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Antiin‰ammatory activities of heat-treated Cassia alata leaf extract and kaempferol 3-O-gentiobioside(K3G) isolated from C. alata as an abundant ‰avonoid glycoside were studied by comparing their activities with the activities of sun-dried C. alata leaf extract. We observed strong inhibitory eŠects on Concanavalin A-induced histamine release from rat peritoneal exudate cells both in the extracts of heat-treated and sun-dried C. alata leaves. Furthermore, the heattreated leaf extract exhibited stronger inhibitory eŠects than the eŠects of the sun-dried leaf extract at low concentrations in the studies of Concanavalin A-induced histamine release, 5-lipoxygenase inhibition, and also inhibition of cyclooxygenases (COX-1 and COX-2), whereas K3G showed weak inhibitory eŠects on Concanavalin A-induced histamine release, 5-lipoxygenase, and COX-1. No anti-hyaluronidase eŠect was detected in any of the materials tested.

Earlier studies have reported the efficacy of type II collagen (C II) in treating rheumatoid arthritis (RA). However, a few studies have investigated the ability of the antigenic collagen to induce oral tolerance, which is defined as active nonresponse to an orally administered antigen. We hypothesized that water-soluble undenatured C II had a similar effect as C II in RA. The present study was designed to examine the oral administration of a novel, water-soluble, undenatured C II (commercially known as NEXT-II) on collagen-induced arthritis (CIA) in mice. In addition, the underlying mechanism of NEXT-II was also identified. After a booster dose (collagen-Freund's complete adjuvant), mice were assigned to control CIA group, or NEXT-II treatment group, to which saline and NEXT-II were administered, respectively. The arthritis index in the NEXT-II group was significantly lower compared with the CIA group. Serum IL-6 levels in the NEXT-II group were significantly lower compared with the CIA group, while serum IL-2 level was higher. Furthermore, oral administration of NEXT-II enhanced the proportion of CD4+CD25+T (Treg) cells, and gene expressions of stimulated dendritic cells induced markers for regulatory T cells such as forkhead box p3 (Foxp3), transforming growth factor (TGF)-β1, and CD25. These results demonstrated that orally administered water-soluble undenatured C II (NEXT-II) is highly efficacious in the suppression of CIA by inducing CD4+CD25+ Treg cells.

Members of the genus Phyllanthus (Euphorbiaceae) include some 500 species and are widespread in temperate and tropical climates. Phyllanthus species have attracted the attention of researchers for their hepatoprotective properties; an aqueous extract of Phyllanthus amarus was demonstrated to exert antihepatitis B virus effects to varying degrees. 1,2) In 2003, various constituents isolated from Phyllanthus species were screened for anti-human hepatitis B virus in vitro. 3)However, little or no attention has been paid to constituents isolated from Phyllanthus niruri L. for other biological studies, thus prompting us to isolate constituents that might have antiplatelet aggregatory effects, as previously detected in the crude extract of P. niruri.4) Furthermore, we isolated methyl brevifolincarboxylate (compound 1) as a constituent responsible for the antiplatelet aggregatory effects. 5)Interestingly, 1 (Fig. 1) was also isolated from Phyllanthus urinaria L.6) and other Phyllanthus species, although no mention was made of its biological activities.7) Therefore, we investigated the vasorelaxant effects of 1 on rat aortic rings in connection with the receptor-operated Ca 2ϩ channel. MATERIALS AND METHODSPlant Material Dried P. niruri leaves were obtained from PT Haldin Pacific Semesta (Jakarta, Indonesia).Chemicals Norepinephrine hydrochloride (NE), nicardipine, ethyleneglycol-bis-(b-aminoethyl ether)-tetraacetic acid (EGTA), and acetylcholine chloride (Ach) were purchased from Sigma Chemical Co. (St. Louis, MO, U.S.A.).Compound 1 (Methyl Brevifolincarboxylate) The extraction, isolation and confirmation of 1 was described in our previous study. 5)Isolation of Rat Aortic Strips Male Wistar rats weighing 240-300 g were killed by bleeding from the carotid arteries under anesthetization. A section of the thoracic aorta between the aortic arch and the diaphragm was removed and placed in oxygenated, modified Krebs-Henseleit solution (KHS) composed of (mM): NaCl 118.0; KCl, 4.7; NaHCO 3 , 25.0; CaCl 2 , 1.8; NaH 2 PO 4 , 1.2; MgSO 4 , 1.2; and glucose, 11.0. The aorta was cleaned by removing loosely attached fat and connective tissue and cut into 3-mm lengths. To detach the endothelium, endothelial cells on each strip were removed by gentle rubbing of the endothelial surface with a disposable cotton applicator. The tissue was placed in a welloxygenated (95% O 2 , 5% CO 2 ) bath of KHS 10 ml at 37°C with the ringed aorta connected to a tissue holder and to a force-displacement transducer (Nihon Kohden, TB-611T). The tissue was equilibrated for 60 min under a resting tension of 1.0 g. During this time the KHS in the tissue bath was replaced every 20 min.Experimental Protocol Experiments were performed according to method in the previous studies.8-10) After equilibration, each aortic ring was contracted by treatment with 3ϫ10 Ϫ7 M NE. The presence of functional endothelial cells was confirmed by demonstrating relaxation with response to 10 Ϫ5 M Ach, and tissues indicating 80% relaxation of the aortic ring were regarded as tiss...

We previously detected compounds with vasorelaxant effects, such as methyl brevifolincarboxylate, from the leaves of Phyllanthus niruri, 2) ebricoic acid from the extract of Phellinus givus, 3) and forsythiaside from the fruit of Forsythia suspensa. 4) In our attempts to search for compounds with vasorelaxant effects from various plants, in the present study we isolated three constituents from the heartwood of Acer nikoense (Aceraceae): A. nikoense is a Japanese folk medicine used as a remedy primarily for hepatic disorders. Constituents previously isolated from the bark and leaves are diarylheptanoids, phenolic compounds, and tannin, 5) and their bioactivities such as antiinflammatory effects 6) and protective effects against hepatic injury 7) were also reported. First, we found that the organic extract from the heartwood of A. nikoense showed vasorelaxant effects on rat aorta with or without endothelium. Second, scopoletin (1), cleomiscosin A (2), and aquillochin (3) were isolated as major constituents using SiO 2 chromatography. 8) Moreover, the results of our literature search revealed that 1 had vasorelaxant effects by inhibiting intracellular calcium mobilization from norepinephrine (NE)-sensitive stores.9) Consequently, we focused on the vasorelaxant effects of 2 and 3 isolated from the organic extract of the heartwood of A. nikoense and investigated their effects in comparison with that of 1, which was used as a positive control in the present study. MATERIALS AND METHODSPlant Material Dried A. nikoense heartwood was obtained from the Medicinal Plant Garden of Hoshi University, and identified by one of the authors (S.N.).Chemicals NE, nicardipine, ethyleneglycol-bis-(b-aminoethyl ether)-tetraacetic acid (EGTA), and acetylcholine chloride (Ach) were purchased from Sigma Chemical (St. Louis, MO, U.S.A.). Authentic samples of 1-3 were obtained from one of the authors (S.N.) (Fig. 1).Extraction and Isolation Dried A. nikoense heartwood (62.5 g) was extracted with MeOH, and the extract solution was evaporated in vacuo. The residual extract (5.0 g) was further extracted successively with diethyl ether, ethyl acetate, and water. Then the extracts were evaporated in vacuo to obtain extracts of 0.51 g, 0.82 g, and 2.07 g from the successivesolvents. Among the extracts tested for vasorelaxant effects on rat aorta, the ether extract exhibited the most potent relaxant effects on NE-induced aortic contraction. Compounds 1, 2, and 3 of A. nikoense were found in the diethyl ether fraction. 8)Assay for Vasorelaxation Experimental studies using animals were conducted in accordance with the Guiding Principles for the Care and Use of Laboratory Animals, Hoshi University, and under the supervision of the Committee on Animal Research of Hoshi University, which is accredited by the Ministry of Education, Science, Sports Culture and Technology of Japan. Isolation of Rat Aortic StripsThe preparation of aortic rings and measurement of tension were performed as previously described.2-4) In brief, male Wistar rats weighing 240-340...

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