Abstract
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.
Highlights
The roots and rhizomes of licorice (Glycyrrhiza) species have been widely used in herbal medicine for a long time
Glycyrrhizic acid, a triterpenoid saponin glycoside, is the major water-soluble constituent of licorice [3, 6]. Glycyrrhetinic acid is another natural triterpenoid in licorice, which is obtained by hydrolyzing glycyrrhizic acid by glucuronidase; it exists in two forms: 18α-glycyrrhetinic acid (18α-GA) and a stereoisomeric form, 18β-glycyrrhetinic acid (18β-GA) [6]
The phosphorylation of c-Jun NH2-terminal kinase (JNK), induced by THF or the 18β-GA-d, was barely detected. These results indicated that the Akt, ERK1/2, and p38 pathways could possibly regulate the pharmacological effects of the 18β-GA-d on human dermal fibroblasts
Summary
The roots and rhizomes of licorice (Glycyrrhiza) species have been widely used in herbal medicine for a long time. Delayed wound healing process with reduced keratinocyte proliferation and migration was observed in AQP-3-knockout mice [22]. AQP-3 has been reported to regulate human skin fibroblast migration, indicating its role in the wound healing process [23]. These findings indicated that AQP-3 played a critical role in regulating the proliferation and migration of skin cells. We explored other possible effects of this 18β-GAd on the biological functions of the skin using primary human dermal fibroblasts derived from. 18ß-GA derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts adult foreskin and HaCaT keratinocytes as cell models. Because AQP-3 is the predominant skin AQP crucial for the physiological functions of the skin such as cell proliferation, migration, and intact barrier function, we evaluated the influence of the 18β-GA-d on the expression of AQP-3 in skin cells
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