Evidence-Based Complementary and Alternative Medicine

Review Article

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

Table 1

Common anti-angiogenic medications used for the management of endometriosis.


Compound/Drugs	Categories	Molecular mechanisms	Major targets		Type	References
Compound/Drugs	Categories	Molecular mechanisms	Anti-angiogenesis targets	Others associated targets	Type	References

Degarelix, Gonadorelin, Triptorelin/ GnRH antagonists	Endocrine therapy Gonadotropin-releasing hormone antagonist Hormone antagonists and related agent	Regression of the endometriotic lesions Increased the apoptotic rate Anti-angiogenesis	VEGF-A↓ TNF-a ↓	Bax↑ FasL↑ Bcl-2↓ IL-1↓ IL-8 ↓	Endometriotic stromal cells	[35]

Dienogest	Contraceptive agents Hormone antagonist Cytochrome P-450 CYP3A4 substrate	Reduced proliferation Increased apoptosis	MVD↓	Ki67↓	In human endometriosis cells	[36]

Bevacizumab	Angiogenesis inhibitor	Inhibited cell proliferation Reduced vascular density Increased apoptosis	VEGF↓		BALB/c mouse model	[37–39]

Ranibizumab	Angiogenesis inhibitor	Reduced endometriotic volumes	VEGF ↓		Rat model	[40]

Thalidomide	Angiogenesis inhibitor	Reduced endometriotic volumes Enhance apoptosis	VEGF-A ↓ myeloperoxidase ↓		Rat model	[41, 42]

Sunitinib	Angiogenesis inhibitor	Enhanced apoptosis	VEGF-A ↓	CD117 ↓	Rat model	[43–45]

Lovastatin Statins	Lipid-lowering agent Hypolipidemic agent	Inhibited angiogenesis and cell proliferation Increased the differentiation of eMSCs Decreased expression of eMSCs markers		BMP2↑ cyclo-oxygenase (COX), and hypoxia-inducible factor 1α (HIF-1)RUNX2 ↑	Endometrial mesenchymal stem cells (eMSCs)	[46]

Simvastatin Statins	Lipid-lowering agent Cytochrome P-450 enzyme inducer/inhibitor	Inhibited the proliferation and the contractility Decreased endometrial implants	VEGF↓ HIF-1α↓	MMP-3 ↓	Human endometriotic stromal cells/clinical research/primate Model	[47–51]

Cabergoline Dopamine agonist	Cytochrome P-450 enzyme inhibitors Dopamine agonists Ergot-derivative dopamine receptor agonists Serotonin 5-HT1 receptor agonists	Inhibited the growth of established endometriosis lesions	VEGFR-2 ↓		Clinical research/rat and mouse models	[52–54]

Quinagolide Dopamine agonist	Dopamine agonist non-ergot-derived selective dopamine D2 receptor agonist	Reduced the levels of IL-6 and VEGF in peritoneal fluid	VEGF ↓	IL-6 ↓	Rat model	[55]

Endostatin Endostar	Angiogenesis inhibitor	Suppression of VEGF in peritoneal fluid	VEGF ↓ MVD↓	MMP-2↓	Mouse and rat models	[56]

Angiostatin	Angiogenesis inhibitor	Reduction of estradiol and progesterone production.		E2↓	Estrogen-supplemented ovariectomized mouse model	[57]

Rosiglitazone	Antidiabetic drug Thiazolidinedione	Inhibited aromatase and COX-2 expression Reduced the vascularized area of lesions Enhanced apoptosis	CD31 ↓ CD34 ↓	PGE2 ↓ PCNA ↓	Human cell culture/ BALB/C mice model	[29]

Fenofibrate Statins	Lipid-lowering agent Cytochrome P-450 enzyme inducer/inhibitor	Reduction of endometriotic lesion	VEGF ↓		Rat model	[59]

HIF-1α: hypoxia-inducible factor 1α; IL-1: interleukin-1; MPO: myeloperoxidase; MVD: microvessel density; VEGF: vascular endothelial growth factor.