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

Abstract

Context: Terrestrosin D (TED), from Tribulus terrestris 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.

Objective: To examine the anti-inflammatory and anti-fibrotic effects of TED against BLM in murine pulmonary tissues.

Materials and methods: 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 (p < 0.05), neutrophils (p < 0.05), lymphocytes (p < 0.05); percentage of macrophages in the monocyte-macrophage system (p < 0.05), and levels of TNF-α (p < 0.01), IL-6 (p < 0.01), IL-8 (p < 0.05), TGF-β1 (p < 0.05), and PDGF-AB (p < 0.05) in the BALF. TED also reduced Hyp content (p < 0.05) in the pulmonary tissue and attenuated the BLM-induced deterioration in lung histopathology.

Discussion and conclusions: 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.

Keywords:

• Anti-fibrosis pharmaceutical
• anti-inflammatory agent
• bleomycin-induced pulmonary inflammation
• pulmonary fibrosis
• hydroxyproline

Disclosure statement

The authors report no conflict of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China under Grant [81160560]; Natural Science Foundation of Inner Mongolia, China under Grant [2011MS1131; 2015MS0809]; Science and Technology Planning Project of Inner Mongolia, China under Grant [20130414]; Academician expert workstation on Pharmacodynamic, Pharmacokinetics and Safety Evaluation research of Mongolian Medicines (Inner Mongolia Science & Technology Department) under Grant [(2016)66].