22
views
0
recommends
+1 Recommend
1 collections
    0
    shares

      Drug Design, Development and Therapy (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the design and development of drugs, as well as the clinical outcomes, patient safety, and programs targeted at the effective and safe use of medicines. Sign up for email alerts here.

      88,007 Monthly downloads/views I 4.319 Impact Factor I 6.6 CiteScore I 1.12 Source Normalized Impact per Paper (SNIP) I 0.784 Scimago Journal & Country Rank (SJR)

       

      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Network Pharmacology-Based Prediction and Verification of the Active Ingredients and Potential Targets of Zuojinwan for Treating Colorectal Cancer

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          Zuojinwan (ZJW), a famous Chinese medicine formula, has been widely used to treat colorectal cancer (CRC). However, its bioactive compounds, potential targets, and molecular mechanism remain largely elusive.

          Aim

          A network pharmacology-based strategy combined with molecular docking studies and in vitro validation were employed to investigate bioactive compounds, potential targets, and molecular mechanism of ZJW against CRC.

          Materials and Methods

          Bioactive compounds and potential targets of ZJW, as well as related genes of CRC, were acquired from public databases. Important ingredients, potential targets, and signaling pathways were determined through bioinformatics analysis, including protein–protein interaction (PPI), the Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Subsequently, molecular docking and cell experiments were performed to further verify the findings.

          Results

          A total of 36 bioactive ingredients of ZJW and 163 gene targets of ZJW were identified. The network analysis revealed that quercetin, baicalein, wogonin, beta-sitosterol, and isorhamnetin may be candidate agents. The AKT1, JUN, CDKN1A, BCL2L1, and NCOA1 could become potential drug targets. The KEGG indicated that PI3K-AKT signaling pathway may play an important role in the effect of ZJW against CRC. Molecular docking suggested that quercetin, baicalein, and wogonin combined well with AKT1 and JUN. The in vitro experiment showed that quercetin, the most important ingredient of ZJW, could induce apoptosis of HCT116 cells through PI3K-Akt signaling pathway. This finding was congruent with the prediction obtained through the network pharmacology approach.

          Conclusion

          This study comprehensively illuminated the active ingredients, potential targets, and molecular mechanism of ZJW against CRC. It also provided a promising approach to uncover the scientific basis and therapeutic mechanism of traditional Chinese medicine (TCM) formula treating for disease.

          Most cited references47

          • Record: found
          • Abstract: found
          • Article: not found

          Exploring the pharmacological mechanism of Yanghe Decoction on HER2-positive breast cancer by a network pharmacology approach.

          Certain Chinese medicine formulae from traditional Chinese Medicine (TCM) are effective for treating and preventing diseases in clinical practice. Yanghe Decoction (YHD) is a Chinese medicine formula that is used to treat breast cancer, especially HER-positive breast cancer; however, the active compounds, potential targets, and pharmacological and molecular mechanism of its action against cancer remain unclear. Therefore, further investigation is required.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            Berberine binds RXRα to suppress β-catenin signaling in colon cancer cells

            Berberine, an isoquinoline alkaloid, is a traditional oriental medicine used to treat diarrhea and gastroenteritis. Recently, we reported that it could inhibit the growth of intestinal polyp in animals and in patients with the familial adenomatous polyposis by downregulating β-catenin signaling. However, the intracellular target mediating the effects of berberine remains elusive. Here, we provide evidence that berberine inhibits β-catenin function via directly binding to a unique region comprising residues Gln275, Arg316 and Arg371 in nuclear receptor retinoid X receptor alpha (RXRα), where berberine concomitantly binding to and synergistically activating RXRα with 9-cis-retinoic acid (9-cis-RA), a natural ligand binding to the classical ligand-binding pocket of RXRα. Berberine binding promotes RXRα interaction with nuclear β-catenin, leading to c-Cbl mediated degradation of β-catenin, and consequently inhibits the proliferation of colon cancer cells. Furthermore, berberine suppresses the growth of human colon carcinoma xenograft in nude mice in an RXRα-dependent manner. Together, our study not only identifies RXRα as a direct protein target for berberine but also dissects their binding mode and validates that berberine indeed suppresses β-catenin signaling and cell growth in colon cancer via binding RXRα, which provide new strategies for the design of new RXRα-based antitumor agents and drug combinations.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Research Progress in the Modification of Quercetin Leading to Anticancer Agents

              The flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone) is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin can prevent neurological disorders and exerts protection against mitochondrial damages. Various in vitro studies have assessed the anticancer effects of quercetin, although there are no conclusive data regarding its mode of action. However, low bioavailability, poor aqueous solubility as well as rapid body clearance, fast metabolism and enzymatic degradation hamper the use of quercetin as therapeutic agent, so intense research efforts have been focused on the modification of the quercetin scaffold to obtain analogs with potentially improved properties for clinical applications. This review gives an overview of the developments in the synthesis and anticancer-related activities of quercetin derivatives reported from 2012 to 2016.
                Bookmark

                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                DDDT
                dddt
                Drug Design, Development and Therapy
                Dove
                1177-8881
                14 July 2020
                2020
                : 14
                : 2725-2740
                Affiliations
                [1 ]Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University , Changsha, Hunan 410011, People’s Republic of China
                [2 ]Department of Pharmacy, The Second Xiangya Hospital, Central South University , Changsha, Hunan 410011, People’s Republic of China
                [3 ]Department of General Surgery, The Second Xiangya Hospital, Central South University , Changsha, Hunan 410011, People’s Republic of China
                [4 ]Hunan Academy of Chinese Medicine, Hunan University of Chinese Medicine , Changsha, Hunan 410013, People’s Republic of China
                Author notes
                Correspondence: Sifang Zhang; Weijun Peng Department of Integrated Traditional Chinese & Western Medicine, The Second Xiangya Hospital, Central South University , Changsha, Hunan410011, People’s Republic of ChinaTel +86-73185292111 Email sifangzhang2005@csu.edu.cn; pengweijun87@csu.edu.cn
                Author information
                http://orcid.org/0000-0002-4813-5073
                http://orcid.org/0000-0003-1352-2310
                http://orcid.org/0000-0003-3126-2508
                http://orcid.org/0000-0001-7708-6314
                http://orcid.org/0000-0002-4506-0942
                Article
                250991
                10.2147/DDDT.S250991
                7369379
                32764874
                3e5a9535-213c-4a45-802b-d0494656db96
                © 2020 Huang et al.

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                : 23 February 2020
                : 02 June 2020
                Page count
                Figures: 12, Tables: 2, References: 58, Pages: 16
                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine
                zuojinwan,colorectal cancer,network pharmacology,pi3k/akt signal pathway

                Comments

                Comment on this article