1. Academic Validation
  2. Acetylcorynoline alleviates acute liver injury via inhibiting TLR4/JNK/NF-ĸB pathway Based on RNA-seq and molecular docking in vivo and in vitro

Acetylcorynoline alleviates acute liver injury via inhibiting TLR4/JNK/NF-ĸB pathway Based on RNA-seq and molecular docking in vivo and in vitro

  • Int Immunopharmacol. 2024 Dec 25;143(Pt 3):113550. doi: 10.1016/j.intimp.2024.113550.
Jun Fu 1 Zhenxu Zhang 1 Yaning Zhao 1 Xin Li 1 Cuihua Jiang 1 Haoran He 1 Jiege Huo 2 Qi Xiao 3 Jie Wu 3 Fenxia Zhu 4 Jiaquan Chen 5
Affiliations

Affiliations

  • 1 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China.
  • 2 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Jiangsu Clinical Innovation Center of Digestive Cancer of Traditional Chinese Medicine, Nanjing 210028, PR China.
  • 3 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China.
  • 4 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028, PR China; Key Laboratory of New Drug Delivery Systems of Chinese Materia Medica, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, PR China. Electronic address: zfxcjq@126.com.
  • 5 Department of Chemistry, School of Science, China Pharmaceutical University, Nanjing 211198, PR China. Electronic address: brunochen@cpu.edu.cn.
Abstract

Acute liver injury is characterized by massive inflammatory cell infiltration, destruction of liver structure and abnormalities in liver function. Acetylcorynoline (AC) is one of the main chemical components of Corydalis bungeana Turcz. which has been shown to have a protective effect against acute liver injury. However, Whether AC is protective against acute liver injury remains unclear. This study aimed to explore the protective mechanism of AC against acute liver injury from in vivo as well as experiments in vitro. In experimental in vivo studies, AC pretreatment reduced the serum levels of ALT and AST and inhibited the expression of inflammatory factors in the liver of LPS/D-GalN-induced mice and alcohol liver disease mice. RNA-sequencing and molecular docking were used to predict that AC exerts its anti-inflammatory effects through the Toll-like Receptor signaling pathway. Using RT-qPCR and Western blotting to detect expression levels of key genes and nodal proteins of the Toll-like Receptor signaling pathway, AC was found to inhibit the phosphorylation of nuclear factor-kappaB (NF-ĸB) and c-Jun amino-terminal kinase (JNK). This finding was validated in cellular experiments. In conclusion, AC exerts its anti-hepatic injury effect by suppressing inflammation through inhibition of the TLR4/JNK/NF-ĸB pathway.

Keywords

Acetylcorynoline; Acute liver injury; Liver inflammation; Molecular docking; RNA-Seq.

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