Expert on Papaya Leaf Suggests Trials for Ebola

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Dr Sanath Hettige, long-time researcher on the effects of papaya leaf on Dengue Fever, proposed publicly in the BMJ on October 2014 evidence to support and request a coordinated clinical trial “worth trying” on papaya leaf to combat Ebola fever.

The reasons for his proposal are summarized by the following research evidence: (excerpt from the BMJ 2014;349:g4997)

PAPAYA LEAF EXTRACT FOR EBOLA PATIENTS – WORTH TRYING

Papaya leaf extract is now proven to be effective for dengue fever. (Not merely by increasing the platelet count). The pathology of Ebola virus seems to be similar to that of Dengue fever. Especially when considering the endothelial dysfunction and the hemorrhagic stage. Therefore I strongly feel that Papaya leaf extract will benefit Ebola patients. Researches have shown many beneficial effects of carioca papaya leaf extract on human body which will benefits to fight viral infections. They include:-

1) Stimulation of the hematopoietic system which stimulates Platelet production, White Blood Cell production and Red Blood Cell production (1, 2, 3, 4).
2) In-vitro erythrocyte membrane stabilization properties (5, 6).
3) Stimulates the immune system which enhances the activity against the viral infection (7).
4) Direct anti-viral activity on dengue virus (8).
5) Animal studies have shown that it prevents chemically induced capillary leakage in Mice (9).
6) Preliminary studies conducted by Dr. Sanath Hettige have shown that Carioca papaya leaf extract prevents the drop in serum-Albumin levels in Dengue patients.
Randomize open label case control trial is on going to find out whether Carioca papaya leaf extract can prevent fluid leakage in Dengue fever (10).
7) Many toxicology studies have not shown any significant toxic effects even at higher doses (11).

Documented by studies below:

1. Hettige, S. (2008). Salutary effects of carica papaya leaf extract in dengue fever patients – pilot study. Sri Lankan Family Physician. 29 (1), p17-19.

2. Hettige.S Dengue: an escalating problem /bmj/reply/2011/07/14/fe4b88000f32cb7b.atom.

3. Subenthiran, S., Choon, T.C., Cheong, K.C., Thayan, R., Teck, M.B., Muniandy, P.K., Afzan, A., Abdullah, N.R., Ismail, Z. (2013). Carica papaya leaves Juice significantly accelerates the rate of increase in platelet count among patients with Dengue fever and Dengue haemorrhagic fever. Evidence based complementary and alternative Medicine. 2013 (ID616737), 7pgs

4. Sathasivam, K., Ramanathan, S., Mansor, S. M., Haris, M. R. M. H., Wernsdorfer, W. H. (2009). Thrombocyte counts in mice after the administration of papaya leaf suspension. Wien Klin Wochenschr-The middle European Journal of Medicine. 121 (3), p19-22.

5. Ranasinghe, P., Ranasinghe, P., Abesekara, W.P.K.M., Premakumara, G.A.S., Perera, Y.S., Gurugama, P., Gunathilake, S.B. (2011). In-vitro erythrocyte membrane stabilization properties of carica papaya L. leaf extracts. 3rd international conference on medicinal plants and herbal medicines. Colombo, Sri Lanka.

6. Imaga, N.O.A., Gbenle, G.O., Okochi, V.I., Akanbi, S.O., Edeoghon, S.O., Oigbochie, V., Kehinde, M.O., Bamiro, S.B.. (2009). Anitisicking property of carica papaya leaf extract. African Journal of Biochemistry Research . 3 (4), p102-106.

7. Otsuki, N., Dang, N. H., Kumagai, E., Kondo, A., Iwata, S., Morimoto, C. (2010). Aqueous extract of carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects. Journal of Ethnopharmacology. 127, p760-767.

8. Flavonoid from carica papaya inhibits ns2bnS3 protease and prevents Dengue 2 viral assembly.
Senthilvel P, Lavanya P, Kumar KM, Swetha R, Anitha P, Bag S, Sarveswari S, Vijayakumar
V, Ramaiah S, Anbarasu A.Bioinformation.2013 Nov 11;9(18):889-95. PMID:24307765 PubMed]

9. Hettiarachchi, K., initials Year of publication, Guinea pig rats fed papaya leaf juice concentrate show intriguing results – Tests recording platelet count rise may give hope for dengue patients. Sunday Times, 15/07/2012. In press.
.
10. Controlled trial on effect of Carica papaya leaf extract on patients with Dengue Fever – SLCTR Registration Number SLCTR/2013/005.

11. Halim, S.Z., Abdullah, N.R., Afzan, A., Rashid, B.A.A., Jantan, I., Ismail, Z. (2011). Study of acute toxicity of carica papaya leaf extract in sprague dawley rats. Journal of Medicinal Plants Research. 5 (2), p1867-1872.

http://www.bmj.com/content/349/bmj.g4997/rr/778249

“The BMJ’s [British Medical Journal] vision is to be the world’s most influential and widely read medical journal. Our mission is to lead the debate on health and to engage, inform, and stimulate doctors, researchers, and other health professionals in ways that will improve outcomes for patients. We aim to help doctors to make better decisions.”

Reference our blog suggesting the same from Sept 1, 2014:
https://papayaleaves.wordpress.com/2014/09/01/researchers-advise-papaya-leaf-for-immunity-disorder-with-similarities-to-ebola/

#ebola

Researchers advise Papaya Leaf for Immunity Disorder With Similarities to effect of Ebola

IMG_1018.GIF
Research by Nam Dang related to the effect of papaya leaf on the immune system may have advice for our ebola crisis. Best of all, papaya leaf is indigenous to these affected African countries and their ethno medicine includes the use of papaya leaf tea.

Follows is an article from 2003 that describes the effect of Ebola on DC cells and also the correlation to diseases such as Dengue H fever (which papaya leaf tea has shown effect). Then the leading research by Nam Dang and others which discusses the effect of carica papaya leaf tea extract and its related effect on the immune system.

Am J Pathol. Dec 2003; 163(6): 2347–2370.
doi: 10.1016/S0002-9440(10)63591-2
PMCID: PMC1892369
Pathogenesis of Ebola Hemorrhagic Fever in Cynomolgus Macaques

Evidence that Dendritic Cells Are Early and Sustained Targets of Infection

Thomas W. Geisbert,* Lisa E. Hensley,* Tom Larsen,* Howard A. Young,† Douglas S. Reed,* Joan B. Geisbert,* Dana P. Scott,* Elliott Kagan,‡ Peter B. Jahrling,* and Kelly J. Davis*
“…While the importance of monocytes/macrophages in EBOV pathogenesis have been well-documented, 28,30,41,43-44 few studies have addressed the importance of DC in EBOV pathogenesis; these cells also play important roles in initiation and regulation of the host immune response. DC are a family of professional antigen-presenting cells, derived from bone marrow, which have the ability to initiate and modulate cell-mediated immune responses. 45,46 Immature DC function as sentinels of the adaptive immune system; they are located in the peripheral tissues where they capture and process exogenous antigens and migrate to regional lymph nodes where they undergo maturation. A wide variety of stimuli, including infectious virus, bacterial antigens, or inflammatory cytokines, can trigger maturation of DC, which is characterized by phenotypic changes, including up-regulation of MHC and costimulatory molecules, and production of IL-12. Presentation of acquired antigen by mature DC leads to T-cell activation. 47,48 Monocytes circulating in the blood could be equally important in the DC response as circulating monocytes counter infection by crossing the endothelial barrier, infiltrating the focus of infection, and developing either into macrophages or DC.
Regarding the importance of EBOV predilection for DC in disease pathogenesis, we speculate that EBOV acts in a manner similar to other viruses that are known to disable the host immune response by attacking and manipulating the very cells that play the most critical roles in initiating the antiviral immune response. DC-tropic viruses such as HIV, 49,50 measles virus, 51-53 LCMV, 54 Dengue, 55 cytomegalovirus, 56 and HSV1 57 have evolved mechanisms to impair the function of DC, thereby enhancing their chance to escape immune surveillance…”
“…The current study demonstrates, for the first time, that DC are early and sustained cellular targets of EBOV in nonhuman primates; that lymphocyte apoptosis is a relatively early event in disease progression, and furthermore, it is the NK cell fraction that is likely lost through increased apoptosis early in the course of infection.”
“…While the importance of monocytes/macrophages in EBOV pathogenesis have been well-documented, 28,30,41,43-44 few studies have addressed the importance of DC in EBOV pathogenesis; these cells also play important roles in initiation and regulation of the host immune response. DC are a family of professional antigen-presenting cells, derived from bone marrow, which have the ability to initiate and modulate cell-mediated immune responses.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892369/

Journal of Ethnopharmacology
journal homepage: http://www.elsevier.com/locate/jethpharm
Aqueous extract of Carica papaya leaves exhibits anti-tumor activity and immunomodulatory effects
Noriko Otsukia,1, Nam H. Dangb,1, Emi Kumagaia, Akira Kondoc, Satoshi Iwataa, Chikao Morimotoa,d,∗
a Division of Clinical Immunology, Advanced Clinical Research Center, The Institute of Medical Science, The University of Tokyo, Japan b Division of Hematology/Oncology, The University of Florida, Gainesville, FL, USA
c Kondo Hospital, 1-6-25, Nishishinhama, Tokushima, Tokushima 770-8008, Japan
d Department of Rheumatology and Allergy, Research Hospital, The Institute of Medical Science, The University of Tokyo, Japan

“It is known that p40, a subunit of IL-12p70, is produced by antigen-presenting cells (APCs), such as monocytes or dendritic cells (DCs). It has also been shown that human IL-12p70 production from DCs is dependent on CD40-40L interactions, whereas p40 pro- duction is not (Cella et al., 1996). Based on these previous reports, it is conceivable that CP extract may modify not only activation of APCs, but also the interaction of T-APCs or T-B cells; namely, CP extract modifies both innate and acquired immunity.”

“…The family of monocyte-chemoattractant proteins, including CCL2 (MCP-1), CCL7 (MCP-3) and CCL8 (MCP-2), are considered to play important roles in the recruitment of monocytes, basophils, plasmacytoid dendritic cells and memory T lymphocytes to sites of inflammation. Their enhanced expression is correlated with vari- ous cytokines, such as IL-1􏰃, TNF-􏰁 and IFN-􏰀 (Viola and Luster, 2008). In addition, patients with high circulating level of CCL2 had significantly higher survival rate than those with low CCL2 pro- duction (Monti et al., 2003)…”

“…Our studies suggest that in addition to its anti- tumor effect, the fact that CP extract enhances production of Th1 type cytokines, such as IL-12, IFN-􏰀 and TNF-􏰁, raises the possibility that CP extract may contribute to the treatment of Th2-mediated allergic disorders, such as allergic rhinitis and bronchial asthma, or as an adjuvant of various vaccines by inducing a shift from Th2 to Th1 type immune response.”

“…Conclusion: Since Carica papaya leaf extract can mediate a Th1 type shift in human immune system, our results suggest that the CP leaf extract may potentially provide the means for the treatment and prevention of selected human diseases such as cancer, various allergic disorders, and may also serve as immunoadjuvant for vaccine therapy.”
http://www.researchgate.net/publication/40448909_Aqueous_extract_of_Carica_papaya_leaves_exhibits_anti-tumor_activity_and_immunomodulatory_effects