RESUMO
Cigarette smoking exacerbates respiratory diseases, while plant-derived polyphenols offer antioxidant and anti-inflammatory benefits. This study exploresd the effects of Rhoifolin (ROF), a polyphenol from Jordanian Teucrium polium, on lung health in rats exposed to tobacco smoke. Male rats were divided into two groups: one exposed to cigarette smoke (CS), and the other to ROF treatment alongside smoke exposure (CS/ROF). ROF was administered orally for 21â days before smoke exposure. Results showed smoke-induced lung inflammation and oxidative stress, mitigated by ROF treatment. Histological examination revealed smoke-related morphological changes in lung tissue. ROF treatment reduced oxidative stress and inflammation, as evidenced by decreased proinflammatory cytokines. In silico docking demonstrated ROF's potential as an inhibitor of proinflammatory cytokines. This study demonstrates the therapeutic potential of ROF and similar polyphenols in mitigating the harmful effects of cigarette smoke on lung health.
Assuntos
Anti-Inflamatórios , Antioxidantes , Pulmão , Estresse Oxidativo , Teucrium , Animais , Masculino , Ratos , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Teucrium/química , Estresse Oxidativo/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/química , Fumaça/efeitos adversos , Simulação de Acoplamento Molecular , Nicotiana/química , Citocinas/metabolismoRESUMO
Repurposing existing drugs appears to be a potential solution for addressing the challenges in the treatment of non-small cell lung cancer (NSCLC). ß-adrenoceptor antagonist drugs (ß-blockers) have tumor-inhibiting effects, making them promising candidates for potential NSCLC treatment. This study investigates the anticancer potential of a subset of ß-blockers in NSCLC cell lines; A549 and H1299. Additionally, it investigates the underlying mechanism behind ß-blockers' anticancer effect by influencing a potential novel target named aldehyde dehydrogenase (ALDH). The MTT assay assessed ß-blockers' cytotoxicity on both cell lines, while Western blot and NADH fluorescence assays evaluated their influence on ALDH protein expression and activity. Carvedilol (CAR) was the most effective blocker in reducing cell survival of A549 and H1299 with IC50 of 18 µM and 13.7 µM, respectively. Significantly, CAR led to a 50% reduction in ALDH expression and 80% decrease in ALDH activity in A549 cells, especially when combined with ß-agonists, in comparison to the control. This effect might be attributed to ß-agonist blockade or an alternative pathway. This novel finding adds to our understanding of CAR's multifaceted anticancer properties, implying that combining CAR with ß-agonists could be a useful strategy for lung cancer treatment.