Plants as source of new therapies for endometriosis: a review of preclinical and clinical studies Original paper
Researched by:
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Karen Pendergrass
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Karen Pendergrass
Karen Pendergrass is a microbiome researcher specializing in microbiome-targeted interventions (MBTIs). She systematically analyzes scientific literature to identify microbial patterns, develop hypotheses, and validate interventions. As the founder of the Microbiome Signatures Database, she bridges microbiome research with clinical practice. In 2012, based on her own investigative research, she became the first documented case of FMT for Celiac Disease—four years before the first published case study.
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Endometriosis
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
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Karen Pendergrass
Researched by:
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Karen Pendergrass
ID
Karen Pendergrass
Microbiome Signatures identifies and validates condition-specific microbiome shifts and interventions to accelerate clinical translation. Our multidisciplinary team supports clinicians, researchers, and innovators in turning microbiome science into actionable medicine.
Karen Pendergrass
What Was Reviewed?
This review comprehensively evaluates plant-derived agents as potential therapies for endometriosis. It focuses on herbal extracts, specific plant bioactive compounds, and Chinese herbal medicine (CHM) formulations, assessing their mechanisms of action, therapeutic potential, and preclinical and clinical evidence supporting their use. The authors aim to establish these agents as alternatives to current treatments with fewer side effects and long-term efficacy.
Who Was Reviewed?
The studies reviewed include human endometriotic cell lines, surgically induced endometriosis models in animals, and clinical trials involving human participants. The scope of the review is broad, encompassing various agents such as Pueraria flower extract (PFE), curcumin, resveratrol, and CHM formulations, along with their effects on biological processes like inflammation, angiogenesis, oxidative stress, and apoptosis.
Summary of Plant-Derived Agents
The table below summarizes the plant-derived agents, their models, mechanisms of action, and key findings.
| Plant/Compound | Model Studied | Mechanism of Action | Key Findings |
|---|---|---|---|
| Pueraria Flower Extract (PFE) | Human endometriotic cell lines, Balb/c mice | Anti-proliferative, anti-inflammatory | Reduced lesion size, suppressed MMP-2 and MMP-9 expression, and cell migration. |
| Resveratrol | Human cell lines, murine models, small clinical trials | Anti-angiogenic, anti-inflammatory, pro-apoptotic | Reduced VEGF expression, lesion size, and inflammatory cytokines (IL-6, TNF-α). |
| Curcumin | Human cell lines, rat models, clinical trials | Anti-inflammatory, anti-angiogenic | Reduced IL-6, IL-8, and VEGF; improved oxidative stress and apoptosis markers. |
| Silymarin | Rat models | Anti-proliferative, antioxidant | Induced lesion regression, apoptosis, and fibrosis while inhibiting angiogenesis. |
| Acai Extract | Sprague-Dawley rats | Anti-inflammatory, anti-angiogenic | Reduced lesion size and markers such as VEGF and COX-2. |
| Chinese Herbal Medicine | Human clinical trials | Multi-targeted (anti-inflammatory, hormonal balance) | Reduced pain and postoperative recurrence, improved quality of life. |
These agents show promise as complementary treatments due to their multi-targeted actions and potential to address limitations of current therapies.
Mechanisms of Action
Mechanistically, the plant-derived agents influence key pathways involving cytokines (IL-6, IL-8, TNF-α), transcription factors (NF-κB), and matrix metalloproteinases (MMPs), making them promising candidates for integrative treatment strategies. The pleiotropic effects of plant-derived agents on critical processes in endometriosis pathogenesis are summarized in the following table:
| Pathological Process | Impacted Markers | Intervention |
|---|---|---|
| Angiogenesis | VEGF, MMP-2, MMP-9 | Resveratrol, curcumin |
| Inflammation | IL-6, IL-8, TNF-α | Resveratrol, acai extract |
| Apoptosis Resistance | Bcl-2 | Silymarin, curcumin |
| Oxidative Stress | ROS, catalase, glutathione peroxidase | Resveratrol, silymarin |
| Proliferation of Lesions | ERK1/2, cyclin D1 | Pueraria flower extract, curcumin |
| Hormonal Dysregulation | Aromatase, COX-2 | Resveratrol, puerarin |
Most Important Findings
The review highlights the multi-targeted action profiles of plant-derived therapies. Resveratrol shows strong evidence in reducing lesion size, VEGF expression, and inflammation across preclinical and limited clinical settings. Curcumin exhibits anti-inflammatory and anti-angiogenic properties by reducing IL-6, IL-8, and VEGF levels, while improving oxidative stress markers. Silymarin is another promising agent with pro-apoptotic and anti-proliferative effects, though its clinical potential is limited by poor bioavailability. Chinese herbal medicine demonstrates efficacy in reducing postoperative recurrence rates and pain, but its variability requires standardized formulations.
Greatest Implications
Plant-derived agents represent a promising addition to multimodal endometriosis treatments, offering pleiotropic benefits and potentially fewer side effects compared to current therapies. They address critical mechanisms such as inflammation, angiogenesis, and oxidative stress, which are central to endometriosis pathology. However, challenges like standardization, bioavailability, and limited clinical evidence remain.
Endometriosis
Endometriosis involves ectopic endometrial tissue causing pain and infertility. Validated and Promising Interventions include Hyperbaric Oxygen Therapy (HBOT), Low Nickel Diet, and Metronidazole therapy.
Pueraria Flower Extract (PFE)
Pueraria lobata (kudzu) is used in traditional medicine for cardiovascular issues, menopause, and alcohol dependence due to its bioactive isoflavones. These compounds, particularly puerarin, offer vasodilatory effects and antioxidant properties, enhancing blood circulation and reducing oxidative stress.
Pueraria Flower Extract (PFE)
Pueraria lobata (kudzu) is used in traditional medicine for cardiovascular issues, menopause, and alcohol dependence due to its bioactive isoflavones. These compounds, particularly puerarin, offer vasodilatory effects and antioxidant properties, enhancing blood circulation and reducing oxidative stress.
Matrix Metalloproteinases (MMPs)
Matrix Metalloproteinases (MMPs) are zinc-dependent enzymes that regulate extracellular matrix remodeling, with critical roles in health, disease, and interactions with the microbiome.