T-cell activation-inhibitory assay: a proposed novel method for screening caloric restriction mimetics

Abstract

Caloric restriction (CR) is a major contributor to good health and longevity. CR mimetics (CRMs) are a group of plant-derived compounds capable of inducing the benefits of CR. Since a longevity gene, SIRT1, inhibits T-cell activation and SIRT1 loss results in increased T-cell activation, we hypothesized that compounds capable of activating SIRT1 signaling can inhibit T-cell activation and function as CRMs. Thus we propose, in the present study, the application of a T-cell activation-inhibitory assay to screen candidate CRMs. Well-known CRMs, such as resveratrol, butein, and fisetin, suppressed the anti-CD3/CD28 antibody-induced activation of mouse spleen T-cells. We next randomly assessed 68 plant-derived compounds for screening novel candidate CRMs using this bioassay and found that all four compounds showing IC 50 values <5 μM, such as curcumin, α-mangostin, nobiletin, and heptamethoxyflavone, have beneficial functions for health such as anti-inflammatory effect. These results suggest that the T-cell activation-inhibitory assay can be used to screen candidate CRMs.

Tipepidine activates AMPK and improves adipose tissue fibrosis and glucose intolerance in high‐fat diet‐induced obese mice

“…32 We have previously reported a practical approach for screening healthy compounds with metabolism-improving actions. 33 Using this screening method, we have identified phytochemicals, including cynandione A 34,35 and N-caffeoyltryptophan, 36 with beneficial effects on metabolism. In a preliminary experiment, we applied this screening method for DR and found a candidate compound, tipepidine (TP; chemically 3-[di-2-thienylmethylene]-1-methylpiperid ine) (Figure 1A), a non-narcotic antitussive drug, which has been used for more than 60 years since its approval in Japan in 1959, and its safety for use in all age groups is well established.…”

“…We have previously reported a practical approach for screening healthy compounds with metabolism‐improving actions 33 . Using this screening method, we have identified phytochemicals, including cynandione A 34,35 and N ‐caffeoyltryptophan, 36 with beneficial effects on metabolism.…”

T-Cell Activation-Inhibitory Assay to Screen Caloric Restriction Mimetics Drugs for Drug Repositioning

“…Kaneko and Nagashima 6) proposed the idea of drug repositioning based on clinical evidence from a voluntary reporting database, such as the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS). Yamamoto et al 7) reported that nafamostat mesylate, a drug used for disseminated intravascular coagulation (DIC), inhibits severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in vitro, suggesting the possibility of repositioning this drug to treat coronavirus pneumonia disease . In this report, we propose another approach of drug repositioning using an experimental assay system.…”