Previously we showed that MS a combined extract of
Previously, we showed that MS-10, a combined extract of Cirsium japonicum var. Maackii (Maxim.) Matsum. (Korean milk thistle) and Thymus vulgaris L., increases the efficiency of estrogen in the estrogen-deficient state by activating the estrogen receptor (ER). MS-10 increased bone mineral density (BMD) in the rat ovariectomized (OVX) model and increased serum insulin-like growth factor-1 (IGF-1) levels in women with menopausal symptoms in a clinical study (Noh et al., 2016). IGF-1 affects multiple aspects of bone health directly, including bone development, regeneration, and growth (Sheng, Lau, & Baylink, 2014). Therefore, MS-10 is expected to improve bone health in women with menopausal symptoms. Thistle itself has been used in oriental medicine to treat hypertension, traumatic hemorrhage, inflammation, and renal cellular injury (Liao, Chen, & Wu, 2010), and has anticancer, antidiabetic, antioxidant, anti-inflammatory, and antifungal effects (Lee et al., 2008, Liu et al., 2007, Yin et al., 2008, Yoon et al., 2011). Thyme also has antioxidant, antimicrobial and antifungal effects (Boruga et al., 2014, Gucwa et al., 2018, Miura et al., 2002).
Materials and methods
Discussion In previous studies, we showed that MS-10 increases the sensitivity of MCF-7 breast cancer Zaragozic Acid A to low-density estrogen by increasing expression of ERα. In that study, sustained intake of MS-10 (1 month) by ovariectomized menopausal animals increased ER expression and BMD levels. BMD reduction and osteoporosis occur at a high rate in women undergoing menopause. Here, we examined the effects of MS-10 on bone health and menopausal symptoms both in vitro (using SaOS-2 osteoblast-like cells) and in vivo (in a clinical trial of menopausal women). A microarray analysis of more than 15,000 genes revealed that MS-10 treatment significantly altered expression of approximately 25 genes, including genes involved in cellular differentiation and proliferation. Regulation of SaOS-2 osteoblast-like cell differentiation is important for ossification and results in decreased proliferation. Recent research demonstrates that long-term exposure to estrogen increases the risk of developing cancer in the breast or the endometrium. Popular botanical supplements (black cohosh, red clover, licorice, hops, dong gui, ginger, and soy) used for women’s health influence key steps in the estrogen chemical carcinogenesis pathway (Snelten, Dietz, & Bolton, 2012). However, MS-10 induced a significant decrease in expression of the CYP1A1, CYP1B1, LIPG, and DKK1 genes, which are associated with abnormal cell proliferation. These genes are commonly characterized as carcinogenic genes. CYP1A1 and CYP1B1 are involved in estrogen catabolism and are implicated in carcinogenesis of hormone-responsive tissues and lower femoral BMD (De Vivo et al., 2002, Quan et al., 2009, Sasaki et al., 2003). Furthermore, a human study found an association between intake of soy isoflavones (phytoestrogens found in soy foods), CYP1A1 and CYP1B1 expression, and breast cancer (Snelten et al., 2012, Wang et al., 2011). LIPG plays a key role in numerous female cancers, including breast cancer (Yu, Han, Wolfson, & Zhou, 2018). LIPG is up-regulated in women with menopausal symptoms and plays a role in lipid metabolism, inflammatory responses, and tumor progression (Muzzio et al., 2007, Rathnayake et al., 2018). DKK1 is involved in osteoclast proliferation and osteoporosis, and is a tumor suppressor gene due to its function as a Wnt signaling antagonist (Kyvernitakis et al., 2014). Inhibition of Wnt signaling by DKK1 increases expression of β-catenin, which promotes osteogenesis (Balemans et al., 2007, Tian et al., 2015). By contrast, expression of PRUNE2 increased significantly after treatment with MS-10. PRUNE2 is a well-known tumor suppressor gene that controls cell proliferation (Salameh et al., 2015). Thus, MS-10 can modulate expression of genes that regulate proliferation in SaOS-2 cells.