Cytotoxic Lavandulyl Flavanones from Sophora flavescens

Kang, Taehee; Jeong, Su Jin; Ko, Won Gil; Kim, Na Young; Lee, Byung‐Hoon; Inagaki, Michio; Miyamoto, Tomofumi; Higuchi, Ryota; Kim, Youn Chul

doi:10.1021/np990567x

Cited by 127 publications

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“…We report here the isolation and the structure elucidation of a flavanone, naringenin 5-methyl ether (1), a flavanone glycoside, pinocembrin-7-glycoside (2) and vomifoliol (3) from the ethyl acetate aerial part extract of Echiochilon fruticosum. The structures were established on the basis of 2D NMR spectroscopic experiments and by comparison of the NMR data with literature values [7][8][9][10]. (Table I) with those of the literature [7][8] thus confirmed the S-configuration of C 2 .…”

Section: Introductionmentioning

confidence: 55%

“…The structures were established on the basis of 2D NMR spectroscopic experiments and by comparison of the NMR data with literature values [7][8][9][10]. (Table I) with those of the literature [7][8] thus confirmed the S-configuration of C 2 . H-NMR spectrum with that of 1 (Table I) permitted us to note on the one hand, the presence of all proton signals of 1 with the exception of that of the methoxyl group at 3.82 ppm, and on the other, one additional signal at δ 7.39 (m, H 4' ).…”

Section: Introductionmentioning

confidence: 55%

“…The attachment of a glucose unit at C 7 (δ 165.6 ppm) was apparent from the heteronuclear H 1'' -C 7 HMBC connectivity ( Figure 2). As in compound 1, the absolute configuration of C 2 was deduced from the comparison of H 2 chemical shifts of 2 with the reported literature values [7][8]. (Table 1) with those reported in literature [9][10] led to its identification as vomifoliol.…”

Section: Introductionmentioning

confidence: 69%

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Isolation and Structure Elucidation of a Flavanone, a Flavanone Glycoside and Vomifoliol from Echiochilon Fruticosum Growing in Tunisia

et al. 2004

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Section: Introductionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 69%

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Isolation and Structure Elucidation of a Flavanone, a Flavanone Glycoside and Vomifoliol from Echiochilon Fruticosum Growing in Tunisia

et al. 2004

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“…The root of S. flavescens is an oriental herbal medicine, used as a diuretic and for the treatment of jaundice, leucorrhea, carbuncles, pyogenic infections of the skin, scabies, enteritis, and dysentery. Recently, biological and pharmacological studies have revealed anti-inflammatory, 12) and antitumor, 13) antioxidant 14) for the crude extracts or isolated constituents of S. flavescens. In particular, MK, the main component of S. flavescens, was reported that had the antioxidant activity, it results in the down-regulation of glutamate-induced neurotoxicity via the induction of heme oxygenase-1 (HO-1).…”

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confidence: 99%

(2S)-2′-Methoxykurarinone Inhibits Osteoclastogenesis and Bone Resorption through Down-Regulation of RANKL Signaling

Kim

et al. 2014

Biological & Pharmaceutical Bulletin

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(2S)-2′-Methoxykurarinone (MK), a compound isolated from the roots of Sophora flavescens, has various physiological properties, such as anti-inflammatory, antipyretic, antidiabetic, and antineoplastic effects. However, the effect of S. flavescens-derived MK on osteoclastogenesis remains unknown. Therefore, we examined the effect and mechanism of action of MK on receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorption. MK inhibited osteoclast differentiation in bone marrow cell-osteoblast cocultures but did not affect the RANKL-to-osteoprotegerin ratio induced by osteoclastogenic factors in osteoblasts. MK also inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages in a dose-dependent manner, without cytotoxicity. Pretreatment with MK significantly suppressed the Akt, p38, c-Jun N terminal kinase (JNK), c-Fos, and nuclear factor of activated T cells c1 (NFATc1) pathways and inhibited the bone-resorbing activity of mature osteoclasts. These results collectively suggest that MK inhibits osteoclast differentiation and bone resorption through RANKL-induced mitogen-activated protein kinases (MAPKs) and c-Fos-NFATc1 signaling pathways. Key words (2S)-2′-methoxykurarinone; bone resorption; osteoclast; osteoporosis; receptor activator of nuclear factor-κB ligand (RANKL)Osteoclasts, which originate from hematopoietic cells of the monocyte macrophage lineage, play a crucial role in bone remodeling.1,2) The bone loss in many important skeletal disorders, such as osteoporosis, rheumatoid arthritis, and bone metastases, occurs mainly because of increased osteoclast activity.3,4) Bone formation is regulated by osteoblasts, which also express the receptor activator of nuclear factor kappa-B ligand (RANKL), which has been identified as a member of the tumor necrosis factor (TNF) superfamily and regulates osteoclast differentiation through cell-to-cell contact.3,4) Osteoblasts and stromal cells also produce a soluble decoy receptor for RANKL, osteoprotegerin (OPG), which inhibits osteoclast formation by interrupting the interaction between RANKL and RANK, resulting in an increase in bone density and bone volume.1,2) Several osteoclastogenic factors, such as 1,25-dihydroxyvitamin D 3 (VitD 3 ) and proinflammatory cytokines, can stimulate osteoclast formation by up-regulating the ratio of RANKL to OPG in osteoblasts or stromal cells.

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“…Sophora flavescens, a leguminous plant, produces diverse 8-lavandulylated flavanones, such as sophoraflavanone G (SFG), kurarinone and kushenol I (Hatayama and Komatsu 1971;Wu et al 1985;Kuroyanagi et al 1999;Kang et al 2000), which are exclusively accumulated in the cork layer of intact roots (Yamamoto et al 1992). Recent pharmaceutical studies showed that the lavandulyl side chain was essential for the antitumor activity and phospholipase-Cg1-inhibition activity of flavonoids isolated from this plant, and that SFG had the most potent activities (Lee et al 1997;Ko et al 2000).…”

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Metabolism of administered (2RS)-naringenin in flavonoid-producing cultured cells of Sophora flavescens

Yamamoto

Kuribayashi

Seshima

et al. 2004

Plant Biotechnology

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Cultured cells of Sophora flavescens produce (2S)-naringenin-derived prenylated flavanone sophoraflavanone G and liquiritigenin-derived trifolirhizin 6Ј-O-malonate. The regulation of flavonoid biosynthesis was examined by analyzing the metabolites produced in the cultured cells fed (2RS)-naringenin. The amount of sophoraflavanone G in cells fed 0.1 or 0.3 mM (2RS)-naringenin was two-fold that in control cells, although the conversion ratio was only 5 to 10% of the administered (2S)-naringenin. On the other hand, (2R)-naringenin, which does not occur naturally, was efficiently converted into its 4Ј,7-di-O-b-D-glucoside. (2S)-Naringenin prenylation activity was higher at the logarithmic growth stage. The cells fed (2RS)-naringenin at a lower concentration (below 0.1 mM), accumulated sophoraflavanone G as the main prenylated flavanone. In contrast, cells fed 0.3 mM (2RS)-naringenin accumulated 8-prenylnaringenin and leachianone G, intermediates of sophoraflavanone G in large amounts. Accumulation of trifolirhizin 6Ј-O-malonate was suppressed by the addition of naringenin.Key words: Naringenin; (2R)-naringenin 4Ј,7-di-O-b-D-glucoside; Sophora flavescens; sophoraflavanone G. Original PaperCopyright © 2004 The Japanese Society for Plant Cell and Molecular Biology precursor of SFG but not TM, to the culture medium, and examined its effect on the production of these secondary metabolites. Materials and methods General(2RS)-Naringenin was purchased from Nacalai Tesque (Kyoto, Japan). HPLC-photodiode array analysis was carried out using a Waters Alliance PDA system (Tokyo, Japan). 1 H and 13 C NMR spectra were recorded in DMSO-d 6 with spectrometers (Varian Unity plus 500 and Varian Gemini 300) operating at 500 MHz and 300 MHz for 1 H, and 125 MHz for 13 C, respectively. Mass spectra were recorded on a JEOL JMS DX-303 spectrometer. UV and CD spectra were measured with a UV-1600 visible spectrophotometer and a J-725N spectrometer, respectively. Plant materials and culture methodsThe origin and subculturing of callus cultures (Yamamoto et al. 1991a) and the establishment of cell suspension cultures (Yamamoto et al. 1996) of S. flavescens were described previously. Cell suspension cultures (0.5 g) were subcultured in 100 ml-flasks containing 20 ml of Murashige and Skoog (1962) medium with 1 mM 2,4-D and 1 mM kinetin at 14 days interval on a rotary shaker at a speed of 100 rpm in the dark at 25°C. For the experiment, filter-sterilized 300 mM (2RS)-naringenin solution in 20 ml of DMSO was aseptically added to the flask (final concentration 0.3 mM), and cultured for another one day. Twenty ml of DMSO was added to the control cells. Isolation and identification of the metabolitesThe naringenin-fed cells collected from 60 flasks (120 g) were extracted three times with MeOH by ultrasonication in ice-water bath for 30 min. The MeOH extract after concentration was resuspended in H 2 O, partitioned with CHCl 3 and n-BuOH, successively. The residual H 2 O layer was passed through Diaion HP-20 column (Mitsubishi Chem, Tokyo, J...

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Cytotoxic Lavandulyl Flavanones from Sophora flavescens

Cited by 127 publications

References 10 publications

Isolation and Structure Elucidation of a Flavanone, a Flavanone Glycoside and Vomifoliol from Echiochilon Fruticosum Growing in Tunisia

Isolation and Structure Elucidation of a Flavanone, a Flavanone Glycoside and Vomifoliol from Echiochilon Fruticosum Growing in Tunisia

(2<i>S</i>)-2′-Methoxykurarinone Inhibits Osteoclastogenesis and Bone Resorption through Down-Regulation of RANKL Signaling

Metabolism of administered (2RS)-naringenin in flavonoid-producing cultured cells of Sophora flavescens

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