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      Lentinus squarrosulus (Mont.) mycelium enhanced antioxidant status in rat model

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          Abstract

          Aim

          Lentinus squarrosulus is an edible wild mushroom commonly found in Asia. This species has several interesting features such as rapid mycelial growth, and hence has the potential to be used as food, functional food, and nutraceuticals. Our previous study shows that L. squarrosulus contains potent antioxidant compounds in vitro. This study aims to investigate the in vivo bioavailability of L. squarrosulus mycelium extract and its antioxidant effect on biomarkers of antioxidant defense and oxidative stress.

          Methods

          Water extract of mycelial biomass of L. squarrosulus was analyzed for in vivo antioxidant effects, including cupric-reducing antioxidant capacity (CUPRAC), glutathione peroxidase (GPx), xanthine oxidase (XO), advanced oxidation protein products (AOPPs), and lipid hydroperoxides (LHPs) at 0 and 28 days. GPx and XO were also analyzed in liver homogenates. Normal Sprague Dawley rats were treated with 250 and 500 mg/kg of extract for 28 days.

          Results

          The serum CUPRAC level increased after treatment with both concentrations, indicating that there was sufficient bioavailability of the extract which contributed to the total antioxidant capacity. GPx activity in both serum and liver was increased and this correlated with LHP level after treatment with 250 mg/kg of extract, but XO activity was significantly decreased after treatment with 500 mg/kg of the extract. Lack of difference between AOPP levels implied that there were no significant changes in oxidative damage of protein after treatment.

          Conclusion

          This study clearly showed that L. squarrosulus mycelium antioxidant extract contains absorbable antioxidants that enter the circulating plasma and cause a significant acute increase in plasma antioxidant capacity. Thus, the water extract of L. squarrosulus mycelium, which can be obtained abundantly by liquid fermentation, may serve as an antioxidant ingredient in functional foods and nutraceuticals.

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          Most cited references 24

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          Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective.

          Antioxidants are emerging as prophylactic and therapeutic agents. These are the agents, which scavenge free radicals otherwise reactive oxygen species and prevent the damage caused by them. Free radicals have been associated with pathogenesis of various disorders like cancer, diabetes, cardiovascular diseases, autoimmune diseases, neurodegenerative disorders and are implicated in aging. Several antioxidants like SOD, CAT, epigallocatechin-3-O-gallate, lycopene, ellagic acid, coenzyme Q10, indole-3-carbinol, genistein, quercetin, vitamin C and vitamin E have been found to be pharmacologically active as prophylactic and therapeutic agents for above mentioned diseases. Antioxidants are part of diet but their bioavailability through dietary supplementation depends on several factors. This major drawback of dietary agents may be due to one or many of the several factors like poor solubility, inefficient permeability, instability due to storage of food, first pass effect and GI degradation. Conventional dosage forms may not result in efficient formulation owing to their poor biopharmaceutical properties. Principles of novel drug delivery systems need to be applied to significantly improve the performance of antioxidants. Novel drug delivery systems (NDDS) would also help in delivery of these antioxidants by oral route, as this route is of prime importance when antioxidants are intended for prophylactic purpose. Implication of NDDS for the delivery of antioxidants is largely governed by physicochemical characteristics, biopharmaceutical properties and pharmacokinetic parameters of the antioxidant to be formulated. Recently, chemical modifications, coupling agents, liposomes, microparticles, nanoparticles and gel-based systems have been explored for the delivery of these difficult to deliver molecules. Results from several studies conducted across the globe are positive and provided us with new anticipation for the improvement of human healthcare.
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            Free radicals and antioxidants in the year 2000. A historical look to the future.

            In the late 1950's free radicals and antioxidants were almost unheard of in the clinical and biological sciences but chemists had known about them for years in the context of radiation, polymer and combustion technology. Daniel Gilbert, Rebeca Gerschman and their colleagues related the toxic effects of elevated oxygen levels on aerobes to those of ionizing radiation, and proposed that oxygen toxicity is due to free radical formation, in a pioneering paper in 1956. Biochemistry owes much of its early expansion to the development and application of chromatographic and electrophoretic techniques, especially as applied to the study of proteins. Thus, superoxide dismutase (SOD) enzymes (MnSOD, CuZnSOD, FeSOD) were quickly identified. By the 1980's Molecular Biology had evolved from within biochemistry and microbiology to become a dominant new discipline, with DNA sequencing, recombinant DNA technology, cloning, and the development of PCR representing milestones in its advance. As a biological tool to explore reaction mechanisms, SOD was a unique and valuable asset. Its ability to inhibit radical reactions leading to oxidative damage in vitro often turned out to be due to its ability to prevent reduction of iron ions by superoxide. Nitric oxide (NO.) provided the next clue as to how SOD might be playing a critical biological role. Although NO. is sluggish in its reactions with most biomolecules it is astoundingly reactive with free radicals, including superoxide. Overall, this high reactivity of NO. with radicals may be beneficial in vivo, e.g. by scavenging peroxyl radicals and inhibiting lipid peroxidation. If reactive oxygen species are intimately involved with the redox regulation of cell functions, as seems likely from current evidence, it may be easier to understand why attempts to change antioxidant balance in aging experiments have failed. The cell will adapt to maintain its redox balance. Indeed, transgenic animals over-expressing antioxidants show some abnormalities of function. There must therefore be a highly complex interrelationship between dietary, constitutive, and inducible antioxidants with the body, under genetic control. The challenge for the new century is to be able to understand these relationships, and how to manipulate them to our advantage to prevent and treat disease.
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              Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout.

              The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2015
                06 November 2015
                : 9
                : 5957-5964
                Affiliations
                [1 ]Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia
                [2 ]Faculty of Industrial Sciences and Technology, Universiti Malaysia Pahang, Gambang, Kuantan, Pahang, Malaysia
                [3 ]Department of Plant Protection, Faculty of Agriculture, Universiti Putra Malaysia, Serdang, Selangor, Malaysia
                [4 ]Department of Biomedical Science, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
                Author notes
                Correspondence: Noorlidah Abdullah, Mushroom Research Centre, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia, Tel +60 3 7967 4371 Fax +60 3 7967 4178, Email noorlidah@ 123456um.edu.my
                Article
                dddt-9-5957
                10.2147/DDDT.S90746
                4642808
                © 2015 Mhd Omar et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Pharmacology & Pharmaceutical medicine

                xanthine oxidase, mushroom, aopp, gpx, cuprac, mycelia

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