Hung Chi-Feng, Hsiao Chien-Yu, Hsieh Wen-Hao, Li Hsin-Ju, Tsai Yi-Ju, Lin Chun-Nan, Chang Hsun-Hsien, Wu Nan-Lin
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
PLoS One. 2017 Aug 16;12(8):e0182981. doi: 10.1371/journal.pone.0182981. eCollection 2017.
Licorice (Glycyrrhiza) species have been widely used as a traditional medicine and a natural sweetener in foods. The 18β-glycyrrhetinic acid (18β-GA) is a bioactive compound in licorice that exhibits potential anti-cancer, anti-inflammatory, and anti-microbial activities. Many synthesized derivatives of 18β-GA have been reported to be cytotoxic and suggested for the treatment of malignant diseases. In this study, we explored the possible pharmacological roles of an 18β-GA derivative in skin biology using primary human dermal fibroblasts and HaCaT keratinocytes as cell models. We found that this 18β-GA derivative did not cause cell death, but significantly enhanced the proliferation of dermal fibroblasts and HaCaT keratinocytes. A scratch wound healing assay revealed that the 18β-GA derivative promoted the migration of fibroblasts. Due to the important role of aquaporin-3 in cell migration and proliferation, we also investigated the expression of aquaporin-3 and found this compound up-regulated the expression of aquaporin-3 in dermal fibroblasts and HaCaT keratinocytes. In dermal fibroblasts, the 18β-GA derivative induced the phosphorylation of Akt, ERK, and p38. The inhibitor of Akt predominantly suppressed the 18β-GA derivative-induced expression of aquaporin-3. Collectively, this compound had a positive effect on the proliferation, migration, and aquaporin-3 expression of skin cells, implying its potential role in the treatment of skin diseases characterized by impaired wound healing or dermal defects.
甘草属植物已被广泛用作传统药物和食品中的天然甜味剂。18β-甘草次酸（18β-GA）是甘草中的一种生物活性化合物，具有潜在的抗癌、抗炎和抗菌活性。据报道，许多18β-GA的合成衍生物具有细胞毒性，并被建议用于治疗恶性疾病。在本研究中，我们以原代人皮肤成纤维细胞和HaCaT角质形成细胞为细胞模型，探讨了一种18β-GA衍生物在皮肤生物学中的可能药理作用。我们发现这种18β-GA衍生物不会导致细胞死亡，但能显著增强皮肤成纤维细胞和HaCaT角质形成细胞的增殖。划痕伤口愈合试验表明，18β-GA衍生物促进了成纤维细胞的迁移。由于水通道蛋白-3在细胞迁移和增殖中具有重要作用，我们还研究了水通道蛋白-3的表达，发现该化合物上调了皮肤成纤维细胞和HaCaT角质形成细胞中水通道蛋白-3的表达。在皮肤成纤维细胞中，18β-GA衍生物诱导了Akt、ERK和p38的磷酸化。Akt抑制剂主要抑制18β-GA衍生物诱导的水通道蛋白-3表达。总体而言，该化合物对皮肤细胞的增殖、迁移和水通道蛋白-3表达具有积极作用，这意味着它在治疗以伤口愈合受损或皮肤缺损为特征的皮肤疾病中具有潜在作用。
