探討光甘草定於防治口腔黏膜下纖維化症的分子機轉

口腔黏膜纖維化症為一種慢性發炎且不可逆的疾病，亦歸屬為口腔癌前病變的一種。嚼食檳榔與口腔黏膜纖維化症相關，但其致病機轉仍待進一步詳細探討，尚無有效療法。前導實驗指出肌纖維母細胞活化造成口腔黏膜纖維化，因此本研究的目的主要透過篩選出有效抑制肌纖維母細胞活化之天然食用萃取物及探討其分子機制，尋找出新的治療方式或預防策略。研究結果發現：纖維化頰黏膜纖維母細胞的增生能有效地被甘草分離出的光甘草定所抑制，相對於正常頰黏膜纖維母細胞則較無影響。纖維化頰黏膜纖維母細胞經光甘草定處理後，能明顯抑制其膠體收縮力。光甘草定同時也能顯著減少纖維化頰黏膜纖維母細胞的移行、侵襲及傷口癒合能力。另外光甘草定可抑制正常頰黏膜纖維母細胞由檳榔素所活化的肌纖維母細胞特性，例如膠體收縮力、移行、侵襲及傷口癒合能力皆受影響。TGFB/Smad促纖維化訊息傳遞路徑及肌纖維母細胞相關標記(如COL1A1及α-SMA)之蛋白質表現量可透過光甘草定而被抑制。綜合以上的結果證實具光甘草定有高度潛能開發為抗口腔黏膜纖維化症之天然物。

Oral submucous fibrosis (OSF) is a chronic inflammatory disease and an irreversible oral potentially malignant disorder. Epidemiological studies have indicated that the development of OSF is associated with the habit of areca nuts chewing, however, the pathological mechanism of OSF has not been fully elucidated and the effective treatments remain to be discovered. Previous studies have revealed that the activation of myofibroblasts are implicated in the oral fibrogenesis, so the current project sought to explore the potential natural compounds to inhibit their activation and the molecular mechanisms in order to aid in the prevention of the malignant transformation of OSF. The results of the present study showed that the proliferation ability of fibrotic buccal mucosal fibroblasts (fBMFs) reduced in response to glabridin, an isoflavone extracted from licorice root, without damaging normal buccal mucosal fibroblasts (BMFs). Administration of glabridin exhibited inhibitory effects on the collagen gel contraction, migration, and invasion abilities of fBMFs. Besides, we found that the treatment of glabridin suppressed the higher collagen gel contraction, migration, invasion, and wound healing capacities induced by arecoline stimulation. Our results demonstrated that glabridin downregulated the pro-fibrosis TGFβ/Smad pathway and the expression of fibrosis markers (such as type I collagen A1 and α-SMA). Collectively, these findings suggested that glabridin may serve as a potential dietary supplement for the amelioration of OSF.