Natural Products as a Major Source of Candidates for Potential Senolytic Compounds obtained by in silico Screening

Abstract

Background: Preclinical studies suggest that senolytic compounds such as quercetin (a natural product) and dasatinib (a synthetic product) decrease senescent cells, reduce inflammation, and alleviate frailty in humans. This evidence has opened a new field of research for studying the effect of these compounds on age-related dysfunction and diseases. Objective: In the present study performed in silico, we identified new potentially senolytic candidates from an extensive database that contains natural products (NPs) and semi-synthetic products (SMSs). Methods: Computer programs Chemminer and rcdk packages, which compared the fingerprints of numerous molecules (40,383) with reference senolytics, and the creation of a pharmacological network built with signaling pathways and targets involved in senescence processes were used to identify compounds with potential activity. Results: Six drug-like candidates (3,4'-dihydroxypropiophenone, baicalein, α, β-dehydrocurvularin, lovastatin, luteolin, and phloretin) were identified. Conclusion: To our knowledge, this is the first time that these six natural molecules have been proposed to most likely have senolytic activity. To validate the methodology employed in the identification of new drug-like senolytics, experimental evidence is needed with models that evaluate senolytic activity.

Inflammaging, cellular senescence, and cognitive aging after traumatic brain injury

“…Similarly, a randomized, placebo-controlled, double-blind study found curcumin supplementation slowed cognitive decline in aged adults ( Rainey-Smith et al, 2016 ). In line with these data, administration of a cocktail containing luteolin, another natural compound with predicted senolytic activity ( Vazquez et al, 2022 ), improved cognitive and neuropsychological function in moderate TBI patients ( Campolo et al, 2021 ). While these promising experimental and early-stage clinical studies suggest a potential therapeutic role for senolytics, additional pre-clinical and randomized controlled trials are needed to define the precise mechanism of action and establish the efficacy of senolytics to improve cognitive outcomes after TBI.…”

Clinical studies with drugs and biologics aimed at slowing or reversing normal aging processes—emerging results and future perspectives

“…Several senolytics, including D + Q and fisetin, are in development for cognitive decline [59], aging frailty, and skeletal health in normal postmenopausal women [7]. A clear advantage of some senolytics (quercetin, fisetin) is that they are natural products [60], but it seems too early to draw conclusions about clinical research with senolytic agents.…”

Selection of Mexican Medicinal Plants by Identification of Potential Phytochemicals with Anti-Aging, Anti-Inflammatory, and Anti-Oxidant Properties through Network Analysis and Chemoinformatic Screening

“…com/) [29] accessed on 15 August 2022 concerning compounds reported as anti-oxidants and anti-inflammatories was performed. To create the reference dataset, we use senolytic and anti-aging compounds obtained from previous work [30,31].…”