Ginsenoside Rg3 Decreases Fibrotic and Invasive Nature of Endometriosis by Modulating miRNA-27b: In Vitro and In Vivo Studies

Abstract

This research aimed to evaluate the potential therapeutic effects of Rg3 on endometriosis and identify target miRNAs. We designed an in vitro study using human endometrial stromal cells (HESCs) obtained from patients with endometriosis and an in vivo study using mouse models. HESCs were treated with Rg3-enhanced red ginseng extract (Rg3E); real-time PCR and microarray profiling, transfection, and western blot were performed. Mouse endometriosis models were developed and supplemented with Rg3E for 8 weeks. Gross lesion size and fibrotic character were analyzed in the mouse models. RNA levels of Ki-67, col-1, CTGF, fibronectin, TGF-β1, MMP2 and MMP9 significantly decreased in HESCs after Rg3E treatment. Microarray analysis revealed downregulation of miR-27b-3p, which is related to fibrosis modulation. Expression of miR-27b-3p was significantly higher in HESCs from patients with endometriosis than that of controls, and Rg3E treatment significantly decreased its expression; the contraction and migration assay revealed significant reductions in both fibrosis and migration potential in Rg3E-treated HESCs from endometriosis patients. A decrease in size and fibrotic character of endometrial lesions from the Rg3E groups was observed in vivo. In conclusion, Rg3 effectively altered fibrotic properties of HESCs from patients with endometriosis, which is likely associated with miR-27b-3p modulation.

Non-Coding RNAs in Endometrial Physiopathology

“…In 2017, Min Kyoung Kim and collaborators demonstrated that the expression of miR-27b-3p, upregulated in human endometrial stromal cells from patients with endometriosis, is reduced after the treatment with Rg3-enhanced red ginseng extract (Rg3E). The authors showed the same effects in vivo in a mouse model [ 166 ]. In 2018, by RNA sequencing, it was demonstrated that 107 miRNAs and 6112 mRNAs were differentially expressed in ectopic endometrium.…”

“…Interestingly, miR-27a and miR-27b, two isoforms of the miR-27 family, seem to be involved in different endometrial pathologies. Their up-regulation in endometrium and serum has been described in EC, in endometriosis and in CE [ 56 , 166 , 197 ] ( Figure 3 ). It would be attractive to demonstrate, by functional experiments, its ability to regulate IGF1 and other messengers, in order to understand its role in endometrial physiopathology and evaluate its prognostic potential and the possibility to plan specific therapy based on RNA interference.…”

Anti‐Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

“…Ginsenoside Rg3 has been shown to inhibit angiogenesis in endometrial lesions in a rat model by blocking VEGFR-2 and inhibiting the PI3K/Akt/mTOR signaling pathway [ 113 ]. Rg3 has been shown to effectively alter the fibrotic properties of human embryonic stem cells (HESCs) in patients with endometriosis, likely via miR-27b-3p modulation [ 114 ].…”

Circular RNA expression profiles and bioinformatics analysis in ovarian endometriosis

“…For example, miR‐143 was reported as upregulated in eutopic endometrial tissues (Ohlsson‐Teague et al, ). Another study in vitro showed that expression of miR‐27b‐3p was significantly higher in human endometrial stromal cells from patients with endometriosis than that of controls, which was related to fibrosis modulation (Kim et al, ). miR‐34a‐5p was significantly downregulated in patients with endometriosis (Ma, Huang, & Chen, ).…”