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      Kangquan Recipe Regulates the Expression of BAMBI Protein via the TGF- β/Smad Signaling Pathway to Inhibit Benign Prostatic Hyperplasia in Rats

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          Kangquan Recipe (KQR) is a traditional Chinese medicine compound made by our research group for the treatment of benign prostatic hyperplasia (BPH). Whether KQR can treat BPH as a single drug or play a role in the treatment of BPH in combination therapy needs further study.

          Aim of the Study

          To investigate the effect of KQR on the expression of TGF- β/Smad signaling pathway-related factors in rats with BPH. In-depth analysis revealed the relevant signal transduction mechanism by which KQR acts to treat BPH.

          Materials and Methods

          Forty-eight male Sprague-Dawley rats were randomly divided into six groups of 8 rats each. In addition to the control group, 40 rats were castrated and then injected with testosterone propionate to form a prostatic hyperplasia model. After 30 days, three groups received different concentrations of KQR (14 g/kg, 7 g/kg, and 3.5 g/kg), and the finasteride group received 0.5 mg/kg finasteride. The BPH group and the control group received the same volume of saline. All groups were treated for a total of 30 days. Rat body weight, prostate volume, wet weight, index, histology, and the mRNA and protein levels of TGF- β, TGF- βR1, TGF- βR2, p-Smad2, p-Smad3, BAMBI, E-cadherin, and N-cadherin in the prostate tissue were measured after the end of treatment.


          Compared with the control group, the BPH group had increased prostate wet weight, volume, and index, and the histology showed significant BPH. Compared with the BPH group, the three KQR groups and the finasteride group all had varying levels of reduction in the prostate wet weight, volume, and index of the prostate and varying degrees of improvement in the histological manifestations of BPH. KQR downregulates the mRNA and/or protein expression of TGF- β, TGF- βR1, TGF- βR2, p-Smad2, p-Smad3, and N-cadherin protein in prostate tissue and increases the mRNA and protein expression of BAMBI and E-cadherin protein.


          In the model of BPH induced by testosterone propionate after castration, KQR can inhibit the conduction of the TGF- β/Smad signaling pathway by upregulating the expression of BAMBI protein and reversing EMT in rat prostate tissue.

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          Most cited references 48

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          Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks

          Epithelial-to-mesenchymal transition (EMT) is a key step in development, wound healing, and cancer development. It involves cooperation of signaling pathways, such as transformation growth factor-β (TGF-β), Sonic Hedgehog (SHH), and WNT pathways. These signaling pathways crosstalk to each other and converge to key transcription factors (e.g., SNAIL1) to initialize and maintain the process of EMT. The functional roles of multi-signaling pathway crosstalks in EMT are sophisticated and, thus, remain to be explored. In this review, we focused on three major signal transduction pathways that promote or regulate EMT in carcinoma. We discussed the network structures, and provided a brief overview of the current therapy strategies and drug development targeted to these three signal transduction pathways. Finally, we highlighted systems biology approaches that can accelerate the process of deconstructing complex networks and drug discovery.
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            Isoquercitrin: pharmacology, toxicology, and metabolism.

            The flavonoid isoquercitrin (quercetin-3-O-β-d-glucopyranoside) is commonly found in medicinal herbs, fruits, vegetables and plant-derived foods and beverages. This article reviews the occurrence, preparation, bioavailability, pharmacokinetics, toxicology and biological activity of isoquercitrin and "enzymatically modified (α-glucosylated) isoquercitrin" (EMIQ). Pure isoquercitrin can now be obtained on a large scale by enzymatic rutin hydrolysis with α-l-rhamnosidase. Isoquercitrin has higher bioavailability than quercetin and displays a number of chemoprotective effects both in vitro and in vivo, against oxidative stress, cancer, cardiovascular disorders, diabetes and allergic reactions. Although small amounts of intact isoquercitrin can be found in plasma and tissues after oral application, it is extensively metabolized in the intestine and the liver. Biotransformation of isoquercitrin includes deglycosylation, followed by formation of conjugated and methylated derivatives of quercetin or degradation to phenolic acids and carbon dioxide. The acceptable daily intake of (95%) isoquercitrin and of EMIQ was estimated to be 5.4 and 4.9mg/kg/day, respectively. Adverse effects of higher doses in rats included mostly (benign) chromaturia; nevertheless some drug interactions may occur due to the modulation of the activity and/or expression of drug metabolizing/transporting systems. With respect to the safety, affordability and beneficial pharmacological activities, highly pure isoquercitrin is a prospective substance for food supplementation.
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              TGF-beta receptor signaling.

               X Feng,  R Derynck (1997)

                Author and article information

                Evid Based Complement Alternat Med
                Evid Based Complement Alternat Med
                Evidence-based Complementary and Alternative Medicine : eCAM
                2 May 2019
                2 May 2019
                : 2019
                1Department of Traditional Chinese Medicine, Zhongshan Hospital, Xiamen University, Xiamen 361004, Fujian Province, China
                2Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen 361102, Fujian Province, China
                Author notes

                Academic Editor: Cheorl-Ho Kim

                Copyright © 2019 Wenfan Chen et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Funded by: National Natural Science Foundation of China
                Award ID: 81674041
                Funded by: Xiamen Science and Technology Bureau Research Project
                Award ID: 3502Z20164013
                Funded by: Natural Science Foundation of Fujian Province
                Award ID: 2018J01395
                Research Article

                Complementary & Alternative medicine


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