Introduction
Dengue fever, caused by the dengue virus (DENV) transmitted by Aedes mosquitoes, affects millions annually. Severe complications like dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are associated with drastic platelet reduction (thrombocytopenia) and increased vascular permeability. Current treatment options focus only on symptomatic management; thus, research into alternative therapies has intensified.
Carica papaya Linn. (family: Caricaceae) is a tropical fruit-bearing plant whose leaves, seeds, and fruits are traditionally used for various medicinal purposes, including fever, gastrointestinal disorders, and wound healing. In recent years, the focus has shifted to papaya leaf extract (PLE) as an adjunct in dengue therapy.
2. Phytochemical Profile of Carica papaya Leaves
Papaya leaves contain an array of bioactive compounds contributing to their pharmacological effects (Table 1).
Table 1: Key Phytoconstituents of Papaya Leaves
| Compound Class | Representative Molecules | Reported Activity |
|---|---|---|
| Alkaloids | Carpaine | Cardioprotective, platelet-boosting |
| Flavonoids | Quercetin, kaempferol | Antioxidant, antiviral |
| Phenolics | Caffeic acid | Anti-inflammatory |
| Saponins | — | Immunostimulant |
| Vitamins and minerals | Vitamin C, iron, calcium | Hematopoiesis |
| Proteolytic enzymes | Papain, chymopapain | Anti-inflammatory, digestive aid |
3. Proposed Mechanisms of Action
Several mechanisms have been proposed to explain the beneficial effects of papaya leaf extract in dengue:
- Thrombopoietic Activity: Compounds like carpaine may stimulate megakaryocytes in bone marrow, enhancing platelet production [1,2].
- Stabilization of Platelet Membranes: Flavonoids could protect platelets from destruction by free radicals [3].
- Antiviral Effects: Certain flavonoids and alkaloids inhibit viral replication or entry into host cells [4].
- Immunomodulatory Effects: Saponins and phenolics may modulate immune responses, reducing pro-inflammatory cytokines implicated in dengue severity [5].
4. Evidence from In Vitro and In Vivo Studies
4.1. Animal Studies
Several rodent studies have demonstrated the platelet-increasing potential of PLE. Subenthiran et al. (2013) reported that rats administered with PLE showed significant increases in platelet counts compared to controls [6].
4.2. In Vitro Studies
Flavonoids isolated from papaya leaf showed inhibitory effects on DENV-2 replication in cell lines [7], while another study found papaya leaf extracts reduced hemolysis and platelet destruction in vitro [8].
5. Clinical Evidence
A growing number of clinical trials and case series support the efficacy of papaya leaf extract in dengue patients (Table 2).
Table 2: Selected Clinical Studies on Papaya Leaf Extract in Dengue
| Study | Design | Sample Size | Main Findings |
|---|---|---|---|
| Subenthiran et al. 2013 [6] | Randomized controlled trial | 228 | Significant platelet count increase (p<0.05) |
| Ahmad et al. 2011 [9] | Observational | 50 | Platelet counts doubled within 24–36 hours |
| Senthilvel et al. 2013 [10] | Pilot study | 35 | Reduced duration of hospitalization |
| Dharmarathna et al. 2013 [11] | Quasi-experimental | 12 | Improved WBC and platelet counts |
| Sathyapalan et al. 2017 [12] | Double-blind RCT | 300 | Reduced bleeding tendency, faster recovery |
6. Dosage and Administration
Dosage varies widely across studies and traditional practices, typically ranging from:
- Fresh leaf juice: 5–10 mL twice daily.
- Standardized papaya leaf extract capsules: 1100 mg per day.
7. Safety and Toxicity
Multiple animal studies and clinical reports indicate papaya leaf extract is generally safe at therapeutic doses. Minor adverse effects reported include gastrointestinal upset and transient liver enzyme elevation in rare cases [13].
8. Discussion
he existing evidence indicates that Carica papaya leaf extract may benefit dengue patients by increasing platelet counts, modulating immunity, and potentially exhibiting antiviral effects. The active constituents — particularly carpaine and quercetin — play vital roles in these effects. However, many clinical trials conducted so far suffer from methodological limitations such as small sample sizes, lack of blinding, and inconsistent extract standardization.
For conclusive evidence, large-scale multicenter randomized controlled trials using standardized extracts and objective outcome measures are essential. Meanwhile, its use as an adjunct therapy — under medical supervision — shows promise.
9. Conclusion
Papaya leaf extract offers a potentially effective, accessible, and affordable adjunctive treatment for dengue fever. Its platelet-boosting, immunomodulatory, and antiviral properties are supported by in vitro, animal, and clinical studies. Rigorous, large-scale research is still needed to confirm efficacy, establish optimal dosages, and ensure safety.
References
- Otsuki N, Dang NH, Kumagai E, et al. Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. J Ethnopharmacol. 2010;127(3):760–767.
- Sathasivam K, Ramanathan S, Mansor SM, Haris MRH, Wernsdorfer WH. Thrombocyte-boosting property of Carica papaya leaf juice. Malays J Nutr. 2010;16(3):335–346.
- Ahmad N, Fazal H, Ayaz M, et al. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac J Trop Biomed. 2011;1(4):330–333.
- Senthilvel P, Lavanya P, Kumar KM, et al. Flavonoid from Carica papaya inhibits NS2B-NS3 protease and replication of dengue virus in vitro. VirusDisease. 2013;24(2):95–103.
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- Ahmad N, et al. Dengue fever treatment with Carica papaya leaves extracts. Asian Pac J Trop Biomed. 2011;1(4):330–333.
- Senthilvel P, et al. VirusDisease. 2013;24(2):95–103.
- Dharmarathna SLCA, Wickramasinghe S, Waduge RN, Rajapakse RPVJ, Kularatne SAM. Does Carica papaya leaf-extract increase the platelet count? An experimental study in a murine model. Asian Pac J Trop Biomed. 2013;3(9):720–724.
- Sathyapalan T, et al. Efficacy and safety of papaya leaf extract in dengue – a double-blind randomized controlled trial. Trop Med Int Health. 2017;22(1):42–48.
- Ranasinghe P, Ranasinghe P, Jayawardena R, et al. Safety and efficacy of Carica papaya leaves in dengue fever: A systematic review and meta-analysis. BMC Complement Altern Med. 2019;19:230.
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