Effect Of Fermented Papaya Preparation Research Articles

The anti-ageing and anti-tumour effects of Fermented Papaya Preparation (FPP®) A new neo-adjuvant cancer therapy?

The anti-ageing and anti-tumour effects of Fermented Papaya Preparation (FPP®) A new neo-adjuvant cancer therapy?

Beneficial Effects of Fermented Papaya Preparation (FPP®) Supplementation on Redox Balance and Aging in a Mouse Model.

In recent decades much attention has been paid to how dietary antioxidants may positively affect the human health, including the beneficial effects of fermented foods and beverages. Fermented Papaya Preparation (FPP®) has been shown to represent a valuable approach to obtain systemic antioxidants effect. In this study, we wanted to verify whether FPP® had a clear and scientifically supported in vivo anti-aging effect together with the induction of a systemic antioxidant reaction. To this purpose we daily treated a mouse model suitable for aging studies (C57BL/6J) with FPP®-supplemented water from either the 6th weeks (early treatment) or the 51th weeks (late treatment) of age as compared to mice receiving only tap water. After 10 months of FPP® treatment, we evaluated the telomerase activity, antioxidants and Reactive Oxygen Species ROS plasmatic levels and the telomeres length in the bone marrow and ovaries in both mice groups. The results showed that the daily FPP® assumption induced increase in telomeres length in bone marrow and ovary, together with an increase in the plasmatic levels of telomerase activity, and antioxidant levels, with a decrease of ROS. Early treatment resulted to be more effective, suggesting a potential key role of FPP® in preventing the age-related molecular damages.

Effects of Fermented Papaya Preparation (FPP) on Safety Outcomes in Older Adults - A Short Report of a Placebo-Controlled Clinical Trial.

Fermented Papaya Preparation (FPP®) has shown antioxidative and anti-inflammatory effects in preclinical and clinical aging studies. However, clinical trials are needed to fully evaluate the safety of FPP® in moderate-functioning, generally healthy older adults. In this randomized (9g/day of FPP® or placebo), crossover design study, we enrolled 30 older moderate-functioning older adults (70-100 years old). The participants completed both a treatment and a placebo condition. After eight (8) weeks on each of these regimens (with a 4-week wash-out period in between), participants had their venous blood drawn for assessment of blood chemistries, metabolic outcomes and inflammatory biomarkers. Participants were asked to report any adverse events during the course of the study and complete post-treatment outcome assessments for anthropometric and metabolic outcomes. The major finding related to safety was that there were no adverse changes in blood chemistries and few adverse events in the FPP® condition, which did not differ from placebo (p>0.05). There were no serious adverse effects in either condition. Twenty-nine (29) participants (mean age 78.2±5.3 yrs) completed the study with 94% adherence to the dosing regimen. There were no significant effects of FPP® on anthropometric and metabolic outcomes. In addition, no effects on markers of inflammation were observed. Our trial demonstrates FPP® supplementation is safe and feasible in adults ages 70 years and older. Based on these findings and the positive effects FPP has demonstrated in previous trials, future trials should examine the effects of FPP® in older adults with impaired health status and/or older adults who may have insufficient anti-oxidant protection due to their genetic background.

Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes

Objectives: Nuclear factor erythroid 2-related factor (Nrf2) in astrocyte plays important roles in brain homeostasis. Fermented papaya preparation (FPP) has anti-oxidative, anti-inflammatory, immunoregulatory properties. The present study investigated the effects of FPP on activation of Nrf2 and release of Nrf2-regulated neuroprotective antioxidants and detoxifying molecules.Methods: Primary cultured astrocytes from rat embryos were treated with FPP for 6 or 24 hours. The expression levels of nuclear Nrf2 and cytoplasmic Nrf2-regulated molecules were determined by western blot analysis and immunohistochemistry. Glutathione levels were measured in cells and medium. Dopaminergic neurons were exposed 6-hydroxydopamine (6-OHDA) with/without pre-treatment with FPP astrocytes. Mice were treated orally with FPP for 2 weeks.Results: FPP increased nuclear translocation of Nrf2 in striatal astrocytes, induced up-regulation of NAD(P)H quinine oxidoreductase-1, glutathione-S transferase and hemeoxygenase-1, and increased glutathione level and the percentage of metallothionein-expressing astrocytes. Moreover, FPP suppressed 6-OHDA-induced dopaminergic neuronal loss in not only neuron-astrocyte mixed culture, but also neuron-rich cultures pre-treated with glial conditioned medium. Two-week oral treatment of mice with FPP resulted in Nrf2 activation and increase in glutathione level in striatum.Discussion: The results indicated that FPP enhances the anti-oxidative capacity through activation of Nrf2 in astrocytes, suggesting it may provide neuroprotection in oxidative stress-related neurodegenerative diseases.

The Effect of Fermented Papaya Preparation on Radioactive Exposure.

Exposure to ionizing radiation causes cellular damage, which can lead to premature cell death or accumulation of somatic mutations, resulting in malignancy. The damage is mediated in part by free radicals, particularly reactive oxygen species. Fermented papaya preparation (FPP), a product of yeast fermentation of Carica papaya Linn, has been shown to act as an antioxidant. In this study, we investigated the potential of FPP to prevent radiation-induced damage. FPP (0-100 μg/ml) was added to cultured human foreskin fibroblasts and myeloid leukemia (HL-60) cells either before or after irradiation (0-18 Gy). After 1-3 days, the cells were assayed for: intracellular labile iron, measured by staining with calcein; reactive oxygen species generation, measured with dichlorofluorescein diacetate; apoptosis, determined by phosphatidylserine exposure; membrane damage, determined by propidium iodide uptake; and cell survival, determined by a cell proliferation assay. DNA damage was estimated by measuring 8-oxoguanine, a parameter of DNA oxidation, using a fluorescent-specific probe and by the comet assay. These parameters were also assayed in bone marrow cells of mice treated with FPP (by adding it to the drinking water) either before or after irradiation. Somatic mutation accumulation was determined in their peripheral red blood cells, and their survival was monitored. FPP significantly reduced the measured radiation-induced cytotoxic parameters. These findings suggest that FPP might serve as a radioprotector, and its effect on DNA damage and mutagenicity might reduce the long-term effects of radiation, such as primary and secondary malignancy.

The Antioxidant Effect of Fermented Papaya Preparation in the Oral Cavity.

Oxidative stress has been recognized to play important roles in various diseases, including of the oral cavity. However, nutritional supplementation of antioxidants to ameliorate the consequences of oxidative stress is debatable. One caveat is that oxidative status is often measured under non-physiological conditions. Here, we investigated the antioxidant potential of fermented papaya preparation (FPP), a product of yeast fermentation of Carica papaya Linn, under conditions that prevail in the oral cavity. Employing highly sensitive luminol-dependent chemiluminescence assays, we show that its antioxidant capacity was augmented by saliva (up to 20-fold, p < 0.0001, at 10 mg) and its components (mucin, albumin) as well as by red blood cells (RBC) and microorganisms present in the normal and pathological environment of the oral cavity. Polyphenols are major plant antioxidants. Using the Folin-Ciocalteu's assay, a very low amount of phenols was measured in FPP suspended in a salt solution. However, its suspension in saliva, albumin, mucin or RBC produced up to sixfold increase, p < 0.001, compared with the sum of polyphenols assayed separately. The results suggested that these enhancing effects were due to the solubilization of antioxidant polyphenols in FPP by saliva proteins and the binding to RBC and microorganisms, thus increasing their availability and activity. Copyright © 2015 John Wiley & Sons, Ltd.

The In Vitro and In Vivo Effects Of Fermented Papaya Preparation On Radiation Exposure

BackgroundVarious forms of radiation (radioactive, UV) cause cellular damage, which may lead to premature cell death or accumulation of somatic mutations which may lead to initiation and progression of malignancy. The damage is mediated in part by free radicals, particularly reactive oxygen species (ROS) (Reizenstein, Med Oncol Tumor Pharmacother. 1991;8:229). Fermented papaya preparation (FPP) is a product of yeast fermentation of Carica papaya Linn. FPP has been shown to have anti-oxidative potential by scavenging ROS, as well as by chelating excess iron (Prus & Fibach J Biol Regul Homeost Agents. 2012;26:203). Free iron species, such as the labile iron pool (LIP), participate in chemical reactions that generate ROS (Haber-Weiss and Fenton reactions). We studied the potential effect of FPP in preventing radiation-induced damage to various intracellular components in cultured human fibroblasts and myeloid leukemia (HL60) cells and in mice. MethodsCultured cells, human foreskin fibroblasts and myeloid leukemia (HL-60), were irradiated at various doses (0-18 Gy (Gammacell® 220, MDS Nordion, Excel, Canada). FPP (Osato Research Institute, Gifu, Japan) (10-100 µg/ml, was added either before or after irradiation. The cells were assayed after 1-3 days: Their survival was estimated by CellTiter 96® Aqueous Non-Radioactive Cell Proliferation assay. Apoptosis was determined by staining for phosphatidylserine exposure (by fluorescent Annexin V) and for intracellular uptake of propidium iodide. ROS was measured by staining with dichlorofluoresceine diacetate, and the LIP - with calcein-AM. The effects on the DNA were estimated by measuring 8-oxyguanine (a marker of DNA oxidation), using a fluorescent specific probe, and DNA instability was measured by the “comet assay”, a single-cell gel electrophoresis procedure. Apoptosis, ROS, LIP and 8-oxyguanine were quantified by flow cytometry. Experiments were also carried out on irradiated mice treated with FPP (by adding it to the drinking water) either before or after irradiation. The above mentioned parameters were assayed in their bone marrow cells in addition to determining their survival. ResultsThe results indicated that FPP has significant (P<0.05) ameliorating effects on radiation-induced increase of LIP and generation of ROS, as well as on the generation of 8-oxyguanine and DNA instability. In addition, apoptosis was decreased and consequently the survival of the cells was increased (Fig. 1A). Moreover, about 60% of 14 Gy-irradiated mice that received 100 mg/ml of FPP in their drinking water were still alive after 30 days (Fig. 1B). [Display omitted] ConclusionsFPP was able to protect the short-term effects of radiation on cultured cells by increasing their viability. A similar effect was found in mice. The improvement in DNA instability induced by FPP may influence the long-term effects of radiation, such as the development of secondary leukemia, in patients who receive radiotherapy for their primary tumors. Disclosures:Fibach:Osato Research Institute, Gifu, Japan: Consultancy, Research Funding. Rachmilewitz:Osato Research Institute, Gifu, Japan: Consultancy, Research Funding.

Protective effect of fermented papaya preparation on stress-induced acute gastric mucosal lesion

Stress ulceration is single or multiple mucosal defects with/without bleeding from the gastric mucosa during the physiologic stress. Oxidative stress (OS) is a key pathogenic factor in psychogenic stress-induced acute gastric mucosal lesion (AGML). Fermented papaya preparation (FPP) is reported to have oxygen radical scavenging activity and is effective in OS-related diseases. Here, we investigated the protective effects and the mechanism of action of FPP on stress-induced AGML in rats, induced by water immersion restraint stress (WIRS). Exposure of rats to 6-hour WIRS resulted in the appearance of splinter hemorrhages and mucosal lesions in the stomach. WIRS induced significant increase in lipid peroxidation and decrease in superoxide dismutase-like activity in both the plasma and gastric mucosa. WIRS also significantly increased myeloperoxidase activity together with Nuclear factor-kappaB (NF-kB) activation in gastric mucosa. FPP reduced all the above changes. The results suggest that oral administration of FPP provides protection against WIRS-induced acute gastric mucosal lesions through its anti-oxidative and anti-inflammatory properties.

The Clinical Effects of Fermented Papaya Preparation® (FPP®) on Oxidative Stress in Patients with HbE/ β -Thalassaemia

Background: Red blood cells (RBC) of patients with thalassaemia are under continuous oxidative stress. Fermented papaya preparation® (FPP®) has been shown to have an antioxidative effect and is postulated to reduce the oxidative stress on RBC. Objective: To study the clinical effects of FPP® treatment in patients with HbE/β-thalassaemia on RBC indices, oxidative stress and quality of life scores. Method: Patients with HbE/β-thalassaemia who do not receive regular blood transfusion were included in the study and were given FPP® daily (3gm 2 times a day) for 12 weeks. Peripheral blood samples were obtained at the initiation of the study and at 4-weekly intervals thereafter for a period of 12 weeks. The following parameters were measured: Haemoglobin (Hb), mean corpuscular volume (MCV), reticulocyte count; Oxidation studies: production of reactive oxygen species (ROS) and intracellular glutathione content (GSH), spontaneously and in response to oxidative stress; Quality of life (QoL) at the start and at the end of 12 weeks using health survey questionnaires. Results: Seven patients (5 females and 2 males) were recruited to the study from January 2006 to April 2006. Median age of the study population was 19 years (range 4 to 27yrs). In vitro analyses showed production of significantly less ROS and more GSH following treatment. There was no significant difference in the Hb, MCV, reticulocyte count, clinical parameters or QoL scores. FPP® was well tolerated by all the patients. Conclusion: Although oxidative stress parameters were decreased, FPP® did not have any significant effect on the Hb levels or QoL. Longer studies on larger sample size are required to study the long-term clinical effect of FPP® on clinical parameters in patients with Hb E/β-thalassaemia.

Assessment of the effect of fermented papaya preparation on oxidative damage in spontaneously hypertensive rat brain using electron spin resonance (ESR) imaging and L-band ESR spectroscopy

Oxidative and nitrosative stress mechanisms are widely implicated in the biological and pathological processes involved in aging, cardiovascular and neurodegenerative diseases. Although this has continued to fuel suggestions of the benefits of antioxidant functional foods, in vivo methods for assessing the integrity of this remain limited. A novel electron spin resonance (ESR) technique for evaluating oxidative stress and location of its damage in the brain of spontaneously hypertensive rats (SHR) has been described [Lee, M.-C., et al. (2004). Assessment of oxidative stress in the SHR brain using electron spin resonance (ESR) imaging and in vivo L-Band ESR. Hypertension Research, 27, 485–492]. The reconstructed 2D ESR images of the distribution of a blood brain barrier-permeable nitroxyl spin probe, 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (MC-PROXYL) was used to investigate the ability of fermented papaya preparation (FPP, a product of yeast fermentation of Carica papaya Linn.) to modulate oxidative stress of SHR brain. Supplementation (5–7 months) with FPP (50 mg/rat/day) significantly increased the decay of the ESR images of the MC-PROXYL, suggesting that FPP may have up-regulated the redox defense activity in the SHR brain. Herein is an in vivo noninvasive technique for the study of oxidative stress and its modulation by dietary factors (that may be intended for applications as neuroprotectants in chronic degenerative disease involving loss of brain function).

Erratum: Effect of fermented papaya preparation on dermal and intestinal mucosal immunity and allergic inflammations Keiichi Hiramoto, Mitsuko Imao, Eisuke F Sato, Masayasu Inoue, Akitane Mori. Journal of the Science of Food and Agriculture. 2008, 88: 1151–1157.

AbstractThe original article to which this Erratum refers was published in Journal of the Science of Food and Agriculture.

Effect of fermented papaya preparation on dermal and intestinal mucosal immunity and allergic inflammations

AbstractBACKGROUND: Fermented papaya preparation (FPP) from yeast fermentation of Carica papaya Linn is a natural health food that is commercially sold in Japan. A previous study revealed that FPP has antioxidant activity. However, the effect of FPP on allergic diseases remains unclear. The aim of the present work was to examine whether the oral administration of FPP to mice restrained two types of contact hypersensitivity models, FITC (Th2 type) induced ear and colon oedema, and oxazolone (Th1 type) induced ear and colon oedema.RESULTS: The sensitisation of FITC or oxazolone increased the plasma levels of IL‐10, IFN‐γ, and TNF‐α. Histological examinations revealed a marked increase of IgA, dendritic cells and inflammatory cells in the colon. When the animals were given FPP before sensitisation by FITC or oxazolone, all the events induced by either FITC or oxazolone decreased markedly.CONCLUSION: These results suggest that the oral administration of the FPP may have a therapeutic potential for the prevention of contact hypersensitive immuno‐response. Copyright © 2008 Society of Chemical Industry

Inhibitory Effect of Fermented Papaya Preparation on Hydroxyl Radical Generation from Methylguanidine

We have previously shown that extremely high level of guanidino compounds such as methylguanidine (MG), known as a neurotoxin and also a nephrotoxin, generate reactive oxygen species (ROS) using an electron spin resonance (ESR) technique with spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). In this in vitro study, the inhibitory effect of fermented papaya preparation (SAIDO-PS501:PS-501) on hydroxyl radical (·OH) generation from MG was examined using an ESR spectrometry, and it was found that PS-501 suppressed ·OH generation from MG in a dose-dependent manner. The ID50 value of PS-501 was 8 mg/ml. On the contrary, glucose itself did not suppress ·OH generation from MG up to100 mg/ml, whereas PS-501 almost completely suppressed ·OH generation from MG at a dose of 100 mg/ml. These results imply that PS-501 itself may have a beneficial effect of preventing ROS- and MG-related diseases.

In Vitro and In Vivo Antioxidant Effect of Fermented Papaya Preparation (FPP) on Blood Cells of Beta-Thalassaemia Patients.

In sickle cell anemia (SCD) and thalassemia, although the basic lesions are mutations in the globin genes, the pathophysiology involves oxidative stress-mediated cell damage in the bone marrow (ineffective erythropoiesis due to apoptosis of early erythroid precursors) and in the peripheral blood (chronic hemolysis of mature RBC). In addition, some patients develop thromboembolic complications and recurrent bacterial infections, the etiology of which is related at least in part, to documented oxidative stress in platelets and neutrophils (PMN), respectively. To study the presence and the role of oxidative stress in thalassemia and SCD, we adapted flow cytometry techniques for measuring the generation of Reactive Oxygen Species (ROS), the content of reduced glutathione (GSH), membrane lipid peroxidation and externalization of phosphatidylserine (PS) moieties in RBC, platelets and PMN. Cells derived from the peripheral blood of patients with beta-thalassemia major, intermedia or SCD showed increased oxidative status (increased ROS, lipid peroxidation and PS externalization, and decreased GSH) compared with their normal counterparts. Incubating fresh blood samples from patients with thalassemia major and thalassemia intermedia with 10 mg/ml FPP for 16 hours at 37oC reduced the oxidative status of RBC as well as platelets and PMN. Experiments carried out in normal and thalassemic mice (Th3/+, a mouse model of human beta-thalassemia intermedia demonstrated that mice treated for one week with 10 mg/ml FPP (dissolved in the drinking water) had reduced oxidative stress compared to control mice. The in-vivo effect of FPP was tested on 9 patients with beta-thalassemia (6 - major and 3 - intermedia) treated with 3 gr FPP per os three times a day for 12–15 weeks. Following the treatment, the ROS in RBC, platelets and PMN decreased and the GSH increased in all patients (see table). Six of these patients responded by a modest increase in RBC, reticulocytes and hemoglobin levels. These results suggest that FPP may have an important clinical efficacy as an antioxidant in thalassemia and sickle cell anemia.The in vivo effect of FPP treatment of beta-thalassemia patientsBaselineAfter treatmentnMean ± SEMean ± SEP-value*RBC9324.07 ± 29.19209.55 ± 23.650.001ROSPlatelets9223.73 ± 26.49109.11 ± 8.710.001PMN9222.72 ± 46.42117.61 ± 8.980.045RBC955.37 ± 5.3794.88 ± 3.710.001GSHPlatelets959.41 ± 4.9897.55 ± 5.26<0.0001PMN958.29 ± 5.3590.06 ± 5.870.005* Paired samples t-test

Molecular effects of fermented papaya preparation on oxidative damage, MAP Kinase activation and modulation of the benzo[a]pyrene mediated genotoxicity

The involvement of oxidative and nitrosative stress mechanisms in several biological and pathological processes including aging, cancer, cardiovascular and neurodegenerative diseases has continued to fuel suggestions that processes can potentially be modulated by treatment with free-radical scavengers and antioxidant. The fermented papaya preparation (FPP) derived from Carica papaya Linn was investigated for its ability to modulate oxidative DNA damage due to H2O2 in rat pheochromocytoma (PC12) cells and protection of brain oxidative damage in hypertensive rats. Cells pre-treated with FPP (50 microg/ml) prior to incubation with H2O2 had significantly increased viability and sustenance of morphology and shape. The human hepatoma (HepG2) cells exposed to H2O2 (50 microM) showed an olive tail moment of 10.56 +/- 1.44 compared to 1.37 +/- 0.29 of the solvent control. A significant reduction (P < or = 0.05) of DNA damage was observed at concentrations > or = 10 microg/ml FPP, with 50 microg/ml FPP reducing the genotoxic effect of H2O2 by about 1.5-fold compared to only H2O2 exposed cells.

P-480 - Improving effect of fermented papaya preparation on scopolamine-induced amnesia in mice

P-480 - Improving effect of fermented papaya preparation on scopolamine-induced amnesia in mice