2. Academic Validation
  3. Isoferulic Acid Mitigates Acute Lung Injury Induced by Sepsis Through the Inhibition of JAK2

Isoferulic Acid Mitigates Acute Lung Injury Induced by Sepsis Through the Inhibition of JAK2

  • Phytother Res. 2025 Jul;39(7):3225-3240. doi: 10.1002/ptr.8526.
Tong Xu 1,  Honglin Xu 2,  Jiayi Zhang 1,  Guanghong Chen 3 4 5,  Xin Han 1,  Guoyong Zhang 1,  Changlei Hu 1,  Mingjie Pang 1,  Jian Gan 6,  Yue Hua 1,  Bin Liu 7,  Yingchun Zhou 1 8
Affiliations

Affiliations

  • 1 School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China.
  • 2 The Tenth Affiliated Hospital, Southern Medical University (Dongguan People's Hospital), Dongguan, China.
  • 3 Department of Cardiovascular Medicine, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China.
  • 4 The First Affiliated Hospital of Guangzhou University of Chinese Medicine/Post-Doctoral Research Station, Guangzhou, Guangdong, China.
  • 5 Guangdong Clinical Research Academy of Chinese Medicine, Guangzhou, Guangdong, China.
  • 6 Division of Hepatobiliopancreatic Surgery, Department of General Surgery, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, China.
  • 7 Department of Traditional Chinese Medicine (Institute of Integration of Traditional and Western Medicine of Guangzhou Medical University, State Key Laboratory of Respiratory Disease), The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China.
  • 8 Department of Traditional Chinese Medicine, Nanfang Hospital (ZengCheng Branch), Southern Medical University, Guangzhou, China.
PMID: 40485414 DOI: 10.1002/ptr.8526
Abstract

Sepsis-induced acute lung injury (ALI), among the most severe organ damages, induces irreversible lung injuries and results in a high mortality rate. The occurrence of ALI is highly correlated with the out-of-control inflammatory factors. Therefore, inflammatory inhibition is a crucial measure for treating sepsis-induced ALI. Isoferulic acid (IFA) possesses effective anti-inflammatory effects; however, its role in ALI and its molecular mechanisms remain to be further explored. This work focused on analyzing the possible role of IFA in combating sepsis-induced IFA and exploring the associated mechanisms. CLP mice and LPS-induced RAW264.7 cells were employed as the in vivo and in vitro experimental models. Effects of IFA on inflammation and its mechanisms were assessed using network pharmacology, molecular docking, surface plasmon resonance imaging (SPRi), qRT-PCR, ELISA, immunofluorescence analysis, and Western blot. According to in vivo and in vitro experimental results, IFA down-regulated inflammatory factors TNF-α, IL-6, and IL-1β in CLP mice and LPS-exposed RAW264.7 cells. IFA treatment significantly improved the sepsis-induced inflammation and protected lung function. Furthermore, as revealed by network pharmacology analysis, JAK2 was an important target for the interaction between IFA and ALI. Moreover, molecular docking and SPR results demonstrated a close binding between IFA and JAK2. Further research revealed that IFA suppressed JAK2/STAT3 pathway activation; besides, the therapeutic effect of IFA on ALI was not enhanced by incubation with the JAK2 Inhibitor (AG490). Our results offer the preliminary evidence that IFA can restore the impaired function of CLP mice and RAW264.7 cells by alleviating the sepsis-induced inflammation. Additionally, IFA mitigates the sepsis-induced ALI through inhibiting JAK2/STAT3 pathway activation. Therefore, IFA may potentially be used to treat sepsis-induced lung injury.

Keywords

JAK2; acute lung injury; isoferulic acid; lipopolysaccharide; network pharmacology; sepsis.

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