Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-β1 in A549 cells through Smad signaling in the cytoplasm

Ren, Zhouxin; Shen, Junling; Mei, Xiaofeng; Hui, Dong; Li, Jiansheng; Yu, Haibin

doi:10.1590/s2175-97902019000218172

Cited by 6 publications

(4 citation statements)

References 32 publications

(37 reference statements)

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“…HE is a known factor suppressing the epithelial-to-mesenchymal transition, thus inhibiting inflammation. Such a mechanism has been proved in idiopathic pulmonary fibrosis (Ren et al, 2019). The pharmacological effect of HE treatment is dose-dependent, as in the case of baicalin (Perruchot et al, 2019).…”

Section: Discussionmentioning

confidence: 94%

“…HE, CH and NA were investigated in terms of their potential use in mastitis treatment. Tracking the effects of polyphenols after intramammary administration is difficult due to the low number of observations made in vivo to date (Burmańczuk et al, 2018), and the extreme complexity of the mechanism of action of polyphenols on the inflammation and generally on the immune system (Zierau et al, 2002;Lee et al, 2015;Hwang et al, 2018;Tejada et al, 2018;Ren et al, 2019;Zhao et al, 2019). This mechanism usually involves many factors at the same time, i.e.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of Hesperidin, Chrysin, and Naringenin on Somatic Cell Count in Mastitis Dairy Cows After Multiple Intramammary Administration

Burmańczuk

Wojciechowska²,

Gbylik-Sikorska

et al. 2022

Annals of Animal Science

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Hesperidin (HE), chrysin (CH) and naringenin (NA) are flavonoids, being the most important group of polyphenols, and show anti-inflammatory properties which have been demonstrated on various models. Polyphenols have a lot of biological properties, such as antioxidative, antiviral, immunomodulatory and anticancer activities. However, the effect on mastitis has not been yet described. This research aimed to analyze the tolerability of selected polyphenols after multiple intramammary administrations (IMM) as well as to investigate their potential impact on somatic cell count (SCC) in mastitis dairy cows. The study was performed on 12 Polish Holstein Black-White cows in their 4th – to 6th lactation. Only animals with inflammation in one-quarter of the udder were selected. The selection was based on SCC and clinical assessment. The experiment was performed with multiple IMM administrations with each of these polyphenols in dairy cows affected with mastitis. Polyphenols were administered at a dose of 30 mg/quarter/day. Milk samples for SCC, blood plasma samples for pharmacokinetics and blood hematology and biochemistry (selected blood parameters were tested) were collected at baseline, treatment period and within the recovery period. Positive effects concerning the number of SCC in milk of mastitic cows were confirmed for all tested polyphenols.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

The Effect of Hesperidin, Chrysin, and Naringenin on Somatic Cell Count in Mastitis Dairy Cows After Multiple Intramammary Administration

Burmańczuk

Wojciechowska²,

Gbylik-Sikorska

et al. 2022

Annals of Animal Science

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“…It has also been demonstrated that inhibition of this signaling pathway may be crucial in reducing this phenomenon during airway remodeling and lung fibrosis. This kind of activity, by affecting Smad proteins, was proven, e.g., for apolipoprotein A1 [48], plant-derived hesperidin, paeoniflorin, and celasterol [49][50][51], as well as for two drugs approved in the treatment of idiopathic pulmonary fibrosis, nintedanib and pirfenidone [52,53]. With regard to compounds increasing the intracellular cAMP level and/or PDE inhibitors, there are several reports indicating an inhibitory effect of these compounds on the TGF-β-Smad signaling pathway.…”

Section: Discussionmentioning

confidence: 95%

Pan-Phosphodiesterase Inhibitors Attenuate TGF-β-Induced Pro-Fibrotic Phenotype in Alveolar Epithelial Type II Cells by Downregulating Smad-2 Phosphorylation

et al. 2022

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Airway remodeling is a pathological process that accompanies many chronic lung diseases. One of the important players in this process are epithelial cells, which under the influence of pro-inflammatory and pro-fibrotic factors present in the airway niche, actively participate in the remodeling process by increasing extracellular matrix secretion, acquiring migration properties, and overproducing pro-fibrotic transducers. Here, we investigated the effect of three new 8-arylalkylamino- and 8-alkoxy-1,3-dimethyl-2,6-dioxo-1,2,3,6-tetrahydro-7H-purin-7-yl-N-(5- (tert-butyl)-2-hydroxyphenyl)butanamides (1, 2, and 3), representing prominent pan-phosphodiesterase (pan-PDE) inhibitors on transforming growth factor type β (TGF-β)-induced alveolar epithelial type II cells (A549 cell line) of a pro-fibrotic phenotype. Our results demonstrate for the first time the strong activity of pan-PDE inhibitors in the prevention of TGF-β-induced mesenchymal markers’ expression and A549 cells’ migration. We also showed an increased p-CREB and decreased p-Smad-2 phosphorylation in TGF-β-induced A549 cells treated with 1, 2, and 3 derivatives, thereby confirming a pan-PDE inhibitor mesenchymal phenotype reducing effect in alveolar epithelial type II cells via suppression of the canonical Smad signaling pathway. Our observations confirmed that PDE inhibitors, and especially those active against various isoforms involved in the airway remodeling, constitute an interesting group of compounds modulating the pro-fibrotic response of epithelial cells.

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“…Amongst the abundance of scientific reports regarding the mechanisms of action of phenolic compounds (including those mentioned in this review), it is not hard to follow an apparent controversy. For example, some phenolic compounds are found to promote injured skin regeneration by inducing the epidermal growth factor and transforming growth factor, whereas the same or similar compounds are shown in different studies to suppress epithelial cancer cell development and spread due to opposing effects on growth regulation factors [190,191]. There is a theory based on the concept of a switch between anti-and pro-oxidant properties of phenolics as a function of microenvironmental factors.…”

Section: Phenolics As Pro-oxidantsmentioning

confidence: 99%

Dermal Drug Delivery of Phytochemicals with Phenolic Structure via Lipid-Based Nanotechnologies

et al. 2021

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Phenolic compounds are a large, heterogeneous group of secondary metabolites found in various plants and herbal substances. From the perspective of dermatology, the most important benefits for human health are their pharmacological effects on oxidation processes, inflammation, vascular pathology, immune response, precancerous and oncological lesions or formations, and microbial growth. Because the nature of phenolic compounds is designed to fit the phytochemical needs of plants and not the biopharmaceutical requirements for a specific route of delivery (dermal or other), their utilization in cutaneous formulations sets challenges to drug development. These are encountered often due to insufficient water solubility, high molecular weight and low permeation and/or high reactivity (inherent for the set of representatives) and subsequent chemical/photochemical instability and ionizability. The inclusion of phenolic phytochemicals in lipid-based nanocarriers (such as nanoemulsions, liposomes and solid lipid nanoparticles) is so far recognized as a strategic physico-chemical approach to improve their in situ stability and introduction to the skin barriers, with a view to enhance bioavailability and therapeutic potency. This current review is focused on recent advances and achievements in this area.

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Hesperidin inhibits the epithelial to mesenchymal transition induced by transforming growth factor-β1 in A549 cells through Smad signaling in the cytoplasm

Cited by 6 publications

References 32 publications

The Effect of Hesperidin, Chrysin, and Naringenin on Somatic Cell Count in Mastitis Dairy Cows After Multiple Intramammary Administration

The Effect of Hesperidin, Chrysin, and Naringenin on Somatic Cell Count in Mastitis Dairy Cows After Multiple Intramammary Administration

Pan-Phosphodiesterase Inhibitors Attenuate TGF-β-Induced Pro-Fibrotic Phenotype in Alveolar Epithelial Type II Cells by Downregulating Smad-2 Phosphorylation

Dermal Drug Delivery of Phytochemicals with Phenolic Structure via Lipid-Based Nanotechnologies

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