Isocorydine Ameliorates IL-6 Expression in Bone Marrow-Derived Macrophages and Acute Lung Injury Induced by Lipopolysaccharide

Abstract

Isocorydine (ICD) is a type of isoquinoline alkaloid originating from Corydalis edulis, which has been used to relieve spasm, dilate blood vessels, and treat malaria as well as hypoxia in clinic. However, its effect on inflammation and underlying mechanisms remains unclear. The aim of our study was to determine the potential effects and mechanisms of ICD on pro-inflammatory interleukin-6 (IL-6) expression in bone marrow-derived macrophages (BMDMs) and acute lung injury mouse model. A mouse model of acute lung injury was established by intraperitoneal injection of LPS and treated with different doses of ICD. The body weight and food intake of mice were monitored to determine the toxicity of ICD. The tissue samples of lung, spleen and blood were taken to assess the pathological symptoms of acute lung injury and the expression levels of IL-6. Further, BMDMs isolated from C57BL/6 mice were cultured in vitro and treated with granulocyte-macrophage colony-stimulating factor (GM-CSF), LPS and different doses of ICD. CCK-8 assay and flow cytometry were performed to assess the viability of BMDMs. The expression of IL-6 was detected by RT-PCR and ELISA. RNA-seq was carried out to detect the differential expression genes of ICD-treated BMDMs. Western blotting was used to detect the change in MAPK and NF-κB signaling pathways. Our findings show that ICD ameliorates IL-6 expression and attenuates phosphorylation of p65 and JNK in BMDMs, and can protect mice from acute lung injury.

Anti-cervical cancer mechanism of bioactive compounds from Alangium platanifolium based on the ‘compound-target-disease’ network

“…A previous study has shown Duguetine N-oxide ( 15 ) have strong antitumor activity against HCT-8, SF-295 and MDA/MB-435 cell lines [ 36 ]. Administration of Isocorydine ( 16 ) may enhance IL-6 expression in bone marrow-derived macrophages while attenuating phosphorylation of p65 and JNK, and contribute to the protection of mice against acute lung injury induced by lipopolysaccharide [ 37 ]. The remaining 12 compounds are other alkaloids, which are rare among the natural products reported in the literature, and we will further investigate them during isolation and purification.…”

Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS)

“…Additionally, environmental stress and infections can directly trigger MAPK activation [96]. Recent studies have underscored the pivotal role of the MAPK pathway in the inflammatory processes in ARDS, primarily through the facilitation of the release of inflammatory cytokines and chemokines [97][98][99]. Besides, accumulating evidence have demonstrated that MAPK activation aggravates lung inflammation of ARDS by upregulating the activity of NLRP3 inflammasome and NF-κB in animal models [100][101][102].…”

Fissistigma oldhamii (Hemsl.) Merr.: Ethnomedicinal, Phytochemistry, and Pharmacological Aspects

“…The case of the isoquinoline alkaloid isocorydine ( 50 ) (also known as artabotrine and luteanin) is interesting because this product was recently shown to display marked anti-inflammatory properties and to protect mice from acute lung injury. Specifically, isocorydine ( 50 ) reduced the expression of pro-inflammatory IL-6 and attenuated the phosphorylation of p65 and JNK in bone-marrow-derived macrophages [ 80 ]. It represents a potent anti-inflammatory agent capable of regulating pro-inflammatory cytokine release via the inhibition of NFκB p65 translocation into the nucleus [ 81 ].…”