# Suppressive Functions of Veratramine on PM2.5-Induced Oxidative Stress

## TL;DR

Veratramine reduces lung damage caused by PM2.5 pollution by fighting oxidative stress and regulating cell pathways.

## Contribution

Veratramine's novel protective effects against PM2.5-induced oxidative injury and autophagy modulation are demonstrated.

## Key findings

- Veratramine enhances cell viability and reduces oxidative stress in PM2.5-exposed cells.
- Veratramine suppresses TLR4 and autophagy markers while promoting mTOR phosphorylation.
- Veratramine restores SGK1 expression, a key cell survival factor reduced by PM2.5.

## Abstract

Background: Particulate matter (PM2.5) inhalation induces pulmonary disorders through oxidative stress. Veratramine (VRT), a steroidal alkaloid derived from Veratrum species, exhibits protective pharmacological potential. Therefore, this study aims to investigate the protective effects of VRT against PM2.5-induced oxidative injury and the underlying molecular mechanisms. Methods: In vitro experiments were conducted using pulmonary artery endothelial cells (HPAECs), which were exposed to PM2.5 (25–100 μg/mL) ± VRT (2–50 μM) or Dexamethasone (DEX; 50 μM) for 24–48 h. Measurements included 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability, Lactate dehydrogenase ELISA, 2′,7′-dichlorodihydrofluorescein diacetate reactive oxygen species (ROS), superoxide dismutase/catalase kits, and Western blots (Bax, serum, and glucocorticoid-regulated kinase 1 (SGK1), microtubule-associated protein 1 light chain 3 (LC3), Toll-like receptor (TLR4), and mechanistic target of rapamycin (mTOR)). Results: PM2.5 exposure reduced HPAEC viability in a dose- and time-dependent manner, likely due to increased lactate dehydrogenase leakage and intracellular ROS accumulation. Oxidative stress correlated with altered superoxide dismutase and catalase activities, with suppression of SGK1, a key factor in cell survival. VRT treatment enhanced cell viability, mitigated oxidative stress, and restored SGK1 expression. Moreover, VRT promoted mTOR phosphorylation and markedly suppressed PM2.5-induced increases in TLR4, MyD88, and the autophagy markers LC3 II and Beclin 1. Conclusions: Collectively, these findings indicate that VRT protects against PM2.5-induced pulmonary injury by modulating oxidative stress and the mTOR-associated autophagy pathway, highlighting its potential as a therapeutic candidate for PM2.5-related respiratory disorders.