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Explore the efficacy of medicinal plants as a rich source of antioxidants and their role in combating oxidative stress. Learn about antioxidant defenses, mechanisms of action, and evaluation methods.
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Medicinal Plants: Are They an Effective Source of Antioxidants? Patrícia Valentão and Paula B. Andrade REQUIMTE/ Department of Pharmacognosy
Oxidizing agents Adapted from M. Schmiederer, “The Wrecking Crew Reactive Oxygen and Nitrogen Species”
Oxidizing agents Auto-oxidation reactions Ischemia-Reperfusion Reactive species RespiratoryBurst Enzymatic reactions Subcellularoganelles Xenobiotics Adapted from Mikkelsen and Wardman, Oncogene 2003, 22, 5734–5754
Antioxidant defences Antioxidant:any substance that, when present at low concentrations compared to those of an oxidizable substrate, significantly delays or prevents oxidation of that substrate Prevention Scavenging Repair Preventive medicine Terapeuthics Food Endogenous Exogenous
Ascorbic acid and GSH Ferritin Metallothionein Cu/Zn SOD Glutathione peroxidase Glutathione transferase -Tocopherol and GSH -Carotene Glutathione peroxidase Glutathione transferase -Tocopherol and GSH Metallothionein Cu/Zn SOD Glutathione peroxidase Glutathione transferase Catalase -Tocopherol -Carotene -Tocopherol Ascorbic acid -Carotene -Tocopherol and GSH Mn SOD Glutathione peroxidase Glutathione transferase Antioxidant defences Cytoplasm E. R. Nucleus Peroxisomes Lysosomes Lipid bilayer of cell membranes Mitochondria
Antioxidant defences Amino acids Chlorophylls Tocopherols Alkaloids Betalains Organosulphur compounds Natural antioxidants Phytic acid Carotenoids Organic acids Phytosterols Iridoids Secoiridoids Phospholipids Phenolic compounds Seabra, R.M.; Andrade, P.B.; Valentão, P.; Fernandes, E.; Carvalho, F.; Bastos, M.L. Em Biomaterials from aquatic and terrestrial organisms. Fingerman, M., Nagabhushanam, R. (Eds.). Science Publishers, Enfield (New Hampshire), USA (2006), 115-174.
Antioxidant defences Phenolic compounds Hydroxycinnamicacids Benzoicacids Flavonoids
Antioxidant defences Phenolic compounds Free radical scavenging Metals chelation Antioxidant activity Enzyme inhibition Cell signalling Partition coefficient Interaction with proteins
Antioxidant potential evaluation Interest in extracts Mechanismofaction Combinationofmethods Reactive species generation Target molecules Distinct response to different oxidative species ROS RNS In vivo systems In vitro systems
DPPH Catharanthus roseus O2¯ NO Ferreres, F.; Pereira, D.M.; Valentão, P.; Andrade, P.B.; Seabra, R.M.; Sottomayor, M. J. Agric. Food Chem. 2008, 56, 9967-9974.
Catharanthus roseus Roots Ferreres, F.; Pereira, D.M.; Valentão, P.; Oliveira, J.M.A.; Faria, J.; Gaspar, L.; Sottomayor, M.; Andrade, P.B.; J. Pharm. Biomed. Anal. 2010, 51, 65-69. Pereira, D.M.; Faria, J.; Gaspar, L.; Ferreres, F.; Valentão, P.; Sottomayor, M.; Andrade, P.B.; Food Chem. 2010, 121, 56-61.
Pieris brassicae/Brassica oleracea var. costata Pierisbrassicae Sequestration Metabolism Brassicaoleraceavar.costata Ferreres, F.; Sousa, C.; Valentão, P.; Pereira, J.A.; Seabra, R.M.; Andrade, P.B. Phytochemistry2007, 68, 361-367. Sousa, C.; Pereira, D.M.; Valentão, P.; Ferreres, F.; Pereira, J.A.; Seabra, R.M.; Andrade, P.B. J. Agric. Food Chem.2009, 57, 2288-2294.
Pieris brassicae/Brassica oleracea var. costata OH Pierisbrassicae O2¯ Pierisbrassicae Brassicaoleraceavar.costata DPPH HOCl Brassicaoleraceavar.costata Andrade, P. B.; Valentão, P.; Sousa, C.; Pereira, D. M.; Ferreres, F. Extracto aquoso da larva de Pieris brassicae e respectiva utilização como antioxidante. Portuguese Patent nº 103931 Sousa, C.; Pereira, D.M.; Valentão, P.; Ferreres, F.; Pereira, J.A.; Seabra, R.M.; Andrade, P.B. J. Agric. Food Chem.2009, 57, 2288-2294.
Brassica oleracea var. costata Cell culture Effect of B. oleracea var. costata aqueous extracts on LDH leakage. Compared to: a. control hepatocytes; b. PQ exposed hepatocytes. *P < 0.05, **P < 0.01, and ***P < 0.001 Sousa, C.; Pontes, H.; Carmo, H.; Dinis-Oliveira, R.J.; Valentão, P.; Andrade, P.B.; Remião, F.; Bastos, M.L.; Carvalho, F. Toxicol. In Vitro 2009, 23, 1131–1138.
Brassica oleracea var. costata Cell culture Effect of B. oleracea var. costata aqueous extract on glutathione. Compared to: a. control hepatocytes; c. PQ+3, d. PQ+12, f. PQ+200, g. PQ+800 exposed hepatocytes. *P < 0.05, **P < 0.01, and ***P < 0.001 Sousa, C.; Pontes, H.; Carmo, H.; Dinis-Oliveira, R.J.; Valentão, P.; Andrade, P.B.; Remião, F.; Bastos, M.L.; Carvalho, F. Toxicol. In Vitro 2009, 23, 1131–1138.
Brassica oleracea var. costata Cell culture Effect of B. oleracea var. costata aqueous extract on ATP. Compared to: a. control hepatocytes; b. PQ exposed hepatocytes. *P < 0.05, **P < 0.01, and ***P < 0.001 Effect of B. oleracea var. costata aqueous extract on lipid peroxidation. a P < 0.05 versus control group Sousa, C.; Pontes, H.; Carmo, H.; Dinis-Oliveira, R.J.; Valentão, P.; Andrade, P.B.; Remião, F.; Bastos, M.L.; Carvalho, F. Toxicol. In Vitro 2009, 23, 1131–1138.
Hypericum androsaemum O2¯ X/XO system XO activity NADH/PMS system HOCl HPLC-DAD phenolic profile of H. androsaemum. Detection at 350 nm. Peaks: (1) 3-O-caffeoylquinic acid; (2) 5-O-caffeoylquinic acid; (3) quercetin 3-sulphate; (4) quercetin 3-galactoside1quercetin 3-glucoside; (5) quercetin 3-arabinoside; (6) quercetin. Valentão, P.; Fernandes, E.; Carvalho, F.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. Biol. Pharm. Bull 2002, 25, 1320-1323.
0 Hypericum androsaemum Cell suspension * Control ** 250 µg/ml lyophilized t -BHP 16 µg/ml lyophilized + t-BHP LDH leakage (%) 62 µg/ml lyophilized + t-BHP 250 µg/ml lyophilized + t-BHP Effect of H. androsaemum infusion on LDH leakage. ∗ P < 0.05, compared with control cells; ∗∗ P < 0.05, compared with t-BHP-treated cells. Valentão, P.; Carvalho, M.; Fernandes, E.; Carvalho, F.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. J. Ethnopharmacol. 2004, 92, 79-84.
Hypericum androsaemum Cell suspension A B * Control Control t-BHP t-BHP 250 mg/Kg lyophilized 250 mg/Kg lyophilized 16 mg/Kg lyophilized + t-BHP Total glutathione (nmol/10 6 cells) 16 mg/Kg lyophilized + t-BHP GSH (nmol/10 6 cells) 62 mg/Kg lyophilized + t-BHP 62 mg/Kg lyophilized + t-BHP * 250 mg/Kg lyophilized + t-BHP 250 mg/Kg lyophilized + t-BHP 0 0 C D * * Control Control t-BHP t-BHP 250 mg/Kg lyophilized 250 mg/Kg lyophilized 16 mg/Kg lyophilized + t-BHP 16 mg/Kg lyophilized + t-BHP GSSG (nmol/10 6 cells) GSSG/Total glutathione 62 mg/Kg lyophilized + t-BHP 62 mg/Kg lyophilized + t-BHP 250 mg/Kg lyophilized + t-BHP 250 mg/Kg lyophilized + t-BHP 0 0.00 Effect of H. androsaemum infusion on rat hepatocytes total glutathione (A), GSH (B), GSSG (C) and GSSG/Total Glutathione (D). ∗P < 0.05, compared with control cells. Valentão, P.; Carvalho, M.; Fernandes, E.; Carvalho, F.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. J. Ethnopharmacol. 2004, 92, 79-84.
0 0 0 0.000 Hypericum androsaemum Mouse liver B A * ** Control Control ** t-BHP t-BHP ** ** ** 100 mg/Kg lyophilized 100 mg/Kg lyophilized Total glutathione (nmol/g liver) 4 mg/Kg lyophilized + t-BHP 4 mg/Kg lyophilized + t-BHP GSH (nmol/g liver) 20 mg/Kg lyophilized + t-BHP 20 mg/Kg lyophilized + t-BHP 100 mg/Kg lyophilized + t-BHP 100 mg/Kg lyophilized + t-BHP C D ** ** Control Control t-BHP t-BHP 100 mg/Kg lyophilized 100 mg/Kg lyophilized 4 mg/Kg lyophilized + t-BHP 4 mg/Kg lyophilized + t-BHP GSSG (nmol/g liver) GSSG/Total glutathione 20 mg/Kg lyophilized + t-BHP 20 mg/Kg lyophilized + t-BHP 100 mg/Kg lyophilized + t-BHP 100 mg/Kg lyophilized + t-BHP Effect of H. androsaemum infusion on hepatic levels of total glutathione (A), GSH (B), GSSG (C) and GSSG/Total Glutathione (D). ∗P < 0.05, compared with control group; ∗∗ P < 0.05, compared with t-BHP treated group. Valentão, P.; Carvalho, M.; Carvalho, F.; Fernandes, E.; Neves, R.P.; Pereira, M.L.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. J. Ethnopharmacol. 2004, 94, 345-351.
0 0.0 Hypericum androsaemum * Cell suspension Control ** t-BHP 250 mg/Kg lyophilized 16 mg/Kg lyophilized + t-BHP Malondialdehyde equivalents (nmol/10 6 cells) 62 mg/Kg lyophilized + t-BHP 250 mg/Kg lyophilized + t-BHP ** Control Mouse liver t-BHP 100 mg/Kg lyophilized 4 mg/Kg lyophilized + t-BHP Malondialdehyde equivalents (nmol/g liver) 20 mg/Kg lyophilized + t-BHP 100 mg/Kg lyophilized + t-BHP Effect of H. androsaemum infusion on lipid peroxidation. * P < 0.05, compared with control cells; ** P < 0.05, compared with t-BHP-treated cells. Valentão, P.; Carvalho, M.; Fernandes, E.; Carvalho, F.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. J. Ethnopharmacol. 2004, 92, 79-84. Valentão, P.; Carvalho, M.; Carvalho, F.; Fernandes, E.; Neves, R.P.; Pereira, M.L.; Andrade, P.B.;Seabra, R.M.;Bastos, M.L. J. Ethnopharmacol. 2004, 94, 345-351.
Antioxidant defences Maintenance of antioxidant properties (ADME) Prevention of target molecule injury Stability after reactive species scavenging Adductsformation: GSH, RNA, DNA, proteins
Absorption Metabolism Protection? Leonardo da Vinci (1452-1519)