International immunopharmacology · 2026
Apigenin-7-O-β-D-glucuronide prophylaxis ameliorates allergic airway inflammation by suppressing the TCF4-mediated Syk pathway.
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Yang Hui, Chen Yewei, Wang Yiping, Zhang Yinan, Li Yan, Liu Xiaoqin, Liu Yin, Tian Mi, Qian Ming, Zhou Lin, Zhang Jinping, Lin Mingbao, Liu Hang
Аннотация
BACKGROUND: Asthma has traditionally been characterized by persistent airway inflammation. Innovative therapeutic target and specific pharmacologic intervention remain essential for effectively managing inflammatory condition.
OBJECTIVES: This study aimed to investigate the preventive potential and mechanism of Apigenin-7-O-β-D-glucuronide (AOG) against asthma.
METHODS: OVA-induced allergic mice model and LPS-induced RAW264.7 macrophages model were established to assess the anti-inflammation effect of AOG. The role of transcription factor TCF4 on Syk-mediated asthma was explored via TCF4 gene silencing. Based on TCF4/Syk pathway, the anti-inflammatory mechanisms of AOG on asthma were elucidated.
RESULTS: AOG treatment during the sensitization phase significantly mitigated airway inflammation in OVA-induced allergic mice by improving lung pathology, suppressing inflammatory cell infiltration, lowering inflammatory cytokines levels, restoring Th1/Th2 balance, and decreasing serum immunoglobulin concentrations, evidenced by suppressing inflammatory mediators (NO, iNOS, COX-2, TNF-α, IL-1β, ROS) in LPS-induced RAW264.7 macrophages. Mechanistically, AOG inhibited the Syk/PKC/NF-κB/cPLA2 pathway in allergic mice lung tissues and macrophages. Furthermore, TCF4 was identified as the upstream regulator of Syk, which drives asthma pathogenesis. TCF4 silencing led to Syk inhibition and significantly alleviated inflammation response both in allergic mice and RAW264.7 macrophages. By co-treating with si-TCF4 or Syk inhibitor, results revealed that AOG's anti-inflammatory effects might be associated with the inhibition of TCF4/Syk.
CONCLUSION: This study demonstrates a novel therapeutic target TCF4 and related down-streaming Syk pathway potentially targeting by AOG for alleviating allergic airway inflammation.
OBJECTIVES: This study aimed to investigate the preventive potential and mechanism of Apigenin-7-O-β-D-glucuronide (AOG) against asthma.
METHODS: OVA-induced allergic mice model and LPS-induced RAW264.7 macrophages model were established to assess the anti-inflammation effect of AOG. The role of transcription factor TCF4 on Syk-mediated asthma was explored via TCF4 gene silencing. Based on TCF4/Syk pathway, the anti-inflammatory mechanisms of AOG on asthma were elucidated.
RESULTS: AOG treatment during the sensitization phase significantly mitigated airway inflammation in OVA-induced allergic mice by improving lung pathology, suppressing inflammatory cell infiltration, lowering inflammatory cytokines levels, restoring Th1/Th2 balance, and decreasing serum immunoglobulin concentrations, evidenced by suppressing inflammatory mediators (NO, iNOS, COX-2, TNF-α, IL-1β, ROS) in LPS-induced RAW264.7 macrophages. Mechanistically, AOG inhibited the Syk/PKC/NF-κB/cPLA2 pathway in allergic mice lung tissues and macrophages. Furthermore, TCF4 was identified as the upstream regulator of Syk, which drives asthma pathogenesis. TCF4 silencing led to Syk inhibition and significantly alleviated inflammation response both in allergic mice and RAW264.7 macrophages. By co-treating with si-TCF4 or Syk inhibitor, results revealed that AOG's anti-inflammatory effects might be associated with the inhibition of TCF4/Syk.
CONCLUSION: This study demonstrates a novel therapeutic target TCF4 and related down-streaming Syk pathway potentially targeting by AOG for alleviating allergic airway inflammation.