Synergistic Effects of Forskolin and Rutin in the Treatment of Pulmonary Fibrosis in Murine Model

Abstract

Pulmonary fibrosis treatment with currently available drugs mostly seems inadequate owing to its progressive and irreversible nature. Persistent activation of underlying mechanisms primarily, oxidative-stress and inflammation in lung leads to pulmonary fibrosis progression and subsequently produces sub-therapeutic control even after prolonged drug therapy. Additionally, due to large dose requirements in the treatment of pulmonary fibrosis unavoidable adverse effects are also an important concern. Thus, alternative drug therapy for pulmonary fibrosis, targeting to the aforementioned chief mechanisms is urgently required. In this view, some phytoconstituents were initially screened for antioxidant and anti-inflammatory activities through in vitro testing. Later, an in vivo study was planned to evaluate and compare the efficacy of two selected compounds namely forskolin (20 mg/kg) and rutin (100 mg/kg), individually and in combination against standard drug pirfenidone (50 mg/kg) using bleomycin-triggered pulmonary fibrosis murine model. Assessment parameters including changes in physical and physiological parameters along with alterations in lung injury markers, oxidative-stress, inflammatory status and fibrotic condition were evaluated during the study. Outcomes of the study exhibited, forskolin and rutin co-administration adequately reversed the physical and physiological changes during pulmonary fibrosis. Besides, it synergistically inhibited biochemical alterations in lung with no significant difference as compared to pirfenidone treatment. Further, forskolin and rutin co-administration showed effectively decline in Szapiel’s and Ashcroft scores and maximally diminish mast cell accumulation than that manifested by pirfenidone in lungs. Overall, efficacy of forskolin and rutin combination against pulmonary fibrosis showed promising potential and hence would contribute in the development of a novel effective treatment regimen in future.