Journal of Ethnopharmacology 111 (2007) 322–328 Treatment with total alkaloids from Radix Linderae reduces inflammation and joint destruction in type II collagen-induced model for rheumatoid arthritis Chan Wang a , Yue Dai a,∗ , Jian Yang a , Guixin Chou b , Changhong Wang b , Zhengtao Wang b a Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical University, 1 Shennong Road, Nanjing 210038, China b Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China Received 14 November 2005; received in revised form 10 May 2006; accepted 23 November 2006 Available online 13 December 2006 Abstract Radix Linderae, the dry roots of Lindera aggregata (Sims) Kosterm., is frequently used in traditional Chinese medicine. It contains alkaloids, volatile oils and sesquiterpene esters. In the present study, we investigated the therapeutic potential and underlying mechanisms of the total alkaloids from Radix Linderae (TARL) on collagen II (CII)-induced arthritis (CIA) in mice. TARL (50, 100 and 200mg/kg), orally administered on the same day of an antigen challenge for 20 consecutive days, alleviated disease severity in a dose-dependent manner but did not significantly affect body weights. The TARL treatment reduced the serum level of anti-CII IgG and suppressed the delayed type hypersensitivity evaluated by its effect against CII-induced ear swelling. TARL also protected joint destruction based on the evidence of reducing the histopathological scores. Furthermore, TARL suppressed CII- and concanavalin A-stimulated lymphocyte proliferation in popliteal lymph nodes, where are close to the affected joints in CIA. These data suggest that TARL is a potential therapeutic agent for rheumatoid arthritis that suppresses inflammation and protects joints from destruction. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Radix Linderae; Alkaloid; Collagen; Arthritis 1. Introduction Rheumatoid arthritis (RA) is a systemic and chronic inflam- matory autoimmune disease affecting 0.5–1% of the entire human population. It has been well characterized by a symmet- ric polyarthritis affecting several joints, accompanying synovial hyperplasia, consequently leading to joint destruction and defor- mity, loss of function, and reduced quality of life (Ono et al., 2004). Although the exact pathogenesis and etiology of the disease remain unclear, the main pathological changes have Abbreviations: TARL, total alkaloids from Radix Linderae; CII, type II collagen; CIA, collagen II-induced arthritis; RA, rheumatoid arthritis; DEX, dexamethasone; GTW, tablets of glucosides from roots of Tripterygium wil- fordii Hook.f.; IgG, immunoglobulin G; DTH, delayed type hypersensitivity; H&E, hematoxylin and eosin; Con A, concanavalin A; MTT, 3-[4,5-dimethyl- 2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide; DMSO, dimethyl sulfoxide ∗ Corresponding author. Tel.: +86 25 85391258; fax: +86 25 85301528. E-mail address: yuedaicpu@hotmail.com (Y. Dai). been defined, such as abnormal immunity, chronic synovitis, inflammatory cell infiltration, pannus formation, destruction of cartilage and bone erosion (Remmers et al., 2002; Lu et al., 2002; Backlund et al., 2002). The development of RA involves a complex interplay of several types of cells, including B and T lymphocytes, macrophages, fibroblast-like synoviocytes, endothelial cells and dendritic cells (Panayi, 1997; Firestein, 2003). Notably, B and T cells play critical roles in the patho- genesis (Andrew, 2002; Leandro et al., 2002a,b). Currently, the clinical need for effective treatment of RA remains unmet and more novel drugs are highly demanded. Lindera aggregata (Sims) Kosterm. (L. strychnifolia Vill) belongs to the Lauraceae family and can be found in the parts of southern China, Japan and southeastern Asia. Radix Linderae, the dry roots of Lindera aggregata, is usually used in traditional Chinese medicine for treating several symptoms including chest and abdomen pain, indigestion, regurgitation, cold hernia and frequent urination (Jiangsu New Medical College, 1979). The extracts of Radix Linderae have been reported to possess 0378-8741/$ – see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2006.11.031