The in vivo Therapeutic Effect of Free Wanderer Powder (逍 遙 散 xiāo yáo sǎn, Xiaoyaosan) on Mice with 4T1 Cell Induced Breast Cancer Model

Abstract

In the present study, we investigated the therapeutic effect of a classical TCM formula, Free Wanderer Powder (逍遙散 xiāo yáo sǎn), in a breast cancer mouse model induced with estrogen-insensitive breast cancer 4T1 cells. Ovariectomized Balb/c mice (6-8 weeks) or sham mice were injected into the fourth mammary fat pad with 4T1 cells in which tumors were palpable 7 days after injection. On the eighth day, the mice were divided into 4 groups and tubefed daily with vehicle, Free Wanderer Powder (逍遙散 xiāo yáo sǎn) formula or tamoxifen for 28 days. Tumor growth inhibition and the decrease of the average tumor mass were most evident in mice treated with Free Wanderer Powder (逍遙散 xiāo yáo sǎn). Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment significantly reduced Bcl-2 and elevated Bax and p53 protein expressions in breast cancer tumor. These results were further confirmed by immunohistochemisty. Tamoxifen could decrease spleen mass and Bcl-2 protein expression, increase the Bax protein expression as well as exert uterotrophic effects by increasing uterus index and inducing the gene expressions in the uterus. Taken together, these results show that Free Wanderer Powder (逍遙散 xiāo yáo sǎn) treatment induced apoptosis at protein level and inhibited the tumor growth in 4T1-induced ovariectomized Balb/c female mice, indicating the possibility of its future use for treatment of estrogen-insensitive breast caner.

Senkyunolide A protects neural cells against corticosterone-induced apoptosis by modulating protein phosphatase 2A and α-synuclein signaling

“… 17 The formula comprises several herbs, including Atractylodis Macrocephale rhizoma , Bupleuri radix , Angelica sinensis , Poria , Glycyrrhizae radix , tree peony bark , Gardenia jasminoides , Paeonia lactiflora pall , mint , and roasted ginger , active components of which are identified to be genipside, paeonol, ferulic acid, paeoniflorin, and senkyunolide A (SenA). 18 – 20 TCM has been used for thousands of years for treating depression-related conditions in China, and Dan-zhi-xiao-yao-san has been proved to be one of the most effective formulae. Dong et al 21 demonstrated that the treatment of rats with general-ized anxiety disease using Dan-zhi-xiao-yao-san relieved the animals of depression symptoms by protecting neural cells in Papez’s circuit against apoptosis.…”

Senkyunolide A protects corticosterone-induced cell apoptosis via modulating protein phosphatase 2A and α-synuclein

“…Xiao-yao-san and modified formula such as Dan-zhi-xiao-yao-san are most commonly used TCM formulas for treating multiple diseases such as depression in China and other Asia countries [17]. Based on TCM theory, Xiao-yan-san mainly used for promoting liver qi circulation, coursing the liver, nourishing liver blood and fortify the spleen [18][19][20]. Dan-zhi-xiao-yao-san is comprised of several herbs including atractylodismacrocephalerhizoma, bupleuri radix, angelicaesinensis, poria, glycyrrihizae radix, tree peony bark, gardenia jasminoides, paeonialactiflora pall, mint and roasted ginger [18][19][20].…”

“…Based on TCM theory, Xiao-yan-san mainly used for promoting liver qi circulation, coursing the liver, nourishing liver blood and fortify the spleen [18][19][20]. Dan-zhi-xiao-yao-san is comprised of several herbs including atractylodismacrocephalerhizoma, bupleuri radix, angelicaesinensis, poria, glycyrrihizae radix, tree peony bark, gardenia jasminoides, paeonialactiflora pall, mint and roasted ginger [18][19][20]. Although xiao-yao-san is one of the mostly commonly used formulas in China for treating depression, the active compound(s) and underlying mechanism are largely unknown.…”

Anxiolytic and neuroprotective effects of the Traditional Chinese Medicinal formulation Dan-zhi-xiao-yao-san in a rat model of chronic stress

“…Xiao-yao-san and its modified formulations, including Dan-zhi-xiao-yao-san, are most commonly used in China and other Asian countries. According to the theories of TCM, Xiao-yao-san formulations repair the liver, promote liver qi circulation, nourish the blood in the liver and fortify the spleen, and these formulations are used clinically to treat a variety of conditions, including menopausal syndrome, anemia, functional uterine bleeding, hepatitis, chronic gastritis, pelvic inflammatory disease, anxiety and depression (8)(9)(10). Dan-zhi-xiao-yao-san is composed of Atractylodis macrocephale rhizoma, Bupleuri radix, Angelicae sinensis, poria, Glycyrrihizae radix, tree peony bark, Gardenia jasminoides, Paeonia lactiflora Pall, mint and roasted ginger.…”