» Articles » PMID: 28469575

Honokiol Alleviates Hypertrophic Scar by Targeting Transforming Growth Factor-β/Smad2/3 Signaling Pathway

Overview
Journal Front Pharmacol
Date 2017 May 5
PMID 28469575
Citations 15
Authors
Affiliations
Soon will be listed here.
Abstract

Hypertrophic scar (HPS) presents as excessive extracellular matrix deposition and abnormal function of fibroblasts. However, there is no single satisfactory method to prevent HPS formation so far. Here, we found that honokiol (HKL), a natural compound isolated from Magnolia tree, had an inhibitory effect on HPS both and . Firstly, HKL could dose-dependently down-regulate the mRNA and protein levels of type I collagen, type III collagen, and α-smooth muscle actin (α-SMA) in hypertrophic scar-derived fibroblasts (HSFs). Secondly, HKL suppressed the proliferation, migration abilities of HSFs and inhibited HSFs activation to myofibroblasts, but had no effect on cell apoptosis. Besides, the rabbit ear scar model further affirmed the inhibitory effects of HKL on collagen deposition, proliferating cell nuclear antigen and α-SMA. Finally, Western blot results showed that HKL reduced the phosphorylation status of Smad2/3, as well as affected the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase1. Taken together, this study demonstrated that HKL alleviated HPS by suppressing fibrosis-related molecules and inhibiting HSFs proliferation, migration as well as activation to myofibroblasts via Smad-dependent pathway. Therefore, HKL could be used as a potential agent for treating HPS and other fibrotic diseases.

Citing Articles

Fraxinellone-mediated targeting of cathepsin B leakage from lysosomes induces ferroptosis in fibroblasts to inhibit hypertrophic scar formation.

Xu W, Lv H, Xue Y, Shi X, Fu S, Li X Biol Direct. 2025; 20(1):17.

PMID: 39905520 PMC: 11796038. DOI: 10.1186/s13062-025-00610-5.


Exosome Derived from Mesenchymal Stem Cells Alleviates Pathological Scars by Inhibiting the Proliferation, Migration and Protein Expression of Fibroblasts via Delivering miR-138-5p to Target SIRT1.

Zhao W, Zhang R, Zang C, Zhang L, Zhao R, Li Q Int J Nanomedicine. 2022; 17:4023-4038.

PMID: 36105616 PMC: 9467851. DOI: 10.2147/IJN.S377317.


TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF-κB signalling.

Ma L, Hua L, Yu W, Ke L, Li L Int Wound J. 2022; 20(4):1008-1019.

PMID: 36056472 PMC: 10031217. DOI: 10.1111/iwj.13950.


The application prospects of honokiol in dermatology.

Li Y, Liang C, Zhou X Dermatol Ther. 2022; 35(8):e15658.

PMID: 35726011 PMC: 9541939. DOI: 10.1111/dth.15658.


Honokiol Inhibits Atrial Metabolic Remodeling in Atrial Fibrillation Through Sirt3 Pathway.

Liu G, Xu W, Zang Y, Lou Q, Hang P, Gao Q Front Pharmacol. 2022; 13:813272.

PMID: 35370645 PMC: 8970047. DOI: 10.3389/fphar.2022.813272.


References
1.
Chiang C, Sheu M, Lin Y, Wu C, Yang C, Chen M . Honokiol ameliorates renal fibrosis by inhibiting extracellular matrix and pro-inflammatory factors in vivo and in vitro. Br J Pharmacol. 2011; 163(3):586-97. PMC: 3101620. DOI: 10.1111/j.1476-5381.2011.01242.x. View

2.
Chalmers R . The evidence for the role of transforming growth factor-beta in the formation of abnormal scarring. Int Wound J. 2011; 8(3):218-23. PMC: 7950816. DOI: 10.1111/j.1742-481X.2011.00771.x. View

3.
Chrysanthopoulou A, Mitroulis I, Apostolidou E, Arelaki S, Mikroulis D, Konstantinidis T . Neutrophil extracellular traps promote differentiation and function of fibroblasts. J Pathol. 2014; 233(3):294-307. DOI: 10.1002/path.4359. View

4.
Wang X, Kravchuk O, Winterford C, Kimble R . The correlation of in vivo burn scar contraction with the level of α-smooth muscle actin expression. Burns. 2011; 37(8):1367-77. DOI: 10.1016/j.burns.2011.07.018. View

5.
Pillai V, Samant S, Sundaresan N, Raghuraman H, Kim G, Bonner M . Honokiol blocks and reverses cardiac hypertrophy in mice by activating mitochondrial Sirt3. Nat Commun. 2015; 6:6656. PMC: 4441304. DOI: 10.1038/ncomms7656. View