Abstract

Acute lung injury (ALI) is a series of syndromes with persistent inflammation and abnormally increased vascular permeability. Sosiho-tang (SSHT), a traditional herbal formula consisting of a mixture of seven herbs, has been used to treat allergic reactions and chronic hepatitis disease in East Asia. In this study, we determined whether SSHT has an inhibitory effect against lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in mice. 0.05, 0.55, and 5.55 mg/kg of SSHT were orally administered to C57BL/6J mice for 7 days prior to the administration of LPS. After 2 h of LPS sensitization, lung tissues were collected to confirm the lung histology and ALI-related inflammatory factors. SSHT ameliorated the LPS-induced alveolar hemorrhage, alveolar wall thickening, and the shrinkage of the alveolar spaces in the ALI mice model. Proinflammatory cytokines including IL-6, TNF-α, and IFN-γ in the lung tissue were significantly regulated in the SSHT-treated groups compared to the LPS only-treated group. Also, increases of IL-6 and TNF-α and decrease of IFN-γ expressions were dose-dependently modulated by SSHT treatment in LPS-induced raw 264.7 cells. Additionally, the translocation of NF-κB into nucleus and phosphorylation of mitogen-activated protein (MAP) kinase were significantly attenuated by the treatment of SSHT in LPS-sensitized ALI mice. SSHT showed anti-inflammatory activities by inhibiting proinflammatory cytokines and NF-κB signaling in LPS-induced ALI. This study demonstrates that SSHT has preventive effects on LPS-induced ALI by regulating inflammatory responses as an alternative for treating lung diseases.

Highlights

  • Acute lung injury (ALI) is a life-threatening medical complication with a range from 52 to 65% of mortality rate in patients [1]

  • Compared to the structure of lung tissues in normal group, the LPS group led to alveolar hemorrhage, alveolar wall thickening, and alveolar spaces shrinkage

  • SSHT treatment relieved alveolar wall thickness and alveolar spaces shrinkage similar to normal group (Figure 1(a)). e ALI score by LPS sensitization was 3.5 times higher than nontreated CTR group (p < 0.05)

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Summary

Introduction

Acute lung injury (ALI) is a life-threatening medical complication with a range from 52 to 65% of mortality rate in patients [1]. ALI is associated with sepsis, traumatic injuries, inhalation, massive blood transfusion, bilateral pulmonary infiltration, and hypoxemia [2]. It is commonly accompanied by systemic inflammatory responses following pulmonary edema, increase of alveolar capillary barrier permeability, and excessive cytokines production in lung [3,4,5]. Treatment of ALI focuses on counterbalance of inflammatory response by regulating inflammatory/antiinflammatory cytokines production [8]. Some studies have reported that methylprednisolone reduces ventilation, respiratory shock, and mortality rate in ALI patients by improving the systemic inflammatory response [9]. Novel treatment derived from natural products with no side effects is required to treat ALI

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