| Kinase Assay: |
| Int J Oncol. 2012 Apr;40(4):1058-65. | | Gomisin N enhances TRAIL-induced apoptosis via reactive oxygen species-mediated up-regulation of death receptors 4 and 5.[Pubmed: 22179661 ] | Pharmacological studies have revealed that lignans isolated from Schisandra chinensis, including Gomisin N, show anticancer, anti-hepatotoxic, anti-oxidative and anti-inflammatory activities. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important member of the tumor necrosis factor superfamily with great potential in cancer therapy.
METHODS AND RESULTS:
The present study investigated whether pretreatment with Gomisin N significantly enhanced TRAIL-induced cleavage of caspase-3, caspase-8 and PARP-1, which are key markers of apoptosis. Pretreatment with z-VAD-FMK, a pan-caspase inhibitor, was able to inhibit apoptosis enhanced by the combination of Gomisin N and TRAIL. These results suggested that Gomisin N could promote TRAIL-induced apoptosis through the caspase cascade. In search of the molecular mechanisms, we elucidated that such enhancement was achieved through transcriptional up-regulation of TRAIL receptors, death receptor 4 (DR4) and DR5. Neutralization of DR4 and DR5 could significantly reduce apoptosis induced by Gomisin N and TRAIL. We also revealed that Gomisin N increased the generation of reactive oxygen species (ROS). N-acetyl cysteine (NAC), an antioxidant, could inhibit ROS production and up-regulation of DR4 and DR5.
CONCLUSIONS:
Overall, our results indicated that Gomisin N was able to potentiate TRAIL-induced apoptosis through ROS-mediated up-regulation of DR4 and DR5. | | Mol Cell Biochem. 2011 Apr;350(1-2):169-75. | | Gomisin N enhances TNF-α-induced apoptosis via inhibition of the NF-κB and EGFR survival pathways.[Pubmed: 21188622] | Tumor necrosis factor (TNF-α) is a pleiotropic cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis. TNF-α-induced apoptosis is limited by TAK1-mediated activation of NF-κB (mainly p65-p50 hetrodimer) signaling pathway. We have recently reported that TAK1 regulates phosphorylation of EGFR at Ser-1046/7 through p38 MAPK, which cooperates with NF-κB in TNF-α-induced apoptosis.
METHODS AND RESULTS:
The present study investigated the effect of gomisins A and N, dibenzocyclooctadiene lignans isolated from the fruit of Schisandra chinensis, on TNF-α-induced apoptosis in HeLa cells. Gomisins A and N strongly promoted TNF-α-induced cleavage of caspase-3 and PARP-1, which are key markers of apoptosis. We found that Gomisin N, but not gomisin A, inhibited the TNF-α-induced activation of NF-κB by suppressing the activation of IKKα. Gomisin N also inhibited p38-mediated phosphorylation of the EGFR at Ser-1046/7 and subsequent endocytosis of EGFR, another prosurvival pathway.
CONCLUSIONS:
The findings suggested that Gomisin N enhanced TNF-α-induced apoptosis by suppressing of NF-κB and EGFR signaling pathways. |
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| Cell Research: |
| Nitric Oxide. 2013 Jan 15;28:47-56. | | Gomisin N in the herbal drug gomishi (Schisandra chinensis) suppresses inducible nitric oxide synthase gene via C/EBPβ and NF-κB in rat hepatocytes.[Pubmed: 23085209] | Gomishi is the dried fruit of Schisandra chinensis Baillon (Fructus Schisandrae chinensis, FSC) and has been used in Japanese Kampo medicine to treat inflammatory and liver diseases. However, it is unclear which constituent of FSC is primarily responsible for its pharmacological effects. FSC was extracted with methanol, fractionated by hydrophobicity, and further purified.
METHODS AND RESULTS:
We measured the effects of each fraction or constituent thereof on the induction of the inflammatory mediator nitric oxide (NO), which was induced by interleukin 1β in primary cultured rat hepatocytes. The hydrophobic fraction markedly suppressed NO induction and reduced the expression of inducible nitric oxide syntheses (iNOS) in interleukin 1β-treated hepatocytes. Gomisin N and γ-schizandrin, two major constituents of the hydrophobic fraction, significantly reduced NO production and the levels of the iNOS protein, mRNA, and antisense transcript. Gomisin N and γ-schizandrin also decreased the transcription of interleukin 1β and inflammatory chemokines. The overexpression of the p65 subunit of nuclear factor κB or CCAAT/enhancer-binding protein β increased the promoter activity of the iNOS gene in the firefly luciferase assay, whereas Gomisin N decreased the promoter activity.
CONCLUSIONS:
The anti-inflammatory activity of FSC and its constituents were analysed, and we demonstrated that Gomisin N and γ-schizandrin are involved in the hepatoprotective effect of the FSC extract, which has therapeutic potential for liver disease. |
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