Presumed molecular mechanisms for herbal medicinal therapies in endometriosis

Potential herbal remedies for endometriosis management: new horizons in clinical trials

Key Points

Highlights:

• Medicinal remedies for endometriosis  such as progestins, androgens, gonadotropin-releasing hormone (GnRH) agonists and aromatase inhibitors are associated with side effects and are not curative. Herbal medicines that have been used for decades for management of endometriosis target cell proliferation and apoptosis, inflammation, oxidative stress, invasion, and attachment. 

Importance:

• As an inflammatory debilitating disease, and being the most common benign gynecological proliferation in women, no successful intervention is known for the treatment of endometriosis.
• Investigations for discovering new agents regarding herbal remedies, including medicinal plants, phytochemicals, and multi-component herbal preparations may be potential products in this regard.

What's done here:

• Herbal medicinal products used for the management of endometriosis and their possible mechanisms of action have been summarized after searching different electronic databases including PubMed, Scopus, Cochrane library and Google Scholar.
• Traditional medicinal plants for endometriosis include; Achillea biebersteinii (Yarrow), the genus Alchemilla (Rosaceae), Allium sativum (garlic), Artemisia princeps (family Asteraceae), Coccinia cordifolia commonly known as Ivy gourd, Copaifera langsdorffii trees, Turmeric, the rhizome of Curcuma longa (Zingiberaceae), Euterpe oleracea (Acai) a palm tree, Pycnogenol®, a standardized extract of the Pinus pinaster bark, Prunella vulgaris (Lamiaceae), flavonoids, tannins, oleanolic acid, betulinic acid, ursolic acid, polysaccharide prunelline, rosmarinic acid, Salvia miltiorrhiza - a popular Chinese traditional plant, Tripterygium wilfordii (thunder god vine), Uncaria tomentosa (cat’s claw), European cranberry bush (Viburnum opulus).
• Phytochemicals are; Apigenin, β-caryophyllene, Curcumin, Epigallocatechin-3-gallate (EGCG), Genistein, Ginsenoside, Parthenolide, Puerarin, Resveratrol, Xanthohumol. 
• Additionally, there are multi-component herbal preparations mostly originating from Chinese herbal formulas and demonstrating their efficacy via anti-inflammatory, antiproliferative, and apoptotic activities.  
• Herbal remedies for endometriosis are mostly investigated at the cellular and experimental levels, well designed clinical trials are recommended to achieve more conclusive results.

Key Results:

• Data collected from studies investigating the effect of herbal products for endometriosis were mainly in vitro and animal and only three clinical trials were found; one on Pinus pinaster bark extract (Pycnogenol) and two on Chinese herbal formulas. The studies on phytochemicals had mostly focused on polyphenolic compounds (epigallocatechin-3-gallate, genistein) and sesquiterpenes (β-caryophyllene, parthenolide). 
• Various molecular mechanisms of action are involved in beneficial effects of herbal medicines and phytochemicals including anti-inflammatory (via reduction of proinflammatory cytokines such as interleukin -1, interleukin -6, interleukin -8, transforming growth factor-beta, tumor necrosis factor-α, nuclear factor-kappa B, growth factors, monocyte chemoattractant protein-1), antioxidant (through downregulation of hydrogen peroxide, malondialdehyde, reactive oxygen species and upregulation of superoxide dismutase), antiproliferative and apoptotic (via enhancing Bcl-2-associated X protein/ B-cell lymphoma-2 and caspase3, 8 and 9 activity), anti-angiogenic (by downregulation of vascular endothelial growth factor receptors/ vascular endothelial growth factor), anti-invasive via decreasing expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix. 
• Studies on herbal medicines for endometriosis are mainly at the cellular and experimental levels, so well designed clinical trials are recommended to achieve more conclusive results.

Lay Summary

Pharmaceutical agents for the management of endometriosis are associated with side effects and are not completely effective. In regard to this, Bina and associates from Tehran University of Medical Sciences have reviewed extensively the literature for herbal remedies.

Herbal medicinal products used for the management of endometriosis and their possible mechanisms of action have been summarized after searching different electronic databases including PubMed, Scopus, Cochrane library and Google Scholar. Data collected from 1980 to 2018 of studies investigating the effect of herbal medicines in endometriosis were in vitro and animal and only three clinical trials were found; one on Pinus pinaster bark extract (Pycnogenol) and two on Chinese herbal formulas. 

Plant-derived medicinal compound has been in use for a long time. Pharmacological targets of herbal medicines for the management of endometriosis include; cell proliferation and apoptosis, inflammation, oxidative stress, invasion, and attachment. 

Various molecular mechanisms of action are involved in beneficial effects of herbal medicines and phytochemicals including anti-inflammatory (via reduction of proinflammatory cytokines such as interleukin -1, interleukin -6, interleukin -8, transforming growth factor-beta, tumor necrosis factor-α, nuclear factor-kappa B, growth factors, monocyte chemoattractant protein-1), antioxidant (through downregulation of hydrogen peroxide, malondialdehyde, reactive oxygen species and upregulation of superoxide dismutase), antiproliferative and apoptotic (via enhancing Bcl-2-associated X protein/ B-cell lymphoma-2 and caspase3, 8 and 9 activity), anti-angiogenic (by downregulation of vascular endothelial growth factor receptors/ vascular endothelial growth factor), anti-invasive via decreasing expression of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and matrix. 

Most studies on the effectiveness of herbal remedies for endometriosis are at cellular and experimental levels, and well designed clinical trials are strongly recommended for more conclusive results.

Research Source: https://www.ncbi.nlm.nih.gov/pubmed/?term=30412733