Project description:We investigated the gene expression profiles of U373MG human astrocytoma cells treated with vehicle (DMSO) or edaravone or carnosic acid) or both edaravone and carnosic acid. Edaravone is a free radical scavenger sold as radicut. Carnosic acid is a phytochemical found in rosemary and sage.
Project description:Gene expression profiling reveals multiple tissue-specific functionality of carnosic acid in a stem-based tool. We evaluated the effects of carnosic acid on human amniotic epithelial stem cells. We performed an untargeted whole-genome transcriptome analysis to explore functionality of carnosic acid in a stem cell-based tool.
Project description:We used Affymetrix microarrays to investigate gene expression changes in the liver of lean female Zucker rats exposed to a normal diet supplemented with a rosemary extract rich in the diterpenic compound, carnosic acid (CA).
Project description:Supercritical rosemary extract (containing 16.90% carnosic acid, 1.90% carnosol and 13.59% volatile compounds) showed antitumor activity on colon cancer cells in vitro. We treated colon cancer cells with the extract and we employed whole genome microarray expression profiling to identify genes potentially involved in its antitumor mechanism of action.
Project description:Brain tumour stem cells (BTSCs) are a population of self-renewing malignant stem cells that play an important role in glioblastoma tumour hierarchy and contribute to tumour growth, therapeutic resistance, and tumour relapse. Thus, targeting of BTSCs within the bulk of tumours represents a crucial therapeutic strategy. Here, we report that Edaravone is a potent drug that impairs BTSCs and impedes glioblastoma tumorigenesis. We show that Edaravone inhibits the self-renewal and growth of BTSCs harbouring a diverse range of oncogenic mutations without affecting non-oncogenic neural stem cells. Global gene expression profiling revealed that Edaravone significantly alters BTSC transcriptome and attenuates the expression of a large panel of genes involved in cell cycle progression, stemness, and DNA repair mechanisms. Mechanistically, we discovered that Edaravone directly targets Notchless homolog 1 (NLE1) and impairs Notch signalling pathway, alters the expression of stem cell markers, and sensitizes BTSC response to ionizing radiation (IR)-induced cell death. Importantly, we show that Edaravone treatment in preclinical models delays glioblastoma tumourigenesis, sensitizes their response to IR and prolongs the lifespan of animals. Our data suggest that repurposing of Edaravone is a promising therapeutic strategy for glioblastoma patients.
Project description:Mammalian skin wounds typically heal with a scar, characterized by fibrotic tissue that disrupts original tissue architecture and function. Therapies to reduce fibrosis and scar formation remain a large unmet clinical need. Rosemary extract, particularly in the form of topical oils and creams, has gained massive popularity within the general public as a potential treatment to reduce scar formation. However, its efficacy and potential mechanism of action remain unknown. We show in adult wound healing mouse models that an ethanol-based rosemary extract reduces fibrosis and promotes scarless wound healing. More specifically, carnosic acid within rosemary leaves acts as an active ingredient and stimulates the TRPA1 nociceptor on cutaneous sensory neurons to promote scarless wound healing. Mice lacking TRPA1 on sensory neurons do not exhibit rosemary-induced tissue regeneration. Taken together, topical rosemary extract may be an effective and cost-efficient therapeutic to reduce scar formation in skin wounds.
Project description:Edaravone is a free-radical scavenger drug that was recently approved for the treatment of amyo-trophic lateral sclerosis (ALS), a neurodegenerative disease. A pathological hallmark of ALS is the accumulation of ubiquitinated or phosphorylated aggregates of the 43-kDa transactive response DNA binding protein (TDP-43) within the cytoplasm of motor neurons. This study revealed the efficacy of edaravone in preventing neuronal cell death in a TDP-43 proteinopathy model and analyzed the molecular changes associated with the neuroprotection. The viability of the neuronal cells expressing TDP-43 was reduced by oxidative stress, and edaravone (≥10 μmol/L) protected in a concentration-dependent manner against the neurotoxic insult. Differential gene expression analysis revealed changes among pathways related to nuclear erythroid 2-related-factor (Nrf2)-mediated oxidative stress response in cells expressing TDP-43. In edaravone-treated cells express-ing TDP-43, significant changes in gene expression were also identified among Nrf2-oxidative re-sponse, unfolded protein response, and autophagy pathways. In addition, the expression of genes belonging to phosphatidylinositol metabolism pathways was modified. These findings suggest that the neuroprotective effect of edaravone involves the prevention of TDP-43 misfolding and en-hanced clearance of pathological TDP-43 in TDP-43 proteinopathy.
