Acute lung injury (ALI) is one of the leading causes of acute respiratory failure (ARF) and respiratory virus caused death. This study aimed to elucidate the potential effect of Anisodamine (ANI 654-2) on influenza A virus (IAV)-induced ALI, as well as its involved mechanism. HE staining showed ANI 654-2 attenuated lung lesions in ALI treated C57BL/6 mice. The alleviated lung lesion was validated with the increased alveolar fluid clearance (AFC) ratio, decreased lung wet/dry (W/D) weight and reduced protein concentration in bronchoalveolar lavage fluid (BALF). Flow cytometry analysis showed that ANI 654-2 reversed the increase of neutrophil count and M1 type macrophage number and the decrease of M2 type macrophage number in IAV-induced ALI mice. ELISA of BALF validated that ANI 654-2 decreased TNF-α, IL-1β, IL-6 and IL-18 while increased IL-10. Mechanically, ANI 654-2 decreased the protein expression of TGF-β1, TGF-β R II, TGF-β RI, TAK1, p-AKT/AKT and p-p105/p105, all of which were elevated with IAV. The effects of ANI 654-2 were validated in IAV treated A549 cells. As a result, TNF-α, IL-1β and IL-6 were partly reverted with activators of TAK1, AKT or NF-κB. Taken together, this study implicated that ANI 654-2 improved IAV-induced ALI via TAK1, AKT and NF-κB regulated inflammation. The study proposed that ANI 654-2 could be a potential therapy for treatment of ALI caused by virus infection. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.

Author