{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T16:55:12Z","timestamp":1794243312687,"version":"4.9.0"},"reference-count":32,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T00:00:00Z","timestamp":1633910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["MLP-901"],"award-info":[{"award-number":["MLP-901"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001412","name":"Council of Scientific and Industrial Research, India","doi-asserted-by":"publisher","award":["MLP-901"],"award-info":[{"award-number":["MLP-901"]}],"id":[{"id":"10.13039\/501100001412","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008802","name":"Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy","doi-asserted-by":"publisher","award":["GAP0183"],"award-info":[{"award-number":["GAP0183"]}],"id":[{"id":"10.13039\/501100008802","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008802","name":"Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy","doi-asserted-by":"publisher","award":["GAP0183"],"award-info":[{"award-number":["GAP0183"]}],"id":[{"id":"10.13039\/501100008802","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bioactive fractions obtained from medicinal plants which have been used for the treatment of multiple diseases could exert their effects by targeting common pathways. Prior knowledge of their usage could allow us to identify novel molecular links. In this study, we explored the molecular basis of action of one such herbal formulation <jats:italic>Cissampelos pareira<\/jats:italic> L. (Cipa), used for the treatment of female hormone disorders and fever. Transcriptomic studies on MCF7 cell lines treated with Cipa extract carried out using Affymetrix arrays revealed a downregulation of signatures of estrogen response potentially modulated through estrogen receptor \u03b1 (ER\u03b1). Molecular docking analysis identified 38 Cipa constituents that potentially bind (\u0394G\u2009&lt;\u2009\u2009\u2212\u20097.5) with ER\u03b1 at the same site as estrogen. The expression signatures in the connectivity map (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clue.io\/;\">https:\/\/clue.io\/;<\/jats:ext-link>) revealed high positive scores with translation inhibitors such as emetine (score: 99.61) and knockdown signatures of genes linked to the antiviral response such as ribosomal protein RPL7 (score: 99.92), which is a reported ER\u03b1 coactivator. Further, gene knockdown experiments revealed that Cipa exhibits antiviral activity in dengue infected MCF7 cells potentially modulated through estrogen receptor 1. This approach reveals a novel pathway involving the ESR1-RPL7 axis which could be a potential target in dengue viral infection.<\/jats:p>","DOI":"10.1038\/s41598-021-99444-0","type":"journal-article","created":{"date-parts":[[2021,10,11]],"date-time":"2021-10-11T10:18:43Z","timestamp":1633947523000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Transcriptome analysis and connectivity mapping of Cissampelos pareira L. provides molecular links of ESR1 modulation to viral inhibition"],"prefix":"10.1038","volume":"11","author":[{"given":"Madiha","family":"Haider","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhwani","family":"Dholakia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksha","family":"Panwar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth","family":"Garg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atish","family":"Gheware","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dayanidhi","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khushboo","family":"Singhal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaunak A.","family":"Burse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Surekha","family":"Kumari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anmol","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Ray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guruprasad R.","family":"Medigeshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Upendra","family":"Sharma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavana","family":"Prasher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitali","family":"Mukerji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,11]]},"reference":[{"key":"99444_CR1","doi-asserted-by":"publisher","first-page":"846","DOI":"10.2174\/1386207318666151019093606","volume":"18","author":"U Chandran","year":"2015","unstructured":"Chandran, U., Mehendale, N., Tillu, G. & Patwardhan, B. Network pharmacology of ayurveda formulation triphala with special reference to anti-cancer property. Comb. Chem. High Throughput Screen. 18, 846\u2013854 (2015).","journal-title":"Comb. Chem. High Throughput Screen."},{"key":"99444_CR2","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1073\/pnas.1413127112","volume":"112","author":"MA Elfawal","year":"2015","unstructured":"Elfawal, M. A., Towler, M. J., Reich, N. G., Weathers, P. J. & Rich, S. M. Dried whole-plant Artemisia annua slows evolution of malaria drug resistance and overcomes resistance to artemisinin. Proc. Natl. Acad. Sci. U. S. A. 112, 821\u2013826 (2015).","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"99444_CR3","doi-asserted-by":"publisher","first-page":"3510","DOI":"10.1073\/pnas.1112209109","volume":"109","author":"N Sehgal","year":"2012","unstructured":"Sehgal, N. et al. Withania somnifera reverses Alzheimer\u2019s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc. Natl. Acad. Sci. 109, 3510\u20133515 (2012).","journal-title":"Proc. Natl. Acad. Sci."},{"key":"99444_CR4","doi-asserted-by":"publisher","first-page":"113185","DOI":"10.1016\/j.jep.2020.113185","volume":"262","author":"V Bhatt","year":"2020","unstructured":"Bhatt, V. et al. Chemical profiling and quantification of potential active constituents responsible for the antiplasmodial activity of Cissampelos pareira. J. Ethnopharmacol. 262, 113185 (2020).","journal-title":"J. Ethnopharmacol."},{"key":"99444_CR5","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1016\/j.jep.2014.06.054","volume":"155","author":"DK Semwal","year":"2014","unstructured":"Semwal, D. K., Semwal, R. B., Vermaak, I. & Viljoen, A. From arrow poison to herbal medicine\u2014The ethnobotanical, phytochemical and pharmacological significance of Cissampelos (Menispermaceae). J. Ethnopharmacol. 155, 1011\u20131028 (2014).","journal-title":"J. Ethnopharmacol."},{"key":"99444_CR6","doi-asserted-by":"publisher","first-page":"62","DOI":"10.4103\/ayu.AYU_208_14","volume":"37","author":"SG Singh","year":"2016","unstructured":"Singh, S. G., Nishteswar, K., Patel, B. R. & Nariya, M. Comparative antipyretic and analgesic activities of Cissampelos pareira Linn. and Cyclea peltata (Lam.) Hook. F. & Thomas. AYU 37, 62\u201366 (2016).","journal-title":"AYU"},{"key":"99444_CR7","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1371\/journal.pntd.0004255","volume":"9","author":"R Sood","year":"2015","unstructured":"Sood, R. et al. Cissampelos pareira Linn: Natural source of potent antiviral activity against all four dengue virus serotypes. PLoS Negl. Trop. Dis. 9, 1\u201320 (2015).","journal-title":"PLoS Negl. Trop. Dis."},{"key":"99444_CR8","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1016\/j.jep.2007.01.023","volume":"111","author":"M Ganguly","year":"2007","unstructured":"Ganguly, M., Borthakur, M. K., Devi, N. & Mahanta, R. Antifertility activity of the methanolic leaf extract of Cissampelos pareira in female albino mice. J. Ethnopharmacol. 111, 688\u2013691 (2007).","journal-title":"J. Ethnopharmacol."},{"key":"99444_CR9","doi-asserted-by":"publisher","first-page":"1929","DOI":"10.1126\/science.1132939","volume":"313","author":"J Lamb","year":"2006","unstructured":"Lamb, J. et al. The connectivity map: Using gene-expression signatures to connect small molecules, genes, and disease. Science (80-.) 313, 1929\u20131935 (2006).","journal-title":"Science (80-.)"},{"key":"99444_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.10.049","author":"A Subramanian","year":"2017","unstructured":"Subramanian, A. et al. A next generation connectivity map: L1000 platform and the first 1,000,000 profiles. Cell https:\/\/doi.org\/10.1016\/j.cell.2017.10.049 (2017).","journal-title":"Cell"},{"key":"99444_CR11","doi-asserted-by":"publisher","first-page":"669","DOI":"10.4103\/0253-7613.194861","volume":"48","author":"J Samanta","year":"2016","unstructured":"Samanta, J., Bhattacharya, S. & Rana, A. C. Antifertility activity of Thevetia peruviana (Pers.) K. Schum leaf in female Sprague-Dawley rat. Indian J. Pharmacol. 48, 669\u2013674 (2016).","journal-title":"Indian J. Pharmacol."},{"key":"99444_CR12","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.psyneuen.2009.04.023","volume":"34","author":"KA Duncan","year":"2009","unstructured":"Duncan, K. A., Jimenez, P. & Carruth, L. L. The selective estrogen receptor-alpha coactivator, RPL7, and sexual differentiation of the songbird brain. Psychoneuroendocrinology 34, 30\u201338 (2009).","journal-title":"Psychoneuroendocrinology"},{"key":"99444_CR13","doi-asserted-by":"publisher","first-page":"1852","DOI":"10.1002\/dneu.20539","volume":"67","author":"KA Duncan","year":"2007","unstructured":"Duncan, K. A. & Carruth, L. L. The sexually dimorphic expression of L7\/SPA, an estrogen receptor coactivator, in zebra finch telencephalon. Dev. Neurobiol. 67, 1852\u20131866 (2007).","journal-title":"Dev. Neurobiol."},{"key":"99444_CR14","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/j.cellimm.2015.01.018","volume":"294","author":"S Kovats","year":"2015","unstructured":"Kovats, S. Estrogen receptors regulate innate immune cells and signaling pathways. Cell. Immunol. 294, 63\u201369 (2015).","journal-title":"Cell. Immunol."},{"key":"99444_CR15","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1007\/s00705-018-4079-0","volume":"164","author":"D Tohma","year":"2019","unstructured":"Tohma, D. et al. An estrogen antagonist, cyclofenil, has anti-dengue-virus activity. Arch. Virol. 164, 225\u2013234 (2019).","journal-title":"Arch. Virol."},{"key":"99444_CR16","doi-asserted-by":"publisher","first-page":"579420","DOI":"10.3389\/fendo.2020.579420","volume":"11","author":"G Notas","year":"2020","unstructured":"Notas, G., Kampa, M. & Castanas, E. G Protein-coupled estrogen receptor in immune cells and its role in immune-related diseases. Front. Endocrinol. (Lausanne) 11, 579420 (2020).","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"99444_CR17","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.3389\/fimmu.2018.01931","volume":"9","author":"V Taneja","year":"2018","unstructured":"Taneja, V. Sex hormones determine immune response. Front. Immunol. 9, 1931 (2018).","journal-title":"Front. Immunol."},{"key":"99444_CR18","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1016\/j.febslet.2015.05.006","volume":"589","author":"A Dalet","year":"2015","unstructured":"Dalet, A., Gatti, E. & Pierre, P. Integration of PKR-dependent translation inhibition with innate immunity is required for a coordinated anti-viral response. FEBS Lett. 589, 1539\u20131545 (2015).","journal-title":"FEBS Lett."},{"key":"99444_CR19","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1038\/nri.2017.63","volume":"17","author":"C McCormick","year":"2017","unstructured":"McCormick, C. & Khaperskyy, D. A. Translation inhibition and stress granules in the antiviral immune response. Nat. Rev. Immunol. 17, 647\u2013660 (2017).","journal-title":"Nat. Rev. Immunol."},{"key":"99444_CR20","doi-asserted-by":"publisher","first-page":"062","DOI":"10.4172\/jaa.1000009","volume":"01","author":"JSY Low","year":"2009","unstructured":"Low, J. S. Y., Chen, K. C., Wu, K. X., Ng, M.M.-L. & Chu, J. J. H. Antiviral activity of emetine dihydrochloride against dengue virus infection. J. Antivir. Antiretrovir. 01, 062\u2013071 (2009).","journal-title":"J. Antivir. Antiretrovir."},{"key":"99444_CR21","doi-asserted-by":"publisher","first-page":"11474","DOI":"10.3390\/molecules200611474","volume":"20","author":"ALC Valad\u00e3o","year":"2015","unstructured":"Valad\u00e3o, A. L. C. et al. Natural plant alkaloid (Emetine) inhibits HIV-1 replication by interfering with reverse transcriptase activity. Molecules 20, 11474\u201311489 (2015).","journal-title":"Molecules"},{"key":"99444_CR22","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/978-94-007-6552-8_16","volume":"68","author":"V M\u00e1s","year":"2013","unstructured":"M\u00e1s, V. & Melero, J. A. Entry of enveloped viruses into host cells: Membrane fusion. Subcell. Biochem. 68, 467\u2013487 (2013).","journal-title":"Subcell. Biochem."},{"key":"99444_CR23","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/v8060160","volume":"8","author":"I Romero-Brey","year":"2016","unstructured":"Romero-Brey, I. & Bartenschlager, R. Endoplasmic reticulum: The favorite intracellular niche for viral replication and assembly. Viruses 8, 1\u201326 (2016).","journal-title":"Viruses"},{"key":"99444_CR24","first-page":"1","volume":"8","author":"P V\u2019kovski","year":"2019","unstructured":"V\u2019kovski, P. et al. Determination of host proteins composing the microenvironment of coronavirus replicase complexes by proximity-labeling. Elife 8, 1\u201330 (2019).","journal-title":"Elife"},{"key":"99444_CR25","doi-asserted-by":"publisher","first-page":"3418","DOI":"10.3390\/ijms21103418","volume":"21","author":"S Bartoloni","year":"2020","unstructured":"Bartoloni, S., Leone, S. & Acconcia, F. Unexpected impact of a hepatitis C virus inhibitor on 17\u03b2-estradiol signaling in breast cancer. Int. J. Mol. Sci. 21, 3418 (2020).","journal-title":"Int. J. Mol. Sci."},{"key":"99444_CR26","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1007\/s13402-017-0322-z","volume":"40","author":"C Busonero","year":"2017","unstructured":"Busonero, C., Leone, S. & Acconcia, F. Emetine induces estrogen receptor alpha degradation and prevents 17\u03b2-estradiol-induced breast cancer cell proliferation. Cell. Oncol. (Dordr.) 40, 299\u2013301 (2017).","journal-title":"Cell. Oncol. (Dordr.)"},{"key":"99444_CR27","doi-asserted-by":"publisher","first-page":"158 LP","DOI":"10.1136\/gutjnl-2018-317065","volume":"69","author":"ER Verrier","year":"2020","unstructured":"Verrier, E. R. et al. Combined small molecule and loss-of-function screen uncovers estrogen receptor alpha and CAD as host factors for HDV infection and antiviral targets. Gut 69, 158 LP-167 LP (2020).","journal-title":"Gut"},{"key":"99444_CR28","first-page":"e00204","volume":"94","author":"N Xu","year":"2020","unstructured":"Xu, N. et al. The pyrimidine analog FNC potently inhibits the replication of multiple enteroviruses. J. Virol. 94, e00204-e220 (2020).","journal-title":"J. Virol."},{"key":"99444_CR29","doi-asserted-by":"publisher","first-page":"8159","DOI":"10.1038\/s41598-020-65152-4","volume":"10","author":"J Sun","year":"2020","unstructured":"Sun, J. et al. Drug repurposing of pyrimidine analogs as potent antiviral compounds against human enterovirus A71 infection with potential clinical applications. Sci. Rep. 10, 8159 (2020).","journal-title":"Sci. Rep."},{"key":"99444_CR30","doi-asserted-by":"publisher","DOI":"10.1080\/01635581.2020.1856893","author":"SK Agrawal","year":"2020","unstructured":"Agrawal, S. K. et al. Anagallis arvensis induces apoptosis in HL-60 cells through ROS-mediated mitochondrial pathway. Nutr. Cancer https:\/\/doi.org\/10.1080\/01635581.2020.1856893 (2020).","journal-title":"Nutr. Cancer"},{"key":"99444_CR31","doi-asserted-by":"publisher","first-page":"W191","DOI":"10.1093\/nar\/gkz369","volume":"47","author":"U Raudvere","year":"2019","unstructured":"Raudvere, U. et al. g:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update). Nucl. Acids Res. 47, W191\u2013W198 (2019).","journal-title":"Nucl. Acids Res."},{"key":"99444_CR32","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1186\/1471-2148-4-37","volume":"4","author":"R Shankar","year":"2004","unstructured":"Shankar, R., Grover, D., Brahmachari, S. K. & Mukerji, M. Evolution and distribution of RNA polymerase II regulatory sites from RNA polymerase III dependant mobile Alu elements. BMC Evol. Biol. 4, 37 (2004).","journal-title":"BMC Evol. Biol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99444-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99444-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99444-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T16:41:26Z","timestamp":1670085686000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-99444-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,11]]},"references-count":32,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["99444"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-99444-0","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,11]]},"assertion":[{"value":"11 May 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 September 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20095"}}