Background:Methyl protodioscin (MPD) is a furostanol bisglycoside with antitumor properties. It has been shown to reduce proliferation, cause cell cycle arrest.Objective:The present study elucidates the mechanism underlying MPD's apoptotic effects, using the A549 human lung cancer cell line.Materials and Methods:The human pulmonary adenocarcinoma cell line A549 was obtained from the Cell Bank of the Animal Experiment Center, North School Region, Sun Yat-Sen University. All of the cells were grown in RPMI 1640 supplemented with 10% fetal calf serum (Hyclone, Logan, UT, USA), penicillin (10,000 U/l), and streptomycin (100 mg/l) at 37°C in a 5% CO2 humidified atmosphere. The induction of apoptosis was observed in flow cytometry and fluorescent staining experiments.Results:MPD showed growth inhibitory effects in A549 cells in a dose- and time-dependent manner. The significant G2/M cell cycle arrest and apoptotic effect were also seen in A549 cells treated with MPD. MPD-induced apoptosis was accompanied by a significant reduction of mitochondrial membrane potential, release of mitochondrial cytochrome c to cytosol, activation of caspase-3, downregulation of Bcl-2, p-Bad, and upregulation of Bax.Conclusion:Our results show that the induction of apoptosis by MPD involves multiple molecular pathways and strongly suggest that Bcl-2 family proteins signaling pathways. In addition, mitochondrial membrane potential, mitochondrial cytochrome c and caspase-3 were also closely associated with MPD-induced apoptotic process in human A549 cells.
Gastric mucosal injury is caused by an imbalance between the mucosal defense and gastro-irritants, leading to gastroenteritis. Diosgenin is a steroidal sapogenin found in the wild Yam plant that has been reported with several pharmacological properties. The aim of this study is to explore the gastroprotective role of diosgenin on gastric mucosal damage caused by HCl/ethanol in rats. Male Sprague-Dawley rats were intragastrically administered with diosgenin (20 mg/kg) before HCl/ethanol (0.15 M HCl in 98 % ethanol) administration. Omeprazole was used as a positive control. Diosgenin-attenuated oxidative stress by enhancing (p < 0.05) antioxidant enzymes, reducing lipid peroxidation (MDA), and modulating nitric oxide (NO) levels. Anti-inflammatory effects of diosgenin were observed by a reduction in pro-inflammatory cytokines (p < 0.05), decreased myeloperoxidase (MPO) activities (p < 0.05), and histopathological observation of gastric mucosal damage. Western blot analysis provided evidence on the downregulation of NF-κβ by diosgenin. The findings showed that diosgenin has a significant protective role on gastric injury caused by HCl/ethanol, through its antioxidant, anti-inflammatory role, and suppression of NF-κβ and MPO activities.
Background/Aims: Acute lung injury (ALI) remains a severe disease that threatens human life around the world. To decrease the mortality of ALI and improve ALI treatment efficacy, the development of more ALI treatments is urgently needed. Whether fibrocytes directly participate in ALI has not been studied. Therefore, a mouse model of ALI was induced with lipopolysaccharide (LPS). Methods: Fibrocytes were harvested from peripheral blood mononuclear cells of bleomycin mice and identified by using flow cytometry to detect the expression of molecular makers. The fibrocytes were injected for the treatment of acute lung injury mice. The curative effects were evaluated by using ELISA to determine the cytokines (including TNF-α, IL-6 and IFN-γ) concentrations in bronchoalveolar lavage fluid (BALF) supernatant. Results: The concentrations of cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interferon-γ (IFN-γ) were increased in mice with ALI induced with LPS. The concentrations of TNF-α, IL-6, and IFN-γ as well as their mRNA and protein expression levels were decreased by administration of fibrocytes. The effect of fibrocytes in ameliorating ALI was time dependent. LPS treatment induced an increase in myeloperoxidase (MPO) activity, whereas the fibrocyte treatment caused inhibition of MPO activity as well as expression of the neutrophil-chemoattractant chemokine macrophage inflammatory protein 2 (MIP-2). Conclusion: Taken together, these data suggest that fibrocytes ameliorated ALI by suppressing inflammatory cytokines and chemokines as well as by decreasing the accumulation of neutrophils in the lung.
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