TY - JOUR
T1 - Shenshuai Yingyang Jiaonang ameliorates chronic kidney disease-associated muscle atrophy in rats by inhibiting ferroptosis mediated by the HIF-1α/SLC7A11 pathway
AU - Ju, Liliang
AU - Diao, Jianxin
AU - Zhang, Jiaxing
AU - Dai, Fahong
AU - Zhou, Hong
AU - Han, Zhongxiao
AU - Hu, Rong
AU - Pei, Tingting
AU - Wang, Fujing
AU - He, Zhuoen
AU - Fu, Xiuqiong
AU - Wang, Mingqing
AU - Xiao, Wei
AU - Ma, Yun
N1 - This work was supported by the National Natural Science Foundation of China under Grant 81973804 , 82004336 , 82074257 and 82174322; Youth Qihuang scholar program of the State Administration of traditional Chinese Medicine; the Natural Science Foundation of Guangdong Province under Grant 2019A1515011034 ; Guangdong Administration of Traditional Chinese Medicine under Grant 20200505160744.
Publisher Copyright:
© 2024 The Authors
PY - 2024/4/30
Y1 - 2024/4/30
N2 - Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy.Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.
AB - Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy.Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.
KW - Chronic kidney disease
KW - Ferroptosis
KW - Gpx4
KW - HIF-1α
KW - Network pharmacology
KW - Traditional Chinese medicine
UR - http://www.scopus.com/inward/record.url?scp=85190437463&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2024.e29093
DO - 10.1016/j.heliyon.2024.e29093
M3 - Journal article
AN - SCOPUS:85190437463
SN - 2405-8440
VL - 10
JO - Heliyon
JF - Heliyon
IS - 8
M1 - e29093
ER -
