# Cumambrin B Alleviates Sepsis-Associated Acute Lung Injury by Activating the Nrf2/HO-1 Pathway

## TL;DR

Cumambrin B protects against sepsis-related lung injury by reducing inflammation and oxidative stress through the Nrf2/HO-1 pathway.

## Contribution

This study reveals a novel protective mechanism of Cumambrin B in sepsis-associated acute lung injury via the Nrf2/HO-1 pathway.

## Key findings

- Cumambrin B reduces lung tissue injury in sepsis-associated acute lung injury in mice.
- CB activates the Nrf2/HO-1 pathway, restoring mitochondrial function and reducing oxidative stress.
- Nrf2 activators enhance CB's anti-inflammatory effects, while Nrf2 inhibitors block them.

## Abstract

Background: Sepsis-associated acute lung injury (SA-ALI) is a prevalent complication observed in patients with severe infection, characterized primarily by uncontrolled inflammatory response. Cumambrin B (CB) is a natural sesquiterpene lactone with anti-inflammatory properties. However, its protective effects against SA-ALI and the underlying molecular mechanisms remain unclear. Methods: Mice that received intraperitoneal lipopolysaccharide (LPS) injection were used to assess the protective effect of CB on SA-ALI. LPS-induced RAW264.7 cells were utilized to delve into the molecular mechanisms responsible for its protective effects. Results: CB markedly alleviated lung tissue injury in mice with SA-ALI. Network pharmacology and combined in vitro and in vivo studies demonstrated that the protective effect of CB against SA-ALI was closely related to its anti-inflammatory and antioxidant activities. Meanwhile, CB restored mitochondrial function and activated the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, Nrf2 activator potentiated the inhibitory effects of CB on inflammation and oxidative stress, whereas these effects were abolished by an Nrf2 inhibitor. Conclusions: CB alleviates SA-ALI by restoring mitochondrial function, attenuating oxidative stress and inflammation via activation of the Nrf2/HO-1 pathway.