The therapeutic effects of traditional Chinese medicine Fusu agent in LPS-induced acute lung injury model rats

Abstract

PurposeAcute lung injury (ALI) is a common and fatal oxidative stress in the lung, mainly induced by endothelial injury and capillary leakage. In our previous study, “Fusu agent”, a traditional Chinese medicine, was found to exert preventive effect on endothelial damage in lipopoly-saccharide (LPS)-induced ALI model rats partially via inhibiting heparanase1 (HPA1) activation and inhibiting the inflammatory factors. However, it is still unknown whether Fusu agent exerts its therapeutic effect in LPS-induced ALI model rats and its potential mechanism.Materials and methodsRats were injected with LPS (3 mg/kg, intraperitoneally) to induced ALI, and the prepared Fusu agent was given (2, 4 or 6 g/kg) 2 hours after LPS challenge. Twenty-four or 48 hours after Fusu agent administration, the biochemical changes in the plasma and lung tissues and the morphological/histological changes in the lung associated with inflammation and injury were evaluated. Human umbilical vein endothelial cells (HUVECs) were employed to confirm the therapeutic effects of Fusu agent and investigate its mechanisms, that is, affecting ROS accumulation, mitochondrial transmembrane potential (MTP) maintenance and decreasing the expression levels of HPA1.ResultsAdministration of Fusu agent obviously improved the lung injury and recovered vascular endothelium loss and injury. CD31 signal, which is a specific marker for endothelial vascular lesions, was decreased after Fusu agent treatment in LPS-induced ALI model rats, indicating its therapeutic effect against endothelial surface layer injury. Meanwhile, Fusu agent also decreased HPA1 expression and inflammatory responses. In vitro, Fusu agent-medicated serum decreased injury and cell death induced by LPS in HUVECs by stabilizing MTP and decreasing the leakage of lactate dehydrogenase. Consistently, Fusu agent-medicated serum downregulated HPA1 induced by LPS stimulation.ConclusionThese findings suggest that Fusu agent exerts its therapeutic effect in both LPS-induced ALI model rats and HUVECs potentially via suppressing HPA1 expression, and thus exerts prosurvival effect via maintaining MTP and attenuating cell injury.

Protective effect of Cordyceps sinensis extract on lipopolysaccharide-induced acute lung injury in mice

“…Numerous studies have shown that it plays a key role in ALI [40]. In ALI, LPS also induces the formation of inflammatory mediators through the NF-κB pathway [41,42]. In resting state, IκBα and NF-κB p65, p50 exist in inactivation state.…”

Lipopolysaccharide-Induced Acute Lung Injury Is Associated with Increased Ran-Binding Protein in Microtubule-Organizing Center (RanBPM) Molecule Expression and Mitochondria-Mediated Apoptosis Signaling Pathway in a Mouse Model

“…The mice had free access to standard diet and water. The acute lung injury mouse model was established according to the method previously published [ 20 , 21 ], with some modifications. Briefly, the ALI mouse model the established via nasal administration of 25 mg/kg LPS (Sigma-Aldrich, St. Louis, MO, USA).…”

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“…Mitochondrial transmembrane potential stabilization and decrease of lactate dehydrogenase leakage. [ 38 ] Carotenoid Crocin LPS-induced acute respiratory distress syndrome in mice and LPS-induced inflammation in HUVEC In vivo and vitro Mice were pretreated with crocin at 15, 30 and 60 mg/kg. After 7 h, ARDS was induced in mice using intravenous LPS (20 mg/kg) administration for 6 h. HUVEC were pretreated with crocin at 20 μM for 1 h following inflammation with LPS at 1 μg/mL during 6 h. Improvement of pulmonary vascular permeability.…”