Vitamins E, C and polyphenols (flavonoids and non-flavonoids) are major natural antioxidants capable of preventing damage generated by oxidative stress. Here we show the capacity of these antioxidants to form non-covalent association within lipid bilayers close to the membrane/cytosol interface. Antioxidant regeneration is significantly enhanced in these complexes.

The aim of this study was to investigate the anticancer effect of a combination of D-fraction polysaccharide from Grifola frondosa (DFP) and vitamin C (VC) on hepatocellular carcinoma in vitro. DFP is a bioactive extract from the maitake mushroom. Anticancer activity was demonstrated using various concentrations of DFP alone or in combination with VC against the human hepatocarcinoma SMMC-7721 cell line. To investigate the anticancer mechanism, studies designed to detect cell apoptosis were conducted. Results from the MTT assay indicated that a combination of DFP (0.2 mg/mL) and VC (0.3 mmol/L) led to a 70% reduction in cell viability. Flow cytometry results indicated that DFP/VC treatment induced apoptosis in approximately 65% SMMC-7721 cells. Cell cycle analysis identified cell cycle arrest at the G2/M phase following DFP/VC treatment for 48 hours. In addition, cellular morphological changes were observed using transmission electron microscopy. Western blot analysis revealed that the upregulation of BAX, downregulation of Bcl-2, activation of poly-(ADP-ribose)-polymerase (PARP), and the release of cytochrome c were observed in cells treated with the combination of DFP/VC, which showed that the mechanism of anticancer activity in the SMMC-7721 hepatocarcinoma cells involved induction of apoptosis.

The purpose of this study was to assess the synergistic effect of polydatin and vitamin C on attenuating cardiotoxicity induced by doxorubicin (DOX) in rats. Polydatin could significantly increase the activity of SOD and the heart rate, attenuate myocardial pathological damage, decrease MDA content, slightly increase arterial pressure and GSH-Px activity, reduce intervals of QRS, QT and ST, and lower FFA content. The combination of polydatin and vitamin C could significantly increase arterial pressure and heart rate, decrease QRS interval and slightly reduce ST and QT intervals, significantly attenuate myocardial pathological damage, increase the activities of GSH-Px,T-SOD, Na(+) K(+) -ATPase and Ca(2+) Mg(2+) -ATPase, and elevate PCr and ATP contents, slightly increase ADP and TAN contents and PCr/ATP, and significantly decrease the contents of MDA and FFA, when compared with those in the DOX group. Meanwhile, the improvement effects on FFA content, the activities of ATPase and SOD and contents of ATP and TAN in combination group were more obvious than those in polydatin group; and the improvement effects on arterial pressure, heart rate, interval of QRS, GSH-Px activity, and MDA, ADP and PCr contents in combination group were slightly obvious when compared with those in polydatin group. In addition, the mRNA expression levels of AMPK-α2 and PPAR-α were slightly improved in combination group. The results illustrate that the combination of polydatin and vitamin C has the ability to enhance the myocardial protective effects by its antioxidative effect and improving energy metabolism. This article is protected by copyright. All rights reserved.

A key characteristic of mushroom polysaccharides that elicit an immunomodulatory response is that they are rich inβ-glucans and low in α-glucans. In this study we analysed nine commercially available preparations from three mushroom species, Reishi (Ganoderma lucidum), Shiitake (Lentinula edodes) and Maitake (Grifola frondosa), for β- and α-glucan content. Based on β- and α-glucan content we selected three extracts to combine into a formula and evaluated the ability of the individual extracts and formula to impact on the expression of cytokines IL-1α, IL-6, IL-10 and TNF-α in human macrophages with and without LPS stimulation. The majority of mushroom extracts and the formula were found to be highly potent immuno-stimulators possessing EC50 values lower than 100 μg/mL. Interestingly the mushroom formula had lower EC50 values in TNF-α expression from LPS stimulated macrophages compared to the individual extracts, suggesting a potential synergistic effect of the mushroom formula. A responseadditivity graph and curve-shift analysis illustrated that indeed the mushroom formula exhibited an immuno-stimulatory synergistic effect on the expression of the majority of cytokines evaluated in both LPS stimulated and non-stimulated human macrophages, with IL-10 having an antagonistic response.This study represents the first report of a synergistic immuno-modulatory response in human macrophages elicited from a mushroom formula rationally derived from β- and α-glucan content.

Studies on the lipid peroxidation and antioxidant changes and their significance during myocardial injury have provided a new insight into the pathogenesis of heart disease. The heart failure subsequent to myocardial infarction may be associated with an antioxidant deficit as well as increased myocardial oxidative stress. The present study was designed to evaluate the effect of the combination of ferulic acid and ascorbic acid on antioxidant defense system and lipid peroxidation against isoproterenol (ISO)-induced myocardial infarction in rats. Induction of rats with isoproterenol (150 mg/kg body weight daily, i.p.) for 2 days resulted in a marked elevation in lipid peroxidation, serum marker enzymes (LDH, CPK, GOT, and GPT), and a significant decrease in activities of endogenous antioxidants (SOD, GPx, GST, CAT, and GSH). Pre-co-treatment with the combination of ferulic acid (20 mg/kg body weight/day) and ascorbic acid (80 mg/kg body weight/day) orally for 6 days, significantly attenuated these changes when compared to the individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. Thus, ferulic acid and ascorbic acid significantly counteracted the pronounced oxidative stress effect of ISO by the inhibition of lipid peroxidation, restoration of antioxidant status, and myocardial marker enzymes levels. In conclusion, these findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on lipid peroxidation and antioxidant defense system during ISO-induced myocardial infarction and associated oxidative stress in rats.

Chagas' disease is an infection that is caused by the protozoan Trypanosoma cruzi, affecting millions of people worldwide. Because of severe side effects and variable efficacy, the current treatments for Chagas' disease are unsatisfactory, making the search for new chemotherapeutic agents essential. Previous studies have reported various biological activities of naphthoquinones, such as the trypanocidal and antitumor activity of vitamin K3. The combination of this vitamin with vitamin C exerted better effects against various cancer cells than when used alone. These effects have been attributed to an increase in reactive oxygen species generation. In the present study, we evaluated the activity of vitamin K3 and vitamin C, alone and in combination, against T. cruzi. The vitamin K3 + vitamin C combination exerted synergistic effects against three forms of T. cruzi, leading to morphological, ultrastructural, and functional changes by producing reactive species, decreasing reduced thiol groups, altering the cell cycle, causing lipid peroxidation, and forming autophagic vacuoles. Our hypothesis is that the vitamin K3 + vitamin C combination induces oxidative imbalance in T. cruzi, probably started by a redox cycling process that leads to parasite cell death.

OBJECTIVES:To evaluate the effect of two inhaled essential oils (black pepper or angelica) on the nicotine habits of students, staff, and faculty on a U.S. college campus.

DESIGN:Comparative study with pre-/post-test measures.

SETTING:Community college in rural East Texas.

PARTICIPANTS:Convenience sample of 20 volunteers from the college community (students, faculty, and staff) who were regular (daily) users of nicotine (cigarettes, snuff, or chewing tobacco).

INTERVENTIONS:Inhalation of one drop of essential oil on a tissue for 2 minutes when participant was craving nicotine.

OUTCOME MEASURES:(1) Pre-inhalation journal recording of self-assessed level of craving for nicotine on a 0-10 scale, (2) post-inhalation journal recording of self-assessed level of craving for nicotine on a 0-10 scale, and (3) minutes that participant waited from start of inhalation until next use of tobacco.

RESULTS:Both black pepper and angelica reduced the level of nicotine craving and allowed a longer delay before next use of tobacco. However, black pepper reduced the level of craving more than did angelica, and angelica allowed for a longer delay than did black pepper.

CONCLUSIONS:Aromatherapy may be useful in nicotine withdrawal. Further studies are warranted.

This research aimed to compare anti-inflammatory effects of oligonol, acupuncture, and quantum light therapy in rat models of estrogen-induced prostatitis. Adult male Wistar albino rats were grouped as follows: Group I, control (n = 10); Group II, chronic prostatitis (n = 10); Group III, oligonol (n = 10); Group IV, acupuncture (n = 10); Group V, quantum (n = 10); Group VI, oligonol plus quantum (n = 10); Group VII, acupuncture plus oligonol (n = 10); Group VIII, quantum plus acupuncture (n = 10); and Group IX, acupuncture plus quantum plus oligonol (n = 10). Chronic prostatitis (CP) was induced by the administration of 17-beta-estradiol (E2) and dihydrotestosterone (DHT). Oligonol was given for 6 weeks at a dose of 60 mg/day. Acupuncture needles were inserted at CV 3/4 and bilaterally B 32/35 points with 1-hour manual stimulation. Quantum therapy was administered in 5-minute sessions three times weekly for 6 weeks. Lateral lobes of prostates were dissected for histopathologic evaluation. Although all of the treatment modalities tested in this study showed anti-inflammatory effects in the treatment of CP in male rats, a synergistic effect was observed for oligonol plus quantum light combination. Monotherapy with oligonol showed a superior anti-inflammatory efficacy as compared to quantum light and acupuncture monotherapies.

Vitamin C is an essential dietary nutrient that has a variety of biological functions. Recent studies have provided promising evidence for its additional health benefits including anti-cancer activity. Vitamin B2, another essential dietary nutrient, is often coexisted with vitamin C in some fruits, vegetables or dietary supplements. The objective of the present study is to determine whether combination of vitamin C and B2 can achieve a synergistic anti-cancer activity. MDA-MB-231, MCF-7 and A549 cells were employed to evaluate the combinatory effects of vitamin C and B2. We found that combination of vitamin C and vitamin B2 resulted in a synergistic cell death induction in all cell lines tested. Further mechanistic investigations revealed that vitamin B2 sensitized cancer cells to vitamin C through inhibition of Akt and Bad phosphorylation. Our findings identified vitamin B2 as a promising sensitizer for improving the efficacy of vitamin C-based cancer chemoprevention and chemotherapy.

The present study evaluated the synergistic effects of the association of ascorbic acid andα-tocopherol on myenteric in the jejunum of diabetic rats. The rats were randomly divided into four equal groups: untreated normoglycemic (UC), untreated diabetic (UD), ascorbic acid and α-tocopherol-treated normoglycemic (CAE) and ascorbic acid and α-tocopherol-treated diabetic (DAE). The rats from the CAE and DAE group received supplementation with ascorbic acid (1g/L in water) and α-tocopherol (1% in chow). At 210-days-old, the animals were sacrified and their jejunum was collected and submitted to immunohistochemistry. Quantitative and/or morphometric analysis were performed. Supplementation with ascorbic acid and α-tocopherol prevented the cell loss of myenteric neurons expressing HuC/D and TrkA in an equivalent proportion. We also observed a reduction of the CGRP nerve fiber varicosities and the prevention of the increased cell body size of submucosal VIP neurons (p<0.05). The association of ascorbic acid andα-tocopherol reduced the deleterious effects of diabetes promoting protection on the enteric neurons.

Curcumin (Cur) is a promising antioxidant and anticancer drug, but several recent studies indicate that Cur exerts its anticancer activity through promoting reactive oxygen species (ROS) generation. In the present study, concentration-dependent regulation of Cur on cell proliferation, viability and ROS generation, and effect of water-soluble antioxidants ascorbic acid (ASA), N-acetyl-cysteine (NAC) and reduced glutathione (GSH) on the antioxidant and anticancer activity of Cur were investigated in human myeloid leukemia cells (HL-60 cells). We found that although Cur concentration- and time-dependently decreased the proliferation and viability of cells, its effect on ROS generation (as indicated by the level of malondialdehyde, MDA) varied with its concentrations. I.e., low concentrations of Cur diminished the ROS generation, while high Cur promoted it. Combined with the opposite effect of 50 microM H2O2 on low or high Cur-induced MDA alteration, cell proliferation arrest and cell death, these results proved that low Cur exerted its anticancer activity through diminishing ROS generation in HL-60 cells, while high Cur through promoting ROS generation. Further studies showed that all water-soluble antioxidants ASA, NAC and GSH significantly enhanced both the antioxidant and the anticancer activity of low Cur. Considering that the extra accumulation of ROS is harmful to normal cells, the data presented here indicate that instead of using high doses, combining low doses of Cur with water-soluble antioxidants is a better strategy for us to improve the anticancer activity of Cur.