Inhibitory Effects of Isoliensinine on Bleomycin-Induced Pulmonary Fibrosis in Mice

Abstract

The effects of isoliensinine (IL), a bisbenzylisoquinoline alkaloid extracted from the Chinese traditional medicine seed embryo of Nelumbo nucifera Gaertn., on bleomycin (BLM)-induced pulmonary fibrosis in mice were investigated. Seventy-two male Kungming mice were divided randomly into eight groups as BLM-IL10, BLM-IL20, BLM-IL40, BLM-Sal, Sal-IL10, Sal-IL20, Sal-IL40 and Sal-Sal groups. BLM (0.1 mg in 0.05 ml saline per animal, once) or saline (0.05 ml per animal, once) was applied intratracheally, and IL (10, 20, 40 mg/kg) or saline was administered orally 3 times per day in the appropriate groups. Animals were sacrificed 14 days after intratracheal treatment. Lung tissue and serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels, tumor necrosis factor α (TNF-α) and transforming growth factor beta 1 (TGF-β₁) were determined by biochemical measurements and immunohistochemistry. BLM treatment resulted in a significant increase of the hydroxyproline content and an obvious lung histological injury as compared to the Sal-Sal group. Administration of IL remarkably suppressed the increase in hydroxyproline content and abated the lung histological injury induced by BLM. There was a decrease in SOD activity and an increase in MDA level in lung tissue and serum in the BLM-Sal group (p < 0.01, p < 0.01, vs. Sal-Sal group, respectively). And IL could obviously enhance the SOD activity and decrease the MDA level in a concentration-dependent manner. Moreover, IL also significantly inhibited the overexpression of TNF-α and TGF-β₁ induced by BLM. These results indicated that IL possessed a significant inhibitory effect on BLM-induced pulmonary fibrosis, probably due to its antioxidant and/or anti-inflammatory activities and inhibitory overexpressing TNF-α and TGF-β₁ induced by BLM.

Abbreviations

bFGF:Basic fibroblast growth factor

BLM:Bleomycin

DAB:Diaminobenzidine tetrahydrochloride

IL:Isoliensinine

IT:Intratracheal

MDA:Malondialdehyde

NBT:Nitroblue tetrazolium

PBS:Phosphate buffer solution

PDGF:Platelet derived growth factor

PF:Pulmonary fibrosis

PO:per os, orally

ROS:Reactive oxygen species

SABC:Strept-avidin-biotin-peroxidase-complex

Sal:Saline

SOD:Superoxide dismutase

TGF-β:Transforming growth factor beta

TNF-α:Tumor necrosis factor α

Isoliensinine - bisbenzylisoquinoline - bleomycin - pulmonary fibrosis - SOD - MDA - TNF-α - TGF-β₁

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