Bioactive Constituents from Chinese Natural Medicines. XX. Inhibitors of Antigen-Induced Degranulation in RBL-2H3 Cells from the Seeds of <i>Psoralea corylifolia</i>

Abstract

The Legminosae plant, Psoralea corylifolia L., is widely distributed from India to Southeast Asian countries. The seeds of this plant have been used as a tonic, to treat uterine hemorrhage, and as a coronary vasodilatory agent in Chinese traditional medicine. [2][3][4][5] Previously, several meroterpenoid [6][7][8][9][10][11] and flavonoid [12][13][14][15][16][17][18][19] constituents were isolated from this natural medicine. In addition, biological studies to determine its antioxidative, 20) antiplatelet, 21) and DNA polymerase and topoisomerase II inhibitory activities 22) were also reported. In the course of our characterization studies on the bioactive constituents in Chinese natural medicines, 1,[23][24][25][26][27][28][29][30][31][32][33][34] the ethyl acetate (EtOAc)-soluble fraction of the methanolic extract from this natural medicine was found to inhibit antigen-IgE-induced degranulation in RBL-2H3 cells. From this active fraction, two meroterpene constituents (1, 2) 35) were newly isolated together with 14 known constituents. This paper deals with the isolation and structural confirmation of the two compounds (1, 2) as well as the inhibitory effects of the constituents from P. corylifolia on antigen-induced degranulation in RBL-2H3 cells.The seeds of P. corylifolia were extracted with methanol under reflux. The methanolic extract was partitioned into an EtOAc-H 2 O (1 : 1, v/v) mixture to furnish the EtOAc-and H 2 O-soluble fractions. The EtOAc-acetate-soluble fraction inhibited antigen-induced degranulation in RBL-2H3 cells [inhibition (%): 39.3Ϯ2.5 (pϽ0.05) at 30 mg/ml], but the H 2 O-soluble fraction did not [inhibition (%): 6.3Ϯ4.4 at 30 mg/ml]. The EtOAc-soluble fraction was subjected to ordinary and reverse-phase silica gel column chromatography and finally HPLC to furnish 1 (0.011% from the natural medicine), 2 (0.009%), bakuchiol 6-10) (3, 8.19%) [d 6.75, 7.21 (2H each, both d, Jϭ8.5 Hz,11,13,10,]. As shown in Fig. 1, the 1 H-1 H correlation spectroscopy ( 1 H-1 H COSY) experiment on 1 indicated the presence of partial structures in bold lines. In the heteronuclear multiple-bond correlations (HMBC) experiment on 1, long-range correlations were observed between the following protons and carbons (1-H 3 , 18-H 3 and 2-C; 1-H 3 , 2-H, 4-H 2 , 7-H, 8-H, 18-H 3 and 3-C; 2-H and 4-C; 15-H 3 and 5-C; 5-H 2 , 7-H 2 , 15-H 3 , 16-H, 17-H 2 and 6-C; 15-H 3 and 7-C; 10,14-H and 8-C; 8-H, 11,13-H and 9-C; 8-H and 10,14-C; 10,14-H and 12-C; 16-H and 15-C; 15-H 3 and 16-C), as shown in Fig. 1. Thus the connectivities of quaternary carbons (3, 6, 9, 12-C) in 1 were clarified and the planar structure of 1 was elucidated. Next, the stereostructure of 1 was characterized in a nuclear Overhauser enhancement spectroscopy (NOESY) experiment, which showed NOE correlations between the following proton pairs (4b-H, 5b-H and 15-H 3 ; 7a-H and 10,14-H, 15-H 3 , 16-H; 8-H and 10,14-H, 15-H 3 ), as shown in Fig. 1 The

Inhibitory Effects of Bakuchiol, Bavachin, and Isobavachalcone Isolated fromPiper longumon Melanin Production in B16 Mouse Melanoma Cells

“…[17][18][19] 2 has been reported to show an antiallergic effect, 20) and 3 has been reported to show antioxidative and antiplatelet activities. 17,21) Recently, 2 and 3 were found to inhibit the activity of acyl-CoA: cholesterol acyltransferase (ACAT), 22) but, their inhibitory activities against melanin biosynthesis have not been reported before.…”

Bioactive Constituents from Chinese Natural Medicines. XXXII. Aminopeptidase N and Aldose Reductase Inhibitors from Sinocrassula indica: Structures of Sinocrassosides B4, B5, C1, and D1-D3

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During the course of our studies on bioactive constituents from Chinese natural medicines, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] we found that the methanolic extract of the whole plant of Sinocrassula indica (Crassulaceae) inhibited the increase of serum glucose levels in both sucrose-and glucose-loaded rats.2) From the methanolic extract, 15 acylated flavonol glycosides, sinocrassosides A 1 -A 12 and B 1 -B 3 (7-21), were isolated together with 11 flavonoids (22-32), 2 megastigmanes (33, 34), Lphenylalanine, and guanosine [1][2][3] and several fravonoid constituents were found to show hepatoprotective effects on Dgalactosamine-induced cytotoxicity in primary cultured mouse hepatocytes.1) As a continuing study on the constituents from S. indica, we additionally isolated six new flavonol glycosides, sinocrassosides B 4 (1), B 5 (2), C 1 (3), D 1 (4), D 2 (5), and D 3 (6). This paper deals with the isolation and structure elucidation of 1-6 as well as aminopeptidase N and aldose reductase inhibitory activities of the isolated compounds.

The methanolic extract from the dried whole plant of S. indica (7.7% from the dried plant) was partitioned into an EtOAc-H 2 O (1 : 1, v/v) mixture to furnish an EtOAc-soluble fraction (2.5%) and an aqueous phase.

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“…(28), together with L-rhamnose and D-glucose, which were identified by HPLC analysis. [1][2][3][4][5][6][7][9][10][11][12][13] The 1 H-(DMSO-d 6 , Table 1) and 13 C-NMR (Table 2) spectra 1a, which were assigned by various NMR experiments, showed signals assignable to meta-coupled aromatic protons [d 6.47, 6.83 (1H each, both d, Jϭ1.8 Hz,6,] and orthoand meta-coupled ABC-type protons [d 6.85 (1H, d, 1438 Vol. 56, No.…”

“…During the course of our studies on bioactive constituents from Chinese natural medicines, [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] we found that the methanolic extract of the whole plant of Sinocrassula indica (Crassulaceae) inhibited the increase of serum glucose levels in both sucrose-and glucose-loaded rats.…”

“…[1][2][3] Acid hydrolysis of 1a with 1.0 M HCl liberated quercetin (28), together with L-rhamnose and D-glucose, which were identified by HPLC analysis. [1][2][3][4][5][6][7][9][10][11][12][13] The 1 H-(DMSO-d 6 , Table 1) and 13 C-NMR (Table 2) August 7, 2008 Jϭ8. 2 Table 1) and 13 …”