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liuwei dihuang pill suppresses metastasis by regulating the wnt pathway and disrupting β-catenin/T cell factor interactions in a murine model of triple-negative breast cancer

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Journal of Traditional Chinese Medicine 2019年第6期39卷 826-832页

作者： Zheng Lixiang Zheng Qing Yu Zhipeng Wang Jian Ren Xiaoying Gong Yan Yang Xue Hunag Ping Weng Meizhi Liu Hongning Liu Haizhou School of Basic Medicine Jiangxi University of Traditional Chinese MedicineNanchang 330004China Jiangxi University of Traditional Chinese Medicine Nanchang 330004China Department of Gastroenterology the First Affiliated Hospital of Nanchang UniversityNanchang 330006China Teaching and Research Office of Internal Medicine of Traditional Chinese Medicine Department of MedicineJiangxi College of Traditional Chinese MedicineFuzhou 340000China School of Humanities Jiangxi University of Traditional Chinese MedicineNanchang 330004China

OBJECTIVE:To investigate if the liuwei dihuang pill(LWDHP)can inhibit metastasis to the liver and lungs in mice bearing triple-negative breast cancer(TNBC),and the molecular mechanism underpinning this ***:Ninety-nine TNBC bearing-mice were distributed randomly to five groups:control(Con),paclitaxel(PTX),low-dose LWDHP(LLP,2.3 g·kg^-1·d^-1),middle-dose LWDHP(MLP,4.6 g·kg^-1·d^-1)and high-dose LWDHP(HLP,9.2 g·kg^-1·d^-1).The LWDHP were administered(p.o.)to the agonal *** morphology of BC cells was observed by hematoxylin&eosin *** of axin-2,β-catenin,T cell factor(TCF),cyclin-D1 and vascular endothelial growth factor(VEGF)was detected by western blotting or immunofluorescence.β-catenin/TCF-1 interaction was measured using a co-immunoprecipitation ***:After LWDHP treatment,metastasis of BC cells to the lungs and liver was inhibited,expression of axin-2 was increased,expression of TCF-1,β-catenin,cyclin-D1 and VEGF was decreased,andβ-catenin/TCF-1 interaction was ***:The LWDHP could inhibit metastasis of BC cells to the liver and *** molecular mechanism underlying this action may be regulation of protein expression andβ-catenin/TCF-1 interactions in the Wnt pathway.

关键词： Triple negative breast neoplasms Neoplasm metastasis Beta catenin T cell transcription factor 1 Wnt signaling pathway liuwei dihuang pill

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Inhibition of N-methyl-N-nitrosourea-induced gastric tumorigenesis by liuwei dihuang pill in db/db mice

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World Journal of Gastroenterology 2017年第23期23卷 4233-4242页

作者： shan zhuang yong-mei jian yong-ning sun department of traditional chinese medicine shanghai jiao tong university affiliated sixth people's hospital

AIM To investigate the inhibitory effect of liuwei dihuang pill(LDP) on gastric tumorigenesis induced by N-methyl-N-nitrosourea(MNU) in diabetic *** Four-week-old mice were divided into four groups: A, 12 db/m mice treated with MNU and saline, as the non-diabetic control; B, 12 db/db mice treated with MNU and saline, as the diabetic control; C, 12 db/db mice treated with MNU and metformin, as the positive control; and D, 12 db/db mice treated with MNU and LDP. MNU was administrated for 20 wk to induce gastric carcinogenesis. LDP was administrated for 10 wk for improvement of insulin resistance. Body weight and food intake were measured every week. Blood samples were collected for assays of fasting blood glucose, insulin, insulin-like growth factor(IGF)-1, adiponectin and leptin. Stomach tissues were collected for histopathological analysis, immunohistochemical staining of Ki67, quantitative reverse transcriptionpolymerase chain reaction and western blotting. RESULTS The incidence of MNU-induced gastric dysplasia was significantly elevated in diabetic(db/db) mice relative to the control(db/m) mice. The incidence of gastricdysplasia was significantly reduced by LDP with suppression of cell proliferation, as demonstrated by a decrease in Ki67 staining. Hyperglycemia, hyperinsulinemia and serum IGF-1 were inhibited by LDP. Expression of IGF-1 and insulin receptor m RNAs was decreased, phosphorylation of IGF-1 receptor and AKT protein was reduced in the stomach tissues by LDP. In addition, adiponectin was increased and leptin was decreased in the serum by LDP. CONCLUSION LDP decreased risk of gastric dysplasia in type 2 diabetic mice by down-regulation of IGF and insulin activity and correction of adipokines disorders.

关键词： Diabetes Gastric cancer liuwei dihuang pill Insulin Insulin-like growth factor

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liuwei dihuang pill(六味地黄丸)Treats Postmenopausal Osteoporosis with Shen(Kidney) Yin Deficiency via Janus Kinase/Signal Transducer and Activator of Transcription Signal Pathway by Up-regulating Cardiotrophin-Like Cytokine Factor 1 Expression

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Chinese Journal of Integrative Medicine 2018年第6期24卷 415-422页

作者： GE Ji-rong XIE Li-hua CHEN Juan LI Sheng-qiang XU Hui-juan LAI Yu-lian QIU Long-long NI Chen-bo Key Research Laboratory of Osteoporosis Syndrome Genomics Fujian Academy of Traditional Chinese Medicine Fuzhou 350003 China

Objectives： To investigate the mechanism of liuwei dihuang pill （六味地黄丸, LDP） in treating postmenopausal osteoporosis （PMOP） with Shen （Kidney） yin deficiency. Methods： In this study, 205 cases of PMOP were divided into the PMOP Shen-yin deficiency group （Group A）, PMOP Shen-yang deficiency group （Group B）, PMOP without Shen deficiency group （Group C）, and control group （Group N）. Real-time polymerase chain reaction （RT-PCR） and Western blot techniques were used to observe the effects of LDP treatment on the cardiotrophin-like cytokine factor 1 （CLCF1）, ankyrin repeat and SOCS box containing 1 （ASB1）, and proldneticin 2 （PROK2） genes and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. Results： The mRNA （P〈0.05） and protein （P〈0.01） expression levels of the CLCF1 gone in Group A were significantly lower than the corresponding levels in Group N. After LDP treatment for 3 months, the mRNA expression levels of the CLCF1 gone were obviously up-regulated （P〈0.01）. After 6-month treatment, the expression levels of CLCF1 mRNA and protein were significantly up-regulated （both P〈0.01）, and the average bone density of the top femur had significantly increased （P〈0.05）. In vitro, CLCF1 overexpression resulted in a significant increase in the total protein and phosphorylated protein levels of JAK2 and STAT3. Conclusions： The CLCF1 gone is an important gone associated with PMOP Shen-yin deficiency and the therapeutic effects of LDP may be mediated by up-regulation of CLCF1 gone expression and activation of the JAK/STAT signaling pathway.

关键词： postmenopausal osteoporosis Chinese medicine Shen (Kidney) yin deficiency cardiotrophin- like cytokine factor 1 gone liuwei dihuang pill Janus kinase/signal transducer and activator of transcription signaling pathway

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Contribution of Borneolum syntheticum to the Intervention Effect of liuwei dihuang pill (六味地黄丸) on Experimental Retinal Degeneration

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Chinese Journal of Integrative Medicine 2018年第6期24卷 442-447页

作者： LIANG Li-na BAI Yu-yang TANG You-zhi CHEN Qiang LI XUE-li MA Qun-ying LIANG Jie LI Jiao Ophthalmology Research Laboratory Eye HospitalChina Academy of Chinese Medical Sciences

Objective： To observe the contribution of Borneolum syntheticum to the intervention effect of liuwei dihuang pill （六味地黄丸, LDP） on experimental retinal degeneration, and initially investigate the mechanism of Borneolum syntheticum as meridian-lead-in drug. Methods： A total of 180 sodium iodate- induced retinital degeneration rats were randomly divided into three groups, including distilled water group, LDP group, and LDP＋Borneolum syntheticum （LDP＋BS） group. Twenty normal rats were fed regularly without any treatment as normal control. On day 7 and 14 after treatment, histopathological study and transferase-mediated deoxyuridine triphosphate-biotin nick end labeling （TUNEL） test were performed to evaluate the retinopathy. Claudin-5 expression at blood-retina barrier （BRB） was detected by Western blot at different time points from 0.5 to 8 h after gavage. Results： On day 7 and 14 after treatment, the retinal lesion grades were significantly different among the three groups （P〈0.05）. The grade in the LDP＋BS group was significantly less than the LDP and distilled water groups （both P〈0.05）, no significant difference was observed between the LDP and distilled water groups （P〉0.05）. The apoptosis rates in the LDP＋BS group was significantly less than the distilled water and LDP groups （both P〈0.05）, while there was no significant difference between LDP and distilled water groups （P〉0.05）. Expression of claudin-5 in LDP＋BS group was significantly less than the other two groups at 0.5, 1 and 2 h after gavage （P〈0.05）. There was no apparent difference among the three groups at 4 and 8 h after gavage （P〉0.05）. Conclusion： Bomeolum syntheticum could strengthen the effect of LDP on experimental retinal degeneration, indicated that Bomeolum syntheticum might play the role of meridian-lead-in drug in the formula. The mechanism may be due to Bomeolum syntheticum could promote the physiologically openness of blood- retina barrier through transiently affecting the expression of claud

关键词： meridian-lead-in drug Bomeolum syntheticum liuwei dihuang pill retinal degeneration

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