Incompatibility Mechanism Between and Focusing on Estrogen-Estrogen Receptor Pathway in Immature/Ovariectomized Mice
Authors: Ting Chen
Ying Xu
Zi-Jia Zhang
Xin Li
Hong-Xia Zheng
Na Lin
Yuan Zhao
Ya-Kun Qu
Journal: Rejuvenation research (2019)
Discipline: CLINICAL MEDICINE
Keywords: Radix paeoniae alba; Veratrum nigrum; estrogen receptor; estrogenic effect; reproductive target tissue.
Affiliations: Department of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China., Department of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract:  Radix paeoniae alba (RPA) and Veratrum nigrum (VN) L. belong to the 18 incompatible medicaments and have been prohibited for thousands of years in China. Previous studies focused on the chemical constituents that induced the toxicological response of the two agents, but this study offers preliminary insight into the pharmacodynamics and mechanism on estrogenic activity, which is responsible for their incompatibility. We undertook a characterization of the interaction on estrogenic activity of RPA and VN using in vivo models of immature and ovariectomized (OVX) mice and in vitro studies focused on estrogen receptor (ER) pathway for further mechanism. VN disturbed the estrogenic efficacy of RPA in promoting development of uterus and vagina in immature mice, and reversing the atrophy of reproductive tissues in OVX mice by decreasing the increase of serum estrogen level and upregulation of ER expression in reproductive tissues by treatment with RPA. Besides, VN antagonized the estrogenic efficacy of RPA in stimulating the binding with ERŒ± and ERŒ≤, increasing ERŒ±/Œ≤-estrogen response element (ERE) luciferase reporter gene expression and promoting MCF-7 cell viability. This study provided evidence that VN antagonized the estrogenic efficacy of RPA by decreasing the up-regulations of estrogen biosynthesis in circulation and ERs in target tissues caused by RPA, and through ER-ERE-dependent pathway. 

Retracted: No

PubPeer comments:
 Figure 2a,b and Figure 4a,b show the exact same set of Western blots (panels a) with quantifications (panels b) - please see attached image. There are several problems here: 1. Why is the same set of blots used in two different figures? Could the authors please explain? 2. If the quantifications in panels b correspond with blots in panels a, why are some numeric values different and why are there different sample IDs? (S-AKI in Figure 2 and LPS in Figure 4)?  , 
 #1 I am glad you can read my article, in fact, I have found this problem for a long time. Due to my mistakes in the galley proofs at the time, I did not find that Figure2a and Figure4a in the manuscript were the same picture, and the pictures when uploading the original pictures for typesetting were not the same (this can be reflected in different versions before).The publisher has admitted that it was their mistake at that time and decided to publish an erratum in the near future. This is a correction article linked to r original article which identifies the error. Thank you for your serious correction. , 
 Thank you for the reply and for your intention to correct the article. Currently the following message is shown on the BioMed Research International (the journal) website when trying to access the article:  Other papers from the same journal seem to open without problems. Does the fact that the paper is not accessible mean that a correction is being prepared? , 
 Thank you for writing again, as you said, maybe the editor recently started to publish an errata to correct previous errors. I regret the inconvenience caused.Below are pictures from the original manuscript and pictures that will appear in future errata  ,