An ethanolic extract of Artemisia dracunculus L. regulates gene expression of ubiquitin–proteasome system enzymes in skeletal muscle: Potential role in the treatment of sarcopenic obesity

Abstract

Objective Obesity is linked to insulin resistance, a primary component of metabolic syndrome and type 2 diabetes. The problem of obesity-related insulin resistance is compounded when age-related skeletal muscle loss, called sarcopenia, occurs with obesity. Skeletal muscle loss results from elevated levels of protein degradation and prevention of obesity-related sarcopenic muscle loss will depend on strategies that target pathways involved in protein degradation. An extract from Artemisia dracunculus, termed PMI5011 improves insulin signaling and increases skeletal muscle myofiber size in a rodent model of obesity-related insulin resistance. This study examines the effect of PMI5011 on the ubiquitin-proteasome system, a central regulator of muscle protein degradation. Materials and Methods Gastrocnemius and vastus lateralis skeletal muscle was obtained from KK-Ay obese diabetic mice fed a control or 1% (w/w) PMI5011-supplemented diet. Regulation of genes encoding enzymes of the ubiquitin-proteasome system was determined using realtime qRT-PCR. Results While MuRF-1 ubiquitin ligase gene expression is consistently down-regulated in skeletal muscle, atrogin-1, Fbxo40 and Traf6 expression is differentially regulated by PMI5011. Genes encoding other enzymes of the ubiquitin-proteasome system ranging from ubiquitin to ubiquitin-specific proteases are also regulated by PMI5011. In addition, expression of the gene encoding the microtubule-associated protein-1 light chain 3 (LC3), a ubiquitin-like protein pivotal to autophagy-mediated protein degradation, is down-regulated by PMI5011 in the vastus lateralis. Conclusion PMI5011 alters the gene expression of ubiquitin-proteasome system enzymes that are essential regulators of skeletal muscle mass. This suggests PMI5011 has therapeutic potential in the treatment of obesity-linked sarcopenia by regulating ubiquitin-proteasome-mediated protein degradation.

Effects of conjugated linoleic acid/n-3 and resistance training on muscle quality and expression of atrophy-related ubiquitin ligases in middle-aged mice with high-fat dietinduced obesity

“…Muscle atrophy induced by an HFD is explained through various mechanisms, including an imbalance between protein synthesis and degradation. The ubiquitin proteasome system catalyzes the degradation of most cellular proteins 46 and is one of the major pathways regulating muscle protein degradation; this system plays a central role in controlling muscle size 1 . Atrogin1 and MuRF1 are two E3 ubiquitin ligases that are important regulators of ubiquitin-mediated protein degradation in skeletal muscle.…”

The Interactome in the Evolution From Frailty to Sarcopenic Dependence

“…AMPK activates the autophagy-initiating serine/threonine protein kinase ULK1 (ULK1), whereas the PI3K/Akt/mTOR axis acts as a negative regulator of autophagy by blocking the activation of ULK1. Several studies have shown a clear effect of defective autophagy on muscle under conditions of obesity, where reduced activation of AMPK and increased induction of AKT and mTOR were found ( Turpin et al, 2009 ; Kirk-Ballard et al, 2014 ; Barlow and Thomas, 2015 ; Ryu et al, 2020 ). However, the interplay between overweight and autophagy and its implication on muscle wasting are far from fully understood.…”

Phytochemical Research and Evaluation of Tarragon (Artemisia dracunculus L.) as a Food Additive

“…As a result of its rich content, it is known that tarragon plant has anti-inflammatory, antidiabetic, antiseptic activities and is also effective in insomnia, allergic rashes and dermatological treatments. In the studies conducted, it has been stated that the extracts of the plant reduce inflammation in the human skeletal muscular system, improve insulin sensitivity and have a strong healing effect in the treatment of muscle loss and obesity due to old age (Obolskiy et al, 2011;Kirk-Ballard et al, 2014;Vandanmagsar et al, 2014;Karaman and Sezgin, 2022).…”