TY - JOUR
T1 - Glabridin Suppresses LPS-Induced Inflammatory Cascade by Targeting AMPK/JAK2/STAT3 Pathways in Macrophages
AU - Hou, Shaw Min
AU - Cheng, Ssu Wei
AU - Lin, Kao Chang
AU - Yen, Ting Lin
AU - Hsia, Chih Wei
AU - Huang, Wei Chieh
AU - Sheu, Joen Rong
AU - Hsia, Chih Hsuan
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12
Y1 - 2024/12
N2 - Objectives: Inflammation, a crucial biological response defending the body against harmful stimuli, has been a central focus in medicinal research. Licorice root, rich in bioactive compounds, contains glabridin (GBD), a renowned natural flavonoid with anti-inflammatory and antioxidant properties. Despite its recognition, the precise molecular mechanisms underlying GBD's anti-inflammatory effects remain a subject of ongoing investigation. Methods: This study explores the impact of GBD on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages, aiming to unravel intricate molecular pathways, specifically focusing on the potential involvement of the adenosine monophosphate-activated protein kinase (AMPK)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. The study first determined the effective dose of GBD by measuring its impact on the production of pro-inflammatory mediators in response to LPS stimulation. The novelty of this study lies in subsequent examination of GBD's effects under LPS-induced inflammation, an aspect that has not been thoroughly explored in previous research. Results: GBD inhibits the production of LPS-induced pro-inflammatory cytokines and nitric oxide (NO). It also suppresses the expression of iNOS and IL-1β induced by LPS. Furthermore, GBD attenuates LPS-induced phosphorylation of JAK2 and STAT3, concurrently inhibiting AMPK phosphorylation. The study further elucidates the relationship between AMPK and JAK2/STAT3 using JAK2 inhibitor, AG490, and AMPK inhibitor, compound C (CC). Importantly, CC not only inhibits the expression of AMPK but also suppresses the expression of JAK2 and STAT3. This observation strongly suggests that GBD modulates the AMPK/JAK2/STAT3 signaling pathways in LPS-stimulated macrophages. Conclusion: This study reveals that GBD is a promising anti-inflammatory agent with novel inhibitory effects on the AMPK/JAK2/STAT3 pathway, highlighting its potential therapeutic value for inflammatory diseases.
AB - Objectives: Inflammation, a crucial biological response defending the body against harmful stimuli, has been a central focus in medicinal research. Licorice root, rich in bioactive compounds, contains glabridin (GBD), a renowned natural flavonoid with anti-inflammatory and antioxidant properties. Despite its recognition, the precise molecular mechanisms underlying GBD's anti-inflammatory effects remain a subject of ongoing investigation. Methods: This study explores the impact of GBD on lipopolysaccharide (LPS)-induced inflammation in RAW264.7 macrophages, aiming to unravel intricate molecular pathways, specifically focusing on the potential involvement of the adenosine monophosphate-activated protein kinase (AMPK)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. The study first determined the effective dose of GBD by measuring its impact on the production of pro-inflammatory mediators in response to LPS stimulation. The novelty of this study lies in subsequent examination of GBD's effects under LPS-induced inflammation, an aspect that has not been thoroughly explored in previous research. Results: GBD inhibits the production of LPS-induced pro-inflammatory cytokines and nitric oxide (NO). It also suppresses the expression of iNOS and IL-1β induced by LPS. Furthermore, GBD attenuates LPS-induced phosphorylation of JAK2 and STAT3, concurrently inhibiting AMPK phosphorylation. The study further elucidates the relationship between AMPK and JAK2/STAT3 using JAK2 inhibitor, AG490, and AMPK inhibitor, compound C (CC). Importantly, CC not only inhibits the expression of AMPK but also suppresses the expression of JAK2 and STAT3. This observation strongly suggests that GBD modulates the AMPK/JAK2/STAT3 signaling pathways in LPS-stimulated macrophages. Conclusion: This study reveals that GBD is a promising anti-inflammatory agent with novel inhibitory effects on the AMPK/JAK2/STAT3 pathway, highlighting its potential therapeutic value for inflammatory diseases.
KW - adenosine monophosphate-activated protein kinase
KW - Glabridin
KW - inflammation
KW - Janus kinase 2/signal transducer and activator of transcription 3
KW - lipopolysaccharide
KW - macrophages
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U2 - 10.1177/1934578X241296724
DO - 10.1177/1934578X241296724
M3 - Article
AN - SCOPUS:85211901856
SN - 1934-578X
VL - 19
JO - Natural Product Communications
JF - Natural Product Communications
IS - 12
ER -