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        Phase II Trial of Epigallocatechin-3-Gallate in Acute Radiation-Induced Esophagitis for Esophagus Cancer

        Xiaoling Li,Ligang Xing,Yujun Zhang,Peng Xie,Wanqi Zhu,Xiangjiao Meng,Yinxia Wang,Lingling Kong,Hanxi Zhao,Jinming Yu 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.1

        Acute radiation-induced esophagitis (ARIE) is among the most serious form of toxicities associated with definitive radiotherapy or chemoradiotherapy used for treatment of patients with esophageal cancer. Our preliminary phase I and II trials of lung cancer patients who received radiotherapy indicated epigallocatechin-3-gallate (EGCG) as a promising therapeutic option against ARIE. Therefore, we conducted a prospective phase II study to validate the efficacy and safety of EGCG in the treatment of ARIE. The patients who received chemoradiotherapy or definitive radiotherapy for treatment of esophageal cancer in the Shandong Cancer Hospital and Institute in China were enrolled for the present study. EGCG (440 μM) was administered with first onset of ARIE and then at weeks after final radiotherapy. The patients were monitored every week for dysphagia, Radiation Therapy Oncology Group (RTOG) score, and esophagitis-related pain. Moreover, tumor response and the effect on survival following the treatment were also evaluated. Comparison of the RTOG score in the first, second, third, fourth, fifth, and even sixth week after EGCG prescription and the first and second week after radiotherapy with baseline indicates a significant reduction. The tumor response rate was 86.3%. The overall survival rate in 1, 2, and 3 years was found to be 74.5%, 58%, and 40.5%. Oral administration of EGCG solution seems to be feasible for treating ARIE in patients with esophageal cancer who receive radiation therapy. EGCG might be an ARIE-reliever without compromising the efficacy of radiation therapy. A randomized study with a control group is needed for further evaluation.

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        Computational and experimental characterization of estrogenic activities of 20(S, R)-protopanaxadiol and 20(S, R)-protopanaxatriol

        Tiehua Zhang,Shuning Zhong,Ligang Hou,Yongjun Wang,XiaoJia Xing,Tianzhu Guan,Jie Zhang,Tiezhu Li 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.5

        Background: As the main metabolites of ginsenosides, 20(S, R)-protopanaxadiol [PPD(S, R)] and 20(S, R)-protopanaxatriol [PPT(S, R)] are the structural basis response to a series of pharmacological effects of their parent components. Although the estrogenicity of several ginsenosides has been confirmed, however, the underlying mechanisms of their estrogenic effects are still largely unclear. In this work, PPD(S, R) and PPT(S, R) were assessed for their ability to bind and activate human estrogen receptor α(hERα) by a combination of in vitro and in silico analysis. Methods: The recombinant hERα ligand-binding domain (hERa-LBD) was expressed in E. coli strain. The direct binding interactions of ginsenosides with hERα-LBD and their ERα agonistic potency were investigated by fluorescence polarization and reporter gene assays, respectively. Then, molecular dynamics simulations were carried out to simulate the binding modes between ginsenosides and hERα-LBD to reveal the structural basis for their agonist activities toward receptor. Results: Fluorescence polarization assay revealed that PPD(S, R) and PPT(S, R) could bind to hERα-LBD with moderate affinities. In the dual luciferase reporter assay using transiently transfected MCF-7 cells, PPD(S, R) and PPT(S, R) acted as agonists of hERα. Molecular docking results showed that these ginsenosides adopted an agonist conformation in the flexible hydrophobic ligand-binding pocket. The stereostructure of C-20 hydroxyl group and the presence of C-6 hydroxyl group exerted significant influence on the hydrogen bond network and steric hindrance, respectively. Conclusion: This work may provide insight into the chemical and pharmacological screening of novel therapeutic agents from ginsenosides.

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