RESEARCH ON PAPAYA LEAVES TO DENGUE (Part 2)

RESEARCH RELATED DONE to investigate the platelet increasing property of Carica Papaya Leaves Juice (CPLJ) in patients with Dengue Fever (DF) recently. An open labeled randomized controlled trial was carried out on 228 patients with DF and Dengue Haemorrhagic Fever (DHF). Reported that approximately half the patients received the juice, for 3 consecutive days while the others remained as controls and received the standard management. Their full blood count was monitored 8 hours for 48 hours. Comparison of mean platelet count between intervention and control group showed that mean platelet count in intervention group was significantly higher than control group. This article in "Anim Agriculture Technology'' blog I am happy to share a study regarding this research. 

The results stated that a total of 145 patients were recruited into the interventional group while 145 patients were recruited into the control group. At the end of the study, 111 patients from the interventional group and 117 controls were included in the statistical analysis. Sixty-two patients were excluded from the analysis as 38 patients were lost to followup and 24 patients had incomplete data (missing results due to sample rejection). The demographic characteristics and baseline biochemistry investigation of respondents by treatment. In terms of dengue status, all patients recruited had either dengue NS1 or IgM or both detected, while the percentage distribution of the dengue serotypes among them was DEN1 (30.4%), DEN2 (28.4%), DEN 3 (20.6%), and DEN 4 (20.6%). Hence, all serotypes were well represented in the study. Stydy also found thar presents the multiple comparisons of mean platelet count 8 hours after admission with mean platelet count at 16, 24, 32, 40, and 48 hours after admission for interventional and control group Multiple paired t-test was conducted to demonstrate if there was any significant difference in mean platelet count for each comparison. Hence, Bonferroni correction was applied to reduce the possibility of rejecting a true null hypothesis (committing a type 1 error). Based on the number of patients recruited with complete data (111 patients from the intervention group and 117 control), the power of study was 87.0% (standard deviation of platelet count of 40,000, type I error probability of 0.01, and the true difference in mean platelet count of 20,000 between the intervention and control group). Overall, there was a significant increase in mean platelet count over 40 hours in both groups.  The study conducted shows that there is a rationale behind the use of CPLJ in the treatment of some of DF and DHF. It is definitely worth investigating this plant for its potential medicinal benefits. With rapid urbanization and global travel leading to drastic demographic changes, dengue is a threat to almost 40% of the world's population. There is still no specific treatment for dengue. Previous attempts to identify a potential antiviral for the treatment of dengue has been faced with several challenges such as the presence of four distinct viral serotypes which frequently undergo mutations, finding an appropriate model for infection and protective action of a given drug as well as yield interesting therapeutic avenues for tailored response modifier drugs. The current available mouse model (AG129) available has its limitations such as low viral load and a short period of viraemia. The journey to drug discovery through the study of immune-modulatory effects against dengue infection lies on the research of generic compounds and natural products.

Research groups around Asia have attempted to study the efficacy of CPLJ in rapidly increasing platelet counts in DF as well as DHF induced thrombocytopenia but there has been no conclusive evidence drawn from those studies. Dengue is generally a self-limiting disease and the disease induced thrombocytopenia usually reverses itself after taking a slight dip during the phase of defervescence. However, a significant number of patients succumb to the disease during the thrombocytopenic period. Many mechanisms come into play during the critical phase of the disease to help reverse the disease state at this point. Animal studies in elucidating safety data have been conducted on normal Sprague Dawley rats using freeze dried CPLJ; however, no significant increase in platelet count was observed among the rats given the juice and the rats kept as control. This was probably due to the fact that the juice was freeze dried and certain essential compounds could have been lost during the process of freeze drying or perhaps the right disease model was not used for the study. Haematocrit level, which is an important parameter which is usually monitored to determine the rate of improvement in haemoconcentration, was found to be significantly reduced in both groups of people. White Blood cell count which is found to be reduced in viral infections was also found to increase in both groups.

The RNA was extracted from the blood of the patients recruited and gene expression of two genes, namely, the ALOX 12 and the PTAFR which were conducted so far. There was a 15-fold increase in the ALOX 12 gene activity among the patients in the experimental group as compared to those in the control group at the end of the 3 days. ALOX 12 is known to be associated with increased megakaryocyte production as well as its conversion to platelets through 12-HETE mediated pathway which in turn leads to increased platelet production. A study was conducted at the Royal College of Surgeons, Ireland, to determine the platelet specific genes. The Alox 12 gene was highly expressed in platelets and found to be a platelet specific gene by McRedmond et al. A study conducted in Temple University School of Medicine, Philadelphia provided evidence that ALOX12 is a direct target of transcription factor RUNX1 in megakaryocytes and platelets. RUNX1 is a transcription factor that regulates the expression of haemopoietic-specific genes. When there is RUNX1 haplodeficiency, it affects overall haemopoiesis and hence, ALOX 12 expression in platelets is decreased. There was also an agonist-induced decreased 12-HETE production in platelets with the decrease in ALOX 12 expression. This provides further evidence that platelet production is associated with ALOX 12 expression. claim that the juice consumption during the course of dengue infection has the potential to induce the rapid production of platelets. This was clearly demonstrated by the significant increase in the mean platelet count after 40 hours and 48 hours of juice consumption. The PTAFR gene which is known to be responsible for increased platelet production and aggregation was expressed 13.42-folds among the patients who consumed the juice as compared to the control group indicating that the juice had played an important role in addressing the arresting of bleeding tendencies among these patients. A study conducted in Brazil showed that injection of Platelet Activating Factor (PAF/PTAFR) in mice induced an increase in platelet count. However, after a certain level, further administration of PAF failed to induce platelet production indicating autosensitization. These findings show that PAF/PTAFR can induce the release of platelets which may be relevant to thrombocytosis . We are currently investigating many other genes to determine other roles of the CPLJ other than its role in platelet production and activation. As all plants C. papaya leaves are rich in compounds of different properties. Further studies need to be conducted before determining the inflammatory pathways affected by the juice, unopposed. However, it can be concluded that the administration of CPLJ in DF and DHF is safe and does induce the rapid increase in platelet count. It may play a valuable role in the management of DF in the near future. Thanks...

By,

M Anem,

Senior Agronomist,

Malacca City,

Malacca,

Malaysia.

(Febuary 2025).