Aloperine Protects Mice against Bleomycin-induced Pulmonary Fibrosis by Attenuating Fibroblast Proliferation and Differentiation

Wanling Yin,Zhijun Zhang,Jing Han,Siyuan Wang,Zaomu Han

doi:10.1038/s41598-018-24565-y

Abstract

Aloperine is a quinolizidine alkaloid extracted from Sophora alopecuroides. It has been proven to alleviate oxidative stress and effectively promote tumor cell apoptosis in mice. Herein, we investigated whether aloperine could also mediate its protective effects on bleomycin (BLM)-induced pulmonary fibrosis. Pathological staining, western blot, RT-PCR and flow cytometry were used to evaluate the impact of aloperine on the development of pulmonary fibrosis. The effect of aloperine on fibroblast proliferation, differentiation and related signaling pathways were next investigated to demonstrate the underlying mechanisms. In the present report, we showed that aloperine provided protection for mice against BLM-induced pulmonary fibrosis as manifested by the attenuated lung injury and reduced fibrosis along with alleviated fibroblast proliferation and differentiation. Additionally, we provided in vitro evidence revealing that aloperine inhibited cellular proliferation in PDGF-BB-stimulated mouse lung fibroblasts by repressed PI3K/AKT/mTOR signaling and fibroblast to myofibroblast differentiation by repressed TGF-β/Smad signaling. Overall, our data showed that aloperine could protect the mice against BLM-induced pulmonary fibrosis by attenuated fibroblast proliferation and differentiation, which indicated that aloperine may be therapeutically beneficial for IPF patients.

Highlights

Aloperine is a kind of alkaloid extracted from sophora alopecuroides and has been reported to execute therapeutic effects against pulmonary hypertension[16], renal injury[17] and neuropathic pain[18] through attenuating oxidative stress, and multiple myeloma[19], and colon cancer[20] though increasing cell apoptosis
A significantly attenuated lung injury and pulmonary fibrosis were noted in aloperine-treated mice as evidenced by hematoxylin and eosin (H&E) and Sirius red staining (Fig. 1A)
The severity of pulmonary fibrosis was much lower as manifested by the lower Ashcroft scores (5.45 ± 0.51 versus 3.78 ± 0.43, p < 0.05; Fig. 1B), while mice originating from the phosphate-buffered saline (PBS) + Alo group manifested similar levels of fibrotic scores to those of mice derived from the PBS + AA group

Summary

Introduction

Aloperine is a kind of alkaloid extracted from sophora alopecuroides and has been reported to execute therapeutic effects against pulmonary hypertension[16], renal injury[17] and neuropathic pain[18] through attenuating oxidative stress, and multiple myeloma[19], and colon cancer[20] though increasing cell apoptosis. These observations prompted us to hypothesize that aloperine may be a good candidate drug for the prevention and treatment of bleomycin (BLM) -induced pulmonary fibrosis, since oxidative stress and apoptosis are involved in its pathogenesis[21,22]. Our data suggested that treatment with aloperine could be a viable strategy for the prevention and treatment of pulmonary fibrosis in clinical settings

Methods

Results

Conclusion