Comparison of Hibiscus sabdariffa L. Extract and Enalapril with Regard to Their Effect on Lung Fibrosis in a Bleomycin-induced Rat Model of Lung Fibrosis

Background: Pulmonary fibrosis is an idiopathic and chronic inflammatory interstitial lung disease that responds only weakly to available medical therapies and has a potentially fatal prognosis. Hibiscus sabdariffa L. contains several antioxidants, such as protocatechuic acid (PCA) and anthocyanins, which may be beneficial for the treatment of fibrosis. Objectives: The purpose of this study was to investigate the inhibitory effect of the H. sabdariffa L. extract (HSE) on angiotensin-converting enzyme (ACE) and compare it with that of enalapril in a rat model of bleomycin-induced pulmonary fibrosis. Methods: Female Wistar rats (weighing 180 g-235 g) were randomly divided into seven groups (n = 8). The negative and positive control groups were intratracheally administered a single dose of saline (1 mL/kg) and bleomycin (7.5 UI/kg/mL) respectively. The treatment groups were orally administered enalapril (20 mg/kg), PCA (100 mg/kg) and HSE (100, 200, and 400 mg/kg) daily for one week before and three weeks after bleomycin administration. The animals were sacrificed 24 hours after the last administration of the therapeutic agent. The transforming growth factor-beta(1), platelet-derived growth factor, tumor necrosis factor-alpha and angiotensin II (ANG II) levels in the bronchoalveolar lavage fluid (BALF) and also the malondialdehyde (MDA) and hydroxyproline (HP) levels in lung tissue were measured. The presence of fibrosis, inflammatory cells, connective tissue and collagen deposition in the lung was microscopically evaluated using Masson's trichrome staining. Results: The results showed a significant increase in the lung index and the levels of MDA, HP, ANG II and pro-inflammatory cytokines after bleomycin administration. Pre-treatment with enalapril, PCA and HSE resulted in a reduction in the levels of the above factors. Enalapril and HSE (400 mg/kg) treatment could mitigate the progression of fibrosis clearly via ACE blocking and a decrease in the level of oxidative stress. Enalapril, PCA and HSE could prevent the infiltration of fibroblasts, inflammatory cells and alveolar thickening caused by bleomycin. Conclusions: Our results indicate that HSE, which has demonstrated anti-hypertensive effects in herbal medicine, can be useful for the treatment of inflammatory and fibrotic disorders.