Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects
Abstract
1. Introduction
2. Methods
3. Pathophysiological Mechanisms of Dengue
4. Pharmacological Effects of Papaya Against Dengue
4.1. Oxidative Stress
4.2. Cytokine Storm and Interferons
4.3. Immune Cell Infiltration
4.4. Platelets and Thrombocytopenia
5. Nutrition and Bioactive Compound of Papaya Against Dengue
6. Clinical Trials of Carica papaya Leaf Extract in Dengue Patients
7. Conclusions and Future Prospects
Author Contributions
Funding
Conflicts of Interest
References
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Experimental Models | Dose, Time, and Route of Papaya Extract Treatment | Major Research Outcomes | Alterations in Molecular Markers | Ref. |
---|---|---|---|---|
DENV-2 induced AG129 Mice | FCPLJ 500 and 1000 mg/kg BW for 3 days Orally | Modulating the release of certain cytokines | ↑ MCP-1, G-CSF, IL-6, and TNF-α, CCL2/ MCP-1, ↓ CCL6/MRP-1, CCL8/MCP-2, CCL12/MCP-5, CCL17/TARC, IL1R1, IL1RN/IL1Ra, NAMPT/PBEF1, PF4/CXCL4, CCL12/MCP-5, IL1R1 | [6] |
ATCC VR-induced AG129 Mice | FCPLJ 1000 mg/kg BW for 3 days Orally | Affected the regulation of genes endothelial permeability regulation | ↑ CCL2, ↓ ITGB3, ICAM1, FN1 | [6] |
Mouse | CPLE, 0.2 mL/2 g BW/day for 7 days Orally | Increase platelet count and RBC | ↑ Platelet, RBC, | [57] |
DENV-2 induced AG129 Mice | FCPLJ 500 and 1000 mg/kg BW for 3 days Orally | Augmentation of WBC, neutrophil, and anti-inflammatory activity | ↑ WBC, neutrophil ↓ GM-CSF, GRO-alpha, IL-6, MCP-1, MIP-1 beta, IL-1 beta, IFN-γ, TNF-α | [58] |
Hydroxyurea-induced thrombocytopenic mice | MLCC 0.72 mL/100 g for 3 days Orally | Increase platelet, RBC, and WBC | ↑ Platelet, WBC, RBC ↓ Carrageenan induced edema, vascular permeability | [59] |
Cyclophosphamide-induced thrombocytopenic rat | CPLAE 400 and 800 mg/kg p.o. 15 days | Increase platelet levels and reduce clotting duration. | ↑ Platelet | [60] |
Cyclophosphamide-induced thrombocytopenic rats | SCPLE 50 and 150 mg/kg BW, p.o. 14 days | Reduce bleeding time and clotting time | ↑ PC, TLC, DLC, DTH ↓ TNF-α | [61] |
Wistar rats | MLCC 0.18, 0.36 and 0.72 mL/100g BW for 3 days Orally | Stimulate immunological cell proliferation, enhancement of phagocytic activity, and modulation of cytokine responses. | ↑ Platelet, WBC, BMC, PM, SC ↓ TNF-α, IL-6, IFNγ, | [62] |
Anagrelide-induced Sprague Dawley rats | CPLE 0.2 mg/mL,1 mg/mL, for 10 days Orally | Augmentation of platelet | ↑ Platelet | [63] |
Non-mouse-adapted NGC strain DEN-2-induced AG129 mice | FCPLJ 500 and 100 mg/kg BW for 3 days Orally | Morbidity decreased | Did not influence the levels of plasma NS1 and viral RNA. | [64] |
Carboplatin-induced thrombocytopenia in mice | CPLJ 5 and 10 mL/kg for 21 days Orally | Prevents fall in platelet count | ↑ Platelet | [65] |
Cyp-induced thrombocytopenic rats | CPLJ 200 and 400 mg/kg BW for 14 days Orally | Boost platelet count and normalize clotting time. | ↑ Platelet, cMpl | [66] |
Hydroxyurea-induced thrombocytopenic Wistar rats | MLJCP 0.18, 0.36 and 0.72 mL/100 gm BW For 3 days Orally | Augmentation of platelet | ↓ TPO, PAF ↑ Platelet, IL-6 | [67] |
Experimental Models | Dose and Time of Papaya Extract | Major Research Outcomes | Alterations in Molecular Markers/Active Ingredients | Ref. |
---|---|---|---|---|
Vero CCL-81 cell | (12.5, 25, 50 and 100 μg/mL) for 5 days at 37 °C | Cytotoxic effect, immunomodulator | DENV2 viral titer ↓, viral foci ↓ | [18] |
PRP and PPP treated with CPLE | 10 µM ADP-induced 10 mL blood incubated with CPLE for 30 min | Reduction in platelet aggregation | ↓ Platelet aggregation | [68] |
CPLE-treated blood cells | 9.375, 18.75, 37.5, 75, 150 and 300 µg/mL for 20 min at 55 °C | Erythrocyte membrane-stabilizing potential; inhibition of hemolysis, antibiotics, antiviral, and antitumor agents. | Hemolysis of erythrocytes ↓ | [69] |
CPLE-treated ES cell | 2.5 g in 2.5 mL water | Platelet propagation from ES cell | PAR4 thrombin receptor-activating peptide AYPGFK, ↑ TPO. | [70] |
CPLE-treated LLC-MK2 cell line | 2 g in 100 mL DMSO for 5 days | Cytotoxic effect; anti-DENV2 activity | Protocatechuic acids, erythrocyte glutathione peroxidase, Th1 ↑ | [71] |
Sl. No | No. of Subjects | Daily Dose | Follow Up Time | Alterations in Various Parameters | Ref. |
---|---|---|---|---|---|
1 | 285 | 275–550 mg syrup | 3 times; 5 days | ↑ Platelet, WBC, and RBC | [7] |
2 | 51 | 1100 mg (1 tablet), leaf extract | 3 times; 5 days | ↑ Platelet | [16] |
3 | 1 male | 25 mL, aqueous leaf extract | Twice daily; 5 days | ↑ PLT, WBC, and NEUT | [82] |
4 | 80 | 13.2 gm of CPC | 12 capsules twice daily; 2–7 days | ↑ Platelet, ↓ Hematocrit | [116] |
5 | 228 | 50 g, leaves juice | Once daily; 3 days | ↑ Platelet | [117] |
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Shoyshob, T.Z.; Heya, I.A.; Afrin, N.; Enni, M.A.; Asha, I.J.; Moni, A.; Hannan, M.A.; Uddin, M.J. Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects. Immuno 2024, 4, 629-645. https://doi.org/10.3390/immuno4040037
Shoyshob TZ, Heya IA, Afrin N, Enni MA, Asha IJ, Moni A, Hannan MA, Uddin MJ. Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects. Immuno. 2024; 4(4):629-645. https://doi.org/10.3390/immuno4040037
Chicago/Turabian StyleShoyshob, Tanvir Zaman, Irin Amin Heya, Nusrat Afrin, Mansura Akter Enni, Israt Jahan Asha, Akhi Moni, Md. Abdul Hannan, and Md. Jamal Uddin. 2024. "Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects" Immuno 4, no. 4: 629-645. https://doi.org/10.3390/immuno4040037
APA StyleShoyshob, T. Z., Heya, I. A., Afrin, N., Enni, M. A., Asha, I. J., Moni, A., Hannan, M. A., & Uddin, M. J. (2024). Protective Mechanisms of Carica papaya Leaf Extract and Its Bioactive Compounds Against Dengue: Insights and Prospects. Immuno, 4(4), 629-645. https://doi.org/10.3390/immuno4040037