Papaya Leaf Tea: Oral Enzyme Therapy

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Oral Enzyme Therapy combines various proteases (protein dissolving enzymes) in order to prevent disease, assist the body to fight various cancers, and lessen the negative effects of chemotherapy and radiation. The proteolytic enzymes papain and chymopapain are found naturally in the papaya leaf.

Memorial Sloan Cancer Center Site explains possible Mechanism of Action:
“PEs (proteolytic enzymes) are thought to exert immunomodulatory effects by causing increased release of reactive oxygen species by polymorphonuclear leukocytes (7) or by production of tumor necrosis factor-alpha and interleukins IL-6 and IL-1B that cause cytotoxic effects (1) (2). The antiangiogenic effects that papain exhibits in VEGF-activated human endothelial cells is concentration-dependent and likely due to interference with AKT, MEK1/2 and SAPK/JNK phosphorylation (15). Bromelain has been shown to lower the tumorigenic/metastatic capacities of sarcoma L-1 cells (3). It also inhibited glioma cell migration and invasion by affecting expression of integrins, necessary for cellular migration and invasion (5). In B16 murine melanoma models, PEs inhibited metastasis by reducing expression of CD44 and CD54 molecules (6).”
http://www.mskcc.org/cancer-care/herb/proteolytic-enzymes

One example of a clinical trial that documented the lessened effect of radiation on cancer patients who took oral enzyme therapy is below:

Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects.

Authors
Dale PS1, Tamhankar CP, George D, Daftary GV.
Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S29-34.
http://www.ncbi.nlm.nih.gov/m/pubmed/11561869/

“CONCLUSIONS: In patients with locally advanced cancer of the uterine cervix, oral enzyme therapy was found to be effective in significantly reducing radiation therapy-related side effects such as genitourinary symptoms, subcutaneous changes and reactions of the vaginal mucosa.”

In another clinical study, oral enzyme therapy was an effective complementary treatment for patients undergoing chemotherapy and radiation:

“…CONCLUSION: Complementary treatment of colorectal cancer patients with OE improves their quality of life by reducing both the signs and symptoms of the disease and the adverse reactions associated with adjuvant antineoplastic therapies. This epidemiological retrolective cohort analysis provides evidence that patients may also benefit by a prolongation of survival time. OE were generally well tolerated.”

PMID 11561874 [PubMed – indexed for MEDLINE]

Influence of a complementary treatment with oral enzymes on patients with colorectal cancers–an epidemiological retrolective cohort study.

Authors
Popiela T1, Kulig J, Hanisch J, Bock PR.
Cancer Chemother Pharmacol. 2001 Jul;47 Suppl:S55-63.

http://www.ncbi.nlm.nih.gov/m/pubmed/11561874/?i=3&from=/11561869/related

Papaya Leaf Tea as a natural oral enzyme therapy solution may contain a more complete set of necessary compounds to allow for absorption by the body. This theory is presented in part in the blog below:

https://papayaleaves.wordpress.com/2014/10/10/sset-of-minerals-in-papaya-leaf-may-explain-medicinal-value/

Picture above; Mr Jacob Jeyasekaran
Of the Julia Ruffin Project

The Julia Ruffin Project promotes, researches, and test-farms papaya leaf tea.

#cancer

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Papain in Papaya Leaf has Potential for Tumors; Breast Cancer

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The Scottish Doctor John Beard discovered that by injecting the proteases taken from a young calf into a cancerous human tumor his patients could be cured.

Research in Brazil on the protease papain (can be taken from the raw papaya fruit or the leaves of the papaya tree) shows a potential contemporary use of papain on implant surgery to prevent painful fibrous buildup.

This is similar action to Dr Beard’s thinking centuries ago to inject a cancerous, fibrous tumor with a protein dissolving enzyme. It seems this action may also have systemic effect via the bloodstream, as Dr Nam Dang proved similar effect on tumors as well from the action of papaya leaf tea.

See the Brazilian study from 2008:

INTERNATIONAL JOURNAL OF BIOLOGY AND BIOMEDICAL ENGINEERING

“The capsular contracture is the most common adverse effect after breast implant [1]. Fibrotic tissue promotes compression around the implant which distorts and deforms the mass which then compromises the aesthetic result and is associated with painful symptoms [2]-[4]. The development of a fibrotic capsule around foreign material is a physiologic reaction of the organism to protect itself from material it does not recognize [5]. The severity of capsule contracture is directly related to the degree of the local inflammatory reaction [6] and does not depend on the implant surface employed [7]. Although it is not clear the pathogenesis of capsular contracture, this phenomenon seems to be multifactorial [8].
Currently, there is no effective preventive measure for capsule contracture [8]. The conventional treatment may be surgical, by capsulectomy (or capsulotomy) or implant replacement and pharmacological using steroids, anti- leukotrienes, anti-TGF-β, antibiotics or antiinflamatories [2], [3].
Up to now there has been no accurate and reproducible pathologic model for examining capsular contracture [9]. This study assumes that eventual interference by papain (PA) on normal healing could be useful in further studies of a more complex model with induced capsule contracture [9].
Some authors have speculated on the possible modulator action of certain proteolytic enzymes present around the implants in the early stages of healing [10], [11].
Papain is a thiol endopeptidase plant whose activity is similar to the lysosomal cathepsin B enzyme with fibrinolytic and proteolytic action on the normal healing mechanism [12].
It has been suggested that the papain could be helpful when used locally around the implant at the surgical procedure, promoting tissue repair with less fibrotic tissue, thus avoiding the capsule contracture.
The aim of this study was to investigate the papain effects on the fibrous capsule thickness, collagen fibers density and myofibroblasts around textured implants in rats.
Abstract— Objective: To study the tissue repair around the textured mammary implants under the action of papain (PA). Conclusion: The papain drug decreased the fibrous capsule formation around the textured silicon implants in rats.”

The papain local depot impairs the capsule fibrous healing around textured silicone implants in rats.
Marcio Moreira, Djalma José Fagundes, Sanderland José Tavares Gurgel

http://www.naun.org/main/NAUN/bio/19-152.pdf

Papain in the Papaya Leaf May Drive Cancer Cell Attack

Traditionally the enzyme papain, a protease unique to papaya, has been harvested from the unripe fruit. The leaves are also packed with papain, but in a more consumable state as tea.

Enzyme scientists Beard and Howell showed the effect of proteases (like papain) on cancer and other disease. Theoretically the protein-dissolving enzyme papain eats the protein coating around the cancer cell.

The Brazilian research below on papain, cancer, ecoli and toxicity below is of interest.

http://www.hindawi.com/journals/bmri/2010/197898/

Journal of Biomedicine and Biotechnology
Volume 2010 (2010), Article ID 197898, 8 pages
http://dx.doi.org/10.1155/2010/197898
Research Article
Genotoxic and Cytotoxic Safety Evaluation of Papain (Carica papaya L.) Using In Vitro Assays
Claudia R. da Silva,1,2,3,4 Marcia B. N. Oliveira,1,2 Ellen S. Motta,2 Gabriella S. de Almeida,1,3 Leandro L. Varanda,1,3 Marcelo de Pádula,3,4 Alvaro C. Leitão,3 and Adriano Caldeira-de-Araújo1,2
1Laboratório de Análise de Toxicidade em Fitoterápicos, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, 20551-030 Rio de Janeiro, RJ, Brazil
2Laboratório de Radio e Fotobiologia, Departamento de Biofísica e Biometria, Instituto de Biologia Roberto Alcantara Gomes, UERJ, 20551-030 Rio de Janeiro, RJ, Brazil
3Laboratório de Radiobiologia Molecular, Instituto de Biofísica Carlos Chagas Filho, UFRJ, 21941-902 Rio de Janeiro, RJ, Brazil
4Laboratório de Diagnóstico Molecular e Hematologia, Departamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, UFRJ, 21941-902 Rio de Janeiro, RJ, Brazil
Received 23 November 2009; Revised 16 March 2010; Accepted 16 March 2010
Academic Editor: Michael Cunningham
Copyright © 2010 Claudia R. da Silva et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Papain, a phytotherapeutic agent, has been used in the treatment of eschars and as a debriding chemical agent to remove damaged or necrotic tissue of pressure ulcers and gangrene. Its benefits in these treatments are deemed effective, since more than 5000 patients, at the public university hospital at Rio de Janeiro, Brazil, have undergone papain treatment and presented satisfactory results. Despite its extensive use, there is little information about toxic and mutagenic properties of papain. This work evaluated the toxic and mutagenic potential of papain and its potential antioxidant activity against induced- oxidative stress in Escherichia coli strains. Cytotoxicity assay, Growth inhibition test, WP2-Mutoxitest and Plasmid-DNA treatment, and agarose gel electrophoresis were used to investigate if papain would present any toxic or mutagenic potential as well as if papain would display antioxidant properties. Papain exhibited negative results for all tests. This agent presented an activity protecting cells against -induced mutagenesis.
1. Introduction
The belief that natural medicines are much safer than synthetic drugs has caused exceptional growth in human exposure to natural products, as plants, phytotherapeutic agents, and phytopharmaceutical products. This fact has lead to a resurgence of scientific interest in their biological effects. In most countries there is no universal regulatory system insuring the safety and activity of natural products and they had not been sufficiently investigated analytically or toxicologically [1].
Herbal medicines can be potentially toxic to human health. In this way, scientific research has shown that many plants used in traditional and folk medicine are potentially toxic, mutagenic, and carcinogenic [1–9].
Carica papaya L. (C. papaya L.) is the most important species within the Caricaceae genus, being widely cultivated for consumption as a fresh fruit, as juices, and as dried and crystallized fruit. Papaya also has several industrial uses [10–12]. Biochemically, its leaves and fruits are complex, representing sources of several proteins and alkaloids with important pharmaceutical, medical, and industrial applications. The juice is used for curing warts, cancer, and tumors. Leaves have been poultice into nervous pain. The hypoglycemic effect has been reported. It is used to treatment of infected wounds, malignant tumors, and burns [10].
The juice of ripe papaya displayed in vivo and in vitro activities against oxidative stress [13, 14]. It is an efficient scavenger of highly reactive hydroxyl radicals () formed during 60Co irradiation [13].
The green (unripe) papaya, which is rich in papain, is used for dressing of ulcers. This treatment is described as effective and it is recommended in preference to other dressings for chronic skin ulcers. It has been used in many countries such as England, Nigeria, Ghana, Gambia, India, and Jamaica [15]. In spite of its extensive use, the following disadvantages were described, as problems concerning the availability of green papaya and difficulties in preparing and storing papaya [15].
The demonstration of the phytotherapeutic potential of a given species is a difficult task, since plant extracts consist of complex mixtures of major compounds, minor concomitant agents, and fibers, which can all be involved in the observed effects. Thus, given the difficulties in determining the contribution of a specific substance in the biological effects exerted by whole extracts, the aim of this work was the study of papain isolated from C. papaya, which possesses vast application in medicine.
Papain, a purified protein extracted from the latex of the unripe papaya, is widely used by Brazilian nurses in traditional medicine. It can be an alternative to green papaya and it can be used as phytotherapeutic agent in the treatment of pressure ulcers, gangrene, eschars, and as a debriding chemical agent to remove damaged or necrotic tissue [16]. Papain is sometimes used in association with hydrous magnesium silicate (talc). Its benefits in these treatments are deemed effective, since more than 5000 patients at the Pedro Ernesto University Hospital, at Rio de Janeiro/Brazil, have undergone papain treatment and presented satisfactory results [16]. Despite its extensive use, there is little information about toxic, mutagenic, and antioxidant properties of papain itself or even unripe papaya, which contains high concentration of papain [12].
Short-term tests have been used to check compounds for their ability to induce lesions in DNA, which may lead to genotoxicity, cytotoxicity, or mutagenicity. The experimental techniques using microbial cells such as Escherichia coli (E. coli) and Salmonella typhimurium (S. typhimurium), as well as assays using DNA as the target molecule, allowed the development of new tools to investigate toxic and mutagenic potentials of many physical and chemical agents and their correlation with the effects in eukaryotic systems [1, 17–20].
Hydrogen peroxide (H2O2) is a normal cell metabolite formed in several enzymatic and nonenzymatic reactions. H2O2 leads to oxidative stress, mutagenicity, loss of cell function, and ultimately apoptosis or necrosis [18, 21, 22]. In E. coli, a major component of the H2O2 toxicity is attributed to DNA damage mediated by the Fenton reaction, which generates reactive oxygen species (ROSs), such as [21–27]. E. coli possesses a number of antioxidant enzymes and DNA repair activities encoded by several genes (xthA, mutY, oxyR, among others) to counteract DNA damage caused by oxidative stress. Mutant strains lacking one or more of those genes are usually hypersensitive to H2O2 [18, 21, 22, 26]. So, Blanco and coworkers (1998) designed a series of E. coli WP2 tester strains (IC203 up to IC207, used in this study), which are useful for the screening of mutations resulting from oxidative stress as well in studies on antioxidants [18].
It is well documented that oxidative damage has been implicated in various systemic chronic diseases such as cancer, Alzheimer’s disease, rheumatoid arthritis, cardiovascular disease, cataracts, and other ageing processes. Reactive oxygen species (ROSs) are essential intermediates in oxidative metabolism. Nonetheless, when generated in excess, ROSs in various active forms can damage tissues [28].
In recent years, there has been a considerable interest in finding natural antioxidants from plant materials to replace synthetic molecules. Data from both scientific reports and laboratory studies show that plants contain a large variety of substances that possess antioxidant activity. Phytochemicals with antioxidant effects include some cinnamic acids, coumarins, diterpenes, flavonoids, lignans, monoterpenes, phenylpropanoids, tannins, and triterpenes. Natural antioxidants occur in all higher plants and in all parts of the plant (wood, bark, stems, pods, leaves, fruit, roots, flowers, pollen, and seeds) [29, 30].
The present work was carried out to evaluate the potential cytotoxic and mutagenic effects of papain using E. coli strains and plasmid DNA. In addition, we have also investigated papain antioxidant and antimutagenic activities against oxidative stress induced by H2O2.