Rheumatoid Arthritis In China Research Articles

Periplocoside A, a pregnane glycoside from Periploca sepium Bge, prevents concanavalin A-induced mice hepatitis through inhibiting NKT-derived inflammatory cytokine productions

Periploca sepium Bge, a traditional Chinese herb medicine, is widely used for treating rheumatoid arthritis in china. Periplocoside A (PSA), a pregnane glycoside, is a new nature product compound isolated from P. sepium Bge. We examined the protective effects of PSA, on concanavaline A (ConA)-induced hepatitis. Pretreatment with PSA dramatically ameliorated ConA-induced liver injury, which was characterized by reducing serum alanine transaminase (ALT), pathogenic cytokines of interleukin (IL)-4 and interferon (IFN)-γ levels, impeding the liver necrosis, and thus elevating the survival rate. In vitro, PSA inhibited IL-4 and IFN-γ productions of α-galactosylceramide (α-GalCer) or anti-CD3-activated Natural killer T (NKT) cells. Enzyme Linked Immunosorbent Assay (ELISA) and Reverse Transcription Polymerase Chain Reaction (RT-PCR) assays revealed PSA suppressed IL-4 transcription and IFN-γ translation. In conclusion, PSA had significantly preventative effect on ConA-induced hepatitis, which was closely associated with inhibition of NKT-derived inflammatory cytokine productions. These findings suggested that PSA has the therapeutic potential for treatment of human autoimmune-related hepatitis.

Prolonged cutaneous analgesia in rats induced by 3‐acetylaconitine as an additive

Abstract3‐Acetylaconitine (3AA) is an “aconitine‐like” plant alkaloid that has been used as an analgesic agent for the treatment of chronic pain and rheumatoid arthritis in China. Aconitine‐like alkaloids appear to target the CNS for their analgesic action, although they also display local anesthetic properties. We tested whether 3AA prolonged cutaneous analgesia in rats when co‐injected with lidocaine (0.5%) and epinephrine (1:200,000), a mixture commonly used in infiltration anesthesia. Inhibition of the cutaneous trunci muscle reflex was evaluated quantitatively by pinpricks applied to the injected area. Co‐injection of lidocaine and epinephrine with 3AA ranging within 50–125 µM elicited complete cutaneous analgesia in vivo lasting 3–12 h, and full recovery occurred after ∼5–8 days in a 3AA concentration‐dependent manner. In contrast, cutaneous analgesia induced by the mixture of lidocaine and epinephrine or by 3AA alone in rats was significantly shorter. No adverse systemic effects or local toxicities were evident after injection of 3AA as an additive. Our results suggest that “aconitine‐like” alkaloids could be exploited as an additive for long‐lasting cutaneous analgesia. Drug Dev Res 69: 83–88, 2008. © 2008 Wiley‐Liss, Inc.

Rheumatic diseases in China.

IntroductionEpidemiological studies of rheumatic diseases have been conducted during the past 20 years in China. The aim of this study was to clarify prevalence rates of common rheumatic diseases in China.MethodsRelevant reports of population-based surveys conducted from 1980 to 2006 were retrieved. Studies using the World Health Organization-International League of Associations for Rheumatology COPCORD (Community Oriented Program for Control of Rheumatic Diseases) protocol and those that did not employ this protocol but were published in recognized journals were identified and analyzed.ResultsThirty-eight surveys including 241,169 adults from 25 provinces/cities were pooled for analysis. The prevalence of rheumatic complaints ranged from 11.6% to 46.4%, varying by locality, study protocol and age of the people surveyed. Prevalence of symptomatic osteoarthritis (OA) varied from 5.1% to 20.8%, with common sites of involvement being the lumbar spine, knee joint and cervical spine. Compared with rates of radiographic and symptomatic knee OA in the USA, elderly men in Beijing exhibited similar prevalence rates and elderly women exhibited a higher prevalence. The prevalence of hip OA and hand OA was much lower in Chinese than in Caucasian populations, but both kinds of OA were more common in coal miners. The prevalence of ankylosing spondylitis ranged from 0.2% to 0.54% among Han ethnic Chinese and were lower among mixed ethnic populations. The prevalence of psoriatic arthritis ranged from 0.01% to 0.1%, and that of reactive arthritis was 0.02%; undifferentiated spondyloarthropathy was identified in 0.64% to 1.2% of the individuals included in the surveys. The prevalence of rheumatoid arthritis (RA) ranged from 0.2% to 0.93%, with the highest rate being reported from a Taiwan urban area. In mainland China there were no significant differences in prevalence of RA between the northern and southern parts of China, or between different ethnic groups. The prevalence of hyperuricemia increased after the 1980s. The prevalence of gout was found to have increased in recent decades from 0.15% to 1.98%, apart from in the Taiwan aborigines, among whom the highest prevalence rate of 11.7% was recorded. The prevalence of primary Sjögren's syndrome in Beijing was 0.77% by the Copenhagen criteria and 0.33% by the San Diego criteria. The prevalence of soft tissue rheumatism was 2.5% to 5.7%. Fibromyalgia was seldom observed in China.ConclusionRheumatic diseases are common in China. The prevalence of rheumatic complaints varied with the locality surveyed. The prevalence of OA is comparable with that in Western countries but varies in terms of joint involvement. The prevalence of ankylosing spondylitis is similar to that in Caucasians. Except in Taiwan, the prevalence of RA in China is lower than that in developed countries. The prevalence of hyperuricemia and gout increased after the 1980s, but it remains lower than that in developed countries. More studies are required to evaluate prevalence rates among minority groups in the west and northwest parts of China, and further study is needed to address fibromyalgia in China.

Bulleyaconitine A Isolated from Aconitum Plant Displays Long-acting Local Anesthetic Properties In Vitro and In Vivo

Bulleyaconitine A (BLA) is an active ingredient of Aconitum bulleyanum plants. BLA has been approved for the treatment of chronic pain and rheumatoid arthritis in China, but its underlying mechanism remains unclear. The authors examined (1) the effects of BLA on neuronal voltage-gated Na channels in vitro under the whole cell patch clamp configuration and (2) the sensory and motor functions of rat sciatic nerve after single BLA injections in vivo. BLA at 10 microm did not affect neuronal Na currents in clonal GH3 cells when stimulated infrequently to +50 mV. When stimulated at 2 Hz for 1,000 pulses (+50 mV for 4 ms), BLA reduced the peak Na currents by more than 90%. This use-dependent reduction of Na currents by BLA reversed little after washing. Single injections of BLA (0.2 ml at 0.375 mm) into the rat sciatic notch not only blocked sensory and motor functions of the sciatic nerve but also induced hyperexcitability, followed by sedation, arrhythmia, and respiratory distress. When BLA at 0.375 mm was coinjected with 2% lidocaine (approximately 80 mm) or epinephrine (1:100,000) to reduce drug absorption by the bloodstream, the sensory and motor functions of the sciatic nerve remained fully blocked for approximately 4 h and regressed completely after approximately 7 h, with minimal systemic effects. BLA reduces neuronal Na currents strongly at +50 mV in a use-dependent manner. When coinjected with lidocaine or epinephrine, BLA elicits prolonged block of both motor and sensory functions in rats with minimal adverse effects.

Discovery and synthesis of new immunosuppressive alkaloids from the stem of Fissistigma oldhamii (Hemsl.) Merr.

Three new alkaloids ( 1– 3) and twenty-one known compounds were isolated from the stem of Fissistigma oldhamii (Hemsl.) Merr. which was the ruler herb in an approved Traditional Chinese herbal formula used for treatment of rheumatoid arthritis in China and synthesis of one new immunosuppressive alkaloid was achieved. These compounds, including the crude extracts of this herb, exhibited strong activities in the inhibition of T and B cell proliferation.

Rheumatology in China--brief introduction of the development of Chinese rheumatology

arthritis ranged from 0.26 to 0.5%, with an average of 0.36%. A study conducted in both the Northern and Southern parts of China estimated that the prevalence of ankylosing spondylitis was 0.26%. The positive rate of HLA-B27 in patients of ankylosing spondylitis was >90%, while the rate in the general population was only 6-7%. Another survey conducted in 30 000 textile workers in Shanghai showed that the prevalence of systemic lupus erythematosus in males was 70 per 100 000 persons; and in females, the rate was 113 per 100 000 persons. Data from hospitals in Beijing showed that among patients with systemic lupus erythematosus who visited a doctor, those aged 14-39 yrs comprised 70% of the population, and the male to female ratio was 1:13 while the ratio was 1:4 in patients aged between 40 and 59 yrs. An epidemiology investigation of osteoarthritis conducted in 13 451 steel workers in Shanghai showed that the prevalence of symptomatic osteoarthritis was 2.2% and asymptomatic osteoar- thritis was 53%. The prevalence of osteoarthritis was 11, 27 and 62% in the age groups 30-39, 40-49 and 50-59 yrs, respectively. Looking at primary Sjogren's syndrome, an investigation was conducted in 1992 in all adults (total 2060) living in a suburban region of Beijing, including screening with anti-nuclear antibodies (ANA), rheumatoid factor and anti-SSA(Ro)/anti-SSB(La) as well as a questionnaire. For those who were positive in any of the screen tests, additional tests for keratoconjunctivitis sicca and salivary gland involvement were performed. The results showed that the prevalence of primary Sjogren's syndrome in the Beijing area was 0.77% based on the Copenhagen criteria and 0.29% based on the San Diego criteria. Therefore, we concluded that primary Sjogren's syndrome is not a rare disease in China. Recently, another investigation was conducted to explore the current therapeutic strategy for rheumatoid arthritis in China. Eleven regions and 56 hospitals took part in this study. So far, 2202 patients with rheumatoid arthritis have been registered, 436 males and 1766 females, with the average age of 48.66 16.05 (8-90) yrs and mean disease duration of 86.49 98.47 (1-664) months. The involved joints at the onset of disease were hand (61.76%), knee (35.6%), wrist (34.29%), shoulder (18.89%), foot (17.71%), ankle (17.57%), elbow (15.03%), hip (5.00%) and spine (3.95%). The first drug taken by patients was non-steroidal anti- inflammatory drugs (NSAIDs) (53.04%), disease-modifying anti-rheumatic drugs (DMARDs) (21.21%), glucocorticosteroids (16.89%), Chinese traditional medicine (9.49%) and drugs with unknown component (11.99%). The first DMARD prescribed was methotrexate (60.81%), sulphasalazine (22.55%), leflunomide (16.01%), hydroxychloroquine (7.88%) D-penicillamine (7.29%), etc. The average time from joint pain to joint function impair- ment was 36.38 66.63 months, and the time to joint deformity was 55.61 73.87 months. Investigation also revealed that the average time from joint pain to DMARDs prescription in patients without joint deformity was 36.33 68.48 months, while the time was 75.69 98.43 months in patients with joint deformity, suggesting that early prescription of DMARDs could effectively prevent joint destruction. With the development of the Chinese economy and improvement of the living standards of the Chinese people, gout, a formerly rare disease, has become more and more common and been increasingly recognized since the 1990s. An epidemiology survey on gout is underway. It is also noteworthy that with the development of the Chinese economy, government investment on medical research has increased. Chinese medical society becomes more open

Periplocoside E, an Effective Compound fromPeriploca sepiumBge, Inhibited T Cell Activation in Vitro and in Vivo

Periploca sepium Bge, a traditional Chinese herb medicine, is used for treating rheumatoid arthritis in China. Followed the bioactivity-guided isolation, the most potent immunosuppressive compound, periplocoside E (PSE), a pregnane glycoside, had been identified from P. sepium Bge. We investigated the immunosuppressive effects of PSE in vitro and in vivo. The results showed that PSE in a dose-dependent manner significantly inhibited the proliferation of splenocytes induced by concanavalin A and mixed lymphocyte culture reaction at no cytotoxic concentrations (<5 microM). Administration of PSE suppressed a delayed-type hypersensitivity reaction, and ovalbumin (OVA) induced antigen-specific immune responses in mice. In vivo treatment with PSE dose dependently suppressed OVA-induced proliferation and cytokine [interleukin (IL)-2 and interferon (IFN)-gamma] production from splenocytes in vitro. Purified T cells from OVA-immunized mice with PSE treatment showed its low ability for activation by OVA plus normal antigen presenting cell stimulation again in vitro. Further studies showed PSE dose dependently inhibited anti-CD3-induced primary T cell proliferation, activation for IL-2Ralpha (CD25) expression, and cytokine (IFN-gamma and IL-2) production also at the transcriptional level. PSE was highly specific and significantly inhibited the activation of extracellular signal-regulated kinase and Jun N-terminal kinase, whereas activation of p38 was not affected in T cells stimulated with anti-CD3. These results demonstrated that PSE is an immunosuppressive compound in P. sepium Bge, which directly inhibits T cell activation in vitro and in vivo. This study provided evidence to understand the therapeutic effects of P. sepium Bge and indicated that this herb is appropriate for treatment of T cell-mediated disorders, such as autoimmune diseases.

「通ひ霊」のＩＩ型コラーゲン誘発関節炎に対する作用

It was demonstrated that the oriental medication‘Tsu-hi-rei’is clinically useful and effective in treatment of patients with rheumatoid arthritis in China. This effect was supposed to be due to immunomodulation by decreasing of rheumatoid factor and immunoglobulin levels and various parameters of inflammation.So a basic experiment to investigate its mechanism of action was scheduled by using collageninduced arthritis in DBA/1J mice. From 4 weeks after booster injection of type II collagen, “Tsu-hi-rei”and western medication such as indomethacin and an immunomodulator were given, and their effects were compared by clinical observation, X-ray findings and pathologic examination. Anti-collagen antibody was also measured in each treatment group by ELISA.“Tsu-hi-rei”showed suppression of collagen-induced arthritis in frequency and severity. The soft X-ray study revealed decreased bone-destruction and, in sera, titers of anticollagen antibody were lower than in controls.These data suggest that“Tsu-hi-rei”has an antiinflammatory and immunosuppressive effect on collagen-induced arthritis.