The alkaloid sinomenine (7,8-didehydro-4-hydroxy-3,7-dimethoxy-17-methylmorphinan-6-one, SIN) is a bioactive alkaloid derived from the Chinese medicinal plant, Sinomenium acutum REHDER & E. H. WILSON (Family Menispermaceae). Chinese doctors have utilized this plant to treat rheumatic and arthritic diseases for over one thousand years. 1)Clinical trials done in China demonstrated that the pure alkaloid SIN had significant therapeutic effects for the patients who suffered from rheumatoid arthritis (RA). 2)RA has been classified as a chronic immune-mediated disease that exhibits overlapping manifestation of inflammatory, abnormal cellular and hormonal immune responses with synovial hyperplasia. SIN had been shown to inhibit lymphocytes proliferation in vitro 3) and improve adjuvant arthritis (AA) and antigen-induced arthritis (AIA) in rats. 4) Recently, SIN was observed inhibiting the expression of cytokines, tumor necrosis factor-alpha (TNF-a) and gamma-interferon (IFN-g), as well as the activity of nuclear factor-kappaB (NF-kB) in adjuvant arthritis (AA) rats. Furthermore SIN has suppressive effects on both Th1 and Th2 immune responses, and Th1 response is more preferentially suppressed by the SIN compared to Th2 response in mice. 5)Experimental autoimmune encephalomyelitis (EAE) is a CD4 ϩ T cell-mediated inflammatory demyelinating disease of the central nervous system (CNS) that is commonly used as a model of multiple sclerosis (MS).6) The generally accepted concept of pathogenesis in both EAE and MS involves episodes of disease onset that correlate with infiltration of activated leukocytes into the CNS, initiation of effector functions through the cytokine network, and production of histopathological lesions that result in neurological deficiencies.7) Proliferation of T cells specific for the immunizing antigen and that these antigen-specific cells produce Th1-type cytokines and transfer are believed to play a key role in this process. 8) In Lewis rats, MBP derived from guinea pig myelin is highly encephalitogenic. This is because MBP contain amino acid residues in the dominant encephalitogenic epitope for the Lewis rat, myelin basic protein (MBP) fragment 68-82 (MBP 68-82 ). MS-like immunopathology can be reproduced in Lewis rats. [9][10][11] As T cell mediated disorders including AA and EAE, some drugs such as immunoglobulins and an anti-rheumatic drug (TAK-603) protect against arthritis and EAE and that this beneficial effect is associated with a decreased proliferation of T cells specific for the immunizing antigen.12,13) For the mechanism of the anti-inflammatory and anti-rheumatic effects of SIN, we explore the effects of SIN on EAE. MATERIALS AND METHODS Experimental AnimalsFemale Lewis rats (Vital River, Beijing, China) were maintained in the SPF animal facility at Laboratory Animal Center of Nanjing Medical University under conventional conditions with laboratory chow and water accessible ad libitum. Animals were housed three or four per cage for at least 1 week prior to study. All animal procedures w...

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Scutellaria baicalensis Georgi is one of the important medicinal herbs widely used for the treatment of various inflammatory diseases in Asia. Baicalin (BA) is a bioactive anti-inflammatory flavone found abundantly in Scutellaria baicalensis Georgi. To explore the therapeutic potential of BA, we examined the effects of systemic administration of the flavone (5 and 10 mg/kg, ip) on relapsing/remitting experimental autoimmune encephalomyelitis (EAE) induced by proteolipid protein 139-151 in SJL/J mice, an experimental model of multiple sclerosis. The mice treated with PBS or BA at day -1 and for 3 consecutive days were observed daily for clinical signs of disease up to 60 days after immunization. In the PBS-EAE group, neurological scores were: incidence (100%), mean day of onset (8.0 ± 0.73), peak clinical score (3.0 ± 0.4), and cumulative disease index (141.8 ± 19.4). In the BA-EAE group (5 or 10 mg kg -1 day -1 , respectively), incidence (95 or 90%), mean day of onset (9.0 ± 0.80 or 9.2 ± 0.75; P = 0.000), peak clinical score (2.2 ± 0.3 or 2.0 ± 0.3; P = 0.000), and cumulative disease index (75.9 ± 10.1 or 62.9 ± 8.4; P = 0.000) decreased, accompanied by the histopathological findings (decrease of dense mononuclear infiltration surrounding vascellum) for the spinal cord. Additionally, the in vitro effects of BA (5, 10, and 25 µM) on mononuclear cells collected from popliteal and inguinal lymph nodes of day-10 EAE mice were evaluated using an MTT reduction assay for cell proliferation, and ELISA to measure IFN-γ and IL-4 cytokines. Compared with the control group, BA caused an increase in IL-4 (EAE-DMSO: 3.56 ± 0.42 pg/mL vs EAE-BA (5, 10, and 25 µM): 6.03 ± 1.1, 7.83 ± 0.65, 10.54 ± 1.13 pg/mL, respectively; P < 0.001); but inhibited IFN-γ (EAE-DMSO: 485.76 ± 25.13 pg/mL vs EAE-BA (5, 10, and 25 µM): 87.08 ± 9.24, 36.27 ± 5.44, 19.18 ± 2.93 pg/mL, respectively; P < 0.001) and the proliferation of mononuclear cells (EAE-DMSO: 0.73 ± 0.021 vs EAE-BA (5, 10, and 25 µM): 0.41 ± 0.015, 0.31 ± 0.018, 0.21 ± 0.11, respectively; P < 0.001) in a concentration-dependent manner. The results suggest that BA might be effective in the treatment of multiple sclerosis.