Three-Way Cell-Based Screening of Antistress Compounds: Identification, Validation, and Relevance to Old-Age-Related Pathologies.
J Gerontol A Biol Sci Med Sci
; 78(9): 1569-1577, 2023 08 27.
Article
em En
| MEDLINE
| ID: mdl-37061830
ABSTRACT
A variety of environmental stress stimuli have been linked to poor quality of life, tissue dysfunctions, and ailments including metabolic disorders, cognitive impairment, and accelerated aging. Oxidative, metal, and hypoxia stresses are largely associated with these phenotypes. Whereas drug development and disease therapeutics have advanced remarkably in last 3 decades, there are still limited options for stress management. Because the latter can effectively decrease the disease burden, we performed cell-based screening of antistress compounds by recruiting 3 chemical models of oxidative (paraquat), metal (cadmium nitrate), or hypoxia (cobalt chloride) stresses. The screening of 70 compounds for their ability to offer protection against oxidative, metal, and hypoxia stresses resulted in the selection of 5 compounds Withaferin-A (Wi-A), methoxy Withaferin-A (mWi-A), Withanone (Wi-N), triethylene glycol (TEG), and Ashwagandha (Withania somnifera) leaf M2-DMSO extract (M2DM). Molecular assays revealed that whereas stress caused increase in (a) apoptosis, (b) reactive oxygen species accumulation coupled with mitochondrial depolarization, (c) DNA double-strand breaks, and (d) protein aggregation, low nontoxic doses of the selected compounds caused considerable protection. Furthermore, Wi-N, TEG, and their mixture-treated normal human fibroblasts (at young, mature, and senescent stages representing progressively increasing accumulation of stress) showed increase in proliferation. Taken together, these results suggested 3-way (oxidative, metal, and hypoxia) antistress potential of Wi-N and TEG that may be useful for management of environmental and old-age-related pathologies.
Palavras-chave
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Qualidade de Vida
/
Withania
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Humans
Idioma:
En
Revista:
J Gerontol A Biol Sci Med Sci
Assunto da revista:
GERIATRIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Japão