Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities

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Abstract

Resveratrol (Res) is a well-known natural product that can exhibit important pharmacological activities such as antioxidant, anti-diabetes, anti-tumor, and anti-inflammatory. An evaluation of its therapeutic effects demonstrates that this naturally occurring bioactive compound can target different molecular pathways to exert its pharmacological actions. Transforming growth factor-beta (TGF-β) is an important molecular pathway that is capable of regulating different cellular mechanisms such as proliferation, migration, and angiogenesis. TGF-β has been reported to be involved in the development of disorders such as diabetes, cancer, inflammatory disorders, fibrosis, cardiovascular disorders, etc. In the present review, the relationship between Res and TGF-β has been investigated. It was noticed that Res can inhibit TGF-β to suppress the proliferation and migration of cancer cells. In addition, Res can improve fibrosis by reducing inflammation via promoting TGF-β down-regulation. Res has been reported to be also beneficial in the amelioration of diabetic complications via targeting the TGF-β signaling pathway. These topics are discussed in detail in this review to shed light on the protective effects of Res mediated via the modulation of TGF-β signaling.

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Animal Communication: When I’m Calling You, Will You Answer Too?

Neil Vickers (2017)

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High absorption but very low bioavailability of oral resveratrol in humans.

Thomas Walle, Faye Hsieh, Mark Delegge … (2004)

The dietary polyphenol resveratrol has been shown to have chemopreventive activity against cardiovascular disease and a variety of cancers in model systems, but it is not clear whether the drug reaches the proposed sites of action in vivo after oral ingestion, especially in humans. In this study, we examined the absorption, bioavailability, and metabolism of 14C-resveratrol after oral and i.v. doses in six human volunteers. The absorption of a dietary relevant 25-mg oral dose was at least 70%, with peak plasma levels of resveratrol and metabolites of 491 +/- 90 ng/ml (about 2 microM) and a plasma half-life of 9.2 +/- 0.6 h. However, only trace amounts of unchanged resveratrol (<5 ng/ml) could be detected in plasma. Most of the oral dose was recovered in urine, and liquid chromatography/mass spectrometry analysis identified three metabolic pathways, i.e., sulfate and glucuronic acid conjugation of the phenolic groups and, interestingly, hydrogenation of the aliphatic double bond, the latter likely produced by the intestinal microflora. Extremely rapid sulfate conjugation by the intestine/liver appears to be the rate-limiting step in resveratrol's bioavailability. Although the systemic bioavailability of resveratrol is very low, accumulation of resveratrol in epithelial cells along the aerodigestive tract and potentially active resveratrol metabolites may still produce cancer-preventive and other effects.

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TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.

Bernhard Schmierer, Caroline Hill (2007)

Ligands of the transforming growth factor-beta (TGFbeta) superfamily of growth factors initiate signal transduction through a bewildering complexity of ligand-receptor interactions. Signalling then converges to nuclear accumulation of transcriptionally active SMAD complexes and gives rise to a plethora of specific functional responses in both embryos and adult organisms. Current research is focused on the mechanisms that regulate SMAD activity to evoke cell-type-specific and context-dependent transcriptional programmes. An equally important challenge is understanding the functional role of signal strength and duration. How are these quantitative aspects of the extracellular signal regulated? How are they then sensed and interpreted, and how do they affect responses?

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Author and article information

Journal

Journal ID (nlm-ta): Biomedicines

Journal ID (iso-abbrev): Biomedicines

Journal ID (publisher-id): biomedicines

Title: Biomedicines

Publisher: MDPI

ISSN (Electronic): 2227-9059

Publication date (Electronic): 31 July 2020

Publication date Collection: August 2020

Volume: 8

Issue: 8

Electronic Location Identifier: 261

Affiliations

[1 ]Department of Basic Science, Faculty of Veterinary Medicine, University of Tabriz, Tabriz 5166616471, Iran; dvm.milad73@ 123456yahoo.com

[2 ]Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Sciences, Kermanshah 6715847141, Iran; najafi_ma@ 123456yahoo.com

[3 ]Department of Genetics, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; Sima.orouei@ 123456gmail.com

[4 ]Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1916893813, Iran; Fzr2000_0007@ 123456yahoo.com (A.Z.); hosseinsaleki2015@ 123456gmail.com (H.S.); negarazami77@ 123456gmail.com (N.A.); Negin.sharifi87@ 123456gmail.com (N.S.)

[5 ]Department of Food Hygiene and Quality Control, Division of Epidemiology & Zoonoses, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417414418, Iran; houshmandi.kia7@ 123456ut.ac.ir

[6 ]Sabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla, 34956 Istanbul, Turkey

[7 ]Center of Excellence for Functional Surfaces and Interfaces (EFSUN), Faculty of Engineering and Natural Sciences, Sabanci University, Tuzla, 34956 Istanbul, Turkey

[8 ]Department of Science in Korean Medicine, College of Korean Medicine, Kyung Hee University, 24 Kyungheedae-ro, Dongdaemun-gu, Seoul 02447, Korea

Author notes

[* ]Correspondence: alizarrabi@ 123456sabanciuniv.edu (A.Z.); ksahn@ 123456khu.ac.kr (K.S.A.)

Author information

Milad Ashrafizadeh https://orcid.org/0000-0001-6605-822X

Masoud Najafi https://orcid.org/0000-0002-6341-9007

Negar Azami https://orcid.org/0000-0002-5215-0217

Negin Sharifi https://orcid.org/0000-0002-1450-642X

Ali Zarrabi https://orcid.org/0000-0003-0391-1769

Kwang Seok Ahn https://orcid.org/0000-0002-2882-0612

Article

Publisher ID: biomedicines-08-00261

DOI: 10.3390/biomedicines8080261

PMC ID: 7460084

PubMed ID: 32752069

SO-VID: 16478b75-b447-4847-a421-fb46f6c08d18

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

Resveratrol Modulates Transforming Growth Factor-Beta (TGF-β) Signaling Pathway for Disease Therapy: A New Insight into Its Pharmacological Activities

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Most cited references 209

Animal Communication: When I’m Calling You, Will You Answer Too?

High absorption but very low bioavailability of oral resveratrol in humans.

TGFbeta-SMAD signal transduction: molecular specificity and functional flexibility.

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