Discovery of diarylheptanoids that activate α7 nAchR-JAK2-STAT3 signaling in macrophages with anti-inflammatory activity in vitro and in vivo

Last modified: May 26, 2022
You are here:
Estimated reading time: 1 min
Research Article: Discovery of diarylheptanoids that activate α7 nAchR-JAK2-STAT3 signaling in macrophages with anti-inflammatory activity in vitro and in vivo
Author|ผู้เขียน: Yuan Lin, Kanjana Wongkrajang, Xiaofei Shen, Ping Wang , Zongyuan Zhou, Thipphawan Chuprajob, Nilubon Sornkaew, Na Yang, Lijuan Yang, Xiaoxia Lu, Ratchanaporn Chokchaisiri, Apichart Suksamrarn, Guolin Zhang, Fei Wang | ทิพวรรณ จูประจบ
Email: thipphawan@siam.edu
Department|Faculty: Department of Chemistry, Faculty of Science, Siam University, Bangkok 10160
ภาควิชา|คณะ: ภาควิชาเคมี คณะวิทยาศาสตร์ มหาวิทยาลัยสยาม กรุงเทพฯ 10160
Published: Bioorganic & Medicinal Chemistry Volume 66, 15 July 2022, 116811

Citation

Yuan L., Wongkrajang K., Xiaofei S., Ping W. , Zongyuan Z., Chuprajob T., Sornkaew N., Na Y., Lijuan Y., Xiaoxia L., Chokchaisiri R., Suksamrarn A., Guolin Z., & Fei W. (2022). Discovery of diarylheptanoids that activate α7 nAchR-JAK2-STAT3 signaling in macrophages with anti-inflammatory activity in vitro and in vivo. Bioorganic & Medicinal Chemistry, 66(116811), 1-17.


ABSTRACT

Acute inflammatory diseases, such as sepsis, are life-threatening illnesses. Regulating the α7 nicotinic acetylcholine receptor (α7 nAchR)-mediated signaling may be a promising strategy to treat sepsis. Diarylheptanoids have long been found to exhibit anti-inflammatory properties. However, the possible mechanism of diarylheptanoids has rarely been investigated. In this study, we isolated and synthesized 49 diarylheptanoids and analogues and evaluated their anti-inflammatory activities. Among them, compounds 28 and 40 markedly blocked lipopolysaccharide (LPS)-induced production of nitric oxide (NO), interleukin-1β (IL-1β) and interleukin-6 in murine RAW264.7 cells. Furthermore, compounds 28 and 40 also effectively  attenuated LPS-induced sepsis, acute lung injury, and cytokines release in vivo. Mechanistically, compounds 28 and 40 significantly induced phosphorylation of janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling and suppression of nuclear factor-κB (NF-κB) pathway. Furthermore, blocking α7 nAchR could effectively abolish compounds 28 and 40-mediated activation of JAK2-STAT3 signaling as well as inhibition of NF-κB activation and NO production in LPS-exposed RAW264.7 cells. Collectively, our findings have identified a new diarylheptanoid, compound 28, as an agonist of α7 nAchR-JAK2-STAT3 signaling, which can be potentially developed as a valuable candidate for the treatment of sepsis, and provide a new lead structure for the development of antiinflammatoryagents targeting α7 nAchR-JAK2-STAT3 signaling.

Keywords:  Diarylheptanoid, α7 nAchR, JAK2-STAT3, NF-κB, Sepsis.


Discovery of diarylheptanoids that activate α7 nAchR-JAK2-STAT3 signaling in macrophages with anti-inflammatory activity in vitro and in vivo

Faculty of Science, Siam University, Bangkok, Thailand

Tags:
Was this article helpful? บทความนี้เป็นประโยชน์หรือไม่?
ไม่ / Dislike 0
Views: 50
Previous: การเพิ่มประสิทธิภาพกระบวนการอนุมัติขนย้ายสินค้าโดยใช้เหมืองกระบวนการ
Next: การลดขั้นตอนการขออนุมัติงบประมาณภายในองค์กรด้วยระบบสารสนเทศ