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Review
. 2023 Apr 6:14:1139460.
doi: 10.3389/fphar.2023.1139460. eCollection 2023.

Potential of resveratrol in the treatment of interstitial lung disease

Rongxiu Huo  1 , Xinxiang Huang  1 , Yanting Yang  1 , Yang Yang  1 , Jinying Lin  1
Affiliations
Review

Potential of resveratrol in the treatment of interstitial lung disease

Rongxiu Huo et al. Front Pharmacol. .

Abstract

Interstitial lung disease (ILD) is a heterogeneous group of diseases characterized by lung injury caused by lung fibroblast proliferation, interstitial inflammation, and fibrosis. Different cell signal transduction pathways are activated in response to various proinflammatory or fibrotic cytokines, such as IL-6, and these cytokines are increased in different ILDs. The overexpressed cytokines and growth factors in ILD can activate TGF-β/Smad2/3/4, NF-κB, and JAK/STAT signal transduction pathways, promote the activation of immune cells, increase the release of pro-inflammatory and pro-fibrotic factors, differentiate fibroblasts into myofibroblasts, and promote the occurrence and development of ILD. This finding suggests the importance of signal transduction pathways in patients with ILD. Recent evidence suggests that resveratrol (RSV) attenuates excessive inflammation and pulmonary fibrosis by inhibiting the TGF-β/Smad2/3/4, NF-κB, and JAK/STAT signal transduction pathways and overactivation of immune cells. In this review, advances in lung protection and the underlying mechanisms of RSV are summarized, and the potential efficacy of RSV as a promising treatment option for ILD is highlighted.

Keywords: adverse reaction; immune cells; interstitial lung disease; resveratrol; signal transduction pathway.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Graphical abstract: Potential targets of RSV in ILD. In immune cells or fibroblasts, RSV exerts anti-inflammatory and antifibrotic effects by inhibiting TGF-β/Smad2/3/4, NF-κB, and JAK/STAT pathways, as well as by regulating heat shock protein 90, inhibiting Akt, ERK1/2 and NF-κB pathways. In addition, RSV can also inhibit SIRT1, reduce α-ASM activation, and play an antifibrotic role. TGF-β, transforming growth factor β; IFN-γ, interferon-γ; TNF-α, tumor necrosis factor; P, phosphate; JAK, janus tyrosine kinase; STAT, signal transducers and activators of transcription; ERK1/2,extracellular signal-regulated protein kinases; AKT, serine-threonine kinase; NF-κB, nuclear factor-kappa B; SIRT1, sirtuin1; α-SMA, α-smooth muscle actin. “ê” indicates activation, and “—׀” indicates inhibition.
FIGURE 2
FIGURE 2
The related mechanism of ILD occurrence. Cytokines and growth factors, after binding to their corresponding receptors in immune cells or myofibroblasts, can be activated through different signal transduction pathways. Activated immune cells can secrete a variety of cytokines. They further activate macrophages; T, B, and NK cells; and myofibroblasts. They are over-activated and can secrete pro-inflammatory and pro-fibrotic cytokines, which is the environment for the formation of inflammation and fibrosis in the lung. Meanwhile, in different autoimmune diseases, B cells secrete corresponding antibodies, which are related to pulmonary fibrosis. In addition, IL-6 can activate myofibroblasts, causing them to undergo EMT and form ECM, which is deposited in the lung. Eventually ILD is formed. IL, interleukin; TGF-β, transforming growth factor β; IFN-γ, interferon-γ; TNF-α, tumor necrosis factor; P, phosphate; JAK, janus tyrosine kinase; STAT, signal transducers and activators of transcription; ERK1/2,extracellular signal-regulated protein kinases; AKT, serine-threonine kinase; NF-κB, nuclear factor-kappa B; SIRT1, sirtuin1; α-SMA, α-smooth muscle actin; ACPA, anticitrullinated peptide antibodie; ECM,extracellular matrix; EMT, epithelial-mesenchymal transition; ILD,Interstitial lung disease.
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