During menopause, estrogen deficiency can lead to many health problems, such as hot flashes, sleep disturbances, joint pain, bone loss, and circulation disorders [20; 21]. Estrogen appears to have beneficial effects in various species models of cardiac, brain, and hind-limb ischemia via angiogenesis, limitation of endothelial dysfunction, and anti-inflammatory and anti-apoptotic effects [22; 23; 24; 25; 26]. Additionally, estrogen is also an important vascular expansion molecule that activates endothelial nitrogen oxide synthase through estrogen receptor alpha-mediation mechanism, causing the expansion of blood vessels [27]. Estrogen regulates gene transcription via estrogen receptors, and its expression elevates the pathophysiological progress of angiogenesis in endothelial cells [28; 29]. Wound healing in postmenopausal women has been shown to be delayed, and the inflammatory response is induced by reduced serum estrogen levels; however, these issues can be recovered through induction of vascular endothelial growth factor (VEGF) or reduction of inflammatory factors by estrogen [1; 26; 30; 31]. The role of estrogen is in the regulation of blood lipid and cholesterol levels, which could affect growth of vascular endothelial cells, and the remedy from ischemic and/or vascular damage leading to various disease models [32; 33; 34].  
Recently, we studied the efficacy of _Tetragonia tetragonoides_ (_Pall._) _Kuntze_ (TTK) therapy on various menopause symptoms [35] in ovariectomized rodents. Ovariectomy is a typical used model for investigation of postmenopausal symptoms due to ovarian hormone deficiency, i.e., estrogen and progesterone [36]. TTK is a halophyte that grows on Jeju Island and the southern coast of Korea. The Korean name of TTK is Beonhaengcho, and it is known as New Zealand spinach in other parts of the world. TTK has similar flavor and texture properties as spinach and is also cooked in a similar manner. Ancient documents, such as the Donguibogam, TTK has been classified as a traditional drug for the treatment of tumors [34], and folk remedies have long prescribed TTK as a food for women's health [34; 35]. Herbal medicines are commonly used as treatments for menopausal multi-symptoms, such as dyslipidemia, energy metabolism, diabetes, bone metabolism, and others in perimenopause [35; 37]. Further, herbal TTK remedies do not affect the reproductive tract or estrogen receptor (ER-alpha and ER-beta)-mediated mechanisms [37; 38]. On the other hand, herbal extracts have been reported to have strong side effects as hormone mimics [39; 40; 41], leading to metabolic disorders such as diarrhea, nausea, headaches, allergic reactions, and dizziness [42]. Extract of TTK has been shown to be effective for treatment of symptoms in a menopause-like symptom rat model, although TTK extract did not affect the classical mechanism of estrogen receptors [35]. In particular, TTK extract has been shown regulates the blood LDL-cholesterol and triglycerides in our previous study [35]. However, the detailed mechanisms of angiogenesis and neo-vasculogenesis under surgical and artificial ischemic conditions have not been elucidated.  
In the present study, we used a murine model of ovariectomy- and hind-limb ischemia to investigate whether or not TTK can improve blood flow rate via angiogenesis and inflammatory responses in the context of vascular surgical damage. The flow rate of peripheral blood rate was analyzed using the laser Doppler blood perfusion system [43], and levels of angiogenic and inflammatory cytokines were evaluated by immunoblotting. Additionally, tube formation and cell mobility in human umbilical vein endothelial cells (HUVECs) were determined in order to elucidate the potential mechanisms underlying improvement of blood flow rate by TTK.