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

Table 3

Main anti-angiogenesis agents for endometriosis that have been isolated from Chinese herbal medicines.

Chinese herbal medicines; Latin name/Chinese name	The main chemical compounds	Molecular targets/; mechanisms	Preclinical or clinical evidence of ant-angiogenesis	Major Targets		Signal pathway	Type	reference
				Anti-angiogenesis targets	Others associtated targets
Curcuma longa (Jianghuang); Rhizoma curcumae(E’zhu); Rhizoma sparganii (Sanleng); Curcuma rcenyujin (Yujing)	Curcumin	Inhibited angiogenesis,; Induced cell apoptosis	Anti-inflammatory, antioxidant, anti-tumor, anti-angiogenesis, anti-metastatic activities; Cell proliferation and apoptosis	VEGF↓; MVD↓; FGF↓; PDGF↓; TNF-α↓	MMP-3↓; MMP-9↓; NF-κB↓; p53 ↓; E2↓; PGE2↓; CA-125↓; G1-phase↓; EGF↓; HER-2↓; IGF-1↓	VEGF signaling pathway	Rat model/In humans	[103–109]
Radix ginseng; (Renshen)	Ginsenoside Rg3	Induced cell apoptosis,; Inhibited angiogenesis	Immune enhancement; Antioxidant; Anti-inflammatory Anti-neuroprotective; Anti-metabolic syndrome	VEGF↓; VEGFR-2↓; ↓	miRNA-27b-3p ↓	PI3K/Akt/mTOR signaling pathway	Endothelial cells/Rat model/human embryonic stem cells (HESCs)	[110–114]
Pueraria lobata; (Gegen)	Puerarin	Induced cell apoptosis,; Inhibited angiogenesis	Estrogen receptors,; Proliferation of endometriotic stromal cells (ESCs)	VEGFA ↓ Ang-1 ↓; Ang-2 ↓	E2↓; PGE2↓; p450 ↓; Cox-2 ↓; cyclin D1↓ cdc25A↓	VEGF signaling pathway	Endometriotic stromal cells	[115–120]
Salvia miltiorrhiza (Danshen)	Tanshinone II A; (other compounds: salvianolic acid, dihydrotanshinone, tanshinone I,et al)	Inhibited angiogenesis	Reduced cell viability; Induced apoptosis; Inhibited cell migration and invasion; Reduced the expression of 14-3-3ζ in EESCs	VEGFR2 ↓; TNF-a↓	p53↓; p21 ↓; DMD2↓ sICAM-1↓; sVCAM-1 ↓; CA125↓; MMP-9↓; IL-18↓; IL-13↓	VEGFR2 pathway,; Akt/JNK signaling pathways	Ectopic endometrial stromal cells	[121–126]
Paeonia lactiflora (Chishao)	Paeoniflorin	Inhibited angiogenesis	Anti-inflammatory; Rrelieved of pain; Influenced estrogen receptor α (ESRα)	HIF-1α↓	ESRα↓		In Human/At network pharmacological and pharmacodynamic levels	[127]
Andrographis paniculata; (Chuanxinlian)	Andrographolide	Inhibited tumor angiogenesis	Reduced lesion size in a rat model; Improved in generalized hyperalgesia; Inhibited COX-2 and TF expression; Influenced phosphorylated p50 and p65; Suppressed proliferation and cell cycle progression; Attenuated DNA-binding activity of NF-κB	NGF↓	NF-κB↓; COX-2↓; TF↓		In endometriotic stromal cells/Rat mode	[128]
Lithospermum erythrorhizon; (Zicao)	Shikonin	Inhibited angiogenesis	Inhibited the growth of human endometrial tissueInhibited the chemotaxis of monocytes,regulated normal T-cell expressed and secreted (mRANTES) levels in a murine model; Inhibited RANTES expression				In a murine model of endometriosis/In U937 cells	[129, 130]

Ang-1: Angiopoietin-1; Ang-2: Angiopoietin-2; Akt: protein kinase B; JNK” c-Jun N-terminal kinase; MDM2: murine double minute2; NF-κB: nuclear factor-kappa B; p450arom: cytochrome P450; sICAM-1: soluble intercellular adhesion molecule-1; sVCAM-1: soluble vascular cell adhesion molecule-1; TF: tissue factor.