Protective Effects of Peperomia pellucida Extract Against Secondhand Smoke-Induced Pulmonary Fibrosis via Antioxidant and Anti-inflammatory Pathways

Secondhand smoke exposure (SHSE) represents a significant external risk factor, which contributes to pulmonary fibrosis onset by activating inflammatory, fibrogenic, and oxidative stress mechanisms. This study explores the efficacy of Peperomia pellucida (PP) in mitigating lung injury caused by SHSE in Wistar rats. Twenty animals were randomly grouped to one of three cohorts: control (CON), SHSE, and SHSE with PP extract (SHSE+PP). Rats were exposed to secondhand smoke for 4 consecutive weeks. The treatment group received PP extract (400 mg/kg) for 1 week before and during 4 weeks of SHSE. Lung tissues were evaluated via histopathology, immunohistochemistry, and glutathione (GSH) assays. SHSE significantly increased lung weight, histopathological scores, and profibrotic (TGF-β) and pro-inflammatory (TNF-α and IL-6) cytokines (p < 0.05). A marked reduction in GSH levels was also observed, indicating increased oxidative stress. In contrast, rats treated with PP extract showed significant improvements in all parameters, including reduced cytokine expression, improved lung architecture, and restored GSH levels (p < 0.05). These effects are likely mediated by bioactive compounds in PP, such as phenolics, phenylpropanoids, sesquiterpenes, and chlorophyll derivatives, which inhibit NF-κB and activate the Nrf2 pathway, thereby reducing inflammation, fibrosis, and oxidative damage. This is the first report demonstrating the protective effect of the extract in SHSE-induced pulmonary fibrogenesis. The results highlight the action of PP as a protective alternative medicine and support further investigation into its clinical application for preventing secondhand smoke-related chronic lung diseases.