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Phytomedicine

Phytomedicine

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Cinnamic Acid Prevents Skeletal Muscle Atrophy in Nephrectomized Rats by Modulating Apoptosis and Endoplasmic Reticulum Stress

Published:30 October 2025 DOI: 10.1016/j.phymed.2025.157499 PMID: 41206996
Chi Zhang , Hao Wang , Zhuoen He , Jinyue He , Fujing Wang , Shihua Yan , Yuzhang Sheng , Ningning Yuan , Yuchi Chen , Xinyao Xu , Yuying Huang , Rong Hu , Mingqing Wang , Wei Xiao

Abstract

Background

Skeletal muscle atrophy is frequently observed in patients with chronic kidney disease (CKD), exacerbating disease progression and diminishing patients’ quality of life. Cinnamic acid (CINN), a low-toxicity phenolic acid derived from Cinnamomum cassia (L.) J. Presl, remains uncharacterized in terms of its efficacy and mechanism against CKD-induced skeletal muscle atrophy.

Purpose

To assess the protective impact of CINN on skeletal muscle atrophy in CKD rats and elucidate its potential molecular mechanisms.

Methods

A 5/6 nephrectomy (5/6 Nx) rat model was constructed and treated with varying concentrations of CINN via gavage. Potential targets and pathways of CINN were identified using network pharmacology and validated through transmission electron microscopy, TUNEL staining, quantitative real-time PCR, and western blot analysis. To confirm whether CINN’s therapeutic effects depended on its interaction with the identified target, in vitro experiments employed specific inhibitors to reverse the observed effects.

Results

CINN therapy enhanced body and muscle mass, serum albumin concentrations, and various clinical markers. Western blot analysis revealed that CINN inhibited protein proteolysis and promoted protein synthesis in the 5/6 Nx group. Network pharmacology and experimental validation indicated that CINN may alleviate skeletal muscle atrophy by reducing apoptosis and endoplasmic reticulum stress through targeting heat shock protein 90 alpha family class A member 1 (HSP90AA1). In vitro experiments using an HSP90AA1 antagonist demonstrated that the muscle-protective effects of CINN were partially reversed when HSP90AA1 was inhibited.

Conclusion

CINN may alleviate CKD-induced skeletal muscle atrophy by inhibiting apoptosis and endoplasmic reticulum stress via its action on HSP90AA1.

Substances (8)

Materials
Procduct Name CAS Molecular Formula Supplier Price
3-INDOXYL SULFATE POTASSIUM SALT 2642-37-7 C8H8KNO4S 139 suppliers $24.00-$5192.00
3-INDOXYL SULFATE POTASSIUM SALT 2642-37-7 C8H8KNO4S 139 suppliers $24.00-$5192.00
3-INDOXYL SULFATE POTASSIUM SALT 2642-37-7 C8H8KNO4S 139 suppliers $24.00-$5192.00
3-INDOXYL SULFATE POTASSIUM SALT 2642-37-7 C8H8KNO4S 139 suppliers $24.00-$5192.00
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 93 suppliers $70.00-$7016.50
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 93 suppliers $70.00-$7016.50
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 93 suppliers $70.00-$7016.50
Z-Vad-fmk, non-methylated 161401-82-7 C21H28FN3O7 93 suppliers $70.00-$7016.50

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