Baicalin relieves complement alternative pathway activation-induced lung inflammation through inhibition of NF-κB pathway.

INTRODUCTION: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. METHODS: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. RESULTS: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. CONCLUSION: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI.

Acteoside attenuates acute lung injury following administration of cobra venom factor to mice.

Background: Acteoside, a water-soluble active constituent of diverse valuable medicinal vegetation, has shown strong anti-inflammatory property. However, studies on the anti-inflammatory property of acteoside in complement-induced acute lung injury (ALI) are limited. Therefore, this study aims to evaluate the anti-inflammatory activity of acteoside in cobra venom factor (CVF)-stimulated human microvascular endothelial cells (HMEC) and in ALI mice model. Methods: In this study, we investigated the effects of acteoside (20, 10, and 5 µg/mL) in vitro in CVF induced HMECs and the activity of acteoside (100, 50, and 20 mg/kg/day bodyweight) in vivo in CVF induced ALI mice. Each eight male mice were orally administered acteoside or the positive drug PDTC (100 mg/kg/day) for 7 days before CVF (35 µg/kg) injection. After injection for 1 h, the pharmacological effects of acteoside were investigated by spectrophotometry, pathological examination, enzyme-linked immunosorbent assay, and immunohistochemistry. Results: In vitro, acteoside (20, 10, and 5 µg/mL) reduced the protein expression of adhesion molecules and pro-inflammatory cytokines and transcriptional activity of NF-κB (P < 0.01). In vivo studies showed that acteoside dose-dependently alleviated lung histopathologic lesion, inhibited the production of the protein content of BALF, leukocyte cell number, lung MPO activity, and expression levels of IL-6, TNF-α, and ICAM-1, and suppressed the C5b-9 deposition and NF-κB activation in CVF-induced acute lung inflammation in mice (P < 0.05, 0.01). Conclusion: This study demonstrates that acteoside exerts strong anti-inflammatory activities in the CVF-induced acute lung inflammation model and suggests that acteoside is a potential therapeutic agent for complement-related inflammatory diseases.