Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways

Santana, Fernanda; Silva, Rafael C. da; Ponci, Vitor; Pinheiro, Aruanã Joaquim Matheus Costa Rodrigues; Olivo, Clarice Rosa; Caperuto, Luciana C.; Arantes-Costa, Fernanda M.; Cláudio, Samuel Rangel; Ribeiro, Daniel Araki; Tibério, Iolanda F.L.C.; Lima-Neto, Lidio Gonçalves; Lago, João Henrique G.; Prado, Carla M.

doi:10.1016/j.bcp.2020.114175

Cited by 22 publications

(22 citation statements)

References 38 publications

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“…Studies showed that inhibition of the STAT3 signaling pathway in mast cells impaired FcεRI-mediated signaling and reduced degranulation in humans [55]. Recently, it has been demonstrated that inhibition of the STAT3 signaling pathway attenuated chronic allergic lung Inflammation in mice [56,57]. These results are in line with our present findings, which demonstrated that treatment with the H 4 R antagonist LINS01007 decreased NF-kB and STAT3 signaling pathways activation, thus reducing the development of allergic murine asthma.…”

Section: Discussionsupporting

confidence: 92%

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

Balbino

Lima

Fernandes

et al. 2020

Cell Physiol Biochem

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BACKGROUND/AIMS: Histamine is an important chemical transmitter involved in inflammatory processes, including asthma and other chronic inflammatory diseases. Its inflammatory effects involve mainly the histamine H4 receptor (H4R), whose role in several studies has already been demonstrated. Our group have explored the effects of 1-[(2,3-dihydro-1-benzofuran-2-yl)methyl]piperazines as antagonists of H4R, and herein the compounds LINS01005 and LINS01007 were studied with more details, considering the different affinity profile on H4R and the anti-inflammatory potential of both compounds. METHODS: We carried out a more focused evaluation of the modulatory effects of LINS01005 and LINS01007 in a murine asthma model. The compounds were given i.p. (1-7 mg/kg) to ovalbumin sensitized BALB/c male mice (12 weeks old) 30 min before the antigen challenging, and after 24 h the cell analysis from the bronchoalveolar lavage fluid (BALF) was performed. The lung tissue was used for evaluation by western blot (COX-2, 5-LO, NF-κB and STAT3 expressions) and histological analysis. RESULTS: Treatment with the more potent H4R antagonist LINS01007 significantly decreased the total cell count and eosinophils in BALF at lower doses when compared to LINS01005. The expression of COX-2, 5-LO, NF-κB and STAT3 in lung tissue was significantly reduced after treatment with LINS01007. Morphophysiological changes such as mucus and collagen production and airway wall thickening were significantly reduced after treatment with LINS01007. CONCLUSION: These results show important down regulatory effect of novel H4R antagonist (LINS01007) on allergic lung inflammation.

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Section: Discussionsupporting

confidence: 92%

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

Balbino

Lima

Fernandes

et al. 2020

Cell Physiol Biochem

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Section: Introductionmentioning

confidence: 99%

“…They are also present in biologically active natural products and biopolymer lignins [3,4]. Biaryls are used for sequencing lignin oligomers [5], oxidative C-C cleavage [6] and pyrolysis behaviour studies [7] and are found to be anti-oxidant and anti-inflammatory agents [8]. Owning biaryl linkages, they can also be employed for biaryl conformation analysis, which is intrinsically difficult due to the absence of proton NMR spin-spin coupling information.…”

Section: Introductionmentioning

confidence: 99%

¹H/¹³C chemical shift calculations for biaryls: DFT approaches to geometry optimization

Nguyen

2021

R. Soc. open sci.

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Twelve common density functional methods and seven basis sets for geometry optimization were evaluated on the accuracy of 1 H/ 13 C NMR chemical shift calculations for biaryls. For these functionals, 1 H shifts calculations for gas phase optimized geometries were significantly less accurate than those for in-solution optimized structures, while 13 C results were not strongly influenced by geometry optimization methods and solvent effects. B3LYP, B3PW91, mPW1PW91 and ω B97XD were the best-performing functionals with lowest errors; among seven basis sets, DGDZVP2 and 6-31G(d,p) outperformed the others. The combination of these functionals and basis sets resulted in high accuracy with CMAE min = 0.0327 ppm (0.76%) and 0.888 ppm (0.58%) for 1 H and 13 C, respectively. The selected functionals and basis set were validated when consistently producing optimized structures with high accuracy results for 1 H and 13 C chemical shift calculations of two other biaryls. This study highly recommends the IEFPCM/B3LYP, B3PW91, mPW1PW91 or ω B97XD/DGDZVP2 or 6-31G(d,p) level of theory for the geometry optimization step, especially the solvent incorporation, which would lead to high accuracy 1 H/ 13 C calculation. This work would assist in the fully structural assignments of biaryls and provide insights into in-solution biaryl conformations.

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“…For instance, Zingerone is a major avor component of ginger, which exhibits remarkable anti-oxidant capacities via activating Nrf2 signaling and thus protects mice from allergic asthma [9]. It has been reported the natural phenylpropanoid derivative Dehydrodieugenol targets STAT3/SOCS3 and MAPK pathways to counteract allergic airway in ammation in asthmatic mice [10]. Other natural compounds exert their anti-asthma activities via modulating a variety of cellular signaling including Wnt/ β-catenin [11], TGF-β [12], NF-κB [13] and phosphatidylinositol 3kinase/protein kinase B (PI3K/Akt) pathways [14].…”

Section: Introductionmentioning

confidence: 99%

Bixin protects mice against bronchial asthma though modulating PI3K/Akt pathway

Zhu

Sun

Liu

et al. 2021

International Immunopharmacology

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Background: Accumulating evidence has implicated the potential of natural compounds in treatment of asthma. Bixin is a natural food coloring isolated from the seeds of Bixa Orellana, which possesses antitumor, anti-in ammatory and antioxidative properties. Nevertheless, its therapeutic effect in asthma has not been elucidated. Methods: Acute and chronic asthma models of Balb/c mice were established by ovalbumin (OVA) sensitization. For the establishment of a glucocorticoids (GCs) resistant asthma model, Freund's Adjuvant (CFA) was injected intraperitoneally with OVA. After Bixin treatment, cells in Bronchoalveolar lavage uid (BALF) were stained with Diff Quick staining and the levels of cytokines were measured by enzyme linked immunosorbent assay (ELISA). The levels of protein in cells and tissues were determined by immunoblotting and/or immunostaining with speci c antibodies. The histological changes were determined by Hematoxylin and eosin (H&E), PAS and MASSON staining.Results: Our present study demonstrated that administration of Bixin suppressed allergic airway in ammation and reversed GCs resistance, as well as alleviated airway remodeling and airway hyperresponsiveness (AHR) in asthmatic mice. In vitro studies showed that Bixin treatment could inhibit the development of epithelial-mesenchymal transition (EMT) mediated by transforming growth factor beta (TGF-β) signaling. Importantly, Bixin antagonized activation of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway both in vitro and in vivo.Conclusions: Above all, our ndings reveal that Bixin functions as a potent antagonist of PI3K/Akt signaling to protect against allergic asthma, highlighting a novel strategy for asthma treatment based on natural products.

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Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways

Cited by 22 publications

References 38 publications

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

¹H/¹³C chemical shift calculations for biaryls: DFT approaches to geometry optimization

Bixin protects mice against bronchial asthma though modulating PI3K/Akt pathway

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Dehydrodieugenol improved lung inflammation in an asthma model by inhibiting the STAT3/SOCS3 and MAPK pathways

Cited by 22 publications

References 38 publications

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

The Novel H4R Antagonist 1-[(5-Chloro-2,3-Dihydro-1-Benzofuran-2-Yl)Methyl]-4-Methyl-Piperazine (LINS01007) Attenuates Several Symptoms in Murine Allergic Asthma

1H/13C chemical shift calculations for biaryls: DFT approaches to geometry optimization

Bixin protects mice against bronchial asthma though modulating PI3K/Akt pathway

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¹H/¹³C chemical shift calculations for biaryls: DFT approaches to geometry optimization