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Hongbin Sun - One of the best experts on this subject based on the ideXlab platform.

  • neuroprotection by combined administration with Maslinic Acid a natural product from olea europaea and mk 801 in the cerebral ischemia model
    Molecules, 2016
    Co-Authors: Yisong Qian, Teng Guan, Xuzhen Tang, Hongbin Sun
    Abstract:

    Glutamate-mediated excitotoxicity is a major cause of ischemic brain damage. MK-801 confers neuroprotection by attenuating the activation of the N-methyl-d-aspartate (NMDA) receptor, but it failed in clinical use due to the short therapeutic window. Here we aim to investigate the effects of Maslinic Acid, a natural product from Olea europaea, on the therapeutic time window and dose range for the neuroprotection of MK-801. Rats were administered with Maslinic Acid intracerebroventricularly and cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) followed by reperfusion. MK-801 was administered at 1 h, 2 h, 3 h and 4 h after ischemia, respectively. The cerebral infarct volume was determined by 2,3,5-Triphenyltetrazolium chloride (TTC) staining, neuronal damage was assessed by Haematoxylin Eosin (H&E) staining, and the expression of glial glutamate transporters and glial fibrillary Acidic protein (GFAP) was evaluated by immunohistochemistry and Western blot post-ischemia. Results showed that the presence of Maslinic Acid extended the therapeutic time window for MK-801 from 1 h to 3 h. Co-treatment of Maslinic Acid and MK-801 at a subthreshold dosage obviously induced neuroprotection after ischemia. The combination of these two compounds improved the outcome in ischemic rats. Moreover, Maslinic Acid treatment promoted the expression of GLT-1 and GFAP post-ischemia. These data suggest that the synergistic effect of Maslinic Acid on neurological protection might be associated with the improvement of glial function, especially with the increased expression of GLT-1. The combination therapy of Maslinic Acid and MK-801 may prove to be a potential strategy for treating acute ischemic stroke.

  • Maslinic Acid promotes synaptogenesis and axon growth via akt gsk 3β activation in cerebral ischemia model
    European Journal of Pharmacology, 2015
    Co-Authors: Yisong Qian, Menghao Huang, Teng Guan, Lan Chen, Liangxun Cao, Xiaojian Han, Longfei Huang, Xuzhen Tang, Hongbin Sun
    Abstract:

    Maslinic Acid, a natural pentacyclic triterpene from Olea europaea plants, possesses neuroprotective effects both in vivo and in vitro. However, the mechanism of its action is not well understood. In this study, we investigated the potential effects of Maslinic Acid on synaptogenesis and axonal regeneration, as well as the possible signal pathway involved in a cerebral ischemia mouse model. Adult male C57BL/6J mice were subjected to 1h of cerebral ischemia by middle cerebral artery occlusion (MCAO). Maslinic Acid (0.1, 1 and 10mg/kg) was administered intragastrically 24h after MCAO once daily for 7 consecutive days. Axonal loss and synaptophysin expression in the ischemic boundary area was evaluated by histological assay. The Akt/GSK-3β signal pathway was determined by western blot analysis. Two Akt inhibitors, LY294002 and MK2206, were used to verify the involvement of Akt/GSK-3β pathway in Maslinic Acid-mediated neuroprotection. Maslinic Acid significantly prevented axonal damage, promoted axonal regeneration and increased synaptophysin expression 7 days after ischemia. In addition, Maslinic Acid treatment was shown to enhance Akt activity and promote GSK-3β phorsphorylation in stoke mice. The increased neurite outgrowth and synaptophysin expression by Maslinic Acid treatment was blocked by the Akt inhibitors both in vivo and in vitro.. These findings suggested that Maslinic Acid promotes synaptogenesis and axonal regeneration by regulating Akt/GSK-3β signaling pathway, which may, in turn, provide neuroprotection.

  • Maslinic Acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase
    Chinese Journal of Natural Medicines, 2014
    Co-Authors: Jun Liu, Hongbin Sun, Xue Wang, Yupeng Chen, Lifei Mao, Jing Shang, Luyong Zhang
    Abstract:

    Abstract Aim To investigate the molecular signaling mechanism by which the plant-derived, pentacyclic triterpene Maslinic Acid (MA) exerts anti-diabetic effects. Method HepG2 cells were stimulated with various concentrations of MA. The effects of MA on glycogen phosphorylase a (GPa) activity and the cellular glycogen content were measured. Western blot analyses were performed with anti-insulin receptor β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β antibodies. The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression. Enzyme-linked immunosorbent assay (ELISA) was used to measure the effect of MA on IRβ auto-phosphorylation. Furthermore, the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet (HFD). Results The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells. Furthermore, MA was shown to induce the phosphorylation level of IRβ-subunit, Akt, and GSK3β. The MA-induced activation of Akt appeared to be specific, since it could be blocked by wortmannin. Finally, MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance, and increased the accumulated hepatic glycogen content. Conclusion The results suggested that Maslinic Acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.

  • anti inflammatory effects of Maslinic Acid a natural triterpene in cultured cortical astrocytes via suppression of nuclear factor kappa b
    European Journal of Pharmacology, 2011
    Co-Authors: Longfei Huang, Yisong Qian, Menghao Huang, Teng Guan, Xuzhen Tang, Hongbin Sun
    Abstract:

    Maslinic Acid (2-α, 3-β-dihydroxyolean-12-en-28-oic Acid) is a natural triterpenoid compound from Olea europaea. This compound prevents oxidative stress and pro-inflammatory cytokine generation in vitro. This study was planned to investigate the anti-inflammatory effects of Maslinic Acid in central nervous system by using rat astrocyte cultures stimulated with lipopolysaccharide (LPS). We evaluated different proteins implicated in the nuclear factor kappa B (NF-κB) signal transducer pathway employing Western blot and quantitative real time PCR techniques. Results demonstrated that Maslinic Acid treatment exerted potent anti-inflammatory action by inhibiting the production of Nitric Oxide and tumor necrosis factor alpha (TNF-α). Western blot analysis showed that Maslinic Acid treatment attenuated LPS-induced translocation of NF-κB p65 subunit to the nucleus and prevented LPS-induced IκBα phosphorylation in a concentration-dependent manner, Moreover, Maslinic Acid significantly suppressed the expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) at protein and mRNA levels. These results suggest that Maslinic Acid can potentially reduce neuroinflammation by inhibiting NF-κB signal transducer pathway in cultured cortical astrocytes.

  • Maslinic Acid a natural triterpenoid compound from olea europaea protects cortical neurons against oxygen glucose deprivation induced injury
    European Journal of Pharmacology, 2011
    Co-Authors: Yisong Qian, Menghao Huang, Teng Guan, Longfei Huang, Xuzhen Tang, Hongbin Sun
    Abstract:

    Maslinic Acid is a triterpenoid compound present in plants of Olea europaea. This compound has been reported to have potent antioxidant, anti-cancer, anti-HIV and anti-inflammatory activities. In this study, we investigated the neuroprotective effect of Maslinic Acid and its mechanism of action. With presence or absence of Maslinic Acid, cortical neurons were subjected to 1h of oxygen-glucose deprivation and 24h of reoxygenation. Cell injury was determined by lactate dehydrogenase (LDH) measurement and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Neuronal apoptosis was evaluated by flow cytometry assay, caspase-3 expression/activity, caspase-9 activity and Bcl-2/Bax ratio. Nitric Oxide (NO) production and inducible nitric oxide synthase (iNOS) expression were also detected. Results showed that Maslinic Acid dose-dependently ameliorated neuron injury and apoptosis. Maslinic Acid treatment normalized the caspase expression/activation and increased the Bcl-2/Bax ratio. In addition, Maslinic Acid inhibited oxygen-glucose deprivation-induced NO production and iNOS expression. These results indicated that Maslinic Acid has beneficial effects on hypoxic neurons by suppressing iNOS activation, which may, in turn, provide neuroprotection.

Meichin Yin - One of the best experts on this subject based on the ideXlab platform.

  • asiatic Acid and Maslinic Acid attenuated kainic Acid induced seizure through decreasing hippocampal inflammatory and oxidative stress
    Epilepsy Research, 2018
    Co-Authors: Zhi-hong Wang, Mei-chin Mong, Meichin Yin, Yachen Yang
    Abstract:

    Seizure is a neurological disorder including hippocampal oxidative and inflammatory stress, and glutamate toxicity. Thus, any agent(s) that mitigate(s) these events in hippocampus might attenuate seizure severity. The effects of asiatic Acid (AA) or Maslinic Acid (MA) pre-administration at 20 or 40mg/kg body weight/day upon inflammatory, oxidative and apoptotic injury in hippocampus of kainic Acid (KA)-treated mice were examined. KA induced seizure-like behavioral patterns, which was attenuated by AA or MA pre-administration. KA stimulated the release of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha and prostaglandin E2 in hippocampus of mice. AA or MA pre-administration decreased the production of these inflammatory factors. AA or MA also diminished KA-induced increase in hippocampal cyclooxygenase-2 activity and relative NF-κB p50/65 binding activity. KA depleted glutathione content and promoted reactive oxygen species generation. AA or MA pre-administration reversed these alterations. KA lowered Bcl-2 mRNA expression and increased Bax mRNA expression. AA or MA treatments reduced Bax mRNA expression. AA or MA pre-administration enhanced glutamine synthetase activity, decreased glutamate level and increased glutamine level in hippocampus of KA treated mice. In addition, AA or MA pre-treatments at 10 and 20μM increased viability and decreased plasma membrane damage in KA treated nerve growth factor (NGF)-differentiated PC12 cells. Both agents also lowered the release of calcium ion induced by KA in NGF-treated PC12 cells. These findings support that asiatic Acid and Maslinic Acid are potent nutraceutical agents for seizure alleviation.

  • Maslinic Acid protected pc12 cells differentiated by nerve growth factor against β amyloid induced apoptosis
    Journal of Agricultural and Food Chemistry, 2015
    Co-Authors: Yuwan Yang, Mei-chin Mong, Meichin Yin, Chiawen Tsai
    Abstract:

    β-Amyloid peptide (Abeta) was used to induce apoptosis in PC12 cells differentiated by nerve growth factor, and the protective activities of Maslinic Acid (MA) at 2-16 μM were examined. Abeta treatment lowered Bcl-2 expression, raised Bax expression, and decreased cell viability. MA pretreatments decreased Bax expression, raised the Bcl-2/Bax ratio, and increased cell viability. MA pretreatments retained glutathione content and decreased subsequent Abeta-induced release of reactive oxygen species, tumor necrosis factor-α, interleukin (IL)-1β, and IL-6. Abeta treatment up-regulated protein expression of p47(phox), gp91(phox), mitogen-activated protein kinase, advanced glycation end product receptor (RAGE), and nuclear factor-κ B (NF-κB). MA pretreatments at 2-16 μM suppressed the expression of proteins including gp91(phox), p47(phox), p-p38, and NF-κB p65, at 4-16 μM down-regulated RAGE and NF-κB p50 expression, and at 8 and 16 μM reduced p-ERK1/2 expression. These novel findings suggest that Maslinic Acid is a potent compound against Abeta-induced cytotoxicity.

  • protective effects of Maslinic Acid against alcohol induced acute liver injury in mice
    Food and Chemical Toxicology, 2014
    Co-Authors: Sheng Lei Yan, Meichin Yin, Hui Ting Yang, Hsiang Lin Lee
    Abstract:

    Abstract Protective effects of Maslinic Acid (MA) at 10, 15 or 20 mg/kg body weight/day against alcohol-induced acute hepatotoxicity in mice were examined. Mice were administrated by MA for 3 weeks, and followed by alcohol treatment. Results showed that MA pre-intake at three doses resulted in its accumulation in the liver; and dose-dependently lowered cytochrome P450 2E1 activity and protein expression at 23.5–51.2% and 21.4–62.3%, respectively (P

  • Maslinic Acid induces mitochondrial apoptosis and suppresses hif 1α expression in a549 lung cancer cells under normoxic and hypoxic conditions
    Molecules, 2014
    Co-Authors: Te Chun Hsia, Wen Hu Liu, Wen Wei Qiu, Jian Luo, Meichin Yin
    Abstract:

    The apoptotic effects of Maslinic Acid (MA) at 4, 8, 16, 32 and 64 μmol/L on human lung cancer A549 cells under normoxic and hypoxic conditions were examined. MA at 4-64 and 16-64 μmol/L lowered Bcl-2 expression under normoxic and hypoxic conditions, respectively (p 0.05). MA at 8-64 and 32-64 μmol/L reduced reactive oxygen species and nitric oxide levels under both conditions (p < 0.05). These findings suggest that Maslinic Acid, a pentacyclic triterpenic Acid, exerted its cytotoxic activities toward A549 cells by mediating mitochondrial apoptosis and the HIF-1α pathway.

  • inhibitory effects of Maslinic Acid upon human esophagus stomach and pancreatic cancer cells
    Journal of Functional Foods, 2014
    Co-Authors: Chunche Lin, Meichin Yin, Sheng Lei Yan
    Abstract:

    Apoptotic, anti-invasive and anti-migratory effects of Maslinic Acid (MA) at 4, 8, or 16 µM in human esophageal squamous cancer cell line, OE33; gastric cancer cell line, SGC-7901; and pancreatic cancer cell line, Panc-1, were examined. MA treatments inhibited OE33 and SGC-7901 cells growth at 21–66% and 32–75%, respectively; but lowered Panc-1 viability at 13–27% only. MA treatments increased cleaved caspase-3 and Bax expression, and raised caspase-3 and caspase-8 activities in OE33 and SGC-7901 cells. MA treatments also increased DNA fragmentation and decreased reactive oxygen species production in these two cell lines. MA treatments declined invasion and migration in OE33 and SGC-7901 cells, and lowered vascular endothelial growth factor and transforming growth factor-beta1 levels in these cells. MA suppressed hypoxia-inducible factor-1alpha, matrix metalloproteinase (MMP)-2 and MMP-9 expression in OE33 and SGC-7901 cells. These findings indicated that this triterpene was a potent agent against esophagus and stomach cancers.

Andres Parra - One of the best experts on this subject based on the ideXlab platform.

  • identification of gut derived metabolites of Maslinic Acid a bioactive compound from olea europaea l
    Molecular Nutrition & Food Research, 2016
    Co-Authors: Gloria Lozanomena, Andres Parra, Emilia M Juan, Marta Sanchezgonzalez, Joana M Planas
    Abstract:

    SCOPE Maslinic Acid has been described to exert a chemopreventive activity in colon cancer. Hereby, we determined Maslinic Acid and its metabolites in the rat intestine previous oral administration as a first step in elucidating whether this triterpene might be used as a nutraceutical. METHODS AND RESULTS Maslinic Acid was orally administered at 1, 2, and 5 mg/kg to male Sprague-Dawley for 2 days. At 24 h after the last administration, the content of the duodenum and jejunum, ileum, cecum, and colon was collected and extracted with methanol 80% prior to LC-APCI-MS analysis. The developed method was validated providing suitable sensitivity (LOQ of 5 nM), good recovery (97.8 ± 3.6%), linear correlation, and appropriate precision (< 9%). Maslinic Acid was detected in all the segments with higher concentrations in the distal part of the intestine. LC-APCI-LTQ-ORBITRAP-MS allowed the identification of 11 gut-derived metabolites that were formed by mono-, dihydroxylation, and dehydrogenation reactions. CONCLUSION Maslinic Acid undergoes phase I reactions resulting in a majority of monohydroxylated metabolites without the presence of phase II derivatives. The high concentration of Maslinic Acid achieved in the intestine suggests that it could exert a beneficial effect in the prevention of colon cancer.

  • Maslinic Acid, a Natural Triterpene, Induces a Death Receptor-Mediated Apoptotic Mechanism in Caco-2 p53-Deficient Colon Adenocarcinoma Cells
    2016
    Co-Authors: Fernando J. Reyes-zurita, Andres Parra, Marta Cascante, Pedro P Medina, Juan Peragon, Eva E. Rufino-palomares, Leticia García-salguero, Jose A Lupianez
    Abstract:

    (Panel A) Maslinic Acid induced apoptosis through activation of caspase-8 in Caco-2 cells (Top), but not in HT29 cells (Bottom). Caco-2 and HT29 cells were treated for 4 h with their corresponding IC50 or IC80 concentrations. Values represent means ± S.D. of four experiments performed in triplicate. Key (***) P

  • interaction between the anti cancer drug diacetyl Maslinic Acid and bovine serum albumin a biophysical study
    Journal of Molecular Liquids, 2015
    Co-Authors: J A Molinabolivar, F Galisteogonzalez, Carnero C Ruiz, Medinao M Donnell, Andres Parra
    Abstract:

    Abstract Steady-state and time-resolved fluorescence, as well as Fourier transform-infrared (FT-IR) spectroscopy studies were made to understand the interaction between diacetyl Maslinic Acid (DMA) and bovine serum albumin (BSA) at pH 7.4. A decrease in fluorescence intensity and a blue shift of the emission peak were observed in the DMA–BSA complex, which were attributed to changes in the microenvironment of the protein fluorophores. Spectroscopic analysis revealed that the fluorescence-quenching mechanism between DMA and BSA was a static procedure. Displacement experiments with site markers indicated that DMA binds to BSA at Sudlow's site I (subdomain IIA). Binding constants for the protein–drug interaction were determined at three different temperatures (298, 305, and 310 K). Enthalpy (ΔH0) and entropy (ΔS0) changes indicated that hydrophobic interactions were the dominant intermolecular forces in the binding of DMA to BSA. The interaction appears to be entropy-driven, and the process spontaneous and endothermic. Enthalpy–entropy compensation suggests that reorganization of water molecules plays an important role. Anisotropy and FT-IR experiments revealed that BSA loses its structure in the presence of DMA. The secondary structure compositions of free BSA and DMA–BSA complex were determined by FT-IR. The binding distance and transfer efficiency for DMA–BSA complex were calculated according to the Foster theory of non-radiative energy transfer.

  • identification in rat plasma and urine by linear trap quadrupole orbitrap mass spectrometry of the metabolites of Maslinic Acid a triterpene from olives
    Journal of Agricultural and Food Chemistry, 2015
    Co-Authors: Marta Sanchezgonzalez, Andres Parra, Gloria Lozanomena, Emilia M Juan, Joana M Planas
    Abstract:

    Maslinic Acid is a natural pentacyclic triterpenoid widely distributed in edible and medicinal plants with health-promoting activities. The identification and quantification of its metabolites is a requirement for a better understanding of the biological effects of this triterpene. Therefore, Maslinic Acid was orally administered to Sprague–Dawley rats at a dose of 50 mg/kg of body weight. Blood and urine were withdrawn at 45 min. Samples were extracted with ethyl acetate prior to liquid chromatography–atmospheric pressure chemical ionization–linear trap quadrupole–Orbitrap (LC–APCI–LTQ–Orbitrap) analysis. Screening of plasma yielded four monohydroxylated derivatives (M1–M4), one monohydroxylated and dehydrogenated metabolite (M5), and two dihydroxylated and dehydrogenated compounds (M6 and M7). In urine, M1, M4, M5, and M6 were detected. Quantification by LC–APCI–mass spectrometry (MS) revealed Maslinic Acid as the prevalent compound in both plasma (81.8%) and urine (73.9%), which indicates that metaboli...

  • spectroscopic investigation on the interaction of Maslinic Acid with bovine serum albumin
    Journal of Luminescence, 2014
    Co-Authors: J A Molinabolivar, F Galisteogonzalez, Carnero C Ruiz, Medinao M Donnell, Andres Parra
    Abstract:

    Abstract Ultraviolet–visible (UV–vis), steady-state and time-resolved fluorescence, and Fourier transform-infrared (FT-IR) spectroscopy were used to study the interaction between Maslinic Acid (MA) and bovine serum albumin (BSA). Binding constants were determined at three different temperatures (298, 304, and 310 K). Spectroscopic analysis revealed that the fluorescence-quenching mechanism between MA and BSA was a static quenching procedure. MA specifically binds to one site of the BSA molecule forming a stable complex with a binding constant of (5.4±0.4)×10 4  M −1 at pH 7.4 and 298 K. From the thermodynamic parameters of the binding process (Δ G 0 , Δ H 0 and Δ S 0 ) it can be inferred that hydrogen bonds and van der Waals interactions are the predominant intermolecular forces responsible for the stabilization of the complex. Anisotropy studies revealed that tryptophan residues of BSA undergo motion restrictions as a result of the interaction with MA. The distance between MA and the fluorophore residue of BSA was evaluated according to the theory of Foster for fluorescence resonance energy transfer (FRET). Observations from FT-IR spectra and three-dimensional fluorescence indicated changes in the conformation of BSA upon ligand binding.

Joana M Planas - One of the best experts on this subject based on the ideXlab platform.

  • cancer chemopreventive activity of Maslinic Acid a pentacyclic triterpene from olives and olive oil
    2021
    Co-Authors: Emilia M Juan, Joana M Planas
    Abstract:

    Abstract Maslinic Acid is a pentacyclic triterpene widely distributed in the plant kingdom and found in several edible vegetables and fruits, being table olives a rich source of this compound. Maslinic Acid is being recognized as a nutraceutical due to its lack of harmful effects and numerous health-protecting properties. The present chapter reviews the current evidence on the chemopreventive activities of Maslinic Acid on colorectal cancer. First, we describe the studies performed in colorectal cancer cells that demonstrate that this pentacyclic triterpene elicits the inhibition of cell proliferation and induction of apoptosis. Second, the chemopreventive activity in experimental models induced by carcinogens as well as in transgenic mice is revised. This pentacyclic triterpene not only reduces the number of preneoplastic lesions but also the incidence of adenomas. In conclusion, the results reported support the hypothesis that a regular consumption of Maslinic Acid might contribute to the prevention of colorectal cancer.

  • reduction of preneoplastic lesions induced by 1 2 dimethylhydrazine in rat colon by Maslinic Acid a pentacyclic triterpene from olea europaea l
    Molecules, 2019
    Co-Authors: Emilia M Juan, Gloria Lozanomena, Marta Sanchezgonzalez, Joana M Planas
    Abstract:

    Maslinic Acid triggers compelling antiproliferative and pro-apoptotic effects in different human cancer cell lines. Hence, the chemopreventive activity was investigated on early stages of carcinogenesis induced by 1,2-dimethylhydrazine (DMH) which is a model that mimics human sporadic colorectal cancer. Male Sprague-Dawley rats were orally administered either Maslinic Acid at 5, 10 or 25 mg/kg dissolved in (2-hydroxypropyl)-β-cyclodextrin 20% (w/v) or the solvent for 49 days. After one week of treatment, animals received three weekly intraperitoneal injections of DMH at the dose of 20 mg/kg. Maslinic Acid reduced the preneoplastic biomarkers, aberrant crypt foci (ACF) and mucin-depleted foci (MDF), already at 5 mg/kg in a 15% and 27%, respectively. The decline was significant at 25 mg/kg with decreases of 33% and 51%, respectively. Correlation analysis showed a significant association between the concentrations of Maslinic Acid found in the colon and the reduction of ACF (r = 0.999, p = 0.019) and MDF (r = 0.997, p = 0.049). The present findings demonstrate that Maslinic Acid induced an inhibition of the initiation stages of carcinogenesis. The assessment of this pentacyclic triterpene at the colon sheds light for designing diets with foods rich in Maslinic Acid to exert a chemopreventive activity in colorectal cancer.

  • identification of gut derived metabolites of Maslinic Acid a bioactive compound from olea europaea l
    Molecular Nutrition & Food Research, 2016
    Co-Authors: Gloria Lozanomena, Andres Parra, Emilia M Juan, Marta Sanchezgonzalez, Joana M Planas
    Abstract:

    SCOPE Maslinic Acid has been described to exert a chemopreventive activity in colon cancer. Hereby, we determined Maslinic Acid and its metabolites in the rat intestine previous oral administration as a first step in elucidating whether this triterpene might be used as a nutraceutical. METHODS AND RESULTS Maslinic Acid was orally administered at 1, 2, and 5 mg/kg to male Sprague-Dawley for 2 days. At 24 h after the last administration, the content of the duodenum and jejunum, ileum, cecum, and colon was collected and extracted with methanol 80% prior to LC-APCI-MS analysis. The developed method was validated providing suitable sensitivity (LOQ of 5 nM), good recovery (97.8 ± 3.6%), linear correlation, and appropriate precision (< 9%). Maslinic Acid was detected in all the segments with higher concentrations in the distal part of the intestine. LC-APCI-LTQ-ORBITRAP-MS allowed the identification of 11 gut-derived metabolites that were formed by mono-, dihydroxylation, and dehydrogenation reactions. CONCLUSION Maslinic Acid undergoes phase I reactions resulting in a majority of monohydroxylated metabolites without the presence of phase II derivatives. The high concentration of Maslinic Acid achieved in the intestine suggests that it could exert a beneficial effect in the prevention of colon cancer.

  • identification in rat plasma and urine by linear trap quadrupole orbitrap mass spectrometry of the metabolites of Maslinic Acid a triterpene from olives
    Journal of Agricultural and Food Chemistry, 2015
    Co-Authors: Marta Sanchezgonzalez, Andres Parra, Gloria Lozanomena, Emilia M Juan, Joana M Planas
    Abstract:

    Maslinic Acid is a natural pentacyclic triterpenoid widely distributed in edible and medicinal plants with health-promoting activities. The identification and quantification of its metabolites is a requirement for a better understanding of the biological effects of this triterpene. Therefore, Maslinic Acid was orally administered to Sprague–Dawley rats at a dose of 50 mg/kg of body weight. Blood and urine were withdrawn at 45 min. Samples were extracted with ethyl acetate prior to liquid chromatography–atmospheric pressure chemical ionization–linear trap quadrupole–Orbitrap (LC–APCI–LTQ–Orbitrap) analysis. Screening of plasma yielded four monohydroxylated derivatives (M1–M4), one monohydroxylated and dehydrogenated metabolite (M5), and two dihydroxylated and dehydrogenated compounds (M6 and M7). In urine, M1, M4, M5, and M6 were detected. Quantification by LC–APCI–mass spectrometry (MS) revealed Maslinic Acid as the prevalent compound in both plasma (81.8%) and urine (73.9%), which indicates that metaboli...

  • population pharmacokinetics of Maslinic Acid a triterpene from olives after intravenous and oral administration in rats
    Molecular Nutrition & Food Research, 2014
    Co-Authors: Marta Sanchezgonzalez, Gloria Lozanomena, Emilia M Juan, Helena Colom, Joana M Planas
    Abstract:

    cope Maslinic Acid is a bioactive minor component of Olea europaea L. with health-enhancing activities and no harmful effects. A pharmacokinetic (PK) study was conducted to determine its bioavailability for future studies of Maslinic Acid in humans. Methods and results Intravenous (1 mg/kg) and oral (50 mg/kg) administrations to Sprague-Dawley rats were performed. Blood was obtained several times over 24 h and PKs were analyzed with NONMEM 7.2, applying a population approach. Body weight was included a priori in the model with fixed allometric exponents, based on allometric principles. Plasma concentrations versus time were best characterized by a two-open compartment model with first-order absorption and linear elimination. Maslinic Acid had a relative rapid oral absorption with a peak concentration after administration at 0.51 h and a bioavailability of 5.13%. Once in bloodstream, it distributed extensively into tissues, since the central and peripheral distribution volumes were 8.41 L/70 kg and 63.6 L/70 kg, respectively. The clearance (8 L/h/70 kg) was related to unaltered renal excretion. The prediction-corrected visual predictive check confirmed its stability and predictive ability. Conclusion An allometric population PK model was performed for Maslinic Acid, which adequately described and predicted plasma concentrations.

Rene Csuk - One of the best experts on this subject based on the ideXlab platform.

  • 2 o 2 chlorobenzoyl Maslinic Acid triggers apoptosis in a2780 human ovarian carcinoma cells
    European Journal of Medicinal Chemistry, 2019
    Co-Authors: Immo Serbian, Bianka Siewert, Ahmed Alharrasi, Rene Csuk
    Abstract:

    Abstract Depending on the conditions of the reactions, Maslinic Acid can be converted into the corresponding 2- O -, 3- O -, or 2,3-di- O -acylated compounds in good yields. These compounds showed in SRB assays a significantly increased cytotoxicity as compared to the parent compound Maslinic Acid. For the most active compound of this series, i.e. 2 -O- (2-chlorobenzoyl) Maslinic Acid ( 5 ), more detailed cell biological tests (i.e. AO/PI dye exclusion experiments, an annexin V assay, and microscopic investigations) on A2780 (human ovarian carcinoma cells) revealed that this compound triggers apoptosis.

  • assessment of the antiangiogenic and anti inflammatory properties of a Maslinic Acid derivative and its potentiation using zinc chloride
    International Journal of Molecular Sciences, 2019
    Co-Authors: Ioana Zinuca Pavel, Stefana Avram, Corina Danciu, Rene Csuk, Flavia Baderca, Andreea Cioca, Elenaalina Moacă, Ciprianvalentin Mihali, Iulia Pinzaru, Danina Muntean
    Abstract:

    Maslinic Acid is a pentacyclic triterpene with a plethora of biological activities, including anti-inflammatory, antioxidant, antimicrobial, cardioprotective, and antitumor effects. New derivatives with improved properties and broad-spectrum activity can be obtained following structural changes of the compound. The present study was aimed to characterize a benzylamide derivative of Maslinic Acid—benzyl (2α, 3β) 2,3-diacetoxy-olean−12-en-28-amide (EM2)—with respect to the anti-angiogenic and anti-inflammatory effects in two in vivo experimental models. Consequently, the compound showed good tolerability and lack of irritation in the chorioallantoic membrane assay with no impairment of the normal angiogenic process during the tested stages of development. In the acute ear inflammation murine model, application of EM2 induced a mild anti-inflammatory effect that was potentiated by the association with zinc chloride (ZnCl2). A decrease in dermal thickness of mice ears was observed when EM2 and ZnCl2 were applied separately or in combination. Moreover, hyalinization of the dermis appeared only when EM2 was associated with ZnCl2, strongly suggesting the role of their combination in wound healing.

  • urea derivates of ursolic oleanolic and Maslinic Acid induce apoptosis and are selective cytotoxic for several human tumor cell lines
    European Journal of Medicinal Chemistry, 2016
    Co-Authors: Sven Sommerwerk, Lucie Heller, Julia Kuhfs, Rene Csuk
    Abstract:

    2,3-Di-O-acetyl-Maslinic Acid benzylamide (5) has previously been shown to possess high cytotoxicity for a variety of human tumor cell lines while being of low cytotoxicity to non-malignant cells. Structural modifications performed on 5 revealed that the presence of these acetyl groups in 5 and the presence of (2β,3β)-configurated centers seems necessary for obtaining high cytotoxicity combined with best selectivity between malignant cells and non-malignant mouse fibroblasts. Compounds carrying an ursane skeleton showed weaker cytotoxicity than their oleanane derived analogs. In addition, the benzylamide function in compound 5 should be replaced by a phenylurea moiety to gain better cytotoxicity while retaining and improving the selectivity. Thus, Maslinic Acid derived N-[2β,3β-di-O-acetyl-17β-amino-28-norolean-12-en-17-yl]phenylurea (45) gave best results showing EC50 = 0.9 μM (for A2780 ovarian cancer cells) with EC50 > 120 μM for fibroblasts (NIH 3T3) and triggered apoptosis while caspase-3 was not activated by this compound.

  • Assessment of antitumoral and antimicrobial effects of a Maslinic Acid derivative
    Victor Babes University of Medicine and Pharmacy Timisoara, 2016
    Co-Authors: Ioana Z. Pavel, Corina Danciu, Rene Csuk, Delia Muntean, Cristina A. Dehelean, Danina M. Muntean
    Abstract:

    INTRODUCTION Maslinic Acid, a naturally occurring triterpene, has been reported to possess several therapeutic effects including antioxidant, anti-inflammatory and antiparasitic properties. Structural changes of the compound led to the development of new derivatives in order to expand the spectrum of activities. OBJECTIVES AND BACKGROUND The present study was purposed to assess the in vitro antitumoral and antibacterial effects of a Maslinic Acid derivative, namely benzyl (2α, 3β) 2,3-diacetoxy-olean-12- en-28-amide (EM2). MATERIALS AND METHODS Four compound concentrations (12.5, 25, 50 and 100 µM) were evaluated for their cytotoxic effect on A375 human melanoma and B164A5 murine melanoma cell lines using the MTT assay. Furthermore, EM2 was tested on ten bacterial strains by means of agar disk diffusion method with the assessment of the inhibition zone diameters at 24h period of time. RESULTS EM2 elicited a dose-dependent cytotoxic effect on both melanoma cell lines. Regarding the antibacterial activity, EM2 determined a significant growth inhibition on Streptococcus pyogenes (20 ± 0.26 mm) and Staphylococcus aureus (13 ± 0.19 mm). CONCLUSIONS The tested Maslinic Acid derivative is a promising antitumoral agent against skin cancer and antimicrobial agent against cocci bacteria. Graphical abstract: EM2 in vitro effect

  • In Vitro Evaluation of the Antimicrobial Ability and Cytotoxicity on Two Melanoma Cell Lines of a Benzylamide Derivative of Maslinic Acid
    Hindawi Limited, 2016
    Co-Authors: Ioana Zinuca Pavel, Corina Danciu, Rene Csuk, Delia Muntean, Cristina A. Dehelean, Camelia Oprean, Danina M. Muntean
    Abstract:

    Maslinic Acid is a pentacyclic triterpene extracted from olives that has been systematically reported to exert several therapeutic effects, such as antitumoral, antidiabetic, antioxidant, anti-inflammatory, antiparasitic, and antiviral properties. Recently, new derivatives of Maslinic Acid have been obtained and expanded the spectrum of biological activities and improved the existing ones. The present study was meant to perform the in vitro assessment of the (i) cytotoxic effects of a benzylamide derivative of Maslinic Acid (“EM2”) (benzyl (2α, 3β) 2,3-diacetoxy-olean-12-en-28-amide) on B164A5 murine melanoma and A375 human malignant melanoma cell lines and the (ii) antimicrobial activity of the compound on several bacterial strains, respectively. We obtained a dose-dependent cytotoxic effect of EM2 that was particularly relevant to the murine cell line. As on the antibacterial activity, EM2 was tested on 10 bacterial strains Bacillus cereus, Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus faecalis, Escherichia coli, Yersinia enterocolitica, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa and one fungus Candida albicans. A significant antimicrobial effect was recorded for Streptococcus pyogenes and Staphylococcus aureus