Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway

Nie, Lulin1,2,3; He, Kaiwu4,5; Qiu, Chaoming1,2,3; Li, Qing1,2; Xiong, Bocheng3; Gao, Chuanyue3; Zhang, Xiufen3; Jing, Mei1,2; Wu, Wei6,7; Liu, Jianjun3; Zhang, Gaoxiao1,2; Zhang, Zaijun1,2; Yang, Xifei3,8; Sun, Yewei1,2; Wang, Yuqiang1,2

2024-04-01

10.1016/j.biopha.2024.116415

BIOMEDICINE & PHARMACOTHERAPY   影响因子和分区

0753-3322

1950-6007

Tetramethylpyrazine nitrone (TBN), a novel derivative of tetramethylpyrazine (TMP) designed and synthesized by our group, possesses multi-functional mechanisms of action and displays broad protective effects in vitro and in animal models of age-related brain disorders such as stroke, Alzheimer's disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Parkinson's disease (PD). In the present report, we investigated the effects of TBN on aging, specifically on muscle aging and the associated decline of motor functions. Using a D-galactose-induced aging mouse model, we found that TBN could reverse the levels of several senescence and aging markers including p16, p21, ceramides, and telomere length and increase the wet-weight ratio of gastrocnemius muscle tissue, demonstrating its efficacy in ameliorating muscle aging. Additionally, the pharmacological effects of TBN on motor deficits (gait analysis, pole-climbing test and grip strength test), muscle fibrosis (hematoxylin & eosin (HE), Masson staining, and alpha SMA staining), inflammatory response (IL-1 beta, IL -6, and TNF-alpha), and mitochondrial function (ATP, mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) were also confirmed in the D-galactose-induced aging models. Further experiments demonstrated that TBN alleviated muscle aging and improved the decline of age-related motor deficits through an AMPK-dependent mechanism. These findings highlight the significance of TBN as a potential anti-aging agent to combat the occurrence and development of aging and age-related diseases.

Tetramethylpyrazine nitrone (TBN) Muscle aging Motor deficits Mitochondrial function AMPK signaling

SCI

英语

其他

Key Basic Research Program of Shenzhen Science and Technology Innovation Commission[JCYJ20200109150717745] ; National Natural Science Foundation of China["82073821","82171583","82301748"] ; Scientific Projects of Guangdong Province["2022A1515012655","2023A1515011983"] ; China Postdoctoral Science Foundation[2023M732374] ; Sanming Project of Medicine in Shenzhen[SZSM202211010] ; Shenzhen Key Medical Discipline Construction Fund[SZXK069]

Research & Experimental Medicine ; Pharmacology & Pharmacy

Medicine, Research & Experimental ; Pharmacology & Pharmacy

WOS:001206675600001

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER

Web of Science

1.Jinan Univ, Coll Pharm, State Key Lab Bioact Mol & Druggabil Assessment, Guangzhou Key Lab Innovat Chem Drug Res Cardiocere, Guangzhou 510632, Peoples R China
2.Jinan Univ, Coll Pharm, Inst New Drug Res, Huangpu Rd, Guangzhou 510632, Peoples R China
3.Shenzhen Ctr Dis Control & Prevent, Shenzhen Key Lab Modern Toxicol, Shenzhen Med Key Discipline Hlth Toxicol 2020 2024, Shenzhen 518055, Peoples R China
4.Jinan Univ, Shenzhen Peoples Hosp, Clin Med Coll 2, Dept Anesthesiol, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China
5.Southern Univ Sci & Technol, Affiliated Hosp 1, 1017 Dongmen North Rd, Shenzhen 518020, Peoples R China
6.Jinan Univ, Integrated Chinese & Western Med Postdoctoral Res, Guangzhou, Peoples R China
7.Southern Med Univ, Shenzhen Hosp, Dept Hematol, Shenzhen, Peoples R China
8.Shenzhen Ctr Dis Control & Prevent, Key Lab Modern Toxicol Shenzhen, Shenzhen, Peoples R China

Nie, Lulin,He, Kaiwu,Qiu, Chaoming,et al. Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway[J]. BIOMEDICINE & PHARMACOTHERAPY,2024,173.

Nie, Lulin.,He, Kaiwu.,Qiu, Chaoming.,Li, Qing.,Xiong, Bocheng.,...&Wang, Yuqiang.(2024).Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway.BIOMEDICINE & PHARMACOTHERAPY,173.

Nie, Lulin,et al."Tetramethylpyrazine Nitrone alleviates D-galactose-induced murine skeletal muscle aging and motor deficits by activating the AMPK signaling pathway".BIOMEDICINE & PHARMACOTHERAPY 173(2024).