Betulin and Crinum asiaticum L. bulbs extract attenuate pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines in bleomycin-induced fibrosis mice model

Abstract

BackgroundPulmonary fibrosis (PF) is a lung disease characterized by scaring of lung tissue that impairs lung functions. The estimated survival time of patients with pulmonary fibrosis is 3–5 years. Bleomycin (BLM) is used clinically in the treatment of Hodgkin lymphoma and testicular germ-cell tumors. Bleomycin’s mechanism of action is the inhibition of DNA and protein synthesis. This happens when leukocytes induce the release of cytokines and chemokines which increase the pro-fibrotic and pro-inflammatory cytokines such as IL-6, TNF-alpha, IL-13, IL-1β and transforming growth factor-beta 1 (TGF-β). Crinum asiaticum L. bulbs (CAE) are widely found in parts of Africa, Asia and Indian Ocean Island. It is also prevalent in southern part of Ghana and traditionally used by the indigenes to treat upper respiratory tract infections, and for wound healing. Betulin (BET) is found in the bulbs of Crinum asiaticum L. but widely isolated from the external bark of birches and sycamore trees. Betulin as a lupine type triterpenes has been researched for their pharmacological and biological activities including anticancer, anti-inflammatory, antimicrobial activities and anti-liver fibrosis effects.Aim of the study: The aim was to study the anti-pulmonary fibrosis effect of Crinum asiaticum L. bulbs extract and betulin in bleomycin-induced pulmonary fibrosis in mice. Materials and methodThere was a single oropharyngeal administration of bleomycin (80 mg/kg) in mice followed by the treatment of CAE and BET after 48 h of exposure to BLM. ResultsThere was increased survival rate in CAE and BET treatment groups compared to the BLM induced group. There was a marked decreased in the levels of hydroxyproline, collagen I and III in the CAE and BET treatment groups compared to BLM-treated group. The treatment groups of CAE and BET significantly down regulated the levels of pro-fibrotic and pro-inflammatory cytokines concentrations such as TGF-β1, MMP9, IL-6, IL-1β and TNF-alpha compared to an increased in the BLM treated groups. The histological findings of the lungs suggested the curative effects of CAE and BET following BLM induced pulmonary fibrosis in mice, the study showed improved lung functions with wide focal area of viable alveolar spaces and few collagen fibers deposition on lungs of treatment groups. ConclusionCAE and BET attenuated pulmonary fibrosis by down regulating pro-fibrotic and pro-inflammatory cytokines as well as improving lung function. This could be a lead in drug discovery where compounds with anti-fibrotic effects could be developed for the treatment of lung injury.