Inhibition of Phospholipase Cγ1 Activity by Amentoflavone Isolated from<i>Selaginella tamariscina</i>

Lee, Hyun Sun; Oh, Won Keun; Kim, Bo Yeon; Ahn, Soon Cheol; Kang, Dae Ook; Shin, Dong In; Kim, Jinwoong; Mheen, Tae Ick; Ahn, Jong Seog

doi:10.1055/s-2006-957887

Cited by 52 publications

(31 citation statements)

References 7 publications

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“…Additionally, flavonoids can inhibit some enzymes, such 0031-9422/$ -see front matter Ó 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.phytochem.2004.11.014 as cyclooxygenase, lipoxygenase and phospholipase A 2 (Lee et al, 1996;Kim et al, 1998;Saponara and Bosisio, 1998), and are also able to chelate metals, which play an important role in metal-induced free radical reactions (Deng et al, 1997). Biflavonoids are dimers of flavonoids, linked by a C-O-C or C-C bond, their biological properties include anti-inflammatory and antiarthritic activites in animals (Harborne, 1967).…”

Section: Introductionmentioning

confidence: 99%

Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation

et al. 2005

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Section: Introductionmentioning

confidence: 99%

Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation

et al. 2005

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“…Since the phosphorylation of IR is essential for the insulin signaling cascade, our results indicate that amentoflavone may act in the cells to enhance insulin signaling. Although there have been several reports on the biological activities of amentoflavone, [9][10][11][12] PTP1B-inhibitory activity of amentoflavone and its cellular effect in insulin signaling is reported for the first time in this study. …”

Section: Resultsmentioning

confidence: 77%

“…1). Although amentoflavone has been reported to possess various pharmacological activities such as antioxidant, 9) anti-HIV, 10) anti-phospholipase Cg1, 11) and vasorelaxant effects, 12) there has been no study with regard to its inhibitory activity against PTP1B. In this study, we investigated the inhibitory effect of amentoflavone on PTP1B and confirmed its cellular effect on IR phosphorylation.…”

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confidence: 74%

Protein Tyrosine Phosphatase 1B Inhibitory Activity of Amentoflavone and Its Cellular Effect on Tyrosine Phosphorylation of Insulin Receptors

Kim

et al. 2007

Biological & Pharmaceutical Bulletin

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Insulin binding to the insulin receptor (IR) results in autophosphorylation on specific tyrosine residues, which in turn further activates the receptor tyrosine kinase and provides binding sites for the recruitment and subsequent phosphorylation of signaling proteins such as insulin receptor substrate (IRS) 1-4.2,3) Phosphorylated IRS activate several signaling cascades that mediate the biological effects of insulin including glucose uptake and glycogen synthesis. 2,3)Protein tyrosine phosphatases (PTPs) catalyze the dephosphorylation of tyrosyl-phosphorylated proteins and are believed important negative regulators of insulin signaling. 2,3)Although several PTPs such as PTP-a, leukocyte antigen-related tyrosine phosphatase (LAR), and SH2-domain-containing phosphotyrosine phosphatase (SHP2) have been implicated in the regulation of insulin signaling, there is substantial evidence supporting PTP1B as the critical PTP controlling the insulin signaling pathway.2,3) PTP1B can interact with and dephosphorylate activated IR as well as IRS proteins.2,3) Its overexpression has been shown to inhibit the IR signaling cascade and increased expression of PTP1B occurs in insulin-resistant states. 4) Furthermore, recent genetic evidence has shown that PTP1B gene variants are associated with changes in insulin sensitivity. 5) As with the insulin signaling pathway, the leptin signaling pathway can be attenuated by PTPs and there is compelling evidence that PTP1B is also involved in this process.2,3) Therefore, it has been suggested that compounds that reduce PTP1B activity or expression levels could not only be used for the treatment of type 2 diabetes but also obesity. Although there have been a number of reports on the design and development of synthetic PTP1B inhibitors, 2,6) there are only a few reports on PTP1B inhibitors derived from plants. 7) In our continuing search for PTP1B inhibitors derived from plants, a MeOH extract of whole plants of Selaginella tamariscina (Selaginellaceae), which have been used to treat infectious diseases and malignant tumors, 8) was found to inhibit PTP1B activity (Ͼ70% inhibition at 30 mg/ml). Further fractionation of the MeOH extract as guided by in vitro PTP1B inhibitory assay afforded an active biflavonoid, amentoflavone (Fig. 1). Although amentoflavone has been reported to possess various pharmacological activities such as antioxidant, 9) anti-HIV, 10) anti-phospholipase Cg1, 11) and vasorelaxant effects, 12) there has been no study with regard to its inhibitory activity against PTP1B. In this study, we investigated the inhibitory effect of amentoflavone on PTP1B and confirmed its cellular effect on IR phosphorylation. MATERIALS AND METHODS Plant MaterialWhole plants of S. tamariscina were purchased from a local market in Daejeon, Korea. A voucher specimen (No. 005-041) has been deposited in our laboratory, KRIBB.Extraction and Isolation Dried whole plants of S. tamariscina (1 kg) were extracted with MeOH (3 l) at 50°C. The MeOH extract (50.5 g) was suspended in H 2 O and partitioned wit...

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“…Several compounds, such as amentoflavone, isocryptomerin, cryptomerine B, and tamariscinoside, have been isolated from ST. 4,20,21 Amentoflavone from ST inhibits the induction of nitric oxide synthase by inhibiting nuclear factor-B activation in macrophages and the phospholipase C-␥1 activity in fibroblasts. 22,23 Lee et al 24 previously reported that treatment with 1,000 g/mL of the water extract of ST for 3 days showed significant cytotoxicity in the human leukemia cell line U937, and some organic solvent extracts of ST increased p53 gene expression and induced G1 arrest. However, under the same experimental conditions, human peripheral blood lympocytes were insensitive to the cytotocixity of ST fractions.…”

Section: Discussionmentioning

confidence: 99%

Selaginella tamariscina Induces Apoptosis via a Caspase-3-Mediated Mechanism in Human Promyelocytic Leukemia Cells

Ahn

Mun

Lee

et al. 2006

Journal of Medicinal Food

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Cell apoptosis is now known to play an important role in the maintenance of cellular homeostasis and anticarcinogenesis. Selaginella tamariscina (ST) is a traditional medicinal plant for treatment of advanced cancer in the Orient. In the present study, the anticancer effect of ST was investigated by analyzing its potential to induce apoptosis in human leukemia HL-60 cells. ST-induced cytotoxicity of HL-60 cells was monitored by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The apoptosis was determined by microscopic examination of apoptotic morphology, determination of DNA fragmentation by electrophoresis, activation of caspase-3, and protein expression of procaspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, Bcl-2, and Bax. ST was cytotoxic to HL-60 cells in a dose-dependent manner. However, ST-induced cytotoxicity was suppressed by reactive oxygen species scavengers, including superoxide dismutase (SOD) and catalase. ST caused DNA fragmentation and nuclear condensation, all characteristics of apoptosis. ST-induced apoptosis is accompanied by the activation of caspase-3 and the specific proteolytic cleavage of PARP. Concomitantly, ST treatments led to an increase in the proapoptotic Bax levels, while Bcl-2 expression was decreased. Moreover, this effect was attenuated by SOD and catalase. These results suggest that oxidative stress may be involved in the cytotoxicity of ST, and that ST-induced apoptosis of HL-60 cells is primarily mediated by the caspase activation pathway.

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Inhibition of Phospholipase Cγ1 Activity by Amentoflavone Isolated fromSelaginella tamariscina

Cited by 52 publications

References 7 publications

Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation

Biflavonoids from Brazilian pine Araucaria angustifolia as potentials protective agents against DNA damage and lipoperoxidation

Protein Tyrosine Phosphatase 1B Inhibitory Activity of Amentoflavone and Its Cellular Effect on Tyrosine Phosphorylation of Insulin Receptors

Selaginella tamariscina Induces Apoptosis via a Caspase-3-Mediated Mechanism in Human Promyelocytic Leukemia Cells

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