Recent Research Papers

REDOX BALANCE SIGNALLING IN OCCUPATIONAL STRESS: MODIFICATION BY NUTRACEUTICAL INTERVENTION

2011-03-08T07:50:39Z

There is an increasing evidence that psychosocial stress can be viewed as a system-wide derangement of cellular homeostasis, with heightened oxidative stress and triggered proinflammatory mechanisms.
The aim of this study was twofold: a) to replicate findings that psychological stress increases oxidative damage and b) to determine whether a fermented papaya preparations known to exert a significant protective antioxidant properties could buffer such increases in nuclear DNA damage while also inducing epigenetic protective mechanisms.
Twenty-eight sedentary men and women (age range: 28-52) reported living a stressful lifestyle but with an overall positive attitude were recruited for this study. Chronic diseases as well severe burnout and use of drugs for anxiety constituted exclusion criteria. Subjects were supplemented for 1 month with 9g/day (4.5g twice a day) of a certified fermented papaya preparation. All subjects were submitted a stress and sleep quality questionnaire together with a diet and lyfe style assessment. Blood was collected at 2 and 4 week, erythrocyte and leukocyte were separated to assess redox balance and heme oxygenase-1 (HO-1) gene expression while bilirubin oxidized metabolites (BOMs) were tested in the urine.
Stress individuals showed a significant abnormality of redox status with increased MDA of erythrocyte and increased level of 8-0HdG in leukocyte and BOMs excretion (p<0.05). Nutraceutical supplementation brought about a normalization of such values already at the 2 week observation (p<0.05) together with a significant upregulation of HO-1 (p<0.01).
Taken altogether this study confirm that stressful occupational life per se, without any overt psychiatric illness, may be associated to increased oxidative stress. Supplementation with functional food affecting redox regulation may be part of the therapeutic armamentarium to be considered in this clinical setting.

Assessment of 8-OH-dG Levels in Leukocytes in stressed subject when supplemented with FPP
§：As compared to controls, stress subjects showed a statistically significant increased level of 8-0HdG (p<0.05)　＊：while nutraceutical supplementation with FPP brought about a steady state significant decrease within normality (p<0.05). At baseline the level of 8-0HdG was significantly correlated to MDA.

Assessment of erythrocyte concentration of redox status and MDA.
As compared to unstressed individuals, stressed subjects showed a significant increased level of erythrocyte SOD and MDA and decreased GPX (p<0.05). FPP supplementation showed a significant decrease of MDA at the second week while either SOD and GPX abnormalities remained unchanged. However, at 4-week observation, all parameter returned to normal level under supplementation with the nutraceutical (p<0.01 vs baseline values)

HO-1 gene expression in PBMC
When tested against GAPDH and CD14, HO1 gene expression in leukocytes appeared to be significantly up-regulated (p<0.01). This effect was already clear at the second week observation and remained unchanged two weeks afterwards.

Urinary excretion of Bilirubin oxidized metabolites (BOM)
§：As compared to unstressed controls, urinary excretion of BOMs in stressed individuals showed a significant over two-fold increase (p<0.01). ＊：Under supplementation with functional food FPP, such values were normalized (p<0.05). There was a significant correlation between BOMs values and respective HO-1 level (r: 0.78, p<0.01) and MDA (r: 0.64, p<0.5) but no significant correlation appeared with other variables tested.

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(1)ReGenera research group, Milan, Italy;
(2)Immunology Research Institute & Clinic, Nagoya, Japan;
(3)Neuroscience Research Institute, Peking University, China:
(4)Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, USA;
(5)Octopus Scientific Association of Bio-　Prevention, Milano, Italy.

Applications and bioefficacy of the functional food supplement fermented papaya preparation

2010-10-27T04:05:50Z

Toxicology(2010)]]> Okezie I. Aruoma, Yuki Hayashi, Francesco Marotta, Pierre Mantello, Eliezer Rachmilewitz, Luc Montagnier

EFFECT OF A FERMENTED NUTRACEUTICAL ON THIOREDOXIN LEVEL AND TNF- α SIGNALLING IN CIRRHOTIC PATIENTS

2010-10-25T04:20:13Z

The aim of this study is to gain further insights into the possible nutraceutical effect on redox balance via thioredoxin (Trx) modulation and on the intrinsic susceptibility of monocytes to generate an inflammatory response. The study group consisted of thirty-two patients with compensated Child A-C, HCV-related cirrhosis. The patients were supplemented for 6 months with 6g/day of a certified fermented papaya preparation (FPP). Fifteen unsupplemented, age/gender-matched healthy subjects served as controls. The patients filled in a detailed diet-life style questionnaire, and blood samples were collected to test routine biochemistry, Trx, redox status (GSH, GSSG, GSH/GSSG ratio, 4-HNE and α-tocopherol). Moreover, isolated monocytes were tested for ex-vivo LPS-stimulated TNFα production and TNFα mRNA. As compared to control, patients with liver cirrhosis showed a significantly higher serum level of Trx. A significant correlation occurred with GSH/GSSG ratio in Child B and C patients.

FPP supplementation brought about a significant reduction of Trx with levels comparable to the ones of healthy controls. Ten patients Child C (31.2%) showed borderline low levels of α-tocopherol while all cirrhotic patients, as a whole, showed a significantly abnormal redox balance. Supplementation with FPP did not modify α-tocopherol depletion but significantly improved redox balance parameters.

Patients with liver cirrhosis showed a significantly upregulated TNF-α production in a time-dependent manner and this effect was more pronounced in more advanced stages of the disease and showed a significant correlation with α-tocopherol level. Supplementation with FPP significantly, although partially, downregulated TNF-α production from monocytes. Taken altogether, it would appear that the typical oxidative-inflammatory biochemical milieu of these patients is mirrored by a significant TNF-α upregulation at a monocyte level while a targeted nutraceutical might be a potentially amenable intervention to be part of validated scheduled treatments.

Ex-vivo LPS-stimulation test of TNF-α production from monocytes and PCR-electrophoresis: nutraceutical modulation. Data were obtained at 3 months observation. A) dotted bars: healthy control: black bars: unsupplemented cirrhotics; grey bars: FPP-supplemented cirrhotics. FPP: fermented papaya preparation. Stimulated monocytes from unsupplemented cirrhotic showed a significant time-course increase of TNFα production, * p< 0.01 vs healthy control. Nutraceutical supplementation partly but significantly decreased such phenomenon, ** p<0.05 vs unsupplemented cirrhotics. Top part of figure A shows the PCR electrophoresis of TNFα expression in LPS-stimulated cells from FPPsupplemented cirrhotic patients (TNFα + FPP) and in unsupplemented patients (TNFα). B) white bars: Child A; black bars: Child C, *p<0.05 vs Child A

Journal of Biological Regulator & Homeostatic Agents vol.24 no.2(2010)]]>
ReGenera Research Group for Aging-Intervention, Milan, Italy
(1)Neuroscience Research Institute, Peking University, Health Science Center, China
(2)Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, USA
(3)Osato Research Institute & Bioscience Lab., Gifu, Japan

Decreased hemolysis following administration of antioxidant--fermented papaya preparation (FPP) to a patient with PNH

2010-10-25T01:43:41Z

A 36-year old woman was diagnosed in 1996 with PNH complaining of generalized weakness and recurrent episodes of nocturnal hemoglobinuria. The diagnosis was confirmed by Ham's test and flow cytometry. The patient received folic acid, iron supplement, and danazol without significant change in her average Hb level which was ~7.5 gm/dl with LDH ~2500 u/lit. Before receiving FPP, she had anemia (Hb=7.4 gr/dl, MCV 95 fl), leukopenia (leukocyte (WBC)=1500/mcl), lactate dehydrogenase (LDH) up to 5300 u/l, indirect bilirubinemia, and elevated plasma Hb (Fig. 1). Serum haptoglobin was undetectable, serum ferritin and transferrin saturation were low, 7 ng/ml and 5%, respectively. A recent bone marrow disclosed erythroid hyperplasia.

FPP supplied as sachets, containing 3 g powder, by Osato Research Institute, Gifu, Japan, was given three times daily for 4 months. Following FPP therapy, Hb level increased by 1 gr/dl, WBC to 3,200 per microliter, and all the hemolytic parameters have been significantly improved (Fig. 1). Malondialdehyde levels, a product of lipid membrane peroxidation, were significantly decreased--which may reduce its mutagenic and leukemogenic effect. The patient was symptomatically improved, with less fatigue and better performance.

Conclusion
The findings indicate a significant amelioration of hemolytic and oxidative stress parameters which was induced and sustained by FPP treatment in a patient with PNH. Antioxidants may serve as inexpensive adjuvant or alternative therapy in PNH.

Fig. 1 Changes in Hb levels, WBC, and in hemolytic and oxidative stress parameters induced and maintained for 3 months following during administration of FPP

Ann Hematol (2010) 89:429-430]]> Hussam Ghoti & Hanna Rosenbaum & Eitan Fibach & Eliezer A. Rachmilewitz

Amelioration of Oxidative Stress in RBC　from Patients with β-thalassemia Major　and Intermedia and E-β-thalassemia Following Administration of Fermented Papaya Preparation

2010-06-30T01:21:17Z

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In β-hemoglobinopathies, such as β-thalassemia (thal) and sickle cell anemia, the primary defects are mutations in the β-globin gene. However, many aspects of the pathophysiology are mediated by oxidative stress. Fermented papaya preparation (FPP), a natural health food product obtained by biofermentation of carica papaya, has been shown to limit oxidative stress both in vitro and in vivo. We studied the effect of FPP on two groups of β-thal patients: β-thal, major and intermedia, (in Israel) and E-β-thal (in Singapore). The results indicated that in both groups FPP treatment increased the content of reduced glutathione (GSH) in red blood cells (RBC), and decreased their reactive oxygen species (ROS) generation, membrane lipid peroxidation, and externalization of phosphatidylserine (PS), indicating amelioration of their oxidative status, without a significant change in the hematological parameters. Since the turnover of the erythron is relatively slow, it is possible that longer duration of treatment, probably with the addition of an iron chelator, is required in order to achieve the latter goals.

Changes in parameters of oxidative stress following administration of FPP to patients with β-thalassemia (■) and E-β thalassemia (◆). The data present the Mean Fluorescence Index (MFI) of cells stained for reactive oxygen species (ROS), reduced glutathione (GSH), lipid peroxidation (LP) and external phosphatidylserine (PS) in H2O2-stimulated (right) and unstimulated (left) samples. Note that ROS, GSH and PS for cells stained for LP, the MFI is reversely proportional to their LP. The results show a decrease in ROS, LP and externalization PS concomitant with an increase in GSH.

(1)Department of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem, Israel
(2)Department of Paediatric Medicine and Genetics Service, KK Women's and Children's Hospital, Singapore
(3)Department of Hematology, The E. Wolfson Medical Center, Holon, Israel

PHYTOTHERAPY RESEARCH Phytother. Res. 24, (2010) ]]> Eitan Fibach(1), Ee-Shien Tan(2), Saumya Jamuar(2), Ivy Ng(2), Johnny Amer(1) and Eliezer A. Rachmilewitz(3)

Improved function of diabetic wound-site macrophages and accelerated wound closure in response to oral supplementation of a fermented papaya preparation

2010-06-30T01:12:13Z

Antioxidants & Redox Signaling. September 1, 2010: 599-606.

Carica papaya Linn is widely known as a medicinal fruit. We sought to study a standardized fermented papaya preparation (FPP) for its effects on wound healing in adult obese diabetic (db/db) mice. FPP blunted gain in blood glucose and improved lipid profile after eight weeks of oral supplementation. However, FPP did not influence weight gain during the supplementation period. FPP (0.2g/kg body weight) supplementation for 8 weeks before wounding was effective in correcting wound closure. Studies on viable macrophages isolated from the wound site demonstrated that FPP supplementation improved respiratory burst function as well as inducible NO production. Reactive oxygen species support numerous aspects of wound healing. Also, NO availability in diabetic wounds is known to be compromised. Diabetic mice supplemented with FPP showed higher abundance of CD68 as well as CD31 at the wound site suggesting effective recruitment of monocytes and improved pro-angiogenic response. This work provides first evidence that diabetic wound outcomes may benefit from FPP supplementation by specifically influencing the response of wound-site macrophages and subsequent angiogenic response. Given that FPP has a long track-record of safe human consumption, testing of the beneficial effects of FPP on diabetic wound related outcomes in a clinical setting is warranted.

Eight weeks of oral FPP supplementation to diabetic(db/db) mice results in：
1.Attenuation in the % gain in blood glucose without any effects on body weight gain（fig.1）.
2.Improved blood lipid profile including lower LDL, TGL and Tchol levels and an increase in HDL levels.
3.Significant increase in the rate of wound closure and wound angiogenesis（fig.2）.
4.Increase in wound closure rate was associated with an augmented nitric oxide and superoxide production by wound macrophages suggesting an improved macrophage function.
5.The iNOS and VEGF gene expression were markedly upregulated in the wounds FPP supplemented db/db mice.

fig.1Percent improvement of plasma glucose levels after the 8 weeks of FPP supplementation.

fig.2 Effect of FPP on wound healing.

fig.3 Improved nitric oxide production by wound macrophages and elevated iNOS gene expression in wound tissue in FPP-supplemented diabetic mice.

fig.4 Elevated abundance of CD68 and VEGF gene in wound of diabetic mice supplemented with FPP.

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Comprehensive Wound Center, Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Medical Center

REGULATING REDOX BALANCE GENE EXPRESSION IN HEALTHY INDIVIDUALS BY NUTRACEUTICALS : A PILOT STUDY

2010-06-30T00:57:45Z

On the other hand, already starting at 2-week observation, FPP brought about a significant upregulation of all gene expressions checked (fig. 1, p<0.05) which remained stable at later testing time. This data applied irrespective of GSTM-1 and h-OGG-1 genotype profile. While post-transcriptional/translation protein modifications do occur and larger and longer studies are awaited, these preliminary data suggest that a transcriptomic modification of key redox and DNA repair genes may offer further insights when attempting to interrelate "nutragenomics" to clinical phenomena.

All subjects fully complied with the study protocol. At either 2 and 4 week observation, plasma level of tested redox parameter did not change after FPP supplementation, besides a non-significant decrease of MDA. On the other hand, already starting at 2-week observation, FPP brought about a significant upregulation of all gene expressions checked (p<0.05) which remained stable at later testing time. This data applied irrespective of GSTM-1 and h-OGG-1 genotype profile. No relation correlation appeared between erythrocyte level of redox parameters or plasma MDA and related gene expression or genotype profile.

(1)ReGenera Research Group, Milano, Italy; (2)ORI Bioscience Laboratory, Gifu, Japan; (3)Dept of Nutrition, Illinois University, Urbana, USA; (4)Gruppo Locorotondo laboratories, Palermo, Italy

Rejuvenation Research Volume13, Number 2 (2010) ]]> Marotta F(1), Koike K(2), Lorenzetti A(1), Jain S(3), Signorelli P(1), Metugriachuk Y(2), Mantello P(2), Locorotondo N(4)

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

2010-01-15T07:40:42Z

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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(50mg/rat/day) significantly increased the decay of the ESR images of the MCPROXYL, suggesting that FPP may have up-regulated the redox defence 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).

Figure 1. Typical 2D ESR images (y-z plane) of MC-PROXYL distribution in isolated brain of SHR rats. ESR was measured at 2.5, 4.5, 6.5, 8.5，10.5, 12.5, 14.5, 16.5 , 18.5 and 20.5 min after i.v. treatment with MC-PROXYL (isolated 30 s after the treatment). As indicated by the attached color scale (16 colors; white and 100 being the maximum ESR signal), ESR images were reproduced in 16 colors and signals lower than 10% of the maximal signal intensity detected in all slices were regarded as noise.

Figure 2. Effects of long supplementation (5-7 months) with FPP on 2D ESR images (y-z plane) of MC-PROXYL distribution in isolated brain of SHR rats. ESR was measured at 2.5, 4.5, 6.5, 8.5，10.5, 12.5, 14.5, 16.5 , 18.5 and 20.5 min after i.v. treatment with MCPROXYL (isolated 30 s after the treatment). The ESR images are reproduced in 16 colors with signals lower than 10% of the maximal signal intensity detected in all slices are regarded as noise.

Figure 3. (A) Typical L-band ESR signal decay of MC-PROXYL in the isolated SHR brain after i.v. injection of MC-PROXYL (●), and the effects of long supplementation (5-7 months) with FPP (○). ESR was measured 2.5 min after i.v. injection of MC-PROXYL (brains isolated 30 s after the treatment). ESR was measured 2.5 min after i.v. injection of MC-PROXYL (brains isolated 30 s after treatment). The logarithmic signal intensity 15of the second peak of the ESR spectrum of MC-PROXYL was plotted against time. Linearity was observed in phase I and phase II of the corresponding semi-logarithmic plots. (B) The logarithmic signal intensity of the second peak of the ESR spectrum of the MC-PROXYL was plotted against time. K1 indicate the decay rate constant (min-1) in phase I as shown in (A). Each K1 indicates the decay rate constant (min-1) for the control and effects of long supplementation (7 months) with FPP. Each column represents the mean ± SEM (n = 3−6). *P < 0.05 vs. corresponding value for controls.

(1)Department of Clinical Care Medicine Division of Pharmacology & ESR Laboratories, Kanagawa Dental College, 82 Inaoka-cho Yokosuka, Kanagawa, Japan 238-8580.
(2)Osato Research Institutes, 1956 Inatomi Ono-cho, Ibi-gun, Gifu, Japan
(3)Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, 230 West 125 Street, New York, NY 10027, USA.
*These authors contributed equally to this work

Jornal of Functional Foods 1(2009) 375-380 ]]> Fumihiko Yoshino(1)*, Masaichi-Chang-il Lee(1)* , Kyo Kobayashi(1) , Yuki Hayashi (2), and　Okezie I Aruoma(3).

Fermented Papaya Preparation as RedoxRegulator in Blood Cells of β-Thalassemic Miceand Patients

2009-09-07T01:02:15Z

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Many aspects of the pathology in β-hemoglobinopathies (β-thalassemia and sickle cell anemia) are mediated by oxidative stress.
We tested fermented papaya preparation (FPP) for its antioxidant effects: The scavenging effect, determined spectrofluorometrically in a cellfree system using 2'-7'-dichlorofluorescin-diacetate (DCF).
Both spontaneous and Ｈ₂Ｏ₂induced DCF oxidations were decreased by FPP in a dose-dependent fashion.
Using flowcytometry, we showed that in vitro treatment of blood cells from β-thalassemic patients with FPP increased the glutathione content of red blood cells (RBC), platelets and polymorphonuclear (PMN) leukocytes, and reduced their reactive oxygen species, membrane lipid peroxidation and externalization of phosphatidylserine. These effects result in (a) reduced thalassemic RBC sensitivity to hemolysis and phagocytosis by macrophages; (b) improved PMN ability to generate oxidative burst - an intra-cellular mechanism of bacteriolysis, and (c) reduced platelet tendency to undergo activation, as reflected by fewer platelets carrying external phosphatidylserine.
Oral administration of FPP to β-thalassemic mice (50 mg/mouse/day for 3 months) and to patients (3g x 3 times/day for 3 months), reduced all the above mentioned parameters of oxidative stress (p<0.001 in mice and p<0.005 in patients).

These results suggest that FPP, as a potent antioxidant, might alleviate symptoms associated with oxidative stress in severe forms of thalassemia.

The effect of FPP in thalassemic patients.

Nine patients with β-thalassemia were treated with PFF per os (3 g X 3 times a day) for a 3month period. Blood samples were drawn and their RBC, platelets (PLT) and polymorphonuclears (PMN) were analyzed for ROS and GSH. The results depict the average mean fluorescence channels (MFC) ± SD for all treated patients before and 3 months after beginning of the treatment, and indicate a significant (p< 0.005) decrease in ROS and an increase in GSH.

(1)Departments of Hematology, Hadassah - Hebrew University Medical Center, Jerusalem,
(2)The E. Wolfson Medical Center, Holon, Israel

PHYTOTHERAPY RESEARCH Phytother. Res. 22, 820・28 (2008) ]]> Johnny Amer(1), Ada Goldfarb(1), Eliezer A. Rachmilewitz(2) and Eitan Fibach(1)

Plasma glucose level decreases as collateral effect of fermented papaya preparation use

2009-09-07T01:00:11Z

Fernented Papaya Preparation(FPP) is a natural healthy food that has antioxidant action, inhibitory effect on oxidative DNA damage and tissue injury, being a potent OH scavanger.
The wide use of FPP, expecially by elderly people, made us note an unknown collateral effect, i.e., blood suger level dropping signs especially in the afternoon.
The aim of the present work was to scientificially verify the possibility that individuals, who are taking the nutriceutical FPP, might have a decrease of plasma suger levels.

For this purpose, 50 subjects, divided in two groups, were enrolled. The first group was made of 25patients: 13 females and 12 males affected by type-2 diabetes mellitus under treatment with the oral antidiabetic drug, glybenclamide.
The control group included 25 clinically-healthy subjects: 16 females and 9 males, matching in age. All subjects were given 3 grams of FPP daily, during lunch, for two months.
The results of this study confirmed the empirical experience that FPP use can induce a significant decrease in plasma suger levels in both healthy subjects and type-2 diabetic patients.
This hypoglycaemic effect, associated with clinical signs, induced the diabetic patients to reduce the dosage of their antidiabetic oral therapy ( in one patient the therapy was really suspended ).

In accordance with these results, the FPP administration is suggested as an adjuvent drug to join the oral antidiabetic therapy in type-2 diabetes meltus.

La Clinica Terapeutica 2006:157(3):195-198 ]]> Department of Clinical Science, University " La Sapienza", Rome, Italy

Molecular effects of fermented papaya preparation on oxidative damage, MAP

2009-09-07T00:58:40Z

2Ｏ₂in rat pheochromocytoma (PC12) cells.

Cells pre-treated with FPP (50µg/ml) prior to incubation with Ｈ₂Ｏ₂ had significantly increased viability and sustenance of morphology and shape. The human hepatoma (HepG2) cells exposed to Ｈ₂Ｏ₂ 2Ｏ₂ by about 1.5-fold compared to only Ｈ₂Ｏ₂ exposed cells.
Similarly, concentrations ≥ 50 µg/ml FPP significantly reduced DNA migration in co-treated cells compared with only the benzo[a]pyrene treated cells with a dose of 100 µg/ml FPP reduced the DNA damage 2-fold.
The potential of FPP to regulate the phosphorylation status of ERK 1/2, Akt, and p38 was analyzed by Western blot analysis.
FPP showed the potential to modulate the Ｈ₂Ｏ₂ -induced ERK, Akt and p38 activation with the reduction of p38 phosphorylation induced by 250µM Ｈ₂Ｏ₂ being more pronounced.
These studies indicate that FPP can modulate oxidative injury supporting the view that prophylactic potentials in neurodegenerative diseases could be facilitated by FPP.

BioFactors 26 (2006)147-159 ]]> Okezie I Aruoma, Renato Colognato, Ilaria Fontana, Joanne Gartlon, Lucia Migliore, Keiko Koike, Sandra Coecke, Evelyn Lamy, Volker Mersch-Sundermann, Inncoronata Laurenza, Luca Benzi, Fumihiko Yoshino, Kyo Kobayashi, Masaichi-Chang-il Lee

OXIDATIVE-INFLAMMATORY DAMAGE IN CIRRHOSIS.

2009-09-07T00:56:31Z

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Oxidative DNA damage occurs as an early event in HCV infection and is an indication of the potential for carcinogenesis. The aim of this study was to test a novel antioxidant/immunomodulator in HCV-related cirrhotics.

The study group consisted of 50 patients with HCV-related cirrhosis with transaminase values less than twofold increased (ALT<80 IU/l). Patients underwent a standardised food-vitamin composition assessment and were randomly allocated into 2 groups. At the beginning, they were assessed for dietary intake, nutritional status and iron level and then given alpha-tocopherol 900IU/day or given 9g/day of a fermented papaya preparation (FPP, Immun'-Âge®, Osato Research Institute, Gifu, Japan) at bedtime for 6 months. Ten healthy subjects served as controls. Patients were checked monthly for: routine tests, Redox Status (GSH, GSH-Px, GSSG, malondialdehyde), plasma -tocopherol, 8-OHdG level in circulating leukocyte DNA and serum levels of cytokines.

Patients with cirrhosis showed a significant imbalance of redox status (low antioxidants/high oxidative stress markers) (p<0.005 vs controls). Both treatment regimens did not affect transaminases as a whole. However, vitamin E supplementation almost normalized ALT only in the limited vitamin-E-deficient subgroup. A significant improvement of redox status was obtained by both regimens. However, only FPP significantly decreased 8-OHdG and the improvement of cytokine balance with FPP was significantly better than with vitamin-E treatment (p<0.05). While the present data seem to suggest a potential supportive role of antioxidants/immunomodulators as FPP in HCV patients, more studies are needed to substantiate their effect on the natural history of the disease.

Journal of Gastroenterology and Hepatology22: 697-703 (2007) ]]> Marotta Francesco, Hepato-Gastroenterology Dept.., S.Giuseppe Hospital, Milan, Italy

Nutraceutical Supplementation: Effect of a Fermented Papaya Preparation on Redox Status and DNA Damage in Healthy Elderly Individuals and Relationship with GSTM1 Genotype

2009-09-02T06:48:02Z

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Our study group consisted of 54 elderly patients without major invalidating diseases who were randomly divided into two fully matched groups. Group A was given a certified fermented papaya preparation 9 g/day by mouth, while group B received placebo.

Treatment was carried out in a cross-over manner with a 3-month supplementation followed by a 6-week washout period. Blood samples were drawn at entry and on a monthly basis to check routine parameters, redox status, and 8-OHdG in circulating leukocyte DNA. Polymorphism analysis of GSTM1 was carried out as well. The glutathione-S transferase M1 (GSTM1) genotype was null (−) in 40% and 46% of groups A and B, respectively. GSTM1 (−) smokers had a significantly higher level of plasma DNA adducts and leukocytes level of 8-OHdG than their GSTM1 (+) counterparts (P< 0.01). There was a weak correlation between cigarettes smoked/day and DNA adduct (r: 0.61, P< 0.05), which also correlated with antioxidant concentrations, but only in GSTM1 (−) smokers (P< 0.01).

The fermented papaya preparation (FPP)-supplemented group showed a significant enhancement of the antioxidant protection (P< 0.01 vs. A) within the subgroups with GSTM1 (−) and of plasma DNA adduct, irrespective of the GSTM1 genotype. Only the GSTM1 (−) subgroup was the one that, under FPP treatment, increased lymphocyte 8-OHdG (P< 0.01). Such preliminary data show that FPP is a promising nutraceutical for improving antioxidant-defense in elderly patients even without any overt antioxidant-deficiency state while helping explain some inconsistent results of prior interventional studies.

(a)HepatoGastroenterology Univ., S. Giuseppe Hospital, Milano, Italy (b)Geriatrics Department, Cornell University Medical Center, New York, USA (c)Immunology Research Institute and Clinic, Nagoya, Japan (d)GAIA, Age-Management Foundation, Pavia, Italy (e)ORI Bioscience Laboratory, Gifu, Japan

Ann.N.Y. Acad. Sci. 1067: 400-407 (2006)]]> FRANCESO MAROTTA(a,e,) MARK WEKSLER(b,) YASUHIRO NAITO(c,) CHISATO YOSHIDA(e,) MAYUMI YOSHIOKA(c,) AND PAOLO MARANDOLA(d)

Aston Martin Racing Le Mans 2007Follow up of Oxidative Stress of 3 racers (DBR9N゜ 009) during 24 Hours race

2009-09-01T03:11:19Z

Two drivers on three were supplemented with Immun'?ge FPP Three sample of urin were collected :- one before race- one at middle race- one after raceTBARS, MDA, Carbonyls and protein level had been analyzed.
MDA, TBARS and Carbonyls levels are increased during the race for all 3 drivers showing that 24 hours car race is an exhausting physical effort. Average increase for the 3 drivers are 3,8 fold for MDA, 3,4 fold for TBARS and 7,2 fold for Carbonyls.
The results of the two supplemented drivers shows that FPP significantly protects them against increase of oxidative stress comparatively of the non supplemented driver.

Even if the number of participants was little, only 3 drivers ofthe same car AMR DBR9 N°009, the difference of oxidativestress parameters level at end of race between thenon supplemented driver with the two other is important.We could also notice that even if the non supplemented driver had the lowest basic level of oxidative stress parameters, at the end he shows the highest one.The difference was an higher oxidative attack for nonsupplemented driver of: - 2,5 fold and 2 fold higher for MDA and TBARS which means an higher attack on lipid compounds of cells (main compoundsof cell's membranes)-5 fold for Carbonyls which means an higher attack on protein compounds of cells (main compound of structure compounds of cells and of enzymes)-This could result to higher fatigue and more muscle's oxidative attack (stiffness, cramps.)Supplemented drivers could experience less fatigue, a quicker and a better recovery during and after such exhaustive effort. This trial confirm other previous trial on Paris-Dakar driver Philippe Gache and our last trial on a best and quicker recovery by help of FPP on high level sportsmen after surgery.(CERS :European Center of Sportsmen Recovery, Cap Breton, France)Like we have already shown with previous clinical trials where oxidative stress was important, Immun'?ge FPP is a natural non doping food supplement able to protect the body against oxidative stress for sportsmen who pratice sports with exhaustive efforts. Endurance car racing is one of them.

]]> Osato Research Institute, Gifu(Japan)
Catherine GARREL, Dept. of Biology, Univ. of Grenoble
Okezie I Aruma, Touro College of Pharmacy, New York(USA)
Harparkash Kaur, London School of Hygiene and Tropical Medcine, London(UK)

Relationship Between Aging and Susceptibility of Erythrocytes to Oxidative Damage: In View of Nutraceutical Interventions

2009-09-01T03:06:48Z

No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitricoxide synthase were found in the elderly (p <0.05 versus "young" controls), whereas superoxide dismutase was unaltered.

Such abnormalities were prevented by FPP supplementation (p <0.01).
RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p <0.01 versus young) but FPP supplementation significantly protected intact RBC (p <0.05).

These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.

G.A.I.A., Age-Management Foundation, Pavia, Italy; Institute of Science & Technology, Mahidol University, Thailand;
ORI Bioscience Lab., Gifu, Japan.

<]]> F. MAROTTA, K. PAVASUTHIPAISIT, C. YOSHIDA, F. ALBERGATI, and P. MARANDOLA

Recent Research Papers

REDOX BALANCE SIGNALLING IN OCCUPATIONAL STRESS: MODIFICATION BY NUTRACEUTICAL INTERVENTION

Applications and bioefficacy of the functional food supplement fermented papaya preparation

EFFECT OF A FERMENTED NUTRACEUTICAL ON THIOREDOXIN LEVEL AND TNF- α SIGNALLING IN CIRRHOTIC PATIENTS

Decreased hemolysis following administration of antioxidant--fermented papaya preparation (FPP) to a patient with PNH

Amelioration of Oxidative Stress in RBC from Patients with β-thalassemia Major and Intermedia and E-β-thalassemia Following Administration of Fermented Papaya Preparation

Improved function of diabetic wound-site macrophages and accelerated wound closure in response to oral supplementation of a fermented papaya preparation

REGULATING REDOX BALANCE GENE EXPRESSION IN HEALTHY INDIVIDUALS BY NUTRACEUTICALS : A PILOT STUDY

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

Fermented Papaya Preparation as RedoxRegulator in Blood Cells of β-Thalassemic Miceand Patients

Plasma glucose level decreases as collateral effect of fermented papaya preparation use

Molecular effects of fermented papaya preparation on oxidative damage, MAP

OXIDATIVE-INFLAMMATORY DAMAGE IN CIRRHOSIS.

Nutraceutical Supplementation: Effect of a Fermented Papaya Preparation on Redox Status and DNA Damage in Healthy Elderly Individuals and Relationship with GSTM1 Genotype

Aston Martin Racing Le Mans 2007Follow up of Oxidative Stress of 3 racers (DBR9N゜ 009) during 24 Hours race

Relationship Between Aging and Susceptibility of Erythrocytes to Oxidative Damage: In View of Nutraceutical Interventions

Amelioration of Oxidative Stress in RBC　from Patients with β-thalassemia Major　and Intermedia and E-β-thalassemia Following Administration of Fermented Papaya Preparation