Honokiol inhibits arecoline-induced oral fibrogenesis through transforming growth factor-β/Smad2/3 signaling inhibition. 2021

Pei-Yin Chen, and Dennis Chun-Yu Ho, and Yi-Wen Liao, and Pei-Ling Hsieh, and Kai-Hsi Lu, and Lo-Lin Tsai, and Sheng-Hua Su, and Cheng-Chia Yu
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan; Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.

OBJECTIVE The habit of areca nut chewing has been regarded as an etiological factor of precancerous oral submucous fibrosis (OSF). In the present study, we aimed to evaluate the anti-fibrosis effect of honokiol, a polyphenolic component derived from Magnolia officinalis. METHODS The cytotoxicity of honokiol was tested using normal and fibrotic buccal mucosal fibroblasts (fBMFs) derived from OSF tissues. Collagen gel contraction, Transwell migration, invasion, and wound healing capacities were examined. Besides, the expression of TGF-β/Smad2 signaling as well as α-SMA and type I collagen were measured as well. RESULTS Honokiol exerted higher cytotoxicity of fBMFs compared to normal cells. The arecoline-induced myofibroblast activities, including collagen gel contractility, cell motility and wound healing capacities were all suppressed by honokiol treatment. In addition, the expression of the TGF-β/Smad2 pathway was downregulated along with a lower expression of α-SMA and type I collagen in honokiol-receiving cells. CONCLUSIONS Our data suggest that honokiol may be a promising compound to alleviate the progression of oral fibrogenesis and prevent the transformation of OSF oral epithelium into cancer.

UI MeSH Term Description Entries
D009061 Mouth Mucosa Lining of the ORAL CAVITY, including mucosa on the GUMS; the PALATE; the LIP; the CHEEK; floor of the mouth; and other structures. The mucosa is generally a nonkeratinized stratified squamous EPITHELIUM covering muscle, bone, or glands but can show varying degree of keratinization at specific locations. Buccal Mucosa,Oral Mucosa,Mucosa, Mouth,Mucosa, Oral
D009914 Oral Submucous Fibrosis Irreversible FIBROSIS of the submucosal tissue of the MOUTH. Fibroses, Oral Submucous,Fibrosis, Oral Submucous,Oral Submucous Fibroses,Submucous Fibroses, Oral,Submucous Fibrosis, Oral
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001114 Areca A plant genus of the family ARECACEAE. Members contain ARECOLINE and CATECHIN. The leaves and nuts have been used as masticatories, stimulants, and astringents in traditional medicine. The common name of betel is also used for PIPER BETLE. The common name of catechu is sometimes used for ACACIA CATECHU. Betel Nut,Areca catechu,Areca catechus,Arecas,Betel Nuts,Nut, Betel,Nuts, Betel,catechus, Areca
D001115 Arecoline An alkaloid obtained from the betel nut (Areca catechu), fruit of a palm tree. It is an agonist at both muscarinic and nicotinic acetylcholine receptors. It is used in the form of various salts as a ganglionic stimulant, a parasympathomimetic, and a vermifuge, especially in veterinary practice. It has been used as a euphoriant in the Pacific Islands. Methylarecaidin,Arecaline,Arecholin,Arecholine,Arecolin
D001713 Biphenyl Compounds Whitish aromatic crystalline organic compounds made up of two conjoined BENZENE rings. Compounds, Biphenyl
D015291 Transforming Growth Factors Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA. Transforming Growth Factor,Factor, Transforming Growth,Factors, Transforming Growth,Growth Factor, Transforming,Growth Factors, Transforming
D017705 Lignans A class of dibenzylbutane derivatives which occurs in higher plants and in fluids (bile, serum, urine, etc.) in man and other animals. These compounds, which have a potential anti-cancer role, can be synthesized in vitro by human fecal flora. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed) Lignan,Neolignan,Neolignans
D051899 Smad2 Protein A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. It regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling. MAD-Related 2 Protein,MADR2 Protein,MAD Related 2 Protein

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