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Phytomedicine

Phytomedicine

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Araloside A alleviates sepsis-induced acute lung injury via PHD2/HIF-1α in macrophages.

Published:20 September 2024 DOI: 10.1016/j.phymed.2024.156089 PMID: 39366158
Jihong Ma , Jie Wang , Jiaqi Wang , Jie Zhou , Chunhui Jiang , Wenhao Chen , Xinbo Zhang , Jingye Pan , Junjie Zhu , Mingwei Chen

Abstract

Background

Acute lung injury (ALI)-induced acute respiratory syndromes is a critical pathological sequala of sepsis. Araloside A (ARA), extracted from Aralia taibaiensis, possesses anti-oxidative and pro-apoptotic effects, as well as a protective effect against inflammatory diseases such as gastric ulcers. However, its impact on progression of ALI remains unknown. This study seeks to assess the therapeutic effect of ARA in sepsis-induced ALI, and to elucidate the underlying mechanism.

Methods

Sepsis-induced ALI was induced in C57BL/6 mice using lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) along with simultaneous administration of ARA. In vitro, bone marrow-derived macrophages (BMDMs) and RAW264.7 cells were exposed to LPS to activate proinflammatory macrophages in the presence/absence of ARA. RNA sequencing of BMDMs was then conducted to elucidate the detailed mechanism.

Results

Treatment of mice with ARA led to a significant reduction in serum level of inflammatory cytokines, ameliorated sepsis-induced ALI (i.e., impaired barrier integrity, cell apoptosis), and increased survival of septic mice. In vitro, ARA effectively inhibited activation of proinflammatory BMDMs. In addition, RNA sequencing revealed that the PHD2/HIF-1α signaling played a critical role in the anti-inflammatory effects of ARA. ARA suppressed proinflammatory macrophages to ameliorate lung inflammation in septic mice by restoring PHD2/HIF-1α signaling.

Conclusions

ARA prevented mice from the fatal effects of sepsis by restoring PHD2/HIF-1α signaling, thereby inhibiting activation of proinflammatory macrophages. These findings suggest that ARA could be a promising therapy for sepsis-induced ALI.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
araloside A 7518-22-1 C47H74O18 152 suppliers $32.00-$1425.00
araloside A 7518-22-1 C47H74O18 152 suppliers $32.00-$1425.00
araloside A 7518-22-1 C47H74O18 152 suppliers $32.00-$1425.00
araloside A 7518-22-1 C47H74O18 152 suppliers $32.00-$1425.00

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