||Amentoflavone is a novel natural inhibitor of human Cathepsin B(CatB), which has antifungal , antioxidant, antiviral, antidiabetic, and neuroprotective activities, it stimulates apoptosis in HSFBs and inhibits angiogenesis of endothelial cells, it is a promising molecule that can be used in hypertrophic scar treatment. Amentoflavone regulated β-catenin and caspase-3 expressions, and inhibited NF-κB signal transduction pathways. |
|Phytother Res. 2013 May;27(5):713-20. |
|Fatty acid synthase inhibition by amentoflavone suppresses HER2/neu (erbB2) oncogene in SKBR3 human breast cancer cells.[Pubmed: 22767439 ]|
|Fatty acid synthase (FASN) is a potential therapeutic target for treatment of cancer and obesity, and is highly elevated in 30% of HER2-overexpressing breast cancers. Considerable interest has developed in searching for novel FASN inhibitors as therapeutic agents in treatment of HER2-overexpressing breast cancers.
METHODS AND RESULTS:
Amentoflavone was found to be effective in suppressing FASN expression in HER2-positive SKBR3 cells. Pharmacological inhibition of FASN by Amentoflavone specifically down-regulated HER2 protein and mRNA, and caused an up-regulation of PEA3, a transcriptional repressor of HER2. In addition, pharmacological blockade of FASN by Amentoflavone preferentially decreased cell viability and induced cell death in SKBR3 cells. Palmitate reduced the cytotoxic effect of Amentoflavone, as the percentage of viable cells was increased after the addition of exogenous palmitate. Amentoflavone-induced FASN inhibition inhibited the translocation of SREBP-1 in SKBR3 cells. Amentoflavone inhibited phosphorylation of AKT, mTOR, and JNK. The use of pharmacological inhibitors revealed that the modulation of AKT, mTOR, and JNK phosphorylation required synergistic Amentoflavone-induced FASN inhibition and HER2 activation in SKBR3 cells.
These results suggest that Amentoflavone modulated FASN expression by regulation of HER2-pathways, and induced cell death to enhance chemopreventive or chemotherapeutic activity in HER2-positive breast cancers.
|Burns. 2014 Aug;40(5):922-9. |
|Amentoflavone inhibits angiogenesis of endothelial cells and stimulates apoptosis in hypertrophic scar fibroblasts.[Pubmed: 24280521]|
|Amentoflavone (8-[5-(5,7-dihydroxy-4-oxo-chromen-2-yl)-2-hydroxy-phenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl) chromen-4-one; AF) is a biflavonoid derived from the extracts of Selaginella tamariscina. It has been shown that AF has diverse biological effects such as antitumour, etc. It is well known that high cell proliferation, viability, angiogenesis and low apoptosis are key factors in hypertrophic scar formation.
METHODS AND RESULTS:
In this study, we report that AF inhibited viability and stimulated apoptosis in hypertrophic scar fibroblasts (HSFBs). Incubation of HSFBs with AF showed its inhibitory effect on cell viability and the exhibition of a series of cellular changes that were consistent with apoptosis. By Western-blot analysis, our data indicated significant increases in the amounts of cleaved caspases 3, 8, 9 and Bax, several apoptotic promoters and a significant decrease in translationally controlled tumour protein (TCTP), an apoptotic inhibitor, in HSFBs treated with AF. Furthermore, AF showed significant inhibitions on the viability, migration and tube formation of endothelial cells, which are associated with angiogenesis. In conclusion, this study suggests that AF stimulates apoptosis in HSFBs and inhibits angiogenesis of endothelial cells.
Therefore, AF is a promising molecule that can be used in hypertrophic scar treatment.
|Arch Pharm Res. 2006 Sep;29(9):746-51. |
|Antifungal effect of amentoflavone derived from Selaginella tamariscina.[Pubmed: 17024847]|
|Amentoflavone is a plant bif avonoid that was isolated from an ethyl acetate extract of the whole plant of Selaginella tamariscina (Beauv.) spring. 1D and 2D NMR spectroscopy including DEPT, HMQC, and HMBC were used to determine its structure.
METHODS AND RESULTS:
Amentoflavone exhibited potent antifungal activity against several pathogenic fungal strains but had a very low hemolytic effect on human erythrocytes. In particular, Amentoflavone induced the accumulation of intracellular trehalose on C. albicans as a stress response to the drug, and disrupted the dimorphic transition that forms pseudo-hyphae during pathogenesis.
In conclusion, Amentoflavone has great potential to be a lead compound for the development of antifungal agents.
|Int Immunopharmacol. 2013 Nov;17(3):907-16. |
|Amentoflavone inhibits iNOS, COX-2 expression and modulates cytokine profile, NF-κB signal transduction pathways in rats with ulcerative colitis.[Pubmed: 24126114]|
|Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative stress, leucocyte infiltration and upregulation of pro-inflammatory cytokines.
METHODS AND RESULTS:
The aim of the present study was to examine the effect of Amentoflavone on a murine model of ulcerative colitis (UC). UC was induced by intracolonic injection of 3% acetic acid in male Wistar rats. Amentoflavone (10 mg/kg·b.wt) or reference drug sulfasalazine (100 mg/kg·b.wt) was administrated intra-peritoneally for 5 consecutive days before induction of colitis with acetic acid. Administration of Amentoflavone was found to reduce the extent of inflammatory colonic injury. This was manifested by a decrease in the score of mucosal injury, by lowered colonic wet weight as well as vascular permeability and diminished lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity reflecting reduced leukocyte infiltration. Furthermore, the mucosal content of lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO) activity confirms that Amentoflavone could significantly inhibit colitis. The treatment also reduced significantly the colonic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and IL-6 levels as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) compared to colitis control group. The histopathological studies also confirm the foregoing findings. Amentoflavone was also able to inhibit the activation and translocation of transcription factors, nuclear factor (NF)-κB subunits (p65/p50).
These results suggest that Amentoflavone exhibits protective effect in acetic acid-induced ulcerative colitis which might be due to its modulation of oxidant/anti-oxidant balance, down-regulation of productions and expressions of pro-inflammatory cytokines, inflammatory mediators and inhibition of NF-κB signal transduction pathways.