Terrestrosin D from <i>Tribulus terrestris</i> attenuates bleomycin-induced inflammation and suppresses fibrotic changes in the lungs of mice

Abstract

<b>Context:</b> Terrestrosin D (TED), from <i>Tribulus terrestris</i> L. (Zygophyllaceae), exhibits anti-tumour and anti-inflammatory activities. However, its effects on bleomycin (BLM)-induced pulmonary inflammation and the subsequent fibrotic changes remain unclear. <b>Objective:</b> To examine the anti-inflammatory and anti-fibrotic effects of TED against BLM in murine pulmonary tissues. <b>Materials and methods:</b> Male SPF mice received saline (control), TED (10 mg/kg), BLM (2.5 mg/kg), or BLM (2.5 mg/kg) + TED (10 mg/kg) group. BLM was administered as a single intranasal inoculation, and TED was intraperitoneally administered once daily. After 2 and 6 weeks of treatment, cell number and differentiation (Giemsa staining) and TNF-α, IL-6, IL-8, TGF-β1, and PDGF-AB levels (ELISA) were determined in the bronchoalveolar lavage fluid (BALF). Hydroxyproline (Hyp) content in the left pulmonary tissue was also determined (ELISA). The right pulmonary tissue was H&E-stained and assessed for the severity of pulmonary fibrosis using the Ashcroft scoring method. Compared with the BLM group, TED decreased inflammatory cell infiltration; number of macrophages (<i>p</i> < 0.05), neutrophils (<i>p</i> < 0.05), lymphocytes (<i>p</i> < 0.05); percentage of macrophages in the monocyte-macrophage system (<i>p</i> < 0.05), and levels of TNF-α (<i>p</i> < 0.01), IL-6 (<i>p</i> < 0.01), IL-8 (<i>p</i> < 0.05), TGF-β1 (<i>p</i> < 0.05), and PDGF-AB (<i>p</i> < 0.05) in the BALF. TED also reduced Hyp content (<i>p</i> < 0.05) in the pulmonary tissue and attenuated the BLM-induced deterioration in lung histopathology. <b>Discussion and conclusions:</b> TED can inhibit BLM-induced inflammation and fibrosis in the lungs of mice, which may be related to reduced inflammatory and fibrotic markers. These results could be further tested in humans through clinical studies.