18ß-glycyrrhetinic acid derivative promotes proliferation, migration and aquaporin-3 expression in human dermal fibroblasts

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.

Computational and Biological Comparisons of Plant Steroids as Modulators of Inflammation through Interacting with Glucocorticoid Receptor

“…Glycyrrhetinic acid, on the other hand, had no significant effect in either model, which is logical in view of its differential effect on serum cytokines. However, previous in vitro studies suggested that glycyrrhetinic acid probably had anti-inflammatory properties [33, 34], which contradict our results. It is possible that the concentration of glycyrrhetinic acid used in the current study was not high enough to show its beneficial effect in in vivo animal models.…”

18β‐Glycyrrhetinic acid: its core biological properties and dermatological applications

“…In addition, GA‐d upregulated the expression of aquaporin‐3 in fibroblasts and keratinocytes. These properties make GA a candidate for the treatment of skin diseases like wounds and dermal defects .…”

The Protective Effects of 18β-Glycyrrhetinic Acid on Imiquimod-Induced Psoriasis in Mice via Suppression of mTOR/STAT3 Signaling

“…18 β -Glycyrrhetinic acid (GA, structure shown in Figure 1 ), an aglycone and active metabolite of glycyrrhizic acid, has been shown to have a series of pharmacological effects such as antioxidative [ 12 , 13 ], antitumor [ 14 – 16 ], and anti-inflammatory [ 17 , 18 ] activities. Moreover, in recent years, this compound has also been reported to show some protective effect in skin disorders [ 19 – 21 ]. However, no report has been issued on the protective effects of GA against imiquimod-induced psoriasis-like skin in vivo .…”