statistically significant differences in IL-1 ft level in serum between groups of different dosages of CPA and model group.Pathological observation: As compared with model group, CPA could produce the decreases in hyperplasia of synovial cells, congestion and dropsy of synovium, hyperplasia of blood vessel, infiltration of inflammatory cell, and formation of pannus. The smooth surface of articular cartilage and the normal subcartilaginous bone were seen in groups of different dosages of CPA. The improvement effects in large dose group were better than those in the middle and small dose groups.3 The regulatory effects of CPA on immunologic function.No obvious effects of on phagocytic index K and phagocytic coefficient a were found in groups of various dosages of CPA. The antibody levels in splenocytes homogenate in groups of various dosages of CPA were significantly lower than that in model group, which showed statistically significant differences (P<0.05-0.01). The large dose group of CPA could produce significant decrease in mice’s ear swelling induced by DNFB (P < 0.01) . The effect was similar to those of prednisone and shirebi group. Obvious effect of CPA on weight index of thymus gland was not found. Spleen weight index in large dose of CPA was lower than that in model group, which showed significant difference (P< 0.01) , This effect was similar to that of prednisone group, and better than that of shirebi group.4 The inhibitory effects on inflammation.CPA could exert an inhibitory effect on capillary permeability of the mice. The differences in inhibitory effect on capillary permeability between the large and middle dose groups and model group were significant statistically (P<0.05). The effect was similar to that of prednisone group, and better than that of shirebi group.Granulomas weights in groups of various dosages of CPA were lower thanthat in model group, and differences in granulomas weight between groupsof the large and middle dose and model group were significant statistically(P<0.05-0.01) . The effect in large dosage of CPA was better than those inprednisone and shirebi group.Conclusions:1 CPA could exert therapeutic effect on primary inflammation and preventive effect on secondary inflammation in rats with arthritis induced by Freund’s complete adjuvant.2 CPA could inhibit the foot swelling of rats with arthritis induced by type II collagen, could exert a suppressed effect on the increase in serum IgG level in rats with arthritis induced by type II collagen and produce a decrease in TNF- a level in serum of the rats. CPA was able to exert immunoregulatory effect on abnormalities of CD4+ and CD8+ T lymphocytesin the rats with arthritis induced by type II collagen. CPA could improve the pathologic changes such as the synovial dropsy, inflammatory cell infiltration, hyperplasia of synovium, generation of pannus, and cartilaginous destruction in the rats with arthritis induced by type II collagen.3 CPA had no effect phagocytic function of reticuloendothelial system in the mice. It could produce a decrease in antibody from splenocyte in mice sensitized by sheep erythrocytes, and possessed the obviously inhibitory effect on delayed allergy induced by DNFB in mice.4 CPA possessed a suppressed effect on the elevation of capillary permeability in mice and could suppress generation of granulomas in the rats.