Therapeutic potential of ginseng based compound in preclinical models of endometriosis

Ginseng components for the treatment of endometriosis

Key Points

Highlight:

• Ginseng, a herb popular in Asian countries and North America, is mainly composed of ginsenosides. The anti-endometriosis effect of ginsenoside metabolite, known as protopanaxadiol (PPD) is examined in this article.

Importance:

• Currently, available drug treatment for endometriosis is still lacking. The current study provides evidence that ginseng based metabolite, PPD may have therapeutic benefit for endometriosis.

What's done here:

• This study examined the anti-endometriosis effect of compounds derived from ginseng, i.e., PPD, protopanaxatriol (PPT), ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) on ectopic endometrial stromal cells and mouse endometriosis model.
• Mechanism of PPD induced anti-endometriosis was also studied through examining cellular autophagy and natural killer cells cytotoxic activity.

Data:

• The compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) decreased the viability of ectopic endometrial stromal cells, with PPD having the highest efficacy.
• PPD promoted progesterone receptor expression of and downregulated the expression of estrogen receptor α in ectopic endometrial stromal cells.
• PPD induced ectopic endometrial stromal cells autophagy.
• Ectopic endometrial stromal cells pretreated with PPD enhanced the cytotoxic activity of natural killer cells.
• PPD suppressed the growth and number of ectopic lesions in a mouse endometriosis model.

Limitation:

• The safety and the toxicity of the compounds in the animal model was not reported.
• Only one type of preclinical animal model of endometriosis was used to test compound efficacy. The inclusion of more than one animal model can be more informative.

Lay Summary

Currently, the drug option for women with endometriosis mainly focus on reducing estrogens levels (e.g., progestins, androgens, gonadotropin-releasing hormone (GnRH) agonists, and aromatase inhibitors). However, these therapies can have low effectiveness with frequent recurrence and considerable side effects. Therefore, there is a need to develop more effective treatments that may be based on other mechanisms of action.

Autophagy is a regulated cellular mechanism in which the cell that mediates natural sequestration of cellular organelles and macromolecules, allowing for orderly degradation of cellular components and the recycling of cellular components. It is an integral process within a healthy cell. Ectopic and eutopic endometrium has been previously shown to have lowered autophagy level. Low autophagy in endometriosis may lead to highly proliferative cells that lack the capacity to undergo cell death. Hence, promoting autophagy may be a useful method to promote anti-endometriosis activity.

Ginseng is a traditional herb, widely used in Asian countries and North America. It contains mainly ginsenosides (e.g., ginsenoside-Rg3 (G-Rg3) and ginsenoside Rh2 (G-Rh2)), and two metabolites of ginsenoside, protopanaxadiol (PPD) and protopanaxatriol (PPT). Previously, these have been associated with a number of pharmaceutical activities, such as antitumor, antioxidant, immunomodulatory, and anti-inflammatory activities. However, the usefulness of these ginseng components has not been studied in endometriosis. This article by Zhang et al. from Laboratory for Reproductive Immunology in Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, China, was published in Cell Death & Disease journal and investigated the anti-endometriosis activity of ginsenosides and the metabolites. In particular, the authors examined whether these compounds can regulate autophagy and estrogen receptor α level in ectopic endometrial stromal cells.

Using cell model (ectopic endometrial stromal cells), the authors found that the compounds PPD, PPT, ginsenoside-Rg3 (G-Rg3), ginsenoside-Rh2 (G-Rh2), and esculentoside A (EsA) led to significant decreases in the viability of the cells, with particularly high activity observed using PPD metabolite. Animal model studies using BALB/C mice with intraperitoneal endometriosis, again suggested that PPD decreased the numbers and suppressed the growth of ectopic lesions. Considering the mechanism of action of PPD, this compound downregulated the expression of estrogen receptor α in the cell model, as well as inducing autophagy and enhanced cytotoxic activity of natural killer cells. Therefore, the results suggest that PPD is a potential therapeutic for endometriosis.

There are several limitations of this study, being preclinical studies, the efficacy of PPD in cells and mice model cannot be directly associated with efficacy in human. It is also unclear whether pure PPD compound in itself is safe to be used in a human. No side effect studies in the animal model were reported in this article. The translatability of animal model is always an important consideration in testing new therapeutic intervention. With only one type of animal model used in this study, full efficacy conclusion cannot be drawn. Nonetheless, this study suggests the potential development of PPD for endometriosis treatment but will require clinical trials to confirm adverse effect and efficacy profiles in human.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/29760378