Hispaglabridin B, a constituent of liquorice identified by a bioinformatics and machine learning approach, relieves protein‐energy wasting by inhibiting forkhead box O1

Abstract

Background and Purpose Liquorice is the root of Glycyrrhiza glabra, which is a popular food in Europe and China that has previously shown benefits for skeletal fatigue and nutrient metabolism. However, the mechanism and active ingredients remain largely unclear. The aim of this study was to investigate the active ingredients of liquorice for muscle wasting and elucidate the underlying mechanisms. Experimental Approach RNA‐Seq and bioinformatics analysis were applied to predict the main target of liquorice. A machine learning model and a docking tool were used to predict active ingredients. Isotope labelling experiments, immunostaining, Western blots, qRT‐PCR, ChIP‐PCR and luciferase reporters were utilized to test the pharmacological effects in vitro and in vivo. The reverse effects were verified through recombination‐based overexpression. Key Results The liposoluble constituents of liquorice improved muscle wasting by inhibiting protein catabolism and fibre atrophy. We further identified FoxO1 as the target of liposoluble constituents of liquorice. In addition, hispaglabridin B (HB) was predicted as an inhibitor of FoxO1. Further studies determined that HB improved muscle wasting by inhibiting catabolism in vivo and in vitro. HB also markedly suppressed the transcriptional activity of FoxO1, with decreased expression of the muscle‐specific E3 ubiquitin ligases MuRF1 and Atrogin‐1. Conclusions and Implications HB can serve as a novel natural food extract for preventing muscle wasting in chronic kidney disease and possibly other catabolic conditions.

Artificial Intelligence in Nutrients Science Research: A Review

“…They used a machine learning model and a docking tool to predict active ingredients. They identified hispaglabridin B (HB) as a possible inhibitor of FoxO1 which was useful for preventing muscle wasting in chronic kidney disease [ 36 ].…”

Paeoniflorin Ameliorates Skeletal Muscle Atrophy in Chronic Kidney Disease via AMPK/SIRT1/PGC-1α-Mediated Oxidative Stress and Mitochondrial Dysfunction

“…In recent years, herbal medicines have attracted a large amount of attention for their potential treatment of CKD. Despite the discovery and extensive application of drug prediction tools for drug effectiveness, there is still a lack of drugs that effectively improve skeletal muscle atrophy in CKD ( Huang et al, 2019 ). Earlier, extensive researcher conducted active ingredients in herbal medicines to control CKD ( Chen et al, 2021 ).…”

Anti-inflammatory and antimicrobial properties of some licorice metabolites

“…Формононетин связывается с эстрогенными рецепторами (ER, эстрогенные рецепторы), модулируя их активность, а также обладает противовоспалительными и антиоксидантными свой ствами [22]. Гиспаглабридин-В обладает крайне выраженными антиоксидантыми свой ствами, способен снижать транскрипционную активность FoxO1 (транскрипционный фактор, участвует в росте органов, реакции тканей на инсулин, регуляции клеточного цикла, ангиогенезе) из-за уменьшения экспрессии мышечно-специфических E3-убиквитин-лигаз MuRF1 (Убиквитин-белковая лигаза E3 TRIM63 или Muscle Ring-Finger Protein-1) и Atrogin1 (F-box protein 32 или FBXO32) [14,15,16,[19][20][21][22][23].…”