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      Antioxidant, Gastroprotective, Cytotoxic Activities and UHPLC PDA-Q Orbitrap Mass Spectrometry Identification of Metabolites in Baccharis grisebachii Decoction

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          Abstract

          The decoction of the local plant Baccharis grisebachii is used as a digestive, gastroprotective, external cicatrizing agent and antiseptic in Argentine. A lyophilized decoction (BLD) from the aerial parts of this plant was evaluated regarding its anti-ulcer, antioxidant and cytotoxic activities and the bioactivities were supported by UHPLC-MS metabolome fingerprinting which revealed the presence of several small bioactive compounds. The antioxidant properties were evaluated by DPPH, TEAC, FRAP and lipoperoxidation inhibition in erythrocytes methods, and the antibacterial activity was evaluated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. The BLD showed a moderate free radical scavenging activity in the DPPH (EC 50 = 106 µg/mL) and lipid peroxidation in erythrocytes assays (67%, at 250 µg/mL). However, the BLD had the highest gastroprotective effect at a dose of 750 mg/kg with a ninety-three percent inhibition of damage through a mechanism that involve NO and prostaglandins using the ethanol-induced gastric damage in a standard rat model. On the other hand, BLD does not induce cytotoxic changes on human tumor and no-tumor cell lines at the concentrations assayed. Regarding the metabolomic analysis, thirty-one compounds were detected and 30 identified based on UHPLC-OT-MS including twelve flavonoids, eleven cinnamic acid derivatives, one coumarin, one stilbene and two other different phenolic compounds. The results support that the medicinal decoction of Baccharis grisebachii is a valuable natural product with gastroprotective effects and with potential to improve human health that opens a pathway for the development of important phytomedicine products.

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          A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention.

          Kaempferol is a polyphenol antioxidant found in fruits and vegetables. Many studies have described the beneficial effects of dietary kaempferol in reducing the risk of chronic diseases, especially cancer. Epidemiological studies have shown an inverse relationship between kaempferol intake and cancer. Kaempferol may help by augmenting the body's antioxidant defence against free radicals, which promote the development of cancer. At the molecular level, kaempferol has been reported to modulate a number of key elements in cellular signal transduction pathways linked to apoptosis, angiogenesis, inflammation, and metastasis. Significantly, kaempferol inhibits cancer cell growth and angiogenesis and induces cancer cell apoptosis, but on the other hand, kaempferol appears to preserve normal cell viability, in some cases exerting a protective effect. The aim of this review is to synthesize information concerning the extraction of kaempferol, as well as to provide insights into the molecular basis of its potential chemo-preventative activities, with an emphasis on its ability to control intracellular signaling cascades that regulate the aforementioned processes. Chemoprevention using nanotechnology to improve the bioavailability of kaempferol is also discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.
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            Kaempferol, a potential cytostatic and cure for inflammatory disorders.

            Kaempferol (3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one) is a flavonoid found in many edible plants (e.g., tea, broccoli, cabbage, kale, beans, endive, leek, tomato, strawberries, and grapes) and in plants or botanical products commonly used in traditional medicine (e.g., Ginkgo biloba, Tilia spp, Equisetum spp, Moringa oleifera, Sophora japonica and propolis). Its anti-oxidant/anti-inflammatory effects have been demonstrated in various disease models, including those for encephalomyelitis, diabetes, asthma, and carcinogenesis. Moreover, kaempferol act as a scavenger of free radicals and superoxide radicals as well as preserve the activity of various anti-oxidant enzymes such as catalase, glutathione peroxidase, and glutathione-S-transferase. The anticancer effect of this flavonoid is mediated through different modes of action, including anti-proliferation, apoptosis induction, cell-cycle arrest, generation of reactive oxygen species (ROS), and anti-metastasis/anti-angiogenesis activities. In addition, kaempferol was found to exhibit its anticancer activity through the modulation of multiple molecular targets including p53 and STAT3, through the activation of caspases, and through the generation of ROS. The anti-tumor effects of kaempferol have also been investigated in tumor-bearing mice. The combination of kaempferol and conventional chemotherapeutic drugs produces a greater therapeutic effect than the latter, as well as reduces the toxicity of the latter. In this review, we summarize the anti-oxidant/anti-inflammatory and anticancer effects of kaempferol with a focus on its molecular targets and the possible use of this flavonoid for the treatment of inflammatory diseases and cancer.
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              Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury.

              Oral administration to fasted rats of either absolute ethanol, 0.6 N hydrochloric acid, 0.2 N sodium hydroxide, 25% sodium chloride, or boiling water produced extensive necrosis of the gastric mucosa. Pretreatment with several prostaglandins of the A, E, or F type, either orally or subcutaneously, prevented such necrosis, and the effect was dose-dependent. This property of prostaglandins is called "cytoprotection." The protective effect against oral administration of absolute ethanol was already maximal 1 min after PGE2 given orally, and 15-30 min after PGE2 given subcutaneously. Cytoprotection by prostaglandins is unrelated to the inhibition of gastric acid secretion since, (a) it is maximal at doses that have no effect on gastric secretion, and (b) anti-secretory compounds (cimetidine, methscopolamine bromide) and antacids are not cytoprotective. Although the mechanism of gastric cytoprotection is unknown, prostaglandins appear to increase the resistance of gastric mucosal cells to the necrotizing effect of strong irritants. These results suggest that certain prostaglandins, by a mechanism other than the inhibition of gastric acid secretion, maintain the cellular integrity of the gastric mucosa, and might be beneficial in the treatment of a variety of diseases in which gastric mucosal injury is present.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                19 March 2019
                March 2019
                : 24
                : 6
                : 1085
                Affiliations
                [1 ]Instituto de Biotecnología-Instituto de Ciencias Básicas, Universidad Nacional de San Juan, Av. Libertador General San Martín 1109 (O), San Juan CP 5400, Argentina; jesicagomez674@ 123456gmail.com (J.G.); blima@ 123456unsj.edu.ar (B.L.); lluna@ 123456unsj.edu.ar (L.L.); gferesin@ 123456unsj.edu.ar (G.E.F.)
                [2 ]CONICET (Consejo Nacional de Ciencia y Tecnología), CABA, Buenos Aires C1405DJR, Argentina; cgamarraluques@ 123456gmail.com
                [3 ]Instituto de Farmacia, Facultad de Ciencias, Universidad Austral de Chile, Campus Isla Teja, Valdivia 5090000, Chile
                [4 ]Center for Interdisciplinary Studies on the Nervous System (CISNe), Universidad Austral de Chile, Valdivia 5090000, Chile
                [5 ]Farmacología, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, San Luis CP5700, Argentina; jdparedes@ 123456unsl.edu.ar (J.D.P.); cmville@ 123456gmail.com (C.M.V.G.); gwendel@ 123456unsl.edu.ar (G.H.W.); alejandraomaria@ 123456gmail.com (A.O.M.)
                [6 ]Instituto de Medicina y Biología Experimental de Cuyo (IMBECU), CCT-Mendoza CONICET, Mendoza CP5500, Argentina
                [7 ]Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Mendoza CP5500, Argentina
                [8 ]Laboratorio de Productos Naturales Depto. de Química, Facultad de Ciencias, Universidad de Antofagasta, Av. Coloso S-N, Antofagasta 1240000, Chile; jorge.borquez@ 123456uantof.cl
                Author notes
                [* ]Correspondence: mario.simirgiotis@ 123456gmail.com (M.J.S.); atapia@ 123456unsj.edu.ar (A.T.); Tel.: +56-063-2244369 (M.J.S.); +54-264-4211700-294 (A.T.)
                [†]

                The work was co-directed by both authors.

                Author information
                https://orcid.org/0000-0003-4552-3123
                Article
                molecules-24-01085
                10.3390/molecules24061085
                6472192
                30893865
                ba80c19b-c23a-498d-af19-27ac438377fc
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 23 January 2019
                : 14 March 2019
                Categories
                Article

                argentinean plants,uhplc orbitrap (q-ot),flavonoids,cinnamic acids derivatives

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