Effect of Gomisin A (TJN-101) on the arachidonic acid cascade in macrophages.

Ohkura, Yasufumi; Mizoguchi, Yasuhiro; Morisawa, Seiji; Takeda, Sigefumi; Aburada, Masaki; Hosoya, Eikichi

doi:10.1254/jjp.52.331

Cited by 31 publications

(22 citation statements)

References 19 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Schizandrin possesses many biological properties (14), including hepatoprotective (15), anti-inflammatory (16), antitumor (17), and antiamnesic effects (18), and a suppressive effect against lipid peroxidation and a potentiating effect on glutathione mediated antioxidation (19). To date, there has been less information concerning its neuroprotective activity against Gluinduced neurotoxicity.…”

Section: +mentioning

confidence: 99%

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Cheng

Hsieh

et al. 2008

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. The neuroprotective effect of schizandrin on the glutamate (Glu)-induced neuronal excitotoxicity and its potential mechanisms were investigated using primary cultures of rat cortical cells. After exposure of primary cultures of rat cortical cells to 10 μM Glu for 24 h, cortical cell cultures exhibited remarkable apoptotic death. Pretreatment of the cortical cell cultures with schizandrin (10, 100 μM) for 2 h significantly protected cortical neurons against Glu-induced excitotoxicity. The neuroprotective activity of schizandrin was the most potent at the concentration of 100 μΜ. Schizandrin reduced apoptotic characteristics by DAPI staining in Glu-injured cortical cell cultures. In addition, schizandrin diminished the intracellular Ca 2+ influx, inhibited the subsequent overproduction of nitric oxide (NO), reactive oxygen species (ROS), and cytochrome c, and preserved the mitochondrial membrane potential. Furthermore, schizandrin also increased the cellular level of glutathione (GSH) and inhibited the membrane lipid peroxidation malondialdehyde (MDA). As indicated by Western blotting, schizandrin attenuated the protein level changes of procaspase-9, caspase-9, and caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP). Taken together, these results suggest that schizandrin protected primary cultures of rat cortical cells against Glu-induced apoptosis through a mitochondria-mediated pathway and oxidative stress.

show abstract

Section: +mentioning

confidence: 99%

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Cheng

Hsieh

et al. 2008

J Pharmacol Sci

View full text Add to dashboard Cite

show abstract

“…Furthermore, the effect of gomisin A was more inhibitive than those of the inhibitorsof tumor promotion, quercetin [7,14], glycyrrhizin and caffeine [15] against TPA-induced inflammation and tumor promotion. This is the first im portant indication that gomisin A exerts an inhibitory ef fect on the arachidonic acid cascade in macrophages [6], which is observed in inflammation associated with the ac tion of tumor promoters in mouse skin [9], Gomisin A has a little toxic to ICR mice: the LD50 for administration of gomisin A p.o. was 878 mg/kg, and its administration s.c. was 855 mg/kg [Aburada et al, personal commun.].…”

Section: Discussionmentioning

confidence: 83%

“…Gomisin A shows an inhibitory effect against certain types of chemically induced hepatotoxicity [l 5], Gomisin A was found to inhibit the biosynthesis of leukotrienes by preventing the release of arachidonic acid [6]. Lipoxy genase and phospholipase A; inhibitors reduce the degree of 12-O-tetradccanoylphorbol-l 3-acetate (TPA)-induced skin tumor promotion in mice [7 l ()].…”

Section: Introductionmentioning

confidence: 99%

Gomisin A Inhibits Tumor Promotion by 12-O-Tetra-decanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin

Yasukawa

Ikeya²,

Mitsuhashi³

et al. 1992

Oncology

Self Cite

View full text Add to dashboard Cite

Gomisin A, isolated from the fruits of Schisandra chinensis, is one of the dibenzocyclooctadiene lignans. Application of 12-O-tetradecanoylphorbol-13-acetate (TPA, 1 μg/ear), a tumor-promoting agent, to the ears of mice induces inflammation. Among seven dibenzocyclooctadiene lignans assayed, gomisin A, gomisin J, and wuweizisu C inhibited the inflammatory activity induced by TPA in mice. The ED₅₀ of these compounds for TPA-induced inflammation was 1.4–4.4 μmol. Gomisin A, with an ED₅₀ of 1.4 μmol, showed the strongest inhibitory effect. Furthermore, at 5 μmol/mouse, it markedly suppressed the promotion effect of TPA (2.5 μg/mouse) on skin tumor formation in mice following initiation with 7,12-dimethylbenz[a]anthracene (50 μg/ mouse). It is assumed that the inhibition of tumor promotion by gomisin A is due to its anti-inflammatory activity.

show abstract

“…Although S. chinensis has many effective compounds regulating brain function, there has been no report regarding the possible anti-neuroinflammatory action. In one study, anti-inflammatory activity of Gomisin A was reported (Yasukawa et al, 1992), but in this case, it was performed in the model of TPA-induced skin tumor formation in mice, and the other two studies were performed in the hepatotoxicity model (Ohkura et al, 1990;Yamada et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Schizandra chinensis Alkaloids Inhibit Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells

Choi¹,

Kwon²,

Jeon³

et al. 2009

Biomolecules and Therapeutics

View full text Add to dashboard Cite

-Schizandra chinensis (S. chinensis) exhibits a harmless, 'adaptogen-type' effect leading to improvements in mental performance and learning efficacy in brain. Activated microglia contributes to neuronal injury by releasing neurotoxic products, which make it important to regulate microglial activation to prevent further cytological as well as functional brain damage. However, the effect of S. chinensis on microglial activation has not been examined yet. We have investigated the effects of four compounds (Gomisin A, Gomisin N, Schizandrin and Schizandrol A) from S. chinensis on lipopolysaccharide (LPS)-induced microglial activation. In this study, BV2 microglial cells were activated with LPS and the microglial activation was assessed by up-regulation of activation markers such as nitric oxide (NO), reactive oxygen species (ROS), and matrix metalloproteinase-9 (MMP-9). The results showed that all four compounds significantly reduced the intracellular level of ROS, the release of NO and MMP-9 as well as LPS-induced phosphorylation of ERK1/2. These results strongly suggested that S. chinensis may be useful to modulate inflammation-mediated brain damage by regulating microglial activation.

show abstract

Effect of Gomisin A (TJN-101) on the arachidonic acid cascade in macrophages.

Cited by 31 publications

References 19 publications

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Schizandrin Protects Primary Cultures of Rat Cortical Cells From Glutamate-Induced Excitotoxicity

Gomisin A Inhibits Tumor Promotion by 12-O-Tetra-decanoylphorbol-13-Acetate in Two-Stage Carcinogenesis in Mouse Skin

Schizandra chinensis Alkaloids Inhibit Lipopolysaccharide-Induced Inflammatory Responses in BV2 Microglial Cells

Contact Info

Product

Resources

About