Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process

Chen, Cheng; Wang, Yongyan; Wang, Ying‐Xia; Cheng, Meng-qun; Yin, JianBing; Zhang, Xuan; Zhao, Hong

doi:10.1016/j.bbrc.2017.12.112

Cited by 38 publications

(13 citation statements)

References 29 publications

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“…Previously, we reported GPS could reverse ethanol-induced liver steatosis and drug-induced liver injury (Lian et al, 2010b;Wang et al, 2010). In addition, it was reported that GPS can ameliorate pulmonary fibrosis (Chen et al, 2018a). However, whether and how GPS could prevent the progression from liver steatosis to liver fibrosis during chronic ethanol consumption is still elusive.…”

Section: Discussionmentioning

confidence: 99%

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

Yang

Shang

Jin

et al. 2020

Biomolecules & Therapeutics

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In current study, we aimed to investigate whether the gentiopicroside (GPS) derived from Gentiana manshurica Kitagawa could block the progression of alcoholic hepatic steatosis to fibrosis induced by chronic ethanol intake. C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli diet for 4 weeks. LX-2 human hepatic stellate cells were treated with GPS 1 h prior to transforming growth factor-β (TGF-β) stimulation, and murine hepatocyte AML12 cells were pretreated by GPS 1 h prior to ethanol treatment. GPS inhibited the expression of type I collagen (collagen I), α-smooth muscle actin (α-SMA) and tissue inhibitor of metal protease 1 in ethanol-fed mouse livers with mild fibrosis. In addition, the imbalanced lipid metabolism induced by chronic ethanol-feeding was ameliorated by GPS pretreatment, characterized by the modulation of lipid accumulation. Consistently, GPS inhibited the expression of collagen I and α-SMA in LX-2 cells stimulated by TGF-β. Inhibition of lipid synthesis and promotion of oxidation by GPS were also confirmed in ethanol-treated AML12 cells. GPS could prevent hepatic steatosis advancing to the inception of a mild fibrosis caused by chronic alcohol exposure, suggesting GPS might be a promising therapy for targeting the early stage of alcoholic liver disease.

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Section: Discussionmentioning

confidence: 99%

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

Yang

Shang

Jin

et al. 2020

Biomolecules & Therapeutics

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“…It has been proved that in bronchoalveolar cells isolated from fluids of lungs pulmonary fibrosis in a mouse model, GPS decreased the levels of proinflammatory cytokines, including TNF-α and IL-1β, and downregulated TGF-β1 and CTGF expression. In vitro , GPS inhibited the EMT of A549 cells stimulated by TGF-β1 to induce transdifferentiation at a dose-dependent manner (Chen et al, 2017b).…”

Section: Introductionmentioning

confidence: 99%

Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition

et al. 2019

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Epithelial-to-mesenchymal transition (EMT) is a self-regulated physiological process required for tissue repair that, in non-controled conditions may lead to fibrosis, angiogenesis, loss of normal organ function or cancer. Although several molecular pathways involved in EMT regulation have been described, this process does not have any specific treatment. This article introduces a systematic review of effective natural plant compounds and their extract that modulates the pathological EMT or its deleterious effects, through acting on different cellular signal transduction pathways both in vivo and in vitro . Thereby, cryptotanshinone, resveratrol, oxymatrine, ligustrazine, osthole, codonolactone, betanin, tannic acid, gentiopicroside, curcumin, genistein, paeoniflorin, gambogic acid and Cinnamomum cassia extracts inhibit EMT acting on transforming growth factor-β (TGF-β)/Smads signaling pathways. Gedunin, carnosol, celastrol, black rice anthocyanins, Duchesnea indica , cordycepin and Celastrus orbiculatus extract downregulate vimectin, fibronectin and N-cadherin. Sulforaphane, luteolin, celastrol, curcumin, arctigenin inhibit β-catenin signaling pathways. Salvianolic acid-A and plumbagin block oxidative stress, while honokiol, gallic acid, piperlongumine, brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL, TWIST and ZEB. Plectranthoic acid, resveratrol, genistein, baicalin, polyphyllin I, cairicoside E, luteolin, berberine, nimbolide, curcumin, withaferin-A, jatrophone, ginsenoside-Rb1, honokiol, parthenolide, phoyunnanin-E, epicatechin-3-gallate, gigantol, eupatolide, baicalin and baicalein and nitidine chloride inhibit EMT acting on other signaling pathways (SIRT1, p38 MAPK, NFAT1, SMAD, IL-6, STAT3, AQP5, notch 1, PI3K/Akt, Wnt/β-catenin, NF-κB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by the natural compounds of plant, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compounds to modulate EMT and its deleterious effects. Overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.

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“…Following administration of 5 mg/kg BLM, which emulates inflammatory stimulation (54), the total number of cells in the BALF was significantly increased, which was subsequently reduced by baicalin treatment (5 mg/kg). Previous studies have revealed that TNF-α is overexpressed in the fibrotic lung tissues of animal models of BLM-induced pulmonary fibrosis (55)(56)(57), which serves a vital role in fibrotic progression (58). TGF-β1 is also a crucial profibrotic cytokine (59,60) and plays a central role in the mechanism of systemic sclerosis-associated pulmonary fibrosis (61,62).…”

Section: Discussionmentioning

confidence: 99%

Baicalin alleviates bleomycin‑induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway

Zhao

et al. 2020

Mol Med Report

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Baicalin is an important flavonoid compound THaT is isolated from the Scutellaria baicalensis Georgi chinese herb and plays a critical role in anti-oxidative, anti-inflammatory, anti-infection and anti-tumor functions. although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin (BLM)-induced pulmonary fibrosis remain to be elucidated. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of pulmonary fibrosis, ELIASA kits were used to test the ROS and inflammation, and western blotting and Tunel were performed to study the apoptosis proteins. In vitro, MTT assay, flow cytometry, western blotting and immunofluorescence were performed to investigate the effects of baicalin on proliferation of fibroblasts. The most significantly fibrotic changes were identified in the lungs of model rats at day 28. Baicalin (50 mg/kg) attenuated the degree of pulmonary fibrosis, and the hydroxyproline content of the lung tissues was decreased in the baicalin group, compared with the BLM group. Further investigation revealed that baicalin significantly increased glutathione peroxidase (GSH-px), total-superoxide dismutase (T-Sod) and glutathione (GSH) levels, whilst decreasing that of serum malondialdehyde (MDA). TUNEL-positive cells were significantly decreased in rats treated with baicalin group, compared with the model group. Furthermore, it was found that BLM promoted fibroblasts viability in a dose-dependent manner in vivo, which was restricted following treatment with different concentrations of baicalin. Moreover, BLM promoted the expression levels of cyclin a, d and e, proliferating cell nuclear antigen, phosphorylated (p)-AKT and p-calcium/calmodulin-dependent protein kinase type. BLM also promoted the transition of cells from the G 0 /G 1 phase to the G 2 /M and S phases, and increased the intracellular ca 2+ concentration, which was subsequently suppressed by baicalin. Collectively, the results of the present study suggested that baicalin exerted a suppressive effect on BLM-induced pulmonary fibrosis and fibroblast proliferation.

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Gentiopicroside ameliorates bleomycin-induced pulmonary fibrosis in mice via inhibiting inflammatory and fibrotic process

Cited by 38 publications

References 29 publications

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

Gentiopicroside Ameliorates the Progression from Hepatic Steatosis to Fibrosis Induced by Chronic Alcohol Intake

Natural Plants Compounds as Modulators of Epithelial-to-Mesenchymal Transition

Baicalin alleviates bleomycin‑induced pulmonary fibrosis and fibroblast proliferation in rats via the PI3K/AKT signaling pathway

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