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Scientific Basis of Botanical Medicine as Alternative Remedies for Rheumatoid Arthritis

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Abstract

Rheumatoid arthritis (RA) is a chronic, systemic autoimmune inflammatory disorder that causes permanent disability and mortality to approximately 1 to 100 people in the world. Patients with RA not only suffer from pain, stiffness, swelling, and loss of function in their joints, but also have a higher risk of cardiovascular disease and lymphoma. Typically prescribed medications, including pain-relieving drugs, nonsteroidal anti-inflammatory drugs (NSAID), and disease-modifying antirheumatic drugs, can help to relieve pain, reduce inflammation and slow the course of disease progression in RA patients. However, the general effectiveness of the drugs has been far from satisfactory. Other therapeutic modalities like TNF-alpha (TNF-α) inhibitors and interleukin-1 receptor antagonists targeting precise pathways within the immune system are expensive and may be associated with serious side effects. Recently, botanical medicines have become popular as alternative remedies as they are believed to be efficacious, safe and have over a thousand years experience in treating patients. In this review, we will summarize recent evidence for pharmacological effects of herbs including Black cohosh, Angelica sinensis, Licorice, Tripterygium wilfordii, Centella asiatica, and Urtica dioica. Scientific research has demonstrated that these herbs have strong anti-inflammatory and anti-arthritic effects. A wide range of phytochemicals including phenolic acids, phenylpropanoid ester, triterpene glycosides, phthalide, flavonoids, triterpenoid saponin, diterpene and triterpene have been isolated and demonstrated to be responsible for the biological effects of the herbs. Understanding the mechanisms of action of the herbs may provide new treatment opportunities for RA patients.

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References

  1. Myasoedova E, Crowson CS, Turesson C, Gabriel SE, Matteson EL (2011) Incidence of extraarticular rheumatoid arthritis in olmsted county, minnesota, in 1995-2007 versus 1985-1994: a population-based study. J Rheumatol 38:983–989

    Article  PubMed  Google Scholar 

  2. Aletaha D, Neogi T, Silman AJ et al (2010) 2010 rheumatoid arthritis classification criteria an american college of rheumatology/european league against rheumatism collaborative initiative. Arthritis Rheum-Us 62:2569–2581

    Article  Google Scholar 

  3. Nordahl S, Alstergren P, Kopp S (2000) Tumor necrosis factor-alpha in synovial fluid and plasma from patients with chronic connective tissue disease and its relation to temporomandibular joint pain. J Oral Maxil Surg 58:525–530

    Google Scholar 

  4. Nawroth PP, Bank I, Handley D, Cassimeris J, Chess L, Stern D (1986) Tumor necrosis factor/cachectin interacts with endothelial cell receptors to induce release of interleukin 1. J Exp Med 163:1363–1375

    Article  PubMed  CAS  Google Scholar 

  5. Suzuki M, Tetsuka T, Yoshida S et al (2000) The role of p38 mitogen-activated protein kinase in IL-6 and IL-8 production from the TNF-alpha- or IL-1beta-stimulated rheumatoid synovial fibroblasts. FEBS Lett 465:23–27

    Article  PubMed  CAS  Google Scholar 

  6. Haworth C, Brennan FM, Chantry D, Turner M, Maini RN, Feldmann M (1991) Expression of granulocyte-macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol 21:2575–2579

    Article  PubMed  CAS  Google Scholar 

  7. Chin JE, Winterrowd GE, Krzesicki RF, Sanders ME (1990) Role of cytokines in inflammatory synovitis. The coordinate regulation of intercellular adhesion molecule 1 and HLA class I and class II antigens in rheumatoid synovial fibroblasts. Arthritis Rheum 33:1776–1786

    Article  PubMed  CAS  Google Scholar 

  8. Cunnane G, Hummel KM, Muller-Ladner U, Gay RE, Gay S (1998) Mechanism of joint destruction in rheumatoid arthritis. Arch Immunol Ther Exp (Warsz) 46:1–7

    CAS  Google Scholar 

  9. Shingu M, Nagai Y, Isayama T, Naono T, Nobunaga M, Nagai Y (1993) The effects of cytokines on metalloproteinase inhibitors (timp) and collagenase production by human chondrocytes and timp production by synovial-cells and endothelial-cells. Clin Exp Immunol 94:145–149

    Article  PubMed  CAS  Google Scholar 

  10. Nagy G, Clark JM, Buzas E et al (2008) Nitric oxide production of T lymphocytes is increased in rheumatoid arthritis. Immunol Lett 118:55–58

    Article  PubMed  CAS  Google Scholar 

  11. Butler DM, Maini RN, Feldmann M, Brennan FM (1995) Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist. Eur. Cytokine Netw 6:225–230

    CAS  Google Scholar 

  12. Eastgate JA, Symons JA, Wood NC, Grinlinton FM, di Giovine FS, Duff GW (1988) Correlation of plasma interleukin 1 levels with disease activity in rheumatoid arthritis. Lancet 2:706–709

    Article  PubMed  CAS  Google Scholar 

  13. Amin AR, Dave M, Attur M, Abramson SB (2000) COX-2, NO, and cartilage damage and repair. Curr Rheumatol Rep 2:447–453

    Article  PubMed  CAS  Google Scholar 

  14. Chabaud M, Durand JM, Buchs N et al (1999) Human interleukin-17 - A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum 42:963–970

    Article  PubMed  CAS  Google Scholar 

  15. Jovanovic DV, Di Battista JA, Martel-Pelletier J et al (1998) IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol 160:3513–3521

    PubMed  CAS  Google Scholar 

  16. LeGrand A, Fermor B, Fink C et al (2001) Interleukin-1, tumor necrosis factor alpha, and interleukin-17 synergistically up-regulate nitric oxide and prostaglandin E-2 production in explants of human osteoarthritic knee menisci. Arthritis Rheum 44:2078–2083

    Article  PubMed  CAS  Google Scholar 

  17. Jovanovic DV, Martel-Pelletier J, Di Battista JA et al (2000) Stimulation of 92-kd gelatinase (matrix metalloproteinase 9) production by interleukin-17 in human monocyte/macrophages - a possible role in rheumatoid arthritis. Arthritis Rheum 43:1134–1144

    Article  PubMed  CAS  Google Scholar 

  18. Pickens SR, Volin MV, Mandelin AM, Kolls JK, Pope RM, Shahrara S (2010) IL-17 contributes to angiogenesis in rheumatoid arthritis. J Immunol 184:3233–3241

    Article  PubMed  CAS  Google Scholar 

  19. Yoshihara Y, Nakamura H, Obata K et al (2000) Matrix metalloproteinases and tissue inhibitors of metalloproteinases in synovial fluids from patients with rheumatoid arthritis or osteoarthritis. Ann Rheum Dis 59:455–461

    Article  PubMed  CAS  Google Scholar 

  20. Burrage PS, Mix KS, Brinckerhoff CE (2006) Matrix metalloproteinases: role in arthritis. Front Biosci 11:529–543

    Article  PubMed  CAS  Google Scholar 

  21. Knauper V, Lopez-Otin C, Smith B, Knight G, Murphy G (1996) Biochemical characterization of human collagenase-3. J Biol Chem 271:1544–1550

    Article  PubMed  CAS  Google Scholar 

  22. Fosang AJ, Last K, Knauper V, Murphy G, Neame PJ (1996) Degradation of cartilage aggrecan by collagenase-3 (MMP-13). FEBS Lett 380:17–20

    Article  PubMed  CAS  Google Scholar 

  23. Okada Y, Nagase H, Harris ED Jr (1986) A metalloproteinase from human rheumatoid synovial fibroblasts that digests connective tissue matrix components. Purif charact J Biol Chem 261:14245–14255

    CAS  Google Scholar 

  24. Flannery CR, Lark MW, Sandy JD (1992) Identification of a stromelysin cleavage site within the interglobular domain of human aggrecan. Evidence for proteolysis at this site in vivo in human articular cartilage. J Biol Chem 267:1008–1014

    PubMed  CAS  Google Scholar 

  25. Conway JG, Wakefield JA, Brown RH et al (1995) Inhibition of cartilage and bone destruction in adjuvant arthritis in the rat by a matrix metalloproteinase inhibitor. J Exp Med 182:449–457

    Article  PubMed  CAS  Google Scholar 

  26. Hishinuma T, Nakamura H, Sawai T, Uzuki M, Itabash Y, Mizugaki M (1999) Microdetermination of prostaglandin E2 in joint fluid in rheumatoid arthritis patients using gas chromatography/selected ion monitoring. Prostaglandins Lipid Mediat 58:179–186

    Article  CAS  Google Scholar 

  27. Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nature-New Biol 240: 200-&

  28. Lemos HP, Grespan R, Vieira SM et al (2009) Prostaglandin mediates IL-23/IL-17-induced neutrophil migration in inflammation by inhibiting IL-12 and IFN gamma production. P Natl Acad Sci USA 106:5954–5959

    Article  CAS  Google Scholar 

  29. Akaogi J, Nozaki T, Satoh M, Yamada H (2006) Role of PGE2 and EP receptors in the pathogenesis of rheumatoid arthritis and as a novel therapeutic strategy. Endocr Metab Immune Disord Drug Targets 6:383–394

    Article  PubMed  CAS  Google Scholar 

  30. Campbell IK, Piccoli DS, Hamilton JA (1990) Stimulation of human chondrocyte prostaglandin E2 production by recombinant human interleukin-1 and tumour necrosis factor. Biochim Biophys Acta 1051:310–318

    Article  PubMed  CAS  Google Scholar 

  31. Sakurai H, Kohsaka H, Liu MF et al (1995) Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides. J Clin Invest 96:2357–2363

    Article  PubMed  CAS  Google Scholar 

  32. Ajuebor MN, Virag L, Flower RJ, Perretti M, Szabo C (1998) Role of inducible nitric oxide synthase in the regulation of neutrophil migration in zymosan-induced inflammation. Immunology 95:625–630

    Article  PubMed  CAS  Google Scholar 

  33. Lotz M (1999) The role of nitric oxide in articular cartilage damage. Rheum Dis Clin N Am 25:269–282

    Article  CAS  Google Scholar 

  34. Ralston SH, Ho LP, Helfrich MH, Grabowski PS, Johnston PW, Benjamin N (1995) Nitric-oxide - a cytokine-induced regulator of bone-resorption. J Bone Miner Res 10:1040–1049

    Article  PubMed  CAS  Google Scholar 

  35. Firestein GS (2003) Evolving concepts of rheumatoid arthritis. Nature 423:356–361

    Article  PubMed  CAS  Google Scholar 

  36. Maruotti N, Cantatore P, Crivellato E, Vacca A, Ribatti D (2007) Macrophages in rheumatoid arthritis. Histol Histopathol 22:581–586

    PubMed  CAS  Google Scholar 

  37. Kinne RW, Brauer R, Stuhlmuller B, Palombo-Kinne E, Burmester GR (2000) Macrophages in rheumatoid arthritis. Arthritis Research 2:189–202

    Article  PubMed  CAS  Google Scholar 

  38. Goldring SR (2003) Pathogenesis of bone and cartilage destruction in rheumatoid arthritis. Rheumatology 42:11–16

    Article  CAS  Google Scholar 

  39. Silverman GJ, Carson DA (2003) Roles of B cells in rheumatoid arthritis. Arthritis Res Ther 5:S1–S6

    Article  PubMed  Google Scholar 

  40. Jones DH, Kong YY, Penninger JM (2002) Role of RANKL and RANK in bone loss and arthritis. Ann Rheum Dis 61:32–39

    Article  Google Scholar 

  41. Dayer JM, Burger D (1999) Cytokines and direct cell contact in synovitis: relevance to therapeutic intervention. Arthritis Res 1:17–20

    Article  PubMed  CAS  Google Scholar 

  42. Burger D, Rezzonico R, Li JM et al (1998) Imbalance between interstitial collagenase and tissue inhibitor of metalloproteinases 1 in synoviocytes and fibroblasts upon direct contact with stimulated T lymphocytes - Involvement of membrane-associated cytokines. Arthritis Rheum 41:1748–1759

    Article  PubMed  CAS  Google Scholar 

  43. Schulzekoops H, Lipsky PE, Kavanaugh AF, Davis LS (1995) Elevated Th1- or Th0-like cytokine messenger-rna in peripheral-circulation of patients with rheumatoid-arthritis - modulation by treatment with anti-icam-1 correlates with clinical benefit. J Immunol 155:5029–5037

    CAS  Google Scholar 

  44. van Hamburg JP, Asmawidjaja PS, Davelaar N et al (2011) Th17 cells, but not Th1 cells, from patients with early rheumatoid arthritis are potent inducers of matrix metalloproteinases and proinflammatory cytokines upon synovial fibroblast interaction, including autocrine interleukin-17A production. Arthritis Rheum 63:73–83

    Article  PubMed  CAS  Google Scholar 

  45. Schett G, Tohidast-Akrad M, Smolen JS et al (2000) Activation, differential localization, and regulation of the stress-activated protein kinases, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase, in synovial tissue and cells in rheumatoid arthritis. Arthritis Rheum 43:2501–2512

    Article  PubMed  CAS  Google Scholar 

  46. Brauchle M, Gluck D, Di Padova F, Han J, Gram H (2000) Independent role of p38 and ERK1/2 mitogen-activated kinases in the upregulation of matrix metalloproteinase-1. Exp Cell Res 258:135–144

    Article  PubMed  CAS  Google Scholar 

  47. Westermarck J, Holmstrom T, Ahonen M, Eriksson JE, Kahari VM (1998) Enhancement of fibroblast collagenase-1 (MMP-1) gene expression by tumor promoter okadaic acid is mediated by stress-activated protein kinases Jun N-terminal kinase and p38. Matrix Biol 17:547–557

    Article  PubMed  CAS  Google Scholar 

  48. Han ZN, Boyle DL, Manning AM, Firestein GS (1998) AP-1 and NF-kappa B regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity 28:197–208

    Article  PubMed  CAS  Google Scholar 

  49. Yan C, Boyd DD (2007) Regulation of matrix metalloproteinase gene expression. J Cell Physiol 211:19–26

    Article  PubMed  CAS  Google Scholar 

  50. Miyazawa K, Mori A, Yamamoto K, Okudaira H (1998) Transcriptional roles of CCAAT/enhancer binding protein-beta, nuclear factor-kappaB, and C-promoter binding factor 1 in interleukin (IL)-1beta-induced IL-6 synthesis by human rheumatoid fibroblast-like synoviocytes. J Biol Chem 273:7620–7627

    Article  PubMed  CAS  Google Scholar 

  51. Nishiya T, Uehara T, Kaneko M, Nomura Y (2000) Involvement of nuclear factor-kappaB (NF-kappaB) signaling in the expression of inducible nitric oxide synthase (iNOS) gene in rat C6 glioma cells. Biochem Biophys Res Commun 275:268–273

    Article  PubMed  CAS  Google Scholar 

  52. Kopp EB, Ghosh S (1995) NF-kappa B and rel proteins in innate immunity. Adv Immunol 58:1–27

    Article  PubMed  CAS  Google Scholar 

  53. Moreland LW, Baumgartner SW, Schiff MH et al (1997) Treatment of rheumatoid arthritis with a recombinant human tumor necrosis factor receptor (p75)-Fc fusion protein. New Engl J Med 337:141–147

    Article  PubMed  CAS  Google Scholar 

  54. Brennan FM, Jackson A, Chantry D, Maini R, Feldmann M (1989) Inhibitory effect of tnf-alpha antibodies on synovial cell interleukin-1 production in rheumatoid-arthritis. Lancet 2:244–247

    Article  PubMed  CAS  Google Scholar 

  55. Smolen JS, Landewe R, Breedveld FC et al (2010) EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs. Ann Rheum Dis 69:964–975

    Article  PubMed  CAS  Google Scholar 

  56. Smolen JS, Avila JC, Aletaha D (2011) Tocilizumab inhibits progression of joint damage in rheumatoid arthritis irrespective of its anti-inflammatory effects: disassociation of the link between inflammation and destruction. Ann Rheum Dis. doi:10.1136/annrheumdis-2011-200395

  57. De Vita S, Zaja F, Sacco S, De Candia A, Fanin R, Ferraccioli G (2002) Efficacy of selective B cell blockade in the treatment of rheumatoid arthritis: evidence for a pathogenetic role of B cells. Arthritis Rheum 46:2029–2033

    Article  PubMed  CAS  Google Scholar 

  58. Blumenthal MG, Brinkman J (eds) (2000) Black cohosh root. In herbal medicine: the expanded commission e monographs. American Botanical Council, Newton, pp 22–27

    Google Scholar 

  59. Schmid D, Gruber M, Woehs F et al (2009) Inhibition of inducible nitric oxide synthesis by Cimicifuga racemosa (Actaea racemosa, black cohosh) extracts in LPS-stimulated RAW 264.7 macrophages. J Pharm Pharmacol 61:1089–1096

    PubMed  CAS  Google Scholar 

  60. Yang CLH, Chik SCC, Li JCB, Cheung BKW, Lau ASY (2009) Identification of the bioactive constituent and its mechanisms of action in mediating the anti-inflammatory effects of black cohosh and related cimicifuga species on human primary blood macrophages. J Med Chem 52:6707–6715

    Article  PubMed  CAS  Google Scholar 

  61. Schmid D, Woehs F, Svoboda M, Thalhammer T, Chiba P, Moeslinger T (2009) Aqueous extracts of Cimicifuga racemosa and phenolcarboxylic constituents inhibit production of proinflammatory cytokines in LPS-stimulated human whole blood. Can J Physiol Pharmacol 87:963–972

    Article  PubMed  CAS  Google Scholar 

  62. Sakai S, Ochiai H, Nakajima K, Terasawa K (1997) Inhibitory effect of ferulic acid on macrophage inflammatory protein-2 production in a murine macrophage cell line, RAW264.7. Cytokine 9:242–248

    Article  PubMed  CAS  Google Scholar 

  63. Hirabayashi T, Ochiai H, Sakai S, Nakajima K, Terasawa K (1995) Inhibitory effect of ferulic acid and isoferulic acid on murine interleukin-8 production in response to influenza-virus infections in-vitro and in-vivo. Planta Med 61:221–226

    Article  PubMed  CAS  Google Scholar 

  64. Hirata A, Murakami Y, Atsumi T et al (2005) Ferulic acid dimer inhibits lipopolysaccharide-stimulated cyclooxygenase-2 expression in macrophages. In Vivo 19:849–853

    PubMed  CAS  Google Scholar 

  65. Qiu SX, Dan C, Ding LS et al (2007) A triterpene glycoside from black cohosh that inhibits osteoclastogenesis by modulating RANKL and TNFalpha signaling pathways. Chem Biol 14:860–869

    Article  PubMed  CAS  Google Scholar 

  66. Chawla AS, Singh M, Murthy MS, Gupta M, Singh H (1987) Anti-inflammatory action of ferulic acid and its esters in carrageenan induced rat paw oedema model. Indian J Exp Biol 25:187–189

    PubMed  CAS  Google Scholar 

  67. Mills SY, Jacoby RK, Chacksfield M, Willoughby M (1996) Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double-blind study. Brit J Rheumatol 35:874–878

    Article  CAS  Google Scholar 

  68. Soeken KL, Miller SA, Ernst E (2003) Herbal medicines for the treatment of rheumatoid arthritis: a systematic review. Rheumatology 42:652–659

    Article  PubMed  CAS  Google Scholar 

  69. Hou TC (ed) (2004) Herbal extracts, Vols. 1, 1st edn. China Medical Scientific Technological Publishing Company, Beijing, pp 173–183

    Google Scholar 

  70. Chen MP, Yang SH, Chou CH et al (2010) The chondroprotective effects of ferulic acid on hydrogen peroxide-stimulated chondrocytes: inhibition of hydrogen peroxide-induced pro-inflammatory cytokines and metalloproteinase gene expression at the mRNA level. Inflamm Res 59:587–595

    Article  PubMed  CAS  Google Scholar 

  71. Zhang RX, Fan AY, Zhou AN et al (2009) Extract of the Chinese herbal formula Huo Luo Xiao Ling Dan inhibited adjuvant arthritis in rats. J Ethnopharmacol 121:366–371

    Article  PubMed  Google Scholar 

  72. Chao WW, Kuo YH, Li WC, Lin BF (2009) The production of nitric oxide and prostaglandin E(2) in peritoneal macrophages is inhibited by Andrographis paniculata, Angelica sinensis and Morus alba ethyl acetate fractions. J Ethnopharmacol 122:68–75

    Article  PubMed  Google Scholar 

  73. Yang C, Niu S, Yu L, Zhu S, Zhu J, Zhu Q (2011) The aqueous extract of angelica sinensis, a popular chinese herb, inhibits wear debris-induced inflammatory osteolysis in mice. J Surg Res

  74. Chao WW, Hong YH, Chen ML, Lin BF (2010) Inhibitory effects of Angelica sinensis ethyl acetate extract and major compounds on NF-kappa B trans-activation activity and LPS-induced inflammation. J Ethnopharmacol 129:244–249

    Article  PubMed  CAS  Google Scholar 

  75. Chu Q, Hashimoto K, Satoh K, Wang QT, Sakagami H (2009) Effect of three herbal extracts on NO and PGE(2) production by activated mouse macrophage-like cells. In Vivo 23:537–544

    PubMed  CAS  Google Scholar 

  76. Fu RH, Hran HJ, Chu CL et al (2011) Lipopolysaccharide-stimulated activation of murine DC2.4 cells is attenuated by n-butylidenephthalide through suppression of the NF-kappaB pathway. Biotechnol Lett 33:903–910

    Article  PubMed  CAS  Google Scholar 

  77. Ozaki Y (1992) Antiinflammatory effect of tetramethylpyrazine and ferulic acid. Chem Pharm Bull 40:954–956

    Article  PubMed  CAS  Google Scholar 

  78. Ju XD, Deng M, Ao YF et al (2010) The protective effect of tetramethylpyrazine on cartilage explants and chondrocytes. J Ethnopharmacol 132:414–420

    Article  PubMed  CAS  Google Scholar 

  79. Yeh JC, Cindrova-Davies T, Belleri M et al (2011) The natural compound n-butylidenephthalide derived from the volatile oil of Radix Angelica sinensis inhibits angiogenesis in vitro and in vivo. Angiogenesis 14:187–197

    Article  PubMed  CAS  Google Scholar 

  80. Yang TH, Jia M, Meng J, Wu H, Mei QB (2006) Immunomodulatory activity of polysaccharide isolated from Angelica sinensis. Int J Biol Macromol 39:179–184

    Article  PubMed  CAS  Google Scholar 

  81. Jung SM, Schumacher HR, Kim H, Kim M, Lee SH, Pessler F (2007) Reduction of urate crystal-induced inflammation by root extracts from traditional oriental medicinal plants: elevation of prostaglandin D(2) levels. Arthritis Res Ther 9

  82. Shibata S (2000) A drug over the millennia: pharmacognosy, chemistry, and pharmacology of licorice. Yakugaku Zasshi-J Pharm Soc Jpn 120:849–862

    CAS  Google Scholar 

  83. Lucas (ed) (1976) Nature's medicines. Melvin Powers/Wilshire Book Company, No. Hollywood, pp 89–94

    Google Scholar 

  84. Huang KH (1959) Use of liquid extract of liquorice for pulmonary tuberculosis. Shandong Yi Kan 21:17–18

    PubMed  CAS  Google Scholar 

  85. Das SK, Das V, Gulati AK, Singh VP (1989) Deglycyrrhizinated liquorice in aphthous ulcers. J Assoc Phys India 37:647

    CAS  Google Scholar 

  86. Krausse R, Bielenberg J, Blaschek W, Ullmann U (2004) In vitro anti-helicobacter pylori activity of extractum liquiritiae, glycyrrhizin and its metabolites. J Antimicrob Chemother 54:243–246

    Article  PubMed  CAS  Google Scholar 

  87. Kakegawa H, Matsumoto H, Satoh T (1992) Inhibitory effects of some natural-products on the activation of hyaluronidase and their antiallergic actions. Chem Pharm Bull 40:1439–1442

    Article  PubMed  CAS  Google Scholar 

  88. Chandrasekaran CV, Deepak HB, Thiyagarajan P et al (2011) Dual inhibitory effect of Glycyrrhiza glabra (GutGard) on COX and LOX products. Phytomedicine 18:278–284

    Article  PubMed  CAS  Google Scholar 

  89. Thiyagarajan P, Chandrasekaran CV, Deepak HB, Agarwal A (2011) Modulation of lipopolysaccharide-induced pro-inflammatory mediators by an extract of Glycyrrhiza glabra and its phytoconstituents. Inflammopharmacology 19:235–241

    Article  PubMed  CAS  Google Scholar 

  90. Kim JK, Oh SM, Kwon HS, Oh YS, Lim SS, Shin HK (2006) Anti-inflammatory effect of roasted licorice extracts on lipopolysaccharide-induced inflammatory responses in murine macrophages. Biochem Bioph Res Co 345:1215–1223

    Article  CAS  Google Scholar 

  91. Uto T, Morinaga O, Tanaka H, Shoyama Y (2012) Analysis of the synergistic effect of glycyrrhizin and other constituents in licorice extract on lipopolysaccharide-induced nitric oxide production using knock-out extract. Biochem Biophys Res Commun 417:473–478

    Article  PubMed  CAS  Google Scholar 

  92. Shin EM, Zhou HY, Guo LY et al (2008) Anti-inflammatory effects of glycyrol isolated from Glycyrrhiza uralensis (Leguminosae) in LPS-induced RAW264.7 macrophages. Int Immunopharmacol 8:1524–1532

    Google Scholar 

  93. Kim YW, Zhao RJ, Park SJ et al (2008) Anti-inflammatory effects of liquiritigenin as a consequence of the inhibition of NF-kappa B-dependent iNOS and proinflammatory cytokines production. Brit J Pharmacol 154:165–173

    Article  CAS  Google Scholar 

  94. Tanaka A, Horiuchi M, Umano K, Shibamoto T (2008) Antioxidant and anti-inflammatory activities of water distillate and its dichloromethane extract from licorice root (Glycyrrhiza uralensis) and chemical composition of dichloromethane extract. J Sci Food Agr 88:1158–1165

    Article  CAS  Google Scholar 

  95. Franceschelli S, Pesce M, Vinciguerra I et al (2011) Licocalchone-C extracted from Glycyrrhiza glabra inhibits lipopolysaccharide-interferon-gamma inflammation by improving antioxidant conditions and regulating inducible nitric oxide synthase expression. Molecules 16:5720–5734

    Article  PubMed  CAS  Google Scholar 

  96. Aly AM, Al-Alousi L, Salem HA (2005) Licorice: a possible anti-inflammatory and anti-ulcer drug. AAPS PharmSciTech 6:E74–E82

    Article  PubMed  Google Scholar 

  97. Kim KR, Jeong CK, Park KK et al (2010) Anti-inflammatory effects of licorice and roasted licorice extracts on tpa-induced acute inflammation and collagen-induced arthritis in mice. J Biomed Biotechnol. doi:10.1155/2010/709378

  98. Gujral ML, Sareen K, Phukan DP, Amma MK (1961) Antiarthritic activity of glycyrrhizin in adrenalectomised rats. Indian J Med Sci 15:624–629

    PubMed  CAS  Google Scholar 

  99. Zhang W, Lu C, Liu Z et al (2007) Therapeutic effect of combined triptolide and glycyrrhizin treatment on rats with collagen induced arthritis. Planta Med 73:336–340

    Article  PubMed  CAS  Google Scholar 

  100. Zhen QS, Ye X, Wei ZJ (1995) Recent progress in research on tripterygium - a male antifertility plant. Contraception 51:121–129

    Article  PubMed  CAS  Google Scholar 

  101. Lipsky PE, Tao XL (1997) A potential new treatment for rheumatoid arthritis: thunder god vine. Semin Arthritis Rheum 26:713–723

    Article  PubMed  CAS  Google Scholar 

  102. Wang B, Ma L, Tao X, Lipsky PE (2004) Triptolide, an active component of the Chinese herbal remedy Tripterygium wilfordii Hook F, inhibits production of nitric oxide by decreasing inducible nitric oxide synthase gene transcription. Arthritis Rheum 50:2995–3003

    Article  PubMed  CAS  Google Scholar 

  103. Tao XL, Lipsky PE (2000) The Chinese anti-inflammatory and immunosuppressive herbal remedy Tripterygium wilfordii Hook F. Rheum Dis Clin N Am 26: 29- +

    Google Scholar 

  104. Shao D, Dunlop WD, Lui EMK, Bernards MA (2008) Immunostimulatory and anti-inflammatory polysaccharides from Tripterygium wilfordii: comparison with organic extracts. Pharm Biol 46:8–15

    Article  CAS  Google Scholar 

  105. Tao XL, Cai JJ, Lipsky PE (1995) The identity of immunosuppressive components of the ethyl-acetate extract and chloroform methanol extract (T2) of tripterygium-wilfordii hook-F. J Pharmacol Exp Ther 272:1305–1312

    PubMed  CAS  Google Scholar 

  106. Mizel SB, Dayer JM, Krane SM, Mergenhagen SE (1981) Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating factor (Interleukin-1). Proc Natl Acad Sci USA-Biol Sci 78:2474–2477

    Article  CAS  Google Scholar 

  107. Maekawa K, Yoshikawa N, Du J et al (1999) The molecular mechanism of inhibition of interleukin-1 beta-induced cyclooxygenase-2 expression in human synovial cells by Tripterygium wilfordii Hook F extract. Inflamm Res 48:575–581

    Article  PubMed  CAS  Google Scholar 

  108. Tao XL, Schulze-Koops H, Ma L, Cai J, Mao YP, Lipsky PE (1998) Effects of Tripterygium wilfordii Hook F extracts on induction of cyclooxygenase 2 activity and prostaglandin E-2 production. Arthritis Rheum 41:130–138

    Article  PubMed  CAS  Google Scholar 

  109. Caterson B, Flannery CR, Hughes GE, Little CB (2000) Mechanisms involved in cartilage proteoglycan catabolism. Matrix Biol 19:333–344

    Article  PubMed  CAS  Google Scholar 

  110. Sylvester J, Liacini A, Li WQ, Dehnade F, Zafarullah M (2001) Tripterygium wilfordii Hook F extract suppresses proinflammatory cytokine-induced expression of matrix metalloproteinase genes in articular chondrocytes by inhibiting activating protein-1 and nuclear factor-kappa B activities. Mol Pharmacol 59:1196–1205

    PubMed  CAS  Google Scholar 

  111. Yu KT, Nuss G, Boyce R et al (1994) Inhibition of Il-1 release from human monocytes and suppression of streptococcal cell-wall and adjuvant-induced arthritis in rats by an extract of tripterygium-wilfordii hook. Gen Pharmacol 25:1115–1122

    Article  PubMed  CAS  Google Scholar 

  112. Chou CT (1997) The antiinflammatory effect of an extract of Tripterygium wilfordii Hook F on adjuvant-induced paw oedema in rats and inflammatory mediators release. Phytother Res 11:152–154

    Article  Google Scholar 

  113. Tao X, Ma L, Mao Y, Lipsky PE (1999) Suppression of carrageenan-induced inflammation in vivo by an extract of the Chinese herbal remedy Tripterygium wilfordii Hook F. Inflamm Res 48:139–148

    Article  PubMed  CAS  Google Scholar 

  114. Gu WZ, Brandwein SR, Banerjee S (1992) Inhibition of type-ii collagen induced arthritis in mice by an immunosuppressive extract of tripterygium-wilfordii hook-F. J Rheumatol 19:682–688

    PubMed  CAS  Google Scholar 

  115. Tao XL, Cush JJ, Garret M, Lipsky PE (2001) A phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordii Hook F in rheumatoid arthritis. J Rheumatol 28:2160–2167

    PubMed  CAS  Google Scholar 

  116. Tao XL, Younger J, Fan FZ, Wang B, Lipsky PE (2002) Benefit of an extract of Tripterygium wilfordii Hook F in patients with rheumatoid arthritis - a double-blind, placebo-controlled study. Arthritis Rheum 46:1735–1743

    Article  PubMed  Google Scholar 

  117. Krakauer T, Chen X, Howard OMZ, Young HA (2005) Triptolide attenuates endotoxin- and staphylococcal exotoxin-induced T-cell proliferation and production of cytokines and chemokines. Immunopharmacol Immunotoxicol 27:53–66

    PubMed  CAS  Google Scholar 

  118. Lin N, Sato T, Ito A (2001) Triptolide, a novel diterpenoid triepoxide from Tripterygium wilfordii Hook. f., suppresses the production and gene expression of pro-matrix metalloproteinases 1 and 3 and augments those of tissue inhibitors of metalloproteinases 1 and 2 in human synovial fibroblasts. Arthritis Rheum 44:2193–2200

    Article  PubMed  CAS  Google Scholar 

  119. Liu QY, Chen TY, Chen GY et al (2006) Immunosuppressant triptolide inhibits dendritic cell-mediated chemoattraction of neutrophils and T cells through inhibiting Stat3 phosphorylation and NF-kappa B activation. Biochem Bioph Res Co 345:1122–1130

    Article  CAS  Google Scholar 

  120. Wang Y, Jia L, Wu CY (2008) Triptolide inhibits the differentiation of Th17 cells and suppresses collagen-induced arthritis. Scand J Immunol 68:383–390

    Article  PubMed  CAS  Google Scholar 

  121. Dai SM, Nishioka K, Yudoh K (2004) Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1 beta and tumour necrosis factor alpha. Ann Rheum Dis 63:1379–1386

    Article  PubMed  CAS  Google Scholar 

  122. Lu Y, Wang WJ, Leng JH, Cheng LF, Feng L, Yao HP (2008) Inhibitory effect of triptolide on interleukin-18 and its receptor in rheumatoid arthritis synovial fibroblasts. Inflamm Res 57:260–265

    Article  PubMed  CAS  Google Scholar 

  123. Liacini A, Sylvester J, Zafarullah M (2005) Triptolide suppresses proinflammatory cytokine-induced matrix metalloproteinase and aggrecanase-1 gene expression in chondrocytes. Biochem Biophys Res Commun 327:320–327

    Article  PubMed  CAS  Google Scholar 

  124. Zhou J, Xiao C, Zhao LH et al (2006) The effect of triptolide on CD4+ and CD8+ cells in Peyer's patch of SD rats with collagen induced arthritis. Int Immunopharmacol 6:198–203

    Article  PubMed  CAS  Google Scholar 

  125. Xiao C, Lu C, Zhao LH et al (2006) The effects of triptolide on enteric mucosal immune responses of DBA/1 mice with collagen-induced arthritis. Planta Med 72:1268–1272

    Article  PubMed  CAS  Google Scholar 

  126. Gu WZ, Brandwein SR (1998) Inhibition of type II collagen-induced arthritis in rats by triptolide. Int J Immunopharmacol 20:389–400

    Article  PubMed  CAS  Google Scholar 

  127. Kim WU, Lee WK, Ryoo JW et al (2002) Suppression of collagen-induced arthritis by single administration of poly(lactic-co-glycolic acid) nanoparticles entrapping type II collagen - a novel treatment strategy for induction of oral tolerance. Arthritis Rheum 46:1109–1120

    Article  PubMed  CAS  Google Scholar 

  128. Wahl SM (1994) Transforming growth-factor-beta - the good, the bad, and the ugly. J Exp Med 180:1587–1590

    Article  PubMed  CAS  Google Scholar 

  129. Xiao C, Zhao LH, Liu ZL et al (2009) The effect of triptolide on CD4 + and CD8 + cells in the Peyer's patch of DA rats with collagen induced arthritis. Nat Prod Res 23:1699–1706

    Article  PubMed  CAS  Google Scholar 

  130. Lin N, Liu CF, Xiao C et al (2007) Triptolide, a diterpenoid triepoxide, suppresses inflammation and cartilage destruction in collagen-induced arthritis mice. Biochem Pharmacol 73:136–146

    Article  PubMed  CAS  Google Scholar 

  131. Bown D (ed) (1995) Encyclopaedia of herbs and their uses. Dorling Kindersley, London, pp 361–365

    Google Scholar 

  132. Chopra R, Nayar S, Chopra I (eds) (1986) Glossary of indian medicinal plants (Including the supplement). Council of Scientific and Industrial Research, New Delhi, pp 51–83

    Google Scholar 

  133. Diwan P, Karwande I, Singh A (1991) Anti-anxiety profile of mandukparni Centella asiatica Linn in animals. Fitoterapia 62:255–257

    Google Scholar 

  134. Boiteau P, Ratsimamanga A (1956) Asiaticoside extracted from Centella asiatica and its therapeutic uses in cicatrization of experimental and refractory wounds (leprosy, cutaneous tuberculosis and lupus). Therapie 11:125–149

    PubMed  CAS  Google Scholar 

  135. Guo JS, Cheng CL, Koo MWL (2004) Inhibitory effects of Centella asiatica water extract and asiaticoside on inducible nitric oxide synthase during gastric ulcer healing in rats. Planta Medica 70:1150–1154

    Article  PubMed  CAS  Google Scholar 

  136. George M, Joseph L, Ramaswamy (2009) Anti-allergic, anti-pruritic, and anti-inflammatory activities of centella asiatica extracts. Afr J Tradit Complement Altern Med 6:554–559

    PubMed  Google Scholar 

  137. Somchit M, Sulaiman M, Zuraini A et al (2004) Antinociceptive and antiinflammatory effects of Centella asiatica. Indian J Pharmacol 36:377–380

    Google Scholar 

  138. Hussin M, Abdul-Hamid A, Mohamad S, Saari N, Ismail M, Bejo MH (2007) Protective effect of Centella asiatica extract and powder on oxidative stress in rats. Food Chem 100:535–541

    Article  CAS  Google Scholar 

  139. Hashim P, Sidek H, Helan MHM, Sabery A, Palanisamy UD, Ilham M (2011) Triterpene composition and bioactivities of centella asiatica. Molecules 16:1310–1322

    Article  PubMed  CAS  Google Scholar 

  140. Won JH, Shin JS, Park HJ et al (2010) Anti-inflammatory effects of madecassic acid via the suppression of NF-kappaB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Med 76:251–257

    Article  PubMed  CAS  Google Scholar 

  141. Liu M, Dai Y, Yao XJ et al (2008) Anti-rheumatoid arthritic effect of madecassoside on type II collagen-induced arthritis in mice. Int Immunopharmacol 8:1561–1566

    Article  PubMed  CAS  Google Scholar 

  142. Li HZ, Gong X, Zhang L et al (2009) Madecassoside attenuates inflammatory response on collagen-induced arthritis in DBA/1 mice. Phytomedicine 16:538–546

    Article  PubMed  CAS  Google Scholar 

  143. Koch E (2001) Extracts from fruits of saw palmetto (Sabal serrulata) and roots of stinging nettle (Urtica dioica): Viable alternatives in the medical treatment of benign prostatic hyperplasia and associated lower urinary tracts symptoms. Planta Medica 67:489–500

    Article  PubMed  CAS  Google Scholar 

  144. Anonymous ed. (2003) Urticae folium/herba. In: European scientific cooperative on phytotherapy. Thieme, Stuttgart, New York: ESCOP Monographs. pp. 521–527 pp

  145. Akbay P, Basaran AA, Undeger U, Basaran N (2003) In vitro immunomodulatory activity of flavonoid glycosides from Urtica dioica L. Phytother Res 17:34–37

    Article  PubMed  CAS  Google Scholar 

  146. Obertreis B, Ruttkowski T, Teucher T, Behnke B, Schmitz H (1996) Ex-vivo in-vitro inhibition of lipopolysaccharide stimulated tumor necrosis factor-a and interleukin-1 beta secretion in human whole blood by Extractum Urticae dioicae foliorum. Arzneim-Forsch/Drug Res 46:389–394

    CAS  Google Scholar 

  147. Harput US, Saracoglu I, Ogihara Y (2005) Stimulation of lymphocyte proliferation and inhibition of nitric oxide production by aqueous Urtica dioica extract. Phytother Res 19:346–348

    Article  PubMed  Google Scholar 

  148. Barnes PJ, Larin M (1997) Mechanisms of disease - nuclear factor-kappa b - a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066–1071

    Article  PubMed  CAS  Google Scholar 

  149. Riehemann K, Behnke B, Schulze-Osthoff K (1999) Plant extracts from stinging nettle (Urtica dioica), an antirheumatic remedy, inhibit the proinflammatory transcription factor NF-kappa-B. FEBS Lett 442:89–94

    Article  PubMed  CAS  Google Scholar 

  150. Lanzavecchia A, Sallusto F (2001) Regulation of T cell immunity by dendritic cells. Cell 106:263–266

    Article  PubMed  CAS  Google Scholar 

  151. Broer J, Behnke B (2002) Immunosuppressant effect of IDS 30, a stinging nettle leaf extract, on myeloid dendritic cells in vitro. J Rheumatol 29:659–666

    PubMed  CAS  Google Scholar 

  152. Schulze-Tanzil G, de Souza P, Behnke B, Klingelhoefer S, Scheid A, Shakibaei M (2002) Effects of the antirheumatic remedy Hox alpha - a new stinging nettle leaf extract - on matrix metalloproteinases in human chondrocytes in vitro. Histol Histopathol 17:477–485

    PubMed  CAS  Google Scholar 

  153. Semerano L, Assier E, Boissier MC (2012) Anti-cytokine vaccination: a new biotherapy of autoimmunity. Autoimmun Rev 12: http://dx.doi.org/10.1016/j.autrev.2012.02.003

  154. Nakken B, Munthe LA, Konttinen YT, Sandberg AK, Szekanecz A, Alex P, Szodoray P (2011) B cells and their targeting in rheumtoid arthritis - current concepts and future perspectives. Autoimmun Rev 11:28–34

    Article  PubMed  CAS  Google Scholar 

  155. Rosenblum H, Amital H (2011) Anti-TNF-therapy: safety aspects of taking the risk. Autoimmun Rev 10:563–568

    Article  PubMed  Google Scholar 

  156. Fillipini M, Bazzani C, Favalli EG et al (2010) Efficacy and safety of anti-tumour necrosis factor in elderly patients with rheumatoid arthrits: an observational study. Clin Rev Allergy Immunol 38:90–96

    Article  CAS  Google Scholar 

  157. Guo KJ, Xu SF, Yin P, Wang W, Song XZ, Liu HF, Xu JQ, Zoccarato I (2011) Active components of common traditional Chinese medicine decoctions have antioxidant function. J Anima Sci 89:3107–3115

    Article  CAS  Google Scholar 

  158. Guimaraes R, Barros L, Carvalho AM, Ferreira IC (2011) Infusions and decoctions of mixed herbs used in folk medicine: synergism in antioxidant potential. Phytother Res 25:1209–1214

    Article  PubMed  Google Scholar 

  159. Hayashi K, Shimura K, Makino T, Mizukami H (2010) Comparison of the contents of kampo decoctions containing ephedra herb when prepared simply or by re-bioling according to the traditional theory. J Nat Med 54:70–74

    Article  CAS  Google Scholar 

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Acknowledgements

This project was supported in part by grants from Prof Francis SK Lau Research Fund and PuraPharm International awarded to Prof. A Lau.

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Correspondence to Allan S. Y. Lau.

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Cindy L. H. Yang and Terry C. T. Or contributed equally to this work.

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Yang, C.L.H., Or, T.C.T., Ho, M.H.K. et al. Scientific Basis of Botanical Medicine as Alternative Remedies for Rheumatoid Arthritis. Clinic Rev Allerg Immunol 44, 284–300 (2013). https://doi.org/10.1007/s12016-012-8329-8

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