Hirsutella sinensis mycelium attenuates bleomycin-induced pulmonary inflammation and fibrosis in vivo.

Tsung-Teng Huang,John D Young,Jan Martel,Ying-Wei Lan,Hsin-Chih Lai,Yun-Fei Ko,David M Ojcius,Kowit-Yu Chong

doi:10.1038/srep15282

Abstract

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. We previously reported that this fungus suppresses interleukin-1β and IL-18 secretion by inhibiting both canonical and non-canonical inflammasomes in human macrophages. However, whether HSM may be used to prevent lung fibrosis and the mechanism underlying this activity remain unclear. Our results show that pretreatment with HSM inhibits TGF-β1–induced expression of fibronectin and α-SMA in lung fibroblasts. HSM also restores superoxide dismutase expression in TGF-β1–treated lung fibroblasts and inhibits reactive oxygen species production in lung epithelial cells. Furthermore, HSM pretreatment markedly reduces bleomycin–induced lung injury and fibrosis in mice. Accordingly, HSM reduces inflammatory cell accumulation in bronchoalveolar lavage fluid and proinflammatory cytokines levels in lung tissues. The HSM extract also significantly reduces TGF-β1 in lung tissues, and this effect is accompanied by decreased collagen 3α1 and α-SMA levels. Moreover, HSM reduces expression of the NLRP3 inflammasome and P2X7R in lung tissues, whereas it enhances expression of superoxide dismutase. These findings suggest that HSM may be used for the treatment of pulmonary inflammation and fibrosis.

Highlights

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties
Fibroblasts treated with the profibrogenic cytokine transforming growth factor-beta 1 (TGF-β 1) show increased expression of α -smooth muscle actin (α -SMA) and fibronectin, which are important markers of myofibroblast differentiation
The second phase involves lung fibrosis which is characterized by extracellular matrix (ECM) remodeling and extensive collagen deposition[49]

Summary

Introduction

Hirsutella sinensis mycelium (HSM), the anamorph of Cordyceps sinensis, is a traditional Chinese medicine that has been shown to possess various pharmacological properties. Several drugs have been developed to treat this condition, the five-year survival rate of IPF remains less than 50% and the drugs’ serious adverse effects pose problems during long-term treatment For these reasons, herbal remedies and traditional Chinese medicines have emerged as attractive alternatives for the treatment of fibrotic lung disease. TGF-β 1 is one of the most studied fibrogenic cytokines that play a role in induction and development of pulmonary fibrosis[9] This cytokine initiates the differentiation of fibroblasts into active myofibroblasts, which promote excessive collagen and ECM deposition, and contribute to the recruitment of inflammatory cells[10]. Enhanced expression of TGF-β 1 in the lungs has been detected in lung fibrosis animal models and IPF patients[14,15] These observations suggest that inhibition of the fibrogenic cytokine TGF-β 1 represents a potential strategy for pulmonary fibrosis therapy

Objectives

Methods

Results

Conclusion