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The Treatment of Rheumatoid Arthritis Using Chinese Medicinal Plants from Pharmacology to Potential Molecular Mechanisms

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The Treatment of Rheumatoid Arthritis Using Chinese Medicinal Plants from Pharmacology to Potential Molecular Mechanisms Journal of Ethnopharmacology 176 (2015) 177–206 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jep Review The treatment of rheumatoid arthritis using Chinese medicinal plants: From pharmacology to potential molecular mechanisms Shaowa Lü a, Qiushi Wang a, Guoyu Li b, Shuang Sun a, Yuyan Guo a, Haixue Kuang a,n a Key Laboratory of Ministry of Education, Department of Pharmacology, Heilongjiang University of Chinese Medicine, Harbin 150040, China b College of Pharmacy, Harbin Medical University, Harbin 150040, China article info abstract Article history: Ethnopharmacological relevance: Rheumatoid arthritis (RA) is a common worldwide public health pro- Received 1 May 2015 blem. Traditional Chinese Medicine (TCM) achieved some results to some extent in the treatment of Received in revised form rheumatoid arthritis (RA). Especially in China, TCM formulas are used in the clinic because of their ad- 2 October 2015 vantages. Some of these TCM formulas have been used for thousands of years in ancient China, they pays Accepted 3 October 2015 much attention to strengthening healthy qi, cleaning heat, and wet, activating blood, etc. So TCM in anti- Available online 22 October 2015 RA drug is considered as a simple and effective method. In addition, TCM are also traditionally used as Keywords: extracts and many Chinese herbs which are considered to be effective for RA. With the advancement of Review technologies and research methods, researchers have devoted themselves to exploring new therapeutic Chinese material medica materials from troves of TCM. The components of TCM are identified and purified, which include alka- Related active compounds loids, coumarins, flavonoids, saponins and so on. However, little or no review works are found in the Rheumatoid arthritis Molecular mechanism research literature on the anti-RA drugs from TCM. The present review aims to provide systematically reorganized information on the ethnopharmacology, phytochemistry and pharmacology of TCM used traditionally against RA. The information recorded in this review will provide new directions for re- searchers in the future. Materials and methods: Relevant scientific literatures were collected from Chinese traditional books and Chinese Pharmacopoeia. Several important pharmacology data, clinical observations, animal experi- ments on effects of anti-RA drugs from TCM and their mechanisms were extracted from a library and electric search (Pubmed, PubChem Compound, Science Direct, Spring Link, Elsevier, Web of Science, CNKI, Wan Fang, Bai du, The Plant List, etc.). We collected information published between 2002 and 2015 on Chinese medicine in the treatment of RA. Information was also acquired from local classic herbal literature, conference papers, government reports, and PhD and MSc dissertations. Results: This review mainly introduces the current research on anti-RA TCM formulas, extracts and compounds from TCM, pharmacological data and potential mechanisms (inhibit osteoclast proliferation, suppress fibroblast-like synoviocytes (FLSs) growth, decrease the expression of inflammatory cytokines, blocking signal pathways, etc.). Conclusions: TCM, as a multi-component and multi-target approach, which is a perfect match with the holistic concept of systems biology, is applicable in the treatment of RA. The synergistic connections of Chinese herbs and mechanisms of related active compounds on RA increase the trust for TCM. TCM as alternative remedies for RA not only has an important position in the world market, but also has an irreplaceable role in the treatment of RA in future. & 2015 Elsevier Ireland Ltd. All rights reserved. Contents 1. Introduction . 178 2. Research progress of drugs against RA. 178 3. TCM formulas against RA . 179 4. Active ingredients of TCM against RA. 181 5. TCM anti-RA effects on several important RA models. 182 n Corresponding author. Fax: þ86 451 82110803. E-mail addresses: [email protected] (S. Lü), [email protected] (Q. Wang), [email protected], [email protected] (H. Kuang). http://dx.doi.org/10.1016/j.jep.2015.10.010 0378-8741/& 2015 Elsevier Ireland Ltd. All rights reserved. 178 S. Lü et al. / Journal of Ethnopharmacology 176 (2015) 177–206 5.1. Collagen-induced arthritis (CIA) model . 186 5.2. Adjuvant arthritis (AA) model. 186 5.3. Pristane-induced arthritis (PIA) model . 186 5.4. Ovalbumin induced arthritis (OIA) model . 189 5.5. TCM theory-integrated disease and syndrome model . 189 6. Actions and mechanisms of important compounds with anti-RA activities . 194 6.1. Cytokines.................................................................................................... 194 6.2. FLS.........................................................................................................200 6.3. The balance between Th1 and Th2 . 200 6.4. Angiogenesis . 200 6.5. Signaling pathways . 200 7. The minority nationalities medicine. 201 8. The medication characteristics of attenuated synergies . 201 9. Conclusion.........................................................................................................201 Authors' contribution . 202 Acknowledgments. 202 References.............................................................................................................202 1. Introduction detail, PubMed search on ‘traditional Chinese medicine and rheumatoid arthritis’, ‘Chinese herbs and rheumatoid arthritis’, Rheumatoid arthritis (RA) is a chronic autoimmune disease that ‘Chinese medicine and rheumatoid arthritis’, ‘animal model and results in a chronic, systemic inflammatory disorder of many tis- rheumatoid arthritis’, CNKI search on ‘类风湿性关节炎和中药’, ‘痹症 sues and organs, and principally attacks flexible (synovial) joints. It 和中药’, and ‘动物模型和类风湿性关节炎’ and some papers in other is a disabling and painful condition, which can lead to substantial databases were collected and analyzed. We summed up the re- loss of function and mobility if not adequately treated. In America, lated literature, this review chiefly focuses on bioactive com- RA is regarded as one of the five most common diseases (cardio- pounds and extracts isolated from TCM and TCM formulas in the vascular disease, arthritis, Alzheimer's disease, cancer, and AIDS) treatment of RA, including anti-RA drug development, TCM theory affecting human health. RA occurs at any age but is more common research, chemical constituents, RA models, mechanisms, etc. in middle age. About 0.24% of the global population suffer from RA, which has a higher disability rate, just below malaria and just above iodine deficiency (Cross et al., 2014). The significant mor- 2. Research progress of drugs against RA tality is thought to be associated with complications (like vascu- litis and interstitial lung disease) from RA (Makol et al., 2014; Although it is impossible to cure RA completely at present, Assayag et al., 2014). Many researchers have done substantial work treatments can alleviate symptoms to some level and slow the in this field, however, the pathogenesis of RA has not been eluci- course of the disease. The goals of treatment are to minimize dated until now. Although the causes of RA are unclear, genetic symptoms such as pain and swelling, to prevent bone deformity susceptibility, environmental triggers, and their interactions may (for example, bone erosion visible in X-rays), and to maintain day- be associated with diseases (Gibofsky, 2014). However in tradi- to-day functioning (Kruger, 2014). These could often be achieved tional Chinese medicine (TCM) theory, the occurrence of RA is by taking two main classes of medications: analgesics such as affected by ‘Wind (feng)’, ‘Damp (shi)’ and ‘Cold (han)’. These three nonsteroidal anti-inflammatory drugs (NSAIDs), and disease- factors jeopardize body homeostasis, which is what we often call modifying antirheumatic drugs (DMARDs) (Halabi et al., 2014). “unbalance of Yin and Yang”. As to therapy, some dispelling wind- However, their therapeutic effect is not satisfactory and is related damp drugs and some blood circulation drugs are mainly used in to some side effects such as nonspecific colitis, small intestinal anti-RA TCM formulas and have good curative effects in clinic. inflammation, complications associated with blood loss and pro- However, some problems are rasied about how TCM formulas treat tein loss. It was reported that a 32-year-old female with a case of RA and which ingredient works. Only when the effect of every mucositis was due to methotrexate (MTX) intoxication that re- herb and every single component are clarified, will we have a sulted from an overdose of MTX. Some symptoms of intoxication better explanation for TCM formulas. Studies on the material were abdominal pain, vomiting, and nausea (Uce Ozkol et al., foundation of medicinal effectiveness and action mechanism of 2014). In addition, glucocorticoids have an effect on anti-in- Chinese medicine are the keys to explain these problems. The flammation and double immunoregulation in the treatment. Stu- mechanism of TCM formulas are elucidated depending on the dies have shown that the glucocorticoids-DMARDs combination molecular biology. With the development of cell molecular biology could reduce some side effects (Mercieca and Kirwan, 2014). In (Sacre et al., 2005) and genetic study (Okada et al., 2014), the re- recent years, North America and Europe have approved several lated study is bound to make scientific explanation on TCM. Be- biological agents for the treatment of RA, such as tumor necrosis cause TCM
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