Abstract
Purpose: To investigate the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced acute lung injury (ALI), as well as explore the underlying mechanism of action.
 Methods: C57BL/6 mice were treated with AEACD by gavage (4.0 g/kg/day) for 5 days before cecal ligation and puncture (CLP) challenge. After 24 h, the pathological morphology of lung tissue and the biochemical parameters in bronchoalveolar lavage fluid (BALF) were determined by H&E staining and enzyme-linked immunosorbent assay (ELISA). Furthermore, the total protein content and lactate dehydrogenase (LDH) level of BALF, as well as the oxidative biomarkers (malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD)) were evaluated in the lung homogenates by ELISA assay. The levels of pro-inflammatory cytokines, TNFα, IL-1β, and IL-6, in lung tissue were measured by qRT-PCR or ELISA. Finally, key proteins in Toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway in lung tissue were evaluated by western blot.
 Results: CLP challenge induced abnormal changes in the histological structures of lung tissue, lung wet-to-dry weight (W/D) ratio, protein content and LDH levels of BALF, which were remarkably reversed by AEACD. In addition, AEACD decreased MDA levels, and increased GSH levels and SOD activity in the lung tissue of CLP–treated mice (p < 0.05). Furthermore, AEACD attenuated the CLP challengeinduced upregulation of TNFα, IL-1β, and IL-6. Finally, AEACD inactivated TLR4/NF-κB pathway by upregulating IκBα and downregulating TLR4 and phosphorylated-p65 levels.
 Conclusion: AEACD administration protects mice against sepsis-induced ALI through the regulation of oxidative stress and inflammatory responses in lung tissues. The underlying mechanism occurs by inhibiting TLR4/NF-κB signaling pathway.
 Keywords: Aconitum carmichaelii Debeaux, Acute lung injury, Sepsis, TLR4, NF-κB
Highlights
Acute lung injury (ALI) is a severe clinical illness that requires intensive care [1]
A recent study revealed that aqueous extract from Aconitum carmichaelii Debeaux (AEACD) suppressed the inflammatory response and improved liver regeneration in acute liver failure via the Toll-like receptor 4 (TLR4)/NF-κB and proliferating cell nuclear antigen (PCNA) signaling pathways [15]
To explore the therapeutic effect of aqueous extract of Aconitum carmichaelii Debeaux (AEACD) on sepsis-induced ALI, cecal ligation and puncture (CLP)-induced mouse sepsis model was established and lung tissues were evaluated with Hematoxylin and eosin (H&E) staining
Summary
Acute lung injury (ALI) is a severe clinical illness that requires intensive care [1]. The reduction of inflammatory responses induced by activating the TLR4/ NF-κB pathway can protect lung tissue from sepsis [11,12]. A recent study revealed that aqueous extract from Aconitum carmichaelii Debeaux (AEACD) suppressed the inflammatory response and improved liver regeneration in acute liver failure via the TLR4/NF-κB and proliferating cell nuclear antigen (PCNA) signaling pathways [15]. It seems that AEACD has a therapeutic effect on ALI through antiinflammatory action. Quantitative polymerase chain reaction (qPCR) was performed with a SYBR Green Plus reagent kit using a QuantStudio 5 Real-Time PCR System (Thermo Fisher, Waltham, USA). Significant difference was set at p < 0.05
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