Luteolin Ameliorates Experimental Lung Fibrosis Both <i>in Vivo</i> and <i>in Vitro</i>: Implications for Therapy of Lung Fibrosis

Chen, Chiu-Yuan; Peng, Wen-Huang; Wu, Li-Chen; Wu, Chun-Chi; Hsu, Shih-Lan

doi:10.1021/jf1031668

Cited by 93 publications

(70 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…For example, luteolin reduces Muc5ac expression stimulated by epidermal growth factor or phorbol 12-myristate 13-acetate in NCI-H292 cells37. Luteolin inhibits bleomycin-induced lung fibrosis46 and alleviates OVA-induced bronchoconstriction and airway hyperreactivity39. Consistent with previous studies, we also found that luteolin suppressed OVA-induced IL upregulation and AHR, suggesting that luteolin may be used as an anti-asthmatic agent.…”

Section: Discussionsupporting

confidence: 89%

Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

Shen

Wang

Lin

et al. 2016

Sci Rep

View full text Add to dashboard Cite

Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients.

show abstract

Section: Discussionsupporting

confidence: 89%

Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

Shen

Wang

Lin

et al. 2016

Sci Rep

View full text Add to dashboard Cite

show abstract

“…The oral administration of luteolin (10 mg/kg) has been shown to effectively suppress neutrophil infiltration, as well as the increase in TNFα and IL-6 levels in bronchoalveolar lavage fluid from bleomycin-instilled C57BL/6J mice (36). Luteolin injected intraperitoneally at different doses of 10 or 25 mg/kg has also beehn shown to significantly increase SOD1 activity and decrease MDA levels in mice with permanent middle cerebral artery occlusion, which results in alleviated neurological deficits, infarct volume and brain water content (37).…”

Section: Discussionmentioning

confidence: 99%

Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects

Xiong

Wang

Yuan

et al. 2016

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Reseda odorata L. has long been used in traditional Asian medicine for the treatment of diseases associated with oxidative injury and acute inflammation, such as endotoxemia, acute lung injury, acute myocardial infarction and hepatitis. Luteolin, the main component of Reseda odorata L., which is also widely found in many natural herbs and vege tables, has been shown to induce heme oxygenase-1 (HO-1) expression to exert anti-inflammatory and antioxidant effects. In this study, we aimed to examine the effects of luteolin on mice with severe acute pancreatitis (SAP), and to explore the underlying mechanisms. Cerulein and lipopolysaccharide were used to induce SAP in male Institute of Cancer Research (ICR) mice in the SAP group. The SAP group was divided into 4 subgroups, as follows: the vehicle, luteolin, zinc protoporphyrin (ZnPP) only, and luteolin (Lut) + ZnPP (luteolin plus zinc protoporphyrin treatment) groups. The wet/dry weight ratios, hematoxylin and eosin staining and pathological scores of pancreatic tissues were assessed and compared to those of the control mice. Amylase, lipase, nuclear factor-κB (NF-κB) and myeloperoxidase activities, and malondialdehyde, tumor necrosis factor α (TNFα), interleukin (IL)-6, IL-10 and HO-1 levels, as well as the expression of HO-1 were determined in serum and/or pancreatic tissue samples. SAP was successfully induced in male mice compared to normal control mice. The wet/dry weight ratios, pathological scores, and amylase and lipase activity, as well as the levels of TNFα and IL-6 were significantly reduced in the pancreatic tissues of the mice in the Lut group compared with those of the mice in the vehicle group. The Lut group exhibited a significant increase in HO-1 expression in the pancreas and enhanced serum HO-1 and IL-10 levels compared with the vehicle group. The suppression of HO-1 activity in the ZnPP group significantly abolished the protective effects of luteolin. NF-κB expression in the pancreatic tissues from the mice in the Lut + ZnPP group was significantly increased following the suppression of HO-1 activity. On the whole, our findings demonstrate that luteolin protects mice from SAP by inducing HO-1-mediated anti-inflammatory and antioxidant activities, in association with the suppression of the activation of the NF-κB pathway.

show abstract

“…The degree of lung tissue inflammation was evaluated quantitatively by H&E staining method. A score ranging from 0 to 4 was assigned according to severity, and the scores were averaged per group [21]. The Masson's trichrome staining method was used to investigate fibrotic degree.…”

Section: Histopathological Assessmentmentioning

confidence: 99%

Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats

et al. 2015

View full text Add to dashboard Cite

We aimed to investigate the preventive effect of Infliximab (IFX), a tumor necrosis factor (TNF)-α inhibitor, on bleomycin (BLC)-induced lung fibrosis in rats. Rats were assigned into four groups as follows: I-BLC group, a single intra-tracheal BLC (2.5 mg/kg) was installed; II-control group, a single intra-tracheal saline was installed; III-IFX + BLC group, a single-dose IFX (7 mg/kg) was administered intraperitoneally (i.p.), 72 h before the intra-tracheal BLC installation; IV-IFX group, IFX (7 mg/kg) was administered alone i.p. on the same day with IFX + BLC group. All animals were sacrificed on the 14th day of BLC installation. Levels of tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, interleukin (IL)-6, periostin, YKL-40, nitric oxide (NO) in rat serum were measured, as well as, myeloperoxidase (MPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity, and reduced glutathione (GSH), hydroxyproline, malondialdehyde (MDA) content in lung homogenates. Lung tissues were stained with hematoxylin and eosin (H&E) for quantitative histological evaluation. The inducible nitric oxide synthase (iNOS) expression and cell apoptosis in the lung tissues were determined quantitatively by immunohistochemical staining (INOS) and by TUNNEL staining, respectively. BLC installation worsened antioxidant status (such as SOD, CAT, GPx, GSH, MPO), while it increased the serum TNF-α, TGF-β, IL-6, periostin, YKL-40, and lipid peroxidation, and collagen deposition, measured by MDA and hydroxyproline, respectively. IFX pretreatment improved antioxidant status as well as BLC-induced lung pathological changes, while it decreased the TNF-α, TGF-β, IL-6, periostin, YKL-40, lipid peroxidation and collagen deposition. Finally, histological, immunohistochemical, and TUNNEL evidence also supported the ability of IFX to prevent BLC-induced lung fibrosis. The results of the present study indicate that IFX pretreatment can attenuate BLC-induced pulmonary fibrosis.

show abstract

Luteolin Ameliorates Experimental Lung Fibrosis Both in Vivo and in Vitro: Implications for Therapy of Lung Fibrosis

Cited by 93 publications

References 34 publications

Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

Luteolin protects mice from severe acute pancreatitis by exerting HO-1-mediated anti-inflammatory and antioxidant effects

Protective Effect of Infliximab, a Tumor Necrosis Factor-Alfa Inhibitor, on Bleomycin-Induced Lung Fibrosis in Rats

Contact Info

Product

Resources

About