The cannabinoid receptor 1 antagonist AM6545 stimulates the Akt-mTOR axis and in vivo muscle protein synthesis in a dexamethasone-induced muscle atrophy model

Dalle, Sebastiaan; Schouten, Moniek; Ramaekers, Monique; Koppo, Katrien

doi:10.1016/j.mce.2023.111854

Cited by 2 publications

(2 citation statements)

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“…CB1 inhibition promotes mitochondrial metabolism, insulin sensitivity, and muscle growth, while CB2 activation enhances muscle metabolism and regeneration by upregulating MyoD and myogenin expression [53]. Consistent with this, studies involving the CB1 antagonist AM6475 or CB2 knockdown have demonstrated significant increases in muscle mass, grip strength, and physical endurance in mice [34,35,54]. Moreover, a mouse study with cancer-induced cachexia revealed that a selective CB2 agonist or overexpression of CB2 reduced muscle wasting and improved exercise performance [36].…”

Section: Discussionmentioning

confidence: 80%

“…Cannabinoid receptors CB1 and CB2 influence diverse physiological processes, including appetite, metabolism, and muscle function [ 32 , 33 ]. Previous studies suggest that CB1 inhibition or CB2 activation promotes muscle mass, strength, and exercise performance in mice [ 34 , 35 , 36 ]. We employed molecular docking to assess whether CC-isolated compounds modulate CB1 or CB2, potentially mitigating muscle atrophy.…”

Section: Resultsmentioning

confidence: 99%

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Cornflower Extract and Its Active Components Alleviate Dexamethasone-Induced Muscle Wasting by Targeting Cannabinoid Receptors and Modulating Gut Microbiota

Nguyen,

Le,

Kang

et al. 2024

Nutrients

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Sarcopenia, a decline in muscle mass and strength, can be triggered by aging or medications like glucocorticoids. This study investigated cornflower (Centaurea cyanus) water extract (CC) as a potential protective agent against DEX-induced muscle wasting in vitro and in vivo. CC and its isolated compounds mitigated oxidative stress, promoted myofiber growth, and boosted ATP production in C2C12 myotubes. Mechanistically, CC reduced protein degradation markers, increased mitochondrial content, and activated protein synthesis signaling. Docking analysis suggested cannabinoid receptors (CB) 1 and 2 as potential targets of CC compounds. Specifically, graveobioside A from CC inhibited CB1 and upregulated CB2, subsequently stimulating protein synthesis and suppressing degradation. In vivo, CC treatment attenuated DEX-induced muscle wasting, as evidenced by enhanced grip strength, exercise performance, and modulation of muscle gene expression related to differentiation, protein turnover, and exercise performance. Moreover, CC enriched gut microbial diversity, and the abundance of Clostridium sensu stricto 1 positively correlated with muscle mass. These findings suggest a multifaceted mode of action for CC: (1) direct modulation of the muscle cannabinoid receptor system favoring anabolic processes and (2) indirect modulation of muscle health through the gut microbiome. Overall, CC presents a promising therapeutic strategy for preventing and treating muscle atrophy.

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