Four Isosteroidal Alkaloids from Fritillaria Alleviate Lipopolysaccharide-Induced Inflammation in vitro and in vivo...

To investigate the anti-inflammatory effects and mechanisms of action of 4 steroidal alkaloids (ebeiedinone, imperialine, chuanbeinone, and peimisine) in Fritillaria.

This study established a lipopolysaccharide (LPS)-induced inflammatory model using mouse leukemia cells of monocyte macrophage (RAW 264.7) cells. The cell toxicity, nitric oxide (NO) release, expression levels of inflammatory factors, and expression levels of anti-inflammatory mechanism proteins and mRNA of ebeiedinone, imperialine, chuanbeinone, and peimisine on RAW 264.7 cells were detected by cell counting kit-8 (CCK8) assay, Griess assay, enzyme-linked immunosorbent assay, Western blot, and real-time quantitative PCR, respectively. An acute lung injury (ALI) rat model was established. Hematoxylin and eosin staining was used to observe the morphological and pathological characteristics of lung tissue in each group of rats. The expression levels of inflammatory factors and anti-inflammatory mechanism proteins and mRNA in the ALI rat model induced by the 2 alkaloids (ebeiedinone, peimisine) were detected.

The 4 alkaloids reduced the release of NO, downregulated the expression of pro-inflammatory factors, regulated the expressions of the TIR domaincontaining adapter protein inducing interferon-beta (TRIF), myeloid differentiation factor 88 (MyD88), nuclear factor kappa-B (NF-κB), and mitogen-activated protein kinases (MAPKs) signaling pathways in LPS-induced RAW 264.7 cells, exerting an anti-inflammatory effect (P<0.05 or P<0.01). Ebeiedinone and peomisine improved pulmonary edema and inflammation levels, regulated the expressions of MyD88, NF-κB, and MAPKs signaling pathways in the ALI rat model, exerting anti-inflammatory effects (P<0.05 or P<0.01).

The 4 alkaloids of Fritillaria exert anti-inflammatory effects in vivo and in vitro through MyD88- and TRIF-dependent signaling pathways, thereby protecting rats from ALI.