TY  - EJOU
AU  - Han, Gyuri 
AU  - Jeong, Yun Hee 
AU  - Kim, Ga Eun 
AU  - Bae, Jong-Sup 

TI  - Anti-Inflammatory Effects of Veratramine against Lipopolysaccharide-Induced Inflammation
T2  - BIOCELL

PY  - 
VL  - 
IS  - 
SN  - 1667-5746

AB  - <b>Objectives:</b> Plant-derived bioactive molecules are increasingly recognized as valuable therapeutic resources for managing diverse pathological conditions, particularly those involving vascular inflammation. This study aimed to determine whether veratramine (VRT), a naturally occurring steroidal alkaloid found in Veratrum species of the Liliaceae family, attenuates LPS-induced vascular and pulmonary inflammation by upregulating heme oxygenase-1 (HO-1) and modulating the Nrf2, nuclear factor (NF)-κB, and signal transducer and activator of transcription (STAT1) signaling pathways. <b>Methods</b>: The study assessed the modulatory effects of VRT on HO-1, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-activated human umbilical vein endothelial cells (HUVECs), as well as on iNOS, tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) expression in LPS-treated mice. The VRT doses (0.06–0.6 mg/kg) in mice were chosen to approximate peripheral concentrations of 2–20 μM, corresponding to the non-cytotoxic, anti-inflammatory range in HUVECs, based on calculations using mouse blood volume and body weight, and no overt acute toxicity was observed at these doses in this model. <b>Results</b>: Treatment with VRT enhanced HO-1 induction, inhibited NF-κB activation, diminished COX-2/PGE<sub>2</sub> and iNOS/NO production, and attenuated STAT1 phosphorylation. In addition, VRT promoted nuclear translocation of Nrf2 and its binding to antioxidant response elements (AREs), thereby suppressing IL-1β expression in HUVECs. The VRT-mediated inhibition of iNOS/NO was abolished by HO-1 silencing through RNA interference. <i>In vivo</i>, VRT markedly reduced iNOS expression in lung tissue and lowered TNF-α levels in bronchoalveolar lavage fluid. <b>Conclusion</b>: Altogether, these findings demonstrate that VRT exhibits substantial anti-inflammatory potential and may serve as a promising candidate for managing inflammation-related vascular disorders.
KW  - Veratramine; endothelium; inducible nitric oxide synthase (iNOS); p-signal transducer and activator of transcription (STAT)-1

DO  - 10.32604/biocell.2026.075139