Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice.
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 alpha (TNF-alpha) and transforming growth factor beta 1 (TGF-beta (1)) 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-alpha and TGF-beta (1) 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-alpha and TGF-beta (1) induced by BLM.
Xiao
Jun-Hua
JH
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China.
Zhang
Jia-Hua
JH
Chen
Hong-Lei
HL
Feng
Xiu-Ling
XL
Wang
Jia-Ling
JL
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001761:Bleomycin; D004305:Dose-Response Relationship, Drug; D007150:Immunohistochemistry; D007536:Isomerism; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008297:Male; D051379:Mice; D031653:Nelumbo; D010636:Phenols / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000517:prevention & control*; D012639:Seeds; D014132:Trachea; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007546:Isoquinolines; D010636:Phenols; D010936:Plant Extracts; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin; C080095:liensinine