Isofraxidin

1 Eleutherococcus sp. 2 Fraxinus sp. 3 Silybum sp. 4 Tanacetum sp.

Protective effects of Isofraxidin against lipopolysaccharide-induced acute lung injury in mice.[Pubmed:25596039]

Int Immunopharmacol. 2015 Feb;24(2):432-439.

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 IF against lipopolysaccharide-induced ALI have not been clarified. The aim of the present study is to explore the protective effects and potential mechanism of IF against LPS-induced ALI in mice. In this study, We found that pretreatment with IF significantly lowered LPS-induced mortality and lung wet-to-dry weight (W/D) ratio and reduced the levels of tumor necrosis factor-alpha (TNF-alpha), 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, IF obviously inhibited lung histopathological changes and cyclooxygenase-2 (COX-2) protein expression. These results suggest that IF has a protective effect against LPS-induced ALI, and the protective effect of IF seems to result from the inhibition of COX-2 protein expression in the lung, which regulates the production of PGE2.

Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits matrix metalloproteinase-7 expression and cell invasion of human hepatoma cells.[Pubmed: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-kappaB) nuclear translocation, and inhibitory kappa B (IkappaB) 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.

Isofraxidin exhibited anti-inflammatory effects in vivo and inhibited TNF-alpha production in LPS-induced mouse peritoneal macrophages in vitro via the MAPK pathway.[Pubmed:22800929]

Int Immunopharmacol. 2012 Oct;14(2):164-71.

Isofraxidin (IF) is a Coumarin compound that can be isolated from medicinal plants, such as Sarcandra glabra (Thunb.). Nakai is widely used in Asian countries for the treatment of anti-bacterial, anti-inflammatory and anti-tumour action. The present investigation was designed to evaluate the effect of IF on inflammation and nociception. In addition, we investigated a potential novel mechanism to explain the anti-inflammatory properties of IF. In vivo, xylene-induced mouse ear edema, carrageenan-induced rat paw edema, LPS-induced mouse endotoxic shock, acetic acid-induced mice writhing and formalin-induced mouse pain models were used to evaluate the anti-inflammatory activity of IF. In vitro, we examined the effects of IF inhibition on TNF-alpha production and the regulation of ERK1/2 and p38 phosphorylation activity in LPS-induced mouse peritoneal macrophages. Our results demonstrated that IF can significantly decrease xylene-induced ear edema, carrageenan-induced paw edema, acetic acid-induced writhing and formalin-induced pain. Moreover, IF greatly inhibited the production of TNF-alpha in the serum of LPS-stimulated mice and peritoneal macrophages, and it decreased phospho-p38 and ERK1/2 protein expression in LPS-stimulated mouse peritoneal macrophages. Overall, our data suggest that IF possesses significant analgesic and anti-inflammatory activities that may be mediated through the regulation of pro-inflammatory cytokines, TNF-alpha and the phosphorylation of p38 and ERK1/2.

Isofraxidin, a potent reactive oxygen species (ROS) scavenger, protects human leukemia cells from radiation-induced apoptosis via ROS/mitochondria pathway in p53-independent manner.[Pubmed: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 protects mice from LPS challenge by inhibiting pro-inflammatory cytokines and alleviating histopathological changes.[Pubmed: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 IF acts via the MAPK pathway to produce anti-inflammatory effects, both in vivo and in vitro. However, the effect and mechanism of action of IF on inflammatory cytokines and NF-kappaB activation in vivo has not been investigated. We therefore aimed to evaluate how IF regulates the production of inflammatory cytokines in vivo by intraperitoneal injection of IF (1, 5 or 15mg/kg) prior to treatment with LPS (1mg/kg, i.p.). Macroscopic, biochemical and histopathological parameters were measured. Treatment with IF prior to LPS challenge decreased mortality rate, body weight loss, organ coefficient and histopathological changes. IF also suppressed the protein expression of NF-kappaB, levels of NO and IL-6 in serum and production of TNF-alpha in liver. Our results show that pretreatment with IF increases the survival rate following LPS stimulation in mice. The effect involves regulation of NF-kappaB signal which, in turn, regulates production of inflammatory cytokine TNF-alpha, suggesting that IF may have a therapeutic effect against LPS-induced inflammatory disease.

Isofraxidin, a coumarin component from Acanthopanax senticosus, inhibits MMP-7 expression and cell invasion of human hepatoma cells. Isofraxidin inhibits the phosphorylation of ERK1/2 in hepatoma cells. Isofraxidin attenuates the expression of iNOS and COX-2, Isofraxidinalso inhibits TLR4/myeloid differentiation protein-2 (MD-2) complex formation.

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