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0  发表于: 2013-11-15  

Traditional Chinese medicine in the treatment of rheumatoid arthritis in recent years

管理提醒: 本帖被 admin 设置为精华(2013-11-15)
Traditional Chinese medicine in the treatment of rheumatoid arthritis in recent years: a general review
                       Chengpeng   Hedongyi
   

Kay words:rheumatoid arthritis, Chinese medicine treatment


In Chinese Medicine (i.e., traditional Chinese medicine,TCM), Rheumatoid arthritis (RA), belongs to the range of “obstinate arthralgia syndrome” and “arthalgia syndrome with arthrentasis”.  Common clinical symptom includes: swelling, stiffness, pain of joints and gradually, joint abnormality or joint function failure. Though RA is hard to be completely cured,  its symptoms can be controlled gradually. Compared with modern medicine, the TCM treatment gains an advantage of integrated adjustment and improvement of living quality.  In this article, we review related literatures of TCM in treatment of RA in recent years.
1   Treatment of TCM
1.1 Treatment based on pattern differentiation 
It is well known in TCM: an appropriate illness pattern differentiation is crucial to effective treatment for any illness.   The patterns of RA can be divided into 2 to 6 types. For example, Gong XF[1] suggested 6 types: cold-dampness type, heat-dampness type, cold-heat complex type, qi-blood deficiency type, asthenia splenonephro yang type,  and liver-kidney yin deficiency type. Guo XZ[2] agreed with 5 types: cold-dampness type,  heat-dampness type, coexistence of phlegm- blood stasis type, Qi-blood deficiency type, and liver-kidney yin deficiency type.  Yang GJ[3] supported 4 types: exterior deficiency and inside overexertion, damp-heat gluing each other, coexistence of phlegm-blood stasis,  yang asthenia and cold predominance. However, Jin ZL4] and Yangli[5] considered: 2 types (cold and dampness type, heat and dampness type) being enough.
1.2 Treatment based on disease stage differentiation
It is well known in TCM, an appropriate disease stage differentiation is vital to effective treatment for any illness. Wangying, et al[6] divided the course of RA into 2 periods: acute episode phase and stationary phase. Furthermore, acute episode phase was also divided into 3 sub-types: heat predominating type, cold predominating type and cold-heat complex type. Wang ZL[7] treated RA by Resolving liver from beginning stage to middle or end stage. Xiaohong, et al[8] divided the course of RA into active stage and stationary phase. The acute stage could be categorized into 2 sub-types (cold-dampness type,  heat-dampness type), while the stationary phase has 3 sub-types (qi-blood deficiency,  yang asthenia causing yin asthenia,  phlegm-blood stasis in channels).
1.3 Treatment by special formula herb decoction 
It is also well known in TCM: herb decoction with special formula may show different or remarkable treatment result. In the study of Lin DT[9], 124 patients of RA was randomly divided into the treatment group (n=66) and the control group (n=58). the former was treated by Bujingjiangusoufeng Decoction,  the later was treated by Diclofenac and prednisone. After 2 months, The total effective rate was 90.91%, superior to that in the control group (P<0.01). Ertengtongbi mixture, which consisted mainly of caulis spatholobi and bittersweet, had been prescribed by Guantong, et al[10] to treat 60 patients of RA.In the 2th,  4th week after treatment,  the effective rate of ACR20, ACR50,  ACR70 were 30.00%, 15.00%, 5.00%;76.67%, 53.33%, 13.33% respectively. Liu SQ, et al[11] randomly divided 60 patients of RA into the treatment group (n=30) and the control group (n=30).the former was treated by Yiqibushenhuoxue Decoction, the later was treated by conventional therapy of modern medicine.2 weeks were taken as a course, and 3 course in total. After every course of treatment, the clinical efficiencies in the treatment group were clear better than those in the control group (P<0.05), especially in the 2th week. It was superior to the later (P<0.05) in improving symptoms and signs, especially swollen and pain of joints, but showed no advantage in improving TCM syndromes and laboratory tests(P>0.05).Zhou CY, et al[12] randomly divided 120 patients of damp-heat syndrome in active stage of rheumatoid arthritis into group1(n=60) treated by Simiaoxiaobi Decoction and the group2(n=30) treated by methotrexate. After 12 weeks, 103 patients finished the survey.Group1 had higher effective rate of WM and TCM(92.3% and 70.6% respectively) than group2(P<0.05), with more rapid analgesic action and lower incidence of adverse reaction(P<0.05). Wujiong, et al[13] randomly divided 97 patients of kidney and liver insufficiency with coexistence of phlegm and blood stasis syndrome in middle or advanced stage of rheumatoid arthritis into group1(n=65) treated with Bushenzhuyu Decoction and the group2 (n=32) treated with Glucosidorum Tripterygll Totorum.  After 8 weeks,   the total effective rate of group1 were 83.08% and were significantly higher than that of group2 (56.25%) (P<0.05).  Cuili,et al[14] treated 30 patients of Damp-Heat syndrome type RA by Dingshirebi Recipe (composed of Flos Lonicerae, Herba Tataxaci, Hedyotic diffusa, largeleaf gentian root, smilacis glabrae rhizoma etc.) for 3 months and used Glucosidorum Tripterygll Totorum as positive control, the total effective rate of the treatment group(96.7%) was better than that of the control group(P<0.05).In the study of Mao ZQ[15],60 patients of RA were randomly divided into two groups with 30 patients in each group. the treatment group was treated by Bitongxiao Tablet(composed of Ephedra herb, Atractylodes Rhizome, Coix Seed,Yam rhizome etc.)while the control group was treated by Zhengqingfengtongning Tablet.After 3 months, the two groups had similar effective rate (P>0.05).Zhou XG[16] randomly divided 77 patients into group1(n=55) treated by Sishenjian Decoction and the group2 (n=22) treated by piroxicam, methotrexate and azathioprine. 4 weeks were taken as a course, and 4 course in total. In the 4th, 16th week, the total effective rates of the treatment group were better than those of the control group(P<0.05); in the 8th week, however, the total effective rates of the two group were similar (P>0.05).Fourteng Decoction(composed of Orientvine Stem, adsura Pepper Stem, Chinese Starjasmine Stem,Tripterygium wilfordii etc.)was applied Renbin[17] to treat 120 patients of RA for 3 months, the total effective rate (73.3%) is superior to the control group with sulfasalazine(53.3%, P<0.05).  Liang RG[18] treated 34 patients in active stage of RA by Fourteng Decoction and used diclofenac, sulfasalazine, methotrexate as positive control.  The two groups had similar effective rate after 3 months (P>0.05).
2 Combined treatment of traditional Chinese medicine and western medicine(WM)
A plenty of clinical reports showed: combined treatment of traditional Chinese medicine and western medicine(WM) would open new and effective therapy for RA. Yun mingdong, et al[19] randomly divided 114 patients of Damp-Heat syndrome type RA into 2 groups. the TCM group was treated by Wutengercao Decoction combined with Nimesulide and methotrexate while the WM group was treated by Nimesulide, methotrexate and leflunomide.The former group was superior to the later in improvement of CRP and ACR50 in the 4th week and DAS28 in the 24th week(P<0.05). Shi xiuyu[20] randomly divided 61 patients into group1(n=31) treated by Chu-Shi-Tong-Bi Decoction combined with methotrexate and the group2 (n=30) treated only by methotrexate. After 2 months, the total effective rate of group1(83.9%)was better than that of group2 (76.7%, P<0.05).Yu JH, et al[21] randomly divided 81 refractory RA patients into 2 groups(30 patients in each group).the treatment group is treated by Guizhishaoyaozhimu Decoction based on therapeutic regimen of the control group (methotrexate and sulfasalazine). After 12 weeks,ACR20, ACR50 and ACR70 of the treatment group were 37.5%,  32.5%, 20% respectively and the total effective rate(90%) is superior to the control group(70.73%).Lin SQ[22] randomly divided 106 patients of RA into group1(n=56) treated by Huoxietongbi Decoction combined with conventional therapy of WM and group2 (n=50) treated by conventional therapy of WM.  After 12 weeks, group1 had higher total effective rate (82.1%) and better improvement of symptoms and signs, ESR, CRP, RF than group2(P<0.05).Wang weiping, et al[23] used conventional therapy of WM as positive control to observe clinic therapeutic effect of Huangqiguizhiwuwu Decoction combined with conventional therapy of WM in treatment of Qi and blood deficiency type RA.  After 3 months, the treatment group had higher total effective rate (90.3%) than the control group (51.7%, P<0.05), with better improvement of joint symptoms (P<0.05).Li SG[24] randomly divided 60 patients of active RA into group1(n=30) treated by Xuanbi Decoction combined with leflunomide and group2 (n=30) treated only by leflunomide.After 8 weeks, the two groups have similar total effective rate (P>0.05).however,   group1 had higher TCM effective rate (93.3%) than group2(53.3%, P<0.01). Bushentongluo Formula combined with methotrexate had been prescribed by Suxiao, et al[25] to treat 40 patients of Damp-Heat syndrome type RA, and methotrexate was taken as positive control(n=40).After 8, 12 weeks, the treatment group had higher total effective rate(86.8%, 92.1% respectively), TCM effective rate(71.1%,92.1% respectively)and improvement rate of ACR20%(84.2%,94.7% respectively)than the control group(P<0.05), with fewer adverse effect(P<0.05).He XL,et al [26]randomly divided 61 patients of active RA into group1(n=31) treated by Tongbi Decoction combined with methotrexate and group2 (n=30) treated by methotrexate.3 months after treatment,  group1 gained better improvement of VEGF(90.3%) than group2 (P<0.05). Through similar research, He XC,et al[27]  indicated markedly the effective rate in treated group(43.3%) was significantly higher than that (26.7%) in control group (P<0.05).  Wangtao, et al[28]  randomly divided 60 patients into 2 groups. The control group(n=30) received therapy of methotrexate and leflunomide only, while the observation group(n=30) received additional modified Zhibi Decoction(composed of peach seed, safflower, lumbricus, Chinese Angelica, Largeleaf Gentian Root etc.). The latter group was superior to the former both in total effective rate(92.66%vs70.39%) and improvement of symptoms, signs or laboratory index (P<0.05), however, with fewer side effect.
3 Experimental study of TCM
Over years, in China, some researches in laboratory study are introduced in RA, which will lead to better to understand the role and mechanism of Chinese medicine in RA treatment.  One topic of  experimental researches was focused on regulation of inflammatory mediator and the key points of immune imbalance in rheumatoid arthritis. Kang XZ, et al[29]  noticed: the therapy of Fengshikang in combination with glucocorticoid could significantly lower glucocorticoid receptor α/βmRNA level in peripheral blood mono-nuclear cell of patients with damp-heat syndrome type RA.  Shao CW[30] observed: Santeng Powder could alleviate the disease, ease the swelling of paw and significantly lower serum levels of TNF-α and IL-1β of AA rats.  Zhangyan, et al[31] discovered: RA Mixture No.1(composed of Orientvine Stem,  Largeleaf Gentian Root,Chinese clematis root, Kadsura Pepper Stem, Nux Vomica etc.)could significantly reduce the level of COX-2 and VEGF in synovium of AA rats,  and the effect was notably better than that of Tripterygium Glycosides (P<0.01).  Yutian[32] reported: the concentrated solution of Guizhishaoyaozhimu Decoction could remarkably inhibit the proliferation of synoviocytes, decrease the level of bcl-2, p53 in vitro and in vivo of AA rats and up-regulate expression of Fas. Zhang chunfang, et al[33] found: Sanbi Decoction could decrease effectively the expression of MMP-3, gelatinase-B and increase the expression of TIMP-1 in synovial tissue of joint, its effect is comparable to that of Tripterygium Glycosides(P>0.05). Anpeng,et al[34] discovered: Bining Particle diameter(composed of stir-baked Radix Paeoniae Alba,  processed aconite root, prepared Radix Glycyrrhizae, Danshen Root, Biond Magnolia Flower etc.) could significantly decrease serum level of IL-6 in the rats and the effect is notably better than that of methotrexate or Wangbi Particle diameter(P<0.05), though its improvement of serum IL-10 level was not different from that of methotrexate(P>0.05). An liping, et al[35]revealed: Dangguiniantong Decoction could enhance the function of peripheral T lymphocytes by markedly decreasing the abnormally high level of serum CD4 in the AA rats.  Yuan lixia[36] observed significant inhibition effects of Dangguiniantong Decoction and its separating prescriptions on the swelling of hind paw and polyarticular arthritis.  He found the abnormally high level of TNF-α, IL-1 in rats was markedly decreased, especially in complete Dangguiniantong Decoction group.
4 Conclusion
TCM is playing a unique role in treating RA, not only high cure rate but also little side effect occurrence, it is beneficial to the improvement of patient’s life quality and the decrease of MD by effect.  However, the management of RA itself is just a long therapeutic procedure.  Compared to the short-term curative effect (which refers to relief of swell, stiffness, pain of joints and limitation of activity),  long term delaying or even stopping the progress of the disease is more significant for us to pursue.  Once obtaining accurate categorical differentiation of symptoms and signs, we must stick to herbal decoction prescription and law requirement until recovery.  Highly think of long-term curative effect is the embodiment of the preventive thought of "preventive treatment of diseases".  
Meanwhile, we noticed: there are some problems in scientific and clinic research of TCM which we must pay attention on:
(1)At present, the improvement of quality of life has been already applied as an important factor for evaluating efficacy in RA treatment abroad, but is seldom applied in TCM study.  This situation would be bad for integration with the international standards. 
(2)Opinions are sharply divided not only on clinical classification of patterns which range from 2 to 6 types but also on curative standard which concludes both new and old, at home and abroad ones.  Hence, we can find out nothing but unconvincing conclusions and curative effects.
(3)Combination of TCM with WM leads to reciprocal advantages and seems more effective than single therapy.  However, there are only limited studies, especially in large sample, multicentre, randomized controlled trial in this field, and the data is still lack.
(4)Currently, more attentions are focused on short-term efficacy rather than long-term one, it would be difficult to fully exhibit the advantage of TCM therapy which inclined to have a slow onset and long duration.  How to seek more effective (with long term result) herb decoction formula remains a big and challenged task.   
(5) Works such as establishing animal models for TCM syndromes research, increasing our emphasis on experimental study of separating prescriptions, uncovering the essence of TCM therapy to offer theoretical basis for treatment of RA, are still of the first priority in the future.





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 Chengpeng   Hedongyi
   Dept of Rheumatology, Shanghai Guanghua Hospital (esp in Combination of Chinese Medicine and Western Medicine), Shanghai Traditional Chinese Medicine University 
Address correspondence and reprint requests to Hedongyi, MD, PhD, Department of Rheumatology, Shanghai Guanghua Hospital (esp in combination of Chinese medicine and Western medicine), Shanghai Traditional Chinese Medicine University 
540 Xinghua Road, Shanghai 200052, P.R. China. 
Tel: 86-21-62805833*3133. E-mail: dongyihe@medmail.com.cn




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