{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T12:30:41Z","timestamp":1764937841882,"version":"3.37.0"},"reference-count":84,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>One of the most widespread arboviral diseases in the world, dengue virus\n                        disease (DVD) is primarily found in tropical and subtropical regions,\n                        affecting 129 countries. The main way that the dengue virus (DENV) spreads\n                        is through the bite of a female Aedes aegypti mosquito. Symptomatic\n                        therapy and supportive care are the primary methods of managing patients\n                        with DENV infection as there is currently no approved antiviral medication\n                        for this condition. Since the guidelines from the AYUSH Ministry, Government\n                        of India, recommend 10\u2009ml of carica papaya leaf extract (CPLE) twice\n                        daily for seven days, to treat dengue fever clinically, we plan to review\n                        the potential of carica papaya in managing DENV infection.<\/jats:p><jats:p>Using terms like dengue, dengue fever, dengue hemorrhagic fever, dengue shock\n                        syndrome, and carica papaya, the literature was searched in databases\n                        like Medline\/PubMed Central\/PubMed, Google Scholar, Science Direct, EBSCO,\n                        Scopus, Web of Science, EMBASE, Directory of open access journals (DOAJ),\n                        and reference lists to find articles relevant to the clinical, in-vivo,\n                            in-vitro, and in-silico studies evaluating the efficacy of\n                            carica papaya in the management of dengue viral infection. This\n                        review included English-language publications that supported the use of\n                            carica papaya in the treatment of dengue fever, but it excluded\n                        publications that were duplicates.<\/jats:p><jats:p>Numerous preclinical and clinical investigations, such as in-vitro,\n                            in-vivo, and in-silico studies, have identified carica\n                            papaya's anti-dengue potential. The pleiotropic effects of\n                            carica papaya, including its anti-thrombocytopenic activity,\n                        immunomodulatory effects, and larvicidal property against the Aedes\n                            aegypti mosquito species, have also been confirmed by numerous\n                            in-vitro and in-vivo studies. These effects can help\n                        patients with dengue fever by elevating their platelet count and alleviating\n                        other symptoms.<\/jats:p><jats:p>To hasten recovery and reduce hospital stays, patients with DENV infection\n                        may take carica papaya leaf extract (CPLE) in addition to supportive\n                        care and symptomatic treatment. Additional randomized controlled clinical\n                        trials would be necessary to confirm the safety and effectiveness of CPLE in\n                        patients with DENV infection.<\/jats:p>","DOI":"10.1055\/a-2509-8644","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T23:47:01Z","timestamp":1737589621000},"page":"49-59","source":"Crossref","is-referenced-by-count":1,"title":["A Review of Potentials of Carica Papaya Leaves in Dengue Viral\n                    Infection \u2013 Insights of Clinical and Preclinical Studies"],"prefix":"10.1055","volume":"75","author":[{"given":"Naina Mohamed Pakkir","family":"Maideen","sequence":"additional","affiliation":[{"name":"Dubai Academic Health Corporation, Dubai, UAE"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rajkapoor","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, J.K.K. Nattraja College of Pharmacy,\n                    Komarapalayam, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arun","family":"Shanmugam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Practice, J.K.K. Nattraja College of Pharmacy,\n                    Komarapalayam, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirunalini","family":"Gobinath","sequence":"additional","affiliation":[{"name":"JSS College of Pharmacy, Ooty, Tamilnadu, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed Harshath Jahir","family":"Hussain","sequence":"additional","affiliation":[{"name":"Ratnam Institute of Pharmacy, Nellore, Andhra Pradesh,\n                    India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"5074","DOI":"10.1016\/j.sjbs.2021.05.023","article-title":"Dengue and human health: A global scenario of its occurrence, diagnosis, and\n                    therapeutics","volume":"28","author":"M J Sabir","year":"2021","journal-title":"Saudi J Biol Sci"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/B978-0-12-819400-3.00016-8","volume-title":"Dengue virus. 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Leaf","volume":"25","author":"S Devi","year":"2020","journal-title":"Majalah Obat Tradisional"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.apjtb.2016.12.009","article-title":"Identification and quantification of flavonoids in Carica papaya leaf and\n                    peroxynitrite-scavenging activity","volume":"7","author":"A Nugroho","year":"2017","journal-title":"Asian Pac J Trop Biomed"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2508","DOI":"10.3390\/agronomy12102508","article-title":"Understanding the complex functional interplay between glucosinolates and\n                    cyanogenic glycosides in Carica papaya","volume":"12","author":"I H Ruhaizat-Ooi","year":"2022","journal-title":"Agronomy"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1111\/ijfs.12618","article-title":"Antioxidant and anticancer capacity of saponin-enriched Carica papaya\n                    leaf extracts","volume":"50","author":"Q V Vuong","year":"2015","journal-title":"International Journal of Food Science &\n                    Technology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"5602729","DOI":"10.1155\/2018\/5602729","article-title":"Saponin bitterness reduction of Carica papaya leaf extracts through\n                    adsorption of weakly basic ion exchange resins","volume":"2018","author":"S N Syed Amran","year":"2018","journal-title":"Journal of Food Quality"},{"key":"ref24","first-page":"274","article-title":"Nutrient composition of Carica papaya leaf extracts","volume":"2","author":"N J Ugo","year":"2019","journal-title":"J Food Sci Nutr Res"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.3390\/nu11071608","article-title":"Nutraceutical potential of Carica papaya in metabolic syndrome","volume":"11","author":"L F Santana","year":"2019","journal-title":"Nutrients"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.31989\/dsn.v1i9.991","article-title":"Phytochemistry and nutraceutical properties of Carica papaya (Linn.): A\n                    review","volume":"1","author":"P Singh","year":"2022","journal-title":"Dietary Supplements and Nutraceuticals"},{"key":"ref27","first-page":"17","article-title":"Salutary effects of Carica papaya leaf extract in dengue fever patients\u2013\n                    a pilot study","volume":"29","author":"S Hettige","year":"2008","journal-title":"Sri Lankan Fam Physician"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S2221-1691(11)60055-5","article-title":"Dengue fever treatment with Carica papaya leaves extracts","volume":"1","author":"N Ahmad","year":"2011","journal-title":"Asian Pac J Trop Biomed"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"e473","DOI":"10.1016\/j.ijid.2012.05.686","article-title":"Effect of papaya leaf extract on platelet count in dengue fever: a randomized\n                    controlled trial (PLEAD Trial)","volume":"16","author":"M Z Assir","year":"2012","journal-title":"Int J Infect Dis"},{"key":"ref30","first-page":"26","article-title":"Effect of papaya leaf juice on platelet and WBC count in dengue fever: a case\n                    report","volume":"1","year":"2013","journal-title":"J Ayurveda Hol Med (JAHM)"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"616737","DOI":"10.1155\/2013\/616737","article-title":"Carica papaya leaves juice significantly accelerates the rate of increase\n                    in platelet count among patients with dengue fever and dengue haemorrhagic\n                    fever","volume":"2013","author":"S Subenthiran","year":"2013","journal-title":"Evid Based Complement Alternat Med"},{"key":"ref32","first-page":"364","article-title":"Effects of papaya leaves on thrombocyte counts in dengue \u2013 a case report","volume":"64","author":"O Siddique","year":"2014","journal-title":"JPMA J Pak Med Assoc"},{"key":"ref33","first-page":"93","article-title":"Therapeutic Potential of Carica papaya L. Leaf Extract in Treatment of\n                    Dengue Patients","volume":"6","author":"C V Kumar","year":"2015","journal-title":"Int J Appl Biol Pharm Technol"},{"key":"ref34","first-page":"109","article-title":"A Pilot Study to Evaluate the Effectiveness of Carica papaya Leaf Extract\n                    in Increasing the Platelet Count in Cases of Dengue with Thrombocytopenia","volume":"149","author":"A C Gowda","year":"2015","journal-title":"Indian Med Gaz"},{"key":"ref35","first-page":"9","article-title":"The effect of Carica papaya leaf extract capsules on platelets count and\n                    hematocrit levels in acute febrile illness with thrombocytopenia patient","volume":"5","author":"A Singhai","year":"2016","journal-title":"Int J Med Res Health Sci"},{"key":"ref36","first-page":"15","article-title":"A Multi-centric, Double-blind, Placebo-controlled, Randomized, Prospective Study\n                    to Evaluate the Efficacy and Safety of Carica papaya Leaf Extract, as\n                    Empirical Therapy for Thrombocytopenia associated with Dengue Fever","volume":"64","author":"P N Kasture","year":"2016","journal-title":"Journal Association of Physicians of India"},{"key":"ref37","first-page":"22","article-title":"Effect of Carica papaya Leaf Extract Capsule on Platelet Count in\n                    Patients of Dengue Fever with Thrombocytopenia","volume":"64","author":"A K Gadhwal","year":"2016","journal-title":"Journal Association of Physicians of India"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"685","DOI":"10.5455\/njppp.2017.7.0202628022017","article-title":"Effect of Carica papaya leaf extract on platelet count in\n                    chemotherapy-induced thrombocytopenic patients: A preliminary study","volume":"7","author":"D Sundarmurthy","year":"2017","journal-title":"Natl J Physiol, Pharm Pharmacol"},{"key":"ref39","first-page":"3752","article-title":"Clinical use of Carica papaya leaf extract in chemotherapy-induced\n                    thrombocytopenia","volume":"10","author":"S M Hussain","year":"2017","journal-title":"Int J Clin Exp Med"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"116","DOI":"10.18203\/2349-3259.ijct20173088","article-title":"A randomized, double-blind, placebo-controlled, proof of concept study to assess\n                    the safety and efficacy of Carica papaya and Tinospora cordifolia leaf\n                    extract (Thrombobliss) in subjects undergoing chemotherapy treatment and\n                    subjects with systemic microbial infection and subsequent reduction in platelet\n                    count","volume":"4","author":"R Babu","year":"2017","journal-title":"Int J Clin Trials"},{"key":"ref41","first-page":"1","article-title":"Assessment of Platelet Levels in Serum Samples of Dengue Patients before and\n                    after Providing Papaya with Other Fruits","volume":"3","author":"A R Krishna","year":"2017","journal-title":"Ann Int Med Dent Res"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"974","DOI":"10.18203\/2349-3933.ijam20183131","article-title":"Effect of Carica papaya leaf extract (CPLE) on thrombocytopenia among\n                    dengue patients of tertiary care hospital, Chitradurga, India","volume":"5","author":"S B Vijeth","year":"2018","journal-title":"Int J Adv Med"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"845","DOI":"10.18203\/2349-3933.ijam20182500","article-title":"Role of Carica papaya leaf extract tablets\/capsules on platelet counts in\n                    cases of dengue thrombocytopenia","volume":"5","author":"K Venugopal","year":"2018","journal-title":"Int J Adv Med"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"99","DOI":"10.21760\/jaims.v3i01.11648","article-title":"Phyto extracts of Carica papaya and Tinospora cordifolia can correct\n                    thrombocytopenia in alcoholic decompensate liver cirrhosis: Case Series","volume":"3","author":"A K Panda","year":"2018","journal-title":"J Ayurveda Integr Med Sci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"974","DOI":"10.18203\/2349-3933.ijam20183131","article-title":"Effect of Carica papaya leaf extract (CPLE) on thrombocytopenia among\n                    dengue patients of tertiary care hospital, Chitradurga","volume":"5","author":"S B Vijeth","year":"2018","journal-title":"India Int J Adv Med"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"170","DOI":"10.18203\/2349-3259.ijct20183376","article-title":"A post-marketing randomized placebo-controlled study to evaluate the efficacy of\n                    study product UPLAT\u00ae (Carica papaya leaf extract+Tinospora cordifolia\n                    extract) in the cancer patients with thrombocytopenia induced by\n                    chemotherapy","volume":"5","author":"R Tiwari","year":"2018","journal-title":"Int J Clin Trials"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1002\/ccr3.2025","article-title":"Use of papaya leaf extract in neonatal thrombocytopenia","volume":"7","author":"A Pandita","year":"2019","journal-title":"Clinical Case Reports"},{"key":"ref49","first-page":"380","article-title":"The effectiveness of Carica papaya leaf extract in children with European\n                    of biomedical and Pharmaceutical sciences the effectiveness of Carica\n                        papaya leaf extract in children with","volume":"6","author":"D Shetty","year":"2019","journal-title":"Eur J Biomed Pharm"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"2952","DOI":"10.21276\/ijprhs.2019.02.06","article-title":"Safety and Efficacy Study of ZyboricaTM Tablet (Carica papaya Leaf\n                    Extract) for Thrombocytopenia Associated with Dengue Fever: A Randomized\n                    Double-Blind Placebo Controlled Trial","volume":"7","author":"L P Spt","year":"2019","journal-title":"International Journal of Pharma Research and Health\n                    Sciences"},{"key":"ref52","first-page":"62","article-title":"Evaluation of the efficacy of Carica papaya leaf extract on platelet\n                    counts in dengue patients","volume":"11","author":"S G Solanki","year":"2020","journal-title":"Journal of Advanced Scientific Research"},{"key":"ref53","first-page":"1","article-title":"Controlled Clinical Trial on Effect of \u2018Carica Papaya\u2019 Leaf Extract on Patients\n                    with Dengue Fever","volume":"3","author":"S Hettige","year":"2020","journal-title":"Journal of Clinical Research and Medicine"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"e0228699","DOI":"10.1371\/journal.pone.0228699","article-title":"Efficacy & safety of Carica papaya leaf extract (CPLE) in severe\n                    thrombocytopenia (\u226430,000\/\u03bcl) in adult dengue \u2013 Results of a pilot 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augmentation","volume":"164","author":"N Sharma","year":"2019","journal-title":"Archives of virology"},{"key":"ref61","first-page":"8374","article-title":"Antiviral activity of Carica papaya extract against experimental dengue\n                    virus 1 infection","volume":"11","author":"M O Galappaththi","year":"2021","journal-title":"Sri Lankan J Infect Dis"},{"key":"ref62","first-page":"667","article-title":"Screening of Carica papaya L. 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