title: Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite.
abstract: The present day lifestyle heavily depends on industrial chemicals in the form of agriculture, cosmetics, textiles and medical products. Since the toxicity of the industrial chemicals has been a concern to human health, the need for alternative non-toxic natural products or adjuvants that serve as antidotes are in high demand. We have investigated the effects of Ayurvedic herb Ashwagandha (Withania somnifera) leaf extract on methoxyacetic acid (MAA) induced toxicity. MAA is a major metabolite of ester phthalates that are commonly used in industry as gelling, viscosity and stabilizer reagents. We report that the MAA cause premature senescence of normal human cells by mechanisms that involve ROS generation, DNA and mitochondrial damage. Withanone protects cells from MAA-induced toxicity by suppressing the ROS levels, DNA and mitochondrial damage, and induction of cell defense signaling pathways including Nrf2 and proteasomal degradation. These findings warrant further basic and clinical studies that may promote the use of withanone as a health adjuvant in a variety of consumer products where the toxicity has been a concern because of the use of ester phthalates.
authors.affiliation: National Institute of Advanced Industrial Science & Technology, Tsukuba, Ibaraki, Japan.
authors.forename: Didik
authors.initials: D
authors.lastname: Priyandoko
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Ishii
authors.forename: Sunil C
authors.initials: SC
authors.lastname: Kaul
authors.forename: Renu
authors.initials: R
authors.lastname: Wadhwa
mesh_terms: D000085:Acetates / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects*; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007221:Industry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010936:Plant Extracts; D018515:Plant Leaves / Q000737:chemistry*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D032341:Withania / Q000737:chemistry*; D054358:Withanolides
chemical_list: D000085:Acetates; D000975:Antioxidants; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016160:Retinoblastoma Protein; D014315:Triterpenes; D016159:Tumor Suppressor Protein p53; D054358:Withanolides; C013598:methoxyacetic acid; C560597:withanone; C030693:Ashwagandha