School of Pharmacy, G H Raisoni University Saikheda, Dist-Pandhurna, Madhya Pradesh, India-480337
However, dengue fever is a common world-wide public health problem associated with severe thrombocytopenia and haemorrhagic complications. Currently, there are no specific antiviral or platelet stimulating treatments, which are described as the current treatments, and top of those are supportive care (fluid therapy, platelet transfusions). The betterment of CPLE has recently been being discussed more for the dengue patients’ platelet recovery, as they independently increase in efficiency. Phytochemical examination of CPLE showed its immunomodulatory, antioxidants and the anti-inflammatory properties. It also emerged from preclinical studies that CPLE drives megakaryocyte growth driven thrombocytopaenia and platelet production as well as inflammatory modulation. In addition, CPLE exhibits an anti-viral activity against the virus, dengue virus. From the observational and controlled point of view, clinical trials that enhance tremendously increase of the values of platelet counts, accelerate the time of recovery, maintain the haematocrits values stable, as well as reduce the duration of hospital stay, without any other cohabiting side effects are proposed. However clinical applicability is threatened by variability in study design, preparation methodology, and that of large scale randomized controlled trials. Future work includes trials in multiple canters, standard dose, optimal combination regimens and approval by the regulatory authorities. CPLE was further validated as a safe and low cost of adjunct therapy to the dengue disease associated thrombocytopenia for the area endemic for the diseases and will thus reduce the disease burden.
1.1 Background on Dengue and Thrombocytopenia
Dengue fever, caused by the Dengue virus (DENV) and transmitted by Aedes aegypti and Aedes albopictus mosquitoes, is a major global health concern, particularly in tropical and subtropical regions. According to the World Health Organization (WHO), approximately 390 million dengue infections occur each year, with around 96 million showing clinical symptoms [1]. The disease presents a wide range of symptoms, from mild febrile illness to severe complications like dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [2]. A key characteristic of severe dengue is thrombocytopenia, a condition marked by a significant drop in platelet count, which heightens the risk of hemorrhagic complications. The underlying causes of dengue-induced thrombocytopenia are multifaceted and include direct viral suppression of megakaryopoiesis, increased platelet destruction due to immune system activity, and platelet sequestration in the spleen [3]. Additionally, dengue infection triggers an excessive immune response, leading to endothelial damage and increased vascular permeability, further compounding the risk of haemorrhagic complications [4].
1.2 Current Management Strategies for Dengue
There is no established antiviral treatment for dengue fever yet. Treatment is primarily supportive, focusing on hydration, fever management, and monitoring hematological parameters. In cases of severe thrombocytopenia (platelet count less than 30,000/µL) with active bleeding, platelet transfusion may be considered; however, its effectiveness remains uncertain, as transfused platelets have a short lifespan and may not significantly impact clinical outcomes [5]. The use of corticosteroids and other immunomodulatory drugs has been explored, but there is limited strong clinical evidence supporting their efficacy. Given the limitations of conventional treatments, there is growing interest in alternative and complementary therapies to aid platelet recovery and improve patient outcomes [6].
1.3 Potential Role of Herbal Medicine in Dengue Management
Herbal therapy has gained significant attention as a complementary approach to managing dengue fever. Various plant extracts have been studied for their hematopoietic, anti-inflammatory, and immunomodulatory properties. Among them, Carica papaya leaf extract (CPLE) has emerged as a promising natural remedy, with reported benefits in increasing platelet production and reducing the severity of thrombocytopenia [7]. CPLE contains bioactive compounds such as flavonoids, alkaloids, and glycosides, which are believed to work by stimulating megakaryocyte proliferation, preventing platelet destruction, and modulating immune responses [8]. Research suggests that papaya leaf extract helps boost platelet count, reduces oxidative stress, and may also have antiviral properties, making it a potential supportive therapy for dengue management [9]. Preclinical and clinical studies have shown encouraging results regarding the effectiveness of CPLE, leading to further exploration of its mechanism of action and safety profile [10]. This review aims to thoroughly evaluate the efficacy and safety of Carica papaya leaf extract in treating dengue-induced thrombocytopenia by analyzing available clinical and preclinical studies. By summarizing key findings from randomized controlled trials, observational studies, and laboratory research, this paper seeks to assess whether CPLE can be incorporated into dengue treatment protocols as a viable therapeutic option [11]. Additionally, potential limitations and gaps in current research will be discussed to guide future investigations into the clinical application of papaya leaf extract [12].
2. Phytochemical Composition of Carica Papaya Leaf Extract
2.1 Overview of Bioactive Compounds in Papaya Leaves
The medicinal properties of Carica papaya leaf extract (CPLE) are attributed to its rich phytochemical composition, which includes bioactive compounds such as alkaloids, flavonoids, tannins, saponins, and glycosides [13]. These compounds exhibit immunomodulatory, anti-inflammatory, and hematopoietic properties, making CPLE a potential therapeutic option for managing thrombocytopenia in dengue fever.
With these beneficial properties, CPLE holds promise as a supportive therapy for dengue-induced thrombocytopenia, warranting further research into its effectiveness and safety.
2.2 Mechanisms of Action Relevant to Thrombocytopenia Treatment
2.2.1 Immunomodulatory Effects
Dengue-induced thrombocytopenia is partly driven by immune-mediated platelet destruction. Research suggests that Carica papaya leaf extract (CPLE) can help regulate immune responses by reducing the levels of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) [10]. This immunomodulatory effect aids in minimizing platelet destruction while also promoting hematopoiesis, the process of blood cell formation [7].
2.2.2 Antioxidant and Anti-inflammatory Effects
Oxidative stress plays a crucial role in platelet dysfunction and endothelial damage during dengue infection. The flavonoids and other polyphenolic compounds in papaya leaf extract act as powerful antioxidants, neutralizing harmful free radicals and protecting platelets from oxidative damage [3]. Additionally, CPLE has been found to inhibit cyclooxygenase (COX) and lipoxygenase (LOX) pathways, which helps reduce inflammation and prevent excessive platelet activation—an essential factor in mitigating dengue-associated haemorrhagic complications [2].
2.2.3 Stimulation of Platelet Production
One of the most extensively studied benefits of CPLE is its ability to stimulate platelet production by enhancing bone marrow activity. Preclinical research has shown that CPLE upregulates the expression of CD110, the thrombopoietin receptor on megakaryocytes, thereby boosting thrombopoiesis and increasing platelet levels in circulation [9]. Furthermore, bioactive compounds in papaya leaves have been shown to support the maturation of megakaryocytes, which further aids in platelet recovery [1]. The bioactive components of Carica papaya leaf extract contribute to its immunomodulatory, antioxidant, anti-inflammatory, and thrombopoietic properties, making it a promising natural remedy for managing dengue-induced thrombocytopenia. By reducing platelet destruction, promoting platelet production, and offering protection against oxidative stress, CPLE has shown significant therapeutic potential. However, further clinical research is needed to establish standardized dosing guidelines and assess its safety profile [11].
3. Preclinical Studies on Carica Papaya Leaf Extract
3.1 In Vitro Studies
Effects on Platelet Production and Aggregation
There have been various in vitro studies investigating the roles of Carica papaya leaf extract (CPLE) in platelet formation and platelet aggregation. Research shows that CPLE enhances megakaryocyte differentiation and platelet production via the upregulation of thrombopoietic pathways [9]. CPLE inhibits platelet aggregation, thereby capable of preventing excessive clotting in dengue patients while still enhancing the overall platelet count. The bioactive compounds of papaya leaves, particularly flavonoids and saponins, are believed to stabilize the platelet membrane and prevent premature platelet destruction, as typically observed in dengue-induced thrombocytopenia [10].
Potential Antiviral Properties Against Dengue Virus
Also, CPLE was explored as a candidate antiviral against the dengue virus. In silico and in vitro studies indicate that flavonoids present in papaya leaves inhibited NS2B-NS3 protease, a key enzyme that is necessary for dengue viral replication, and thus prevents the virus spreading inside the host [8]. These findings are encouraging but further studies are required to determine direct antiviral efficacy of CPLE in dengue-infected cells.
3.2 Animal Studies
Findings on Thrombocytopoiesis in Animal Models
Significant has been offered by preclinical studies in animal models regarding the impact of CPLE on thrombocytopoiesis. Cyclophosphamide induced thrombocytopenic rats and it was observed that CPLE administration caused a dramatic increase in platelet count, hence indicating a stimulatory effect on megakaryocytes. Additionally, CPLE was shown to increase bone marrow activity and thereby may stimulate of thrombopoiesis directly to aid platelet recovery [9]. In another study pharmacokinetics and bioavailability of CPLE in rats were studied, and they found that the bioactive compounds of CPLE are well absorbed and well distributed in the blood. This implies that oral administration of papaya leaf extract could be convenient and effective in delivering its platelet enhancing effects [12].
Mechanistic Insights from Rodent Studies
Studies in rodent indicate how CPLE exerts its thrombopoietic effects. As revealed by the research, papaya leaf extract promotes the expression of CD110 (thrombopoietin receptor) on the megakaryocytes and leads to amplication of produced platelets [9]. The extract has been also shown to reduce the oxidative stress of the hematopoietic tissues preserving the functioning of bone marrow with reconstitution of the platelets [3]. Moreover, multiple studies from oxidative damage models have shown that CPLE decreases inflammatory markers and oxidative stress in alveolar macrophages [14]. This, together with previous results, suggests that these anti-inflammatory properties may have some role in dampening the immune mediated destruction of platelets — a major cause of thrombocytopenia — in dengue patients. The results of in vitro studies indicate that CPLE increases the production of platelet and inhibited the platelet aggregation, are antiviral to dengue virus. Animal studies in which platelet counts are increased and thrombopoietin receptors on megakaryocytes are upregulated further support the fact that it has thrombopoietic effects. Together, these results promise to fulfill the potential of CPLE as a formative CLE to augment dengue immunization, a clinical validation that will have to be rationally undertaken to ensure efficacy and safety for human populations.
4. Clinical Evidence on The Efficacy of Carica Papaya Leaf Extract
4.1 Overview of Clinical Trials and Observational Studies
Thrombocytopenia caused dengue has been assessed in some dengue cases through clinical trial and observational studies of Carica papaya leaf extract (CPLE). However, as in these studies, the methods utilized vary; such as randomized controlled trials (RCTs), cohort studies and case series. Randomised controlled trials (an ideal for clinical research standards considered gold standard in clinical research) have been done to compare CPLE with placebo or standard care and have shown strong evidence of therapeutic potential of CPLE [1,5]. Most clinical studies have been done in adult dengue patients with thrombocytopenia (platelet count <100,000/µL). Pilot studies have less than 50 subjects and greater than 200 patients [3]. These studies have been conducted in dengue focal areas of India, Malaysia and Indonesia where dengue disease burden is high and there is the effort to develop an alternative therapy for dengue management [2,7].
4.2 Effects on Platelet Count and Recovery Time
The effect producing increase in platelet numbers observed in dengue patients is the most widely researched CPLE. Medical trial results prove that CPLE facilitates the recovering of affected patients' platelets. A double-blind placebo-controlled study by has shown that patients receiving papaya leaf extract juice increase in platelet count faster than the placebo group [2]. By day 3 of treatment, the difference was statistically significant, i.e. a thrombopoietic effect on an early time scale. For instance, similar to CPLE capsules [1], study also demonstrated that patients who took CPLE capsules exhibited higher platelet counts, and quicker recoveries time as compared to patients who only received standard supportive care. Showed in a multi-centric RCT that CPLE improved platelet count without undue safety and tolerability in dengue patients [5]. In fact, a meta-analysis of clinical studies suggest that patients treated with CPLE platelet increase around 20,000–30,000/µL within 48 to 72 hours in comparison to patients who received CPLE experiencing minimal or insignificant increase in the placebo group [4].
4.3 Impact on Dengue Symptoms and Recovery
In addition, we also examined the effects of CPLE processes on platelet recover, and dengue symptoms and overall recovery. Furthermore, clinical studies revealed that CPLE results in faster decline of fever in patients relative to the control group [5]. Plasma leakage is the reason why dengue patients have to develop hemoconcentration. The results of studies have found that the preservation of hematocrit stability ‘’helps to reduce risks of dengue hemorrhagic fever (DHF)’’ [7]. Lower duration in hospital: Patients treated with papaya leaf extract in general tended to be discharged one to two days earlier, on average, than in standard care controls [3]. Therefore, these results show that the CPLE may contribute to better overall recovery and lower the amount of healthcare burden in dengue endemic areas.
4.4 Safety and Adverse Effects
With no significant adverse effects on CPLE safety profile, it has been studied in numerous studies and was found to be relatively well tolerated. Mild gastrointestinal symptoms, such as diarrhea or nausea, in some patients [5]. No clinically significant hepatotoxicity or nephrotoxicity in clinical trials [3]. There have been no reports of serious allergic reactions or drug interactions, but more studies are needed to determine long-term safety. Despite the above contraindications, pregnant women and people who have known papaya allergy should avoid CPLE as it can cause allergic reaction or uterine stimulant [5]. It is to be used with caution in patients on anticoagulant therapy since it may exhibit mild effect on platelet function [10]. The clinical studies have provided the compelling evidence of the significant improvement in platelet count, fast recovery and reduction in hospitalization duration of dengue patients treated with Carica papaya leaf extract. Minimal side effects were reported with the extract and there appeared to be no adverse effects. However, there are existing trials that recommend the use of CPLE as an adjunct to dengue treatment, which necessitate more of larger multi center studies and standard dosing guidelines to further future establish its clinical utility [4].
5. Mechanism of Action of Carica Papaya Leaf Extract in Thrombocytopenia
The therapeutic potential of Carica papaya leaf extract (CPLE) in the treatment of dengue patient with thrombocytopenia is to increase the platelet production, modulate proinflammatory cytokines, increase immune function, and either increase viral clearance. There are several studies that have explored related mechanisms underlying its approach to restore platelet levels and to be effective in improving patient outcomes.
5.1 Enhancement of Megakaryocyte Proliferation
Major mechanism to aid in platelet recovery through stimulation of megakaryopoiesis (Megakaryocyte maturation and development into platelets). It has been shown that CPLE upregulates the expression of thrombopoietin receptor (CD110) on megakaryocytes and promotes differentiation and maturation of the platelet producing cells [9]. Bioactive compounds such as flavonoids, alkaloids and glycosides are thought to stimulate the bone marrow activity, which promotes faster platelet regeneration in cases of thrombocytopenia [1]. Administration of CPLE increased platelet counts in thrombocytopenic rats in animal models and therefore may have a role in promoting bone marrow recovery in rats that have been depleted of platelets [9]. This mechanism implies that CPLE not only protects platelets from destruction but also promotes their generation, thereby providing it as an adjunct therapeutic option for thrombocytopenia.
5.2 Modulation of Inflammatory Pathways
The inflammatory cytokines that partially underlie dengue induced thrombocytopenia lead to platelet destruction and decreased bone marrow function. They have also found that CPLE reduces levels of tumor necrosis factor alpha (TNFα) and Interleukin 6 (IL6) which are increased in severe dengue patients and are responsible for platelet depletion [10]. Antioxidant properties: Papaya leaves flavonoids and phenolic compounds have high antioxidant properties that block reactive oxygen species (ROS) radicals which cause platelet dysfunction and endothelial damage [3]. Inhibition of platelet sequestration: CPLE is effective in preventing platelet sequestration in the spleen (Gandrek et al., 2015). Anti-inflammatory and antioxidant properties help to preserve platelet integrity and help maintain release of platelets and limit the severity of thrombocytopenia.
5.3 Role in Viral Clearance and Immune Modulation
There, recent studies suggest that CPLE may have direct antiviral properties towards the dengue virus and that these may thus contribute to its beneficial effects in dengue patients. Slowing the spread of dengue virus in the host: Flavonoids from the papaya leaves were found to inhibit NS2B-NS3 protease, which is essential for dengue virus replication, to inhibit dengue viral replication [8]. Innate immune responses enhancement: CPLE seems to enhance the interferon (IFN) production, which is essential for viral clearance and defence [4]. Immune cell activity regulation: It is believed that CPLE increases the activity of macrophages and T cells, leading to better dengue virus infection fighting power for the body [14].
Table 1 Comparison with Conventional Therapies
|
Therapy |
Mechanism |
Limitations |
|
Intravenous fluids |
Prevents dehydration and maintains blood pressure |
Does not directly address thrombocytopenia |
|
Platelet transfusion |
Provides immediate platelet support |
Limited availability, risk of reactions |
|
Steroids (rarely used) |
Suppresses immune-mediated platelet destruction |
Risk of immunosuppression, no proven benefit |
|
CPLE (herbal therapy) |
Stimulates megakaryopoiesis, reduces inflammation, enhances immunity |
Requires further standardization and dosage optimization |
In contrast to platelet transfusions which only temporarily provide relief, CPLE has potential to naturally stimulate long term platelet production to provide a long-term therapeutic benefit. Moreover, CPLE’s immunomodulatory and antiviral effects are further diverse benefits which boost platelet counts rather than the normal ways of the regular therapies [2,5]. Carica papaya leaf extract exerts the mechanism of action of its use in therapeutics of dengue induced thrombocytopenia with a multi targeted approach, viz.:
1. Increase of megakaryocytes proliferation to increase the number of circulating platelets.
2. Reducing cytokine induced platelet destruction through modulation of inflammatory pathways.
3. It is helping in the clearance and regulation of the immune response as well as clearance and regulation of the overall recovery of the disease.
4. This has great advantages over conventional treatments as they have less side effect and a wider therapeutic potential.
Encouraging results have been seen so far in clinical trials but more work is needed to pin down dosing, formulate the therapy to get it at the best possible time and to determine the safety over time in people with dengue. Nevertheless, Carica papaya leaf extract may have a complementary role in the control of thrombocytopenia in dengue and any other disorders with platelet count abnormalities.
6. Limitations and Challenges in Existing Research on Carica Papaya Leaf Extract
Although much data is now available to substantiate the usefulness of Carica papaya leaf extract (CPLE) in treating dengue induced thrombocytopenia for human, several obstacles and insufficiencies exist in the knowledge base. Such variables as study design variability, differences in dosage and preparation, a lack of large-scale randomized trials, and regulatory concerns are some of these contributors. Mitigating these limitations is necessary to make CPLE a standardized and dependable therapy for Dengue patients.
6.1 Variability in Study Designs
The consistent structure of CPLE is one of the main challenges in evaluating the effectiveness of CPLE because different trials vary in study design:
Heterogeneous methodologies: The result is due to the variability in studies that have been done: Randomized Controlled Trials (RCTs), cohort studies, observational studies and case series [1,2].
Differences in patient selection: Rucaparib has reported efficacy, but this we should note, as different severities of dengue infection, as well as severe thrombocytopenia caused the variances in reported efficacy [3]. Variability in outcome measures: While a large majority of the studies focus on the time to recovery in the platelet count, few studies have examined resolution of dengue symptoms, hospitalization period or viral load decrease [5,7]. However, the lack of uniformity in study designs does not allow for conclusive determination and makes establishment of clinical guidelines for use of CPLE extremely difficult.
6.2 Differences in Dosage and Preparation of Extract
The dosage of CPLE is not standardised, and there are no satisfactory preparation conditions; this results in the inconsistency of the results:
Variability in extraction methods: For example, studies have used fresh leaf juice, dried leaf capsules, aqueous extracts, as well as ethanol-based preparations and each with a different bioactive compound concentration [2,5]. Differences in dosage: Dosages that were reported were from 500 mg to 1100 mg per day in capsule form and from 5 mL to 30 mL daily in liquid form [1,2]. Lack of pharmacokinetic studies: The CPLE absorption, metabolism and elimination are not well studied in the literature and it is thus undue, to determine the right therapeutic dose and frequency of CPLE use [12]. However, treatment efficacy has been demonstrated by CLE but formulations and dosing guidelines do not exist, resulting in lack of consistency and the difficulty of replication of therapeutic efficacy across various clinical settings.
6.3 Lack of Large-Scale Randomized Trials
Although there are a few small-scale studies that have yielded promising results, there is a profound gap of large, multicenter, randomized controlled trails (RCTs) that confirm the findings. Studies in most of these studies have small sample size (n < 200), thus the statistical power and generalizability is at a limit [2,5]. Very few studies with long spacing follow-up are known to test sustained benefits, potential side effects and recurrence rates [4]. Due to their location in dengue endemic countries (India, Malaysia, Indonesia), lack of data from other geographic region has led to questions regarding the external validity [2]. Given that large scale, multi country trials with rigorous methodologies as well as control over a placebo are needed to confirm the safety and efficacy of CPLE for widespread clinical acceptance.
6.4 Regulatory and Standardization Issues
Lack of regulatory oversight is a challenge to integration of CPLE into mainstream clinical practice:
Lack of standardization: Herbal extracts, unlike pharmaceutical drugs, do not have any regulatory guidelines for purity and potency, as well as formulation [12]. Variability in commercial products: CPLE supplements that are sold over the counter are of great variability in composition and concentration and thus their therapeutic effect varies accordingly [13]. Limited FDA and WHO approval: No global health authority has approved, for dengue, CPLE as a treatment so it cannot be integrated into national health systems [4]. To realize the potential of CPLE in clinical practice, standardized extraction protocols, quality control measures, and regulatory approvals are required to assure safety and effectiveness of CPLE. Despite the encouraging therapeutic potential of Carica papaya leaf extract in managing dengue induced thrombocytopenia, there are limitations and challenges associated with the application of this extract in managing the life-threatening complication of dengue. Things such as study design variability, inconsistent dosing and preparation, lack of large scale RCTs and regulatory concerns are also reasons for doubt. Future research should focus on:
1. Confirming efficacy and safety through conducting large and well-designed RCTs.
2. Establishing standardized methods of the extraction, and the corresponding dosages, in order to achieve consistent clinical outcomes.
3. Regulatory guidelines needed for commercial CPLE formulations.By addressing these challenges, CPLE could become a widely accepted, evidence-based adjunct therapy for dengue patients, offering a natural, cost-effective alternative to conventional treatments.
7. Future Directions and Recommendations
The Carica papaya leaf extract (CPLE) has been shown to be promising in the treatment of dengue associated thrombocytopenia in preclinical and clinical studies. However, as yet, we do not know whether or not it works and how safe it is, and more research and development is needed to answer these questions. The future direction for use of the extract, which should be conducted, is high quality clinical trials, standardization of extract preparation, investigation of combination therapies, development of the extract for commercial use as adjunct in the treatment of dengue.
7.1 Need for More Robust, Multi-Center Clinical Trials
Though several small studies involving CPLE’s administration in dengue patients have shown its capacity to boost platelet counts, large scale, multiple center randomized control trials (RCTs) need to confirm these findings: Expanding sample size: Most of the existing studies include very small number of participants (n < 200) that limits statistical power. However, to be more generalizable, it requires larger trials [2,4]. Long-term safety evaluation: A focus of current research is on short term recovery of the platelets, and there are few data on long term effects or toxicity [1]. Future studies should monitor the adverse effects for prolonged periods. Multi-center studies: Applicability to other geographical regions has been limited by the fact that most trials have been conducted in a few dengue endemic countries (India, Malaysia, Indonesia). To determine global effectiveness, further work is needed with different populations and healthcare settings [2].
Placebo-controlled, double-blind trials: However, they say that many studies have poor control groups that may lead to bias. There is a need for definitive conclusions to be established by high quality, double-blind RCTs compared with CPLE and standard care [5]. As a scientifically validated treatment for dengue related thrombocytopenia, CPLE could be conducted by large, well-structured clinical trials.
7.2 Standardization of Extract Preparation and Dosage
The main obstacle in establishing the spread of CPLE via common medicine is none standardization in the method of the extraction, formulation, and dosage:
Consistent bioactive compound concentrations: However, different studies use different forms of extract (capsules, fresh juice, ethanol extracts, and so on) and hence, inconsistent therapeutic effects. It is important to standardize the most ideal preparation method [5,13].
Determining optimal dosage: In capsule form, the reported doses are between 500 mg and 1100 mg per day or in liquid form of 5 and 30 mL daily; no clear definition of optimal therapeutic dose has been reported. Pharmacokinetic studies are required to establish safe and utilizable dosing guideline [2,7].
Quality control measures: Available CPLE supplements are highly purified, highly potent and of very different composition. Consistency in the manufactured products should be guaranteed by regulatory bodies in the implementation of quality assurance protocols [12]. It would increase the clinical reliability and safety of the formulation of CPLE by developing it into a standardized, pharmaceutical grade formulation.
7.3 Exploration of Combination Therapies with Conventional Treatment
CPLE has shown several desired effects in vitro and an vivo, that is anti-inflammatory, platelet enhancing factors and antivirals. It was also shown that it has the potential to synergise with conventional dengue treatments and such synergy will be explored in future research: Combining CPLE with intravenous (IV) fluids: Hydration therapy is the main component of the dengue management. In more ways, this investigation could be essential as it can potentially show if not only can CPLE help with the recovery, but if used with IV fluids can offer a more effective way to treat this infection [1].
Adjunct to platelet transfusion: Platelet transfusions are reserved for severe thrombocytopenia and thus, studies should consider whether CPLE would decrease the numbers required to be transfused or increase the number of days that the platelets survive in circulation [5].
Potential antiviral properties: These were also reported to inhibit dengue virus replication by blocking viral proteases [8]. drug combination (antiviral drugs) determines whether disease duration can be shortened and viral clearance improved, and whether it interferes with the strategy for the treatment of asymptomatic HIV infection.
Interaction with immunomodulatory agents: As dengue is an immune mediated platelet destruction, the combination of CPLE with immunomodulatory therapies (corticosteroids, monoclonal antibodies) may be tested to enhance platelet recovery and decrease immune suppression [9]. Researchers would explore CPLE in conjunction with standard dengue treatments to find other more effective, integrative treatment strategies.
7.4 Potential for Commercial Development as an Adjunct Therapy
As a natural CPLE source, with affordable price and the promising efficacy, CPLE has a potential for commercial development as an adjunct therapy for managing dengue:
Formulation into standardized herbal medicine: As a natural CPLE source, with affordable price and the promising efficacy, CPLE has a potential for commercial development as an adjunct therapy for managing dengue [13].
Inclusion in national dengue treatment guidelines: If these large clinical trials confirm that efficacy, regulatory bodies such as the World Health Organization (WHO) and the Food and Drug Administration (FDA) could use to endorse CPLE as a complementary treatment [4]. Integration into public health programs: In dengue endemic regions, the government health initiatives could take CPLE as a cheap, natural intervention to attenuate dengue complications [2]. Potential expansion to other platelet disorders: Since CPLE stimulates platelet production, its use could possibly be extended from dengue, to cancer chemotherapy induced thrombocytopenia (CCTXN) or idiopathic thrombocytopenic purpura (ITP) [9]. Application of research, regulation approvals and production, will lead to CPLE becoming a widely used, evidence-based therapy in modern medicine. Once the research and regulatory advances progress further, CPLE could serve a breakthrough herbal therapy for dengue-induced thrombocytopenia and might be a safe, cheaper and better option than the conventional methods of therapy.
CONCLUSION
Summary of Findings on Efficacy and Safety
The existing preclinical and clinical studies are reviewed and it is suggested that Carica papaya leaf extract (CPLE) has a big potential to treat dengue induced thrombocytopenia. Studies in clinical trials have time and time again found that dengue patients who take dengue CPLE can recover faster than patients on a placebo or the established supportive care. It is also shown to possess anti-inflammatory; immunomodulatory; and potential antiviral effects that could facilitate better recovery outcome [8,9]. Most such studies also report minimal adverse effects and no significant toxicity in clinical trials Nevertheless, variations among studies in dosage, formulation and extraction method allow for the establishment of no standard treatment protocols [12].
Clinical Relevance and Practical Implications
Considering the global burden of dengue fever, especially in endemic areas such as Latin America, Southeast Asia and South Asia, an economical and effective adjunct therapy, such as CPLE, could be of a great value to current dengue management strategies.
Key clinical implications include:
But for CPLE to be broadly used, it simply must be randomized controlled trials in multiple centers on the scale needed to confirm benefits, standardize dosing recommendations and secure regulatory approval.
Final Remarks on the Potential of Carica papaya Leaf Extract in Dengue Management
However, CPLE’s efficacy, while promising, was limited in currently available research. Nevertheless, CPLE has been shown to increase platelets and facilitates dengue recovery. Because of its natural origin, low cost and minimal side effects, dengue could be treated, or an adjunctive therapy for dengue management, with oral alternative. But it further needs:
1.Confirm efficacy through large, well-designed clinical trials.
2. Establish standardized extraction methods and dosing guidelines.
3.Explore combination therapies with conventional dengue treatments.
4. Secure regulatory approvals for clinical use.
Although this gap must be addressed in order to validate, scientifically, the use of Carica papaya leaf extract as a complementary therapy yielding clinical outcomes, the use of such leaf extract could become widely accepted and acceptably used by global millions of dengue patients.
REFERENCES
Vishu Paradkar, Manas Thakre*, Akansha Bhandarkar, Efficacy of Carica Papaya Leaf Extract in Treating Dengue-Induced Thrombocytopenia: A Review of Clinical and Preclinical Studies, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 4, 222-234. https://doi.org/10.5281/zenodo.15124379
10.5281/zenodo.15124379
