Isofraxidin

Description :

Isofraxidin protects mice from LPS challenge by inhibiting pro-inflammatory cytokines and alleviating histopathological changes. PUMID/DOI：25454811 Immunobiology. 2015 Mar;220(3):406-13. Isofraxidin (IF), the major bioactive component of Sarcandra glabra, has been reported to be an effective anti-inflammatory compound. In a previous study, we showed that Isofraxidin acts via the MAPK pathway to produce anti-inflammatory effects, both in vivo and in vitro. However, the effect and mechanism of action of Isofraxidin on inflammatory cytokines and NF-κB activation in vivo has not been investigated. We therefore aimed to evaluate how Isofraxidin regulates the production of inflammatory cytokines in vivo by intraperitoneal injection of Isofraxidin (1, 5 or 15mg/kg) prior to treatment with LPS (1mg/kg, i.p.). Macroscopic, biochemical and histopathological parameters were measured. Treatment with Isofraxidin prior to LPS challenge decreased mortality rate, body weight loss, organ coefficient and histopathological changes. Isofraxidin also suppressed the protein expression of NF-κB, levels of NO and IL-6 in serum and production of TNF-α in liver. Our results show that pretreatment with IF increases the survival rate following LPS stimulation in mice. The effect involves regulation of NF-κB signal which, in turn, regulates production of inflammatory cytokine TNF-α, suggesting that Isofraxidin may have a therapeutic effect against LPS-induced inflammatory disease. Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice. PUMID/DOI：25596039 Int Immunopharmacol. 2015 Feb;24(2):432-9. Acute lung injury (ALI) is a life-threatening disease characterized by serious lung inflammation and increased capillary permeability, which presents a high mortality worldwide. Isofraxidin (IF), a Coumarin compound isolated from the natural medicinal plants such as Sarcandra glabra and Acanthopanax senticosus, has been reported to have definite anti-bacterial, anti-oxidant, and anti-inflammatory activities. However, the effects of Isofraxidin against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of Isofraxidin against LPS-induced ALI in mice. In this study, We found that pretreatment with Isofraxidin significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) in serum and bronchoalveolar lavage fluid (BALF). We also found that total cells, neutrophils and macrophages in BALF, MPO activity in lung tissues were markedly decreased. Besides, Isofraxidin obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that Isofraxidin has a protective effect against LPS-induced ALI, and the protective effect of Isofraxidin seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2. Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner. PUMID/DOI：24692054 Apoptosis. 2014 Jun;19(6):1043-53. Ionizing radiation (IR) leads to oxidizing events such as excessive reactive oxygen species (ROS) in the exposed cells, resulting in further oxidative damage to lipids, proteins and DNA. To screen the potential radio-protective drug, the intracellular ROS was measured in irradiated U937 cells pretreated with 80 candidate traditional herbal medicine, respectively. Isofraxidin (IF) was one possible radio-protector in these 80 drugs. This study investigated the radio-protective role of IF, a Coumarin compound, in human leukemia cell lines, for the first time. Results indicate that IF protects against IR-induced apoptosis in U937 cells in the time- and concentration- dependent manner. IF decreases IR-induced intracellular ROS generation, especially hydroxyl radicals formation, inhibits IR-induced mitochondrial membrane potential loss and reduces IR-induced high intracellular Ca(2+) levels regardless of ER stress. IF down-regulates the expression of caspase-3, phospho-JNK, phospho-p38 and activates Bax in mitochondria. IF inhibits cytochrome c release from mitochondria to cytosol. IF also moderates IR-induced Fas externalization and caspase-8 activation. IF also exhibits significant protection against IR-induced cell death in other leukemia cell lines such as Molt-4 cells and HL60 cells regardless of p53. Taken together, the data demonstrate that IF protects leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in a p53-independent manner. Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells. PUMID/DOI：20930381 Biol Pharm Bull. 2010;33(10):1716-22. 7-Hydroxy-6,8-dimethoxy-2H-1-benzopyran-2-one (Isofraxidin) is a major coumarin component isolated from the stem bark of Acanthopanax senticosus, a widely used Chinese medicinal herb. We investigated Isofraxidin in its anti-tumor effects on human hepatoma cell lines HuH-7 and HepG2. Isofraxidin significantly inhibited hepatoma cell invasion, without affecting cell attachment or growth. Expression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced matrix metalloproteinase-7 (MMP-7) in hepatoma cells was inhibited by Isofraxidin at the both mRNA and protein levels. This inhibition tended to be greater in cells inoculated at low density than in those at high density. Isofraxidin showed an inhibitory effect on the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in hepatoma cells, whereas activator protein-1 (AP-1) DNA binding activity, nuclear factor-kappa B (NF-κB) nuclear translocation, and inhibitory kappa B (IκB) degradation were affected very little. These results indicate that Isofraxidin inhibits expression of MMP-7 and in vitro cell invasion at a non-toxic level through inhibiting ERK1/2 phosphorylation in hepatoma cell lines, which suggest Isofraxidin might become an effective agent for suppressing hepatoma cell invasion.