Abstract
Background: Chronic obstructive pulmonary disease (COPD) is characterized by persistent inflammation and oxidative stress, primarily driven by cigarette smoke (CS) exposure. While high-intensity interval training (HIIT) and polyphenol-rich supplements such as Yerba Mate (YM) have demonstrated anti-inflammatory and antioxidant properties, the combined effects of HIIT with a niosomal YM formulation (Nio-YM) remain unexplored. Objective: This study aimed to investigate the individual and combined effects of HIIT, YM, and Nio-YM on inflammatory cytokines (IL-6, IL-10, TNF-α), oxidative stress markers (MDA, TAC), and physical performance in a rat model of CS-induced lung injury. Methods: Male rats were randomly allocated into seven groups: control (CON), CS, CS+Vehicle (Veh), CS+YM, CS+Nio-YM, CS+HIIT, and CS+HIIT+Nio-YM. The interventions consisted of an 8 week HIIT protocol, Yerba Mate (YM) extract (0.5 mg/kg, orally), and its niosomal formulation (orally). Lung cytokines (IL-6, IL-10, TNF-α), oxidative stress markers (MDA, TAC), and exercise performance indices (exhaustion running time, maximum running speed) were evaluated. Results: CS exposure markedly increased IL-6, TNF-α, and MDA, while reducing IL-10 and TAC, indicating an inflammatory and oxidative burden. All interventions significantly reversed these alterations. TAC levels were higher in the HIIT and YM groups compared with other treatments, suggesting a stronger enhancement of antioxidant defenses. However, no significant synergistic effects were observed in the HIIT+Nio-YM group. Additionally, the 8-week HIIT protocol significantly improved exhaustion running time and maximum running speed in CS-exposed rats. Conclusion: HIIT, YM, and Nio-YM attenuated CS-induced inflammation and oxidative stress while improving exercise performance. Although the combined intervention did not show additive effects, both HIIT and YM demonstrated robust protective outcomes. These findings support the potential of combining structured exercise with polyphenol-based supplementation as an effective non-pharmacological strategy for mitigating COPD progression.