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

Author:

Nguyen Ngoc Bao12,Le Tam Thi1,Kang Suk Woo1,Cha Kwang Hyun345ORCID,Choi Sowoon1,Youn Hye-Young1,Jung Sang Hoon14,Kim Myungsuk145ORCID

Affiliation:

1. Natural Product Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea

2. Department of Biochemistry and Molecular Biology, College of Dentistry, Gangneung Wonju National University, Gangneung 25451, Republic of Korea

3. Natural Product Informatics Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea

4. Division of Bio-Medical Science and Technology, KIST School, University of Science and Technology (UST), Daejeon 34113, Republic of Korea

5. Department of Convergence Medicine, Wonju College of Medicine, Yonsei University, Wonju 26426, Republic of Korea

Abstract

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.

Funder

Korea Institute of Science and Technology intramural research grants

Publisher

MDPI AG

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