2. Academic Validation
  3. Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway

Aqueous extract of Descuraniae Semen attenuates lipopolysaccharide-induced inflammation by inhibiting ER stress and WNK4-SPAK-NKCC1 pathway

  • J Cell Mol Med. 2024 Aug;28(15):e18589. doi: 10.1111/jcmm.18589.
Po-Chun Hsieh 1 2,  Kun-Lun Huang 3 4,  Chung-Kan Peng 4 5,  Yao-Kuang Wu 6 7,  Guan-Ting Liu 8,  Chan-Yen Kuo 8,  Ming-Chieh Wang 9,  Chou-Chin Lan 6 7
Affiliations

Affiliations

  • 1 Department of Chinese Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • 2 Department of Chinese Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • 3 Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
  • 4 Division of Pulmonary and Critical Care, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan.
  • 5 Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 6 Division of Pulmonary Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • 7 School of Medicine, Tzu Chi University, Hualien, Taiwan.
  • 8 Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
  • 9 Department of Pharmacy, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
PMID: 39135202 DOI: 10.1111/jcmm.18589
Abstract

Sepsis causes systemic inflammatory responses and acute lung injury (ALI). Despite modern treatments, sepsis-related ALI mortality remains high. Aqueous extract of Descuraniae Semen (AEDS) exerts anti-endoplasmic reticulum (ER) stress, antioxidant and anti-inflammatory effects. AEDS alleviates inflammation and oedema in ALI. Sodium-potassium-chloride co-transporter isoform 1 (NKCC1) is essential for regulating alveolar fluid and is important in ALI. The NKCC1 activity is regulated by upstream with-no-lysine kinase-4 (WNK4) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). This study aimed to investigate the effects of AEDS on lipopolysaccharide (LPS)-induced ALI model in A549 cells, considering the regulation of ER stress, WNK4-SPAK-NKCC1 cascades, inflammation and Apoptosis. Cell viability was investigated by the CCK-8 assay. The expressions of the proteins were assessed by immunoblotting analysis assays. The levels of pro-inflammatory cytokines were determined by ELISA. The expression of cytoplasmic CA2+ in A549 cells was determined using Fluo-4 AM. AEDS attenuates LPS-induced inflammation, which is associated with increased pro-inflammatory cytokine expression and activation of the WNK4-SPAK-NKCC1 pathway. AEDS inhibits the WNK4-SPAK-NKCC1 pathway by regulating of Bcl-2, IP3R and intracellular CA2+. WNK4 expression levels are significantly higher in the WNK4-overexpressed transfected A549 cells and significantly decrease after AEDS treatment. AEDS attenuates LPS-induced inflammation by inhibiting the WNK4-SPAK-NKCC1 cascade. Therefore, AEDS is regarded as a potential therapeutic agent for ALI.

Keywords

Descuraniae Semen; acute lung injury; sepsis; sodium‐potassium‐chloride co‐transporter 1.

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