May Dietary Supplementation Augment Respiratory Burst in Wound-Site Inflammatory Cells?

Abstract

Persistent infection contributes to wound chronicity. At the wound site, NADPH oxidase (NOX) activity in immune cells fights infection to enable the healing process. Fermented papaya preparation (FPP) is a carbohydrate-rich nutritional supplement that has demonstrated ability to bolster respiratory burst in experimental rodent systems. In FPP, glucose coexists with fructose and maltose in addition to multiple other sugar alcohols such as inositol. We have previously reported that FPP supplementation augments wound healing in diabetic mice via improvement of respiratory burst activity of wound innate immune cells. In this clinical study ( clinicaltrials.gov : NCT02332993), chronic wound patients were orally supplemented with FPP daily. Inducible production of reactive oxygen species was significantly higher in wound-site immune cells from patients supplemented with FPP and on standard of care (SoC) for wound management compared with those patients receiving SoC alone. Wound closure in FPP-supplemented patients showed improvement. Importantly, the consumption of this mixture of carbohydrates, including significant amounts of glucose, did not increase HbA1c. These observations warrant a full-length clinical trial testing the hypothesis that FPP improves wound closure by augmenting NOX activity in immune cells at the wound site. Antioxid. Redox Signal. 28, 401-405.

Oral Administration of Fermented Papaya (FPP®) Controls the Growth of a Murine Melanoma through the In Vivo Induction of a Natural Antioxidant Response

“…In this sense, many studies have shown that foods (fruit and vegetable) with a high content of antioxidants such as polyphenols and lycopene are the ideal candidates for cancer prevention [28,29,30,31]. Among these the antioxidant and immunostimulant effect of Fermented Papaya (FPP ® ) was already well known [34,35,36,37], which represents an excellent nutraceutical in many pathologies [36,38,42,43,53,54,55,61] and a promising antitumor agent [50,63]. Before this study the knowledge on the antitumor activity of FPP ® was very low or limited to in vitro investigations.…”

“…Papaya is the fruit of the Carica papaya Linn, native to Central America (southern Mexico) and South America and nowadays grown in most tropical countries. Traditionally used as a medicinal fruit, Carica papaya Linn is rich in polyphenols and has antioxidant [38,39], immunostimulants [37,40] anti-inflammatory [41] properties and also beneficial effects in wound healing [42,43,44].…”

“…According to recent studies, FPP ® has proved to be an excellent antioxidant and an excellent nutraceutical adjuvant in combined therapies against several diseases, including tumors [36,37,38,51,52,53]. Actually, FPP ® is not simply a free radical neutralizer, but a free radical regulator [54] and an immunomodulator [42,43,55,56,57]. There is some experimental evidence on the mechanisms by which FPP ® interferes with the production and accumulation of free radicals even if there is much more to be verified [58,59].…”

Potential plants for inflammatory dysfunction in the SARS-CoV-2 infection

“…A decrease in LDL levels was observed in HL individuals from the CX 500 group (reduction of 41 ± 5% to levels before treatment) compared to Placebo. Also, a significant reduction in oxidative stress and inflammatory process components (reduction of 52 ± 11% in advanced oxidation protein products (AOPPs), 32 ± 10% in ischemia-modified albumin (IMA), and 57 ± 7% in hs-CRP) was observed in HL individuals in the CX 1000 group when compared to Placebo group Randomized, placebo-controlled, double-blind study (Viecili et al 2014 ) Carica papaya L. — Caricaceae (Amazon) Supplementation of 6 g Fermented papaya preparation (FPP®)/day for a period of 14 weeks CRP levels (mg/L) significantly decreased with supplementation of FPP® (baseline: 1.519 ± 1.115; after: 1.317 ± 0.715), uric acid (mg/dL) (baseline: 6.654 ± 1.472; after: 6.525 ± 1.315), and LDL/HDL ratio was considerably changed (baseline: 2.923 ± 0.906; after: 2.829 ± 0.663) decreasing risk for diseases worsened by overt inflammation and oxidative stress Randomized controlled clinical trial (Somanah et al 2012 ) C. papaya - Patients were orally supplemented 9 g (3 g/dose, 3 doses/day) with FPP daily In 19 patients, wound closure in FPP-supplemented patients, compared with standard of care (SoC) showed improvement (wound volume %) (SoC: 82; FPP: 45), by increased NADPH oxidase (NOX) activity in immune cells at the wound site (fold change) (SoC: 0.8; FPP: 1.6) after 2 weeks of supplementation Clinical Trial (NCT02332993) (Das et al 2018 ) Caryocar brasiliense A.St.-Hil. — Caryocaraceae (Brazil) 400 mg C. brasiliense oil capsules for 14 days Capsules ingestion decreades high-sensitivity C-reactive protein (hs-CRP) levels (Before: 1.59 ± 0.21; after: 1.55 ± 0.17 mg/dL), TC (Before: 187.78 ± 3.53; after: 187.29 ± 3.22 mg/dL), LDL (Before: 110.82 ± 2.94; after: 108.7 ± 2.64 mg/dL), Thiobarbituric acid reactive substances (TBARS) (Before: 0.0267 ± 0.001; after: 0.0264 ± 0.001 nmol/mL of malondialdehyde — MDA), hypothesizing that pequi oil could reduce exercise-induced inflammation and blood pressure Clinical Trial (Miranda-Vilela et al 2009 ) Euterpe edulis Mart.…”

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

“…FPP ® is a powerful antioxidant and nutraceutical adjuvant in combined therapies against various diseases [22][23][24][25][26][27][28][29], including cancer [22,25,30]. The FPP ® more documented actions are as a free radical regulator [31], as immunomodulator [32][33][34][35][36] and as antioxidant [37,38]. In fact, FPP ® has shown a powerful in vitro anti-oxidative activity on brain cells [39], as well on in vivo experimental model of epilepsy consistently reducing neural release of epileptogenic monoamine [40].…”