1. Academic Validation
  2. Perilla frutescens L. alleviates trimethylamine N-oxide-induced apoptosis in the renal tubule by regulating ASK1-JNK phosphorylation

Perilla frutescens L. alleviates trimethylamine N-oxide-induced apoptosis in the renal tubule by regulating ASK1-JNK phosphorylation

  • Phytother Res. 2022 Nov 24. doi: 10.1002/ptr.7684.
Chen Yong 1 2 Guoshun Huang 1 2 Hongwei Ge 1 2 Yiye Zhu 1 2 Yang Yang 1 2 Yongfei Yu 1 2 Fang Tian 3 Kun Gao 1 4 Enchao Zhou 1 4
Affiliations

Affiliations

  • 1 Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People's Republic of China.
  • 2 No. 1 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, People's Republic of China.
  • 3 Research Center of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People's Republic of China.
  • 4 Inheritance Studio of Traditional Chinese Medicine Master Yanqin Zou, Jiangsu Province Hospital of Chinese Medicine, Nanjing, People's Republic of China.
Abstract

Trimethylamine N-oxide (TMAO) is associated with overall mortality in patients with chronic kidney disease (CKD). Previous findings suggest that P. frutescens (L.) can alleviate renal injury, but its effects and mechanisms underlying alleviation of TMAO-induced kidney damage remain unclear. In this study, a TMAO injury model, in vivo and in vitro, was established to clarify the effects and mechanisms of P. frutescens in alleviating TMAO-induced kidney injury. The results show that TMAO (60 mM/L) can induce the activation of Apoptosis signal-regulating kinase 1 (ASK1)-c-Jun N-terminal kinase (JNK), thus aggravating downstream cell Apoptosis in vitro. The study also found that P. frutescens aqueous extract (PFAE) (5 mg/mL) can inhibit TMAO-induced Apoptosis by downregulating ASK1-JNK phosphorylation. In the in vivo experiments, it was demonstrated that TMAO can increase the levels of blood urea nitrogen and Cystatin C, aggravating renal tubular epithelial Apoptosis. The results also show that PFAE can reduce TMAO-induced renal damage by inhibiting ASK1-JNK phosphorylation in vivo. Our findings confirmed that P. frutescens can alleviate TMAO-induced renal tubule Apoptosis by regulating ASK1-JNK phosphorylation, indicating that P. frutescens may be an effective treatment for alleviating TMAO damage in CKD.

Keywords

ASK1-JNK phosphorylation; Perilla frutescens L.; apoptosis; renal tubular epithelial cell; trimethylamine N-oxide.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-18938
    98.99%, ASK1 Inhibitor