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Ilhan Kim - One of the best experts on this subject based on the ideXlab platform.
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Disulfide between Cys392 and Cys438 of human serum albumin is redox-active, which is responsible for the thioredoxin-supported Lipid Peroxidase activity
Archives of biochemistry and biophysics, 2006Co-Authors: Meekyung Cha, Ilhan KimAbstract:Human serum albumin (HSA) is an abundant protein found in blood plasma and extracellular fluids. Previously, we found that HSA has a distinct thioredoxin (Trx)-dependent Lipid Peroxidase activity in the presence of palmitoyl-CoA. In this paper, we identified the redox-active disulfide, which can be specifically reduced by Trx, responsible for the Trx-dependent Lipid Peroxidase activity. The IIB-III fragment of HSA (Pro299-Leu585) sustained the Trx-dependent Lipid Peroxidase activity. Chemical modification of the Trx-reduced IIB-III with a thiol-specific modification agent resulted in a complete loss of the Peroxidase activity. The analysis of tryptic-peptides derived from the inactivated HSA and IIB-III revealed that Cys392 and Cys438, which exist as an intramolecular disulfide bond in HSA, were preferentially modified in both HSA and IIB-III. Taken together, these results suggested that HSA has a capability to reduce Lipid hydroperoxide with the use of Trx as an in vivo electron donor, and that the redox-active disulfide between Cys392 and Cys438 acts as a primary site of the catalysis for the Trx-linked Lipid Peroxidase activity.
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vibrio cholerae thiol Peroxidase glutaredoxin fusion is a 2 cys tsa ahpc subfamily acting as a Lipid hydroperoxide reductase
Journal of Biological Chemistry, 2004Co-Authors: Meekyung Cha, Seungkeun Hong, Dongsuk Lee, Ilhan KimAbstract:Recently, novel hybrid thiol Peroxidase (TPx) proteins fused with a glutaredoxin (Grx) were found from some pathogenic bacteria, cyanobacteria, and anaerobic sulfur-oxidizing phototroph. The phylogenic tree analysis that was constructed from the aligned sequences showed two major branches. Haemophilus influenzae TPx·Grx was grouped in one branch as a 1-Cys subfamily of the thiol-specific antioxident protein/AhpC family. Most TPx·Grx proteins, including Vibrio cholerae TPx·Grx, were grouped in the 2-Cys subfamily. To explain the existence of two subgroups in novel hybrid TPx proteins, we have compared the kinetics given by V. cholerae TPx·Grx, H. influenzae TPx·Grx, their separated TPx domains, and a set of mutants devoid of the redox-active cysteines. The kinetic study described here demonstrates clearly that V. cholerae TPx·Grx is a 2-Cys TPx subfamily. For the first time, we also demonstrate the Lipid Peroxidase activity of V. cholerae TPx·Grx fusion and suggest the in vivo function of 2-Cys TPx·Grx fusion serving as a Lipid Peroxidase.
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escherichia coli periplasmic thiol Peroxidase acts as Lipid hydroperoxide Peroxidase and the principal antioxidative function during anaerobic growth
Journal of Biological Chemistry, 2004Co-Authors: Meekyung Cha, Woncheol Kim, Changjin Lim, Kanghwa Kim, Ilhan KimAbstract:To clarify the enzymatic property of Escherichia coli periplasmic thiol Peroxidase (p20), the specific Peroxidase activity toward peroxides was compared with other bacterial thiol Peroxidases. p20 has the most substrate preference and Peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the most potent Lipid Peroxidase activity. Despite that the mutation of p20 caused the highest susceptibility toward organic hydroperoxide and heat stress, the cellular level of p20 did not respond to the exposure of oxidative stress. Expression level of p20 during anaerobic growth was sustained at the approximately 50% level compared with that of the aerobic growth. Viability of aerobic p20Delta without glucose was reduced to the approximately 65% level of isogenic strains, whereas viability of aerobic p20Delta with 0.5% glucose supplement was sustained. The deletion of p20 resulted in a gradual loss of the cell viability during anaerobic growth. At the stationary phase, the viability of p20Delta was down to approximately 10% level of parent strains. An analysis of the protein carbonyl contents of p20Delta as a marker for cellular oxidation indicates that severe reduction of viability of anaerobic p20Delta was caused by cumulative oxidative stress. P20Delta showed hypersensitivity toward membrane-soluble organic hydroperoxides. An analysis of protein carbonyl and Lipid hydroperoxide contents in the membrane of the stress-imposed p20Delta demonstrates that the severe reduction of viability was caused by cumulative oxidative stress on the membrane. Taken together, present data uncover in vivo function for p20 as a Lipid hydroperoxide Peroxidase and demonstrate that, as the result, p20 acts as the principal antioxidant in the anaerobic habitats.
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Thioredoxin-linked Lipid hydroperoxide Peroxidase activity of human serum albumin in the presence of palmitoyl coenzyme A
Free radical biology & medicine, 2001Co-Authors: Heeyong Lee, Ilhan KimAbstract:Human Serum Albumin (HSA) exerted a significant Lipid Peroxidase activity with the use of a thiol-reducing equivalent such as dithiothreitol (DTT). Carboxyl group-modified HSA (CM-HSA) showed a 10-fold stronger Lipid Peroxidase activity (1.6 nmol/min/mg) than that of HSA (0.17 nmol/min/mg). Instead of DTT, thioredoxin (Trx) also supported reducing equivalent to the reduction of Lipid hydroperoxide by CM-HSA. Contrast to CM-HSA, HSA did not reduce Lipid peroxide with the use of Trx. In the presence of palmitoyl coenzyme A (palmitoyl-CoA) however, HSA used Trx as an electron donor to the reduction of Lipid hydroperoxide. The Trx-linked Peroxidase activity of HSA sharply increased with elongation in the carbon chain of the acyl moiety of acyl-CoA, showing an optimum activity in the presence of palmitoyl-CoA. Fluorescence study indicates the conformational changes of HSA induced by palmitoyl-CoA. Together, these data suggest that palmitoyl-CoA-bound HSA has a capability to remove Lipid peroxide with the use of electrons given by Trx system.
Maghfiroh Gesty Maharani - One of the best experts on this subject based on the ideXlab platform.
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molecular docking studies flavonoid quercetin isoquercetin and kaempferol of single bulb garlic allium sativum to inhibit lanosterol synthase as anti hypercholesterol therapeutic strategies
International Seminar Metallurgy and Materials, 2020Co-Authors: Maghfiroh Gesty Maharani, Sri Lestari, Betty LukiatiAbstract:Hypercholesterolemia is the highest risk of CVD which is the biggest disease leading death. One of the Indonesian medicinal plants is single bulb garlic with high flavonoids concentration. Lanosterol synthase, an enzyme on the final stage of cholesterol synthesis are the appropriate inhibition stage for drug. This study aimed to analyze the potential of single bulb garlic flavonoids (quercetin, isoquercetin, and kaempferol) in inhibiting lanosterol synthase. Computational docking analysis was performed using Pyrx, Pymol, Discovery studio, also webserver to predict ADMET and biological activity. Lanosterol synthase was obtained from PDB (PDB ID: IW6J) with RO 48-8071 as native ligand used for control. The results showed binding affinity RO 48-8071 (-10.3 kcal/mol), quercetin (-9.8 kcal/mol), isoquercetin (-6.8 kcal/mol), and kaempferol (-9.9 kcal/mol). Based on interaction and bonding distance, flavonoids have more stable than control. Flavonoids also have potential as APOA1, HMOX1 enhancers, Lipid Peroxidase inhibitors, cardioprotectant and hepatoprotectant, high distribution volumes, low toxicity, and clearance. This result indicated that quercetin, isoquercetin, and kaempferol from single bulb garlic could be potential ligand to treat hypercholesterolemia, and could proceed to in vitro and in vivo study by improving the absorption.
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potensi antihiperkolesterolemik senyawa flavonoid quercetin isoquercetin dan kaempferol bawang putih tunggal allium sativum terhadap target enzim lanosterol synthase menggunakan teknik molecular docking
SKRIPSI Jurusan Biologi - Fakultas MIPA UM, 2019Co-Authors: Maghfiroh Gesty MaharaniAbstract:Potensi Anti hiperkolesterolemik Senyawa Flavonoid (Quercetin, Isoquercetin, dan Kaempferol) Bawang Putih Tunggal (Allium sativum) Terhadap Target Enzim Lanosterol Synthase MenggunakanTeknik Molecular Docking Maghfiroh Gesty Maharani1, Sri Rahayu Lestari1, Betty Lukiati1 1Jurusan Biologi, FakultasMatematikadanIlmuPengetahuanAlam UniversitasNegeri Malang, Jalan Semarang No 5 Malang, 65145, Indonesia Email koresponden :srirahayulestari@um.ac.id Abstrak : Jantung dan stroke merupakan penyakit penyebab kematian terbesar di duniadengan faktor risiko tertinggi karena hiperkolesterolemia. Penggunaan tanaman herbal sebagai obat hiperkolesterolemia meningkat seiring dengan bertambahnya efek samping obat sintetis dan rekomendasi oleh WHO. Tanaman obat Indonesia, salah satunya adalah bawang putih tunggal. Kandungan utama bawang putih tunggal selain senyawa organosulfur adalah flavonoid. Tahap akhir sintesis kolesterol yang melibatkan enzim lanosterol synthase, merupakan tahapan paling tepat untuk penghambatan obat. Tujuan penelitian ini adalah memprediksi potensi senyawa flavonoid bawang putih tunggal (quercetin, isoquercetin, dan kaempferol) dalam menghambat enzim lanosterol synthase sebagai antihiperkolesterolemia. Penelitian ini melalui teknik molecular docking dengan software Pyrx, Pymol, Discovery studio serta webserver prediksi potensi dan sifat farmakokinetik. Hasil penelitian menunjukkan senyawa flavonoid bawang putih tunggal memiliki potensi sebagai APOA1 dan HMOX1 enhancer, Lipid Peroxidase inhibitor, cardioprotectant serta hepatoprotectant, memiliki volume distribusi tinggi (> 0,45 logL/kg), nilai clearance dan toksisitas rendah. Hasil docking menunjukkan energi ikatan RO 48-8071 (-10,3 kcal/mol), kaempferol (-9,9 kcal/mol), quercetin (-9,8 kcal/mol), isoquercetin (-6,8 kcal/mol), senyawa flavonoid memiliki ikatan hidrogen dan interaksi hidrofobik, dengan jarak ikatan yang lebih stabil dibandingkan kontrol. Berdasarkan berbagai parameter, senyawa flavonoid memiliki potensi sebagai antihiperkolesterolemia. Hasil prediksi pada penelitian dapat dilanjutkan untuk menguji senyawa flavonoid bawang putih tunggal secara in vitro dan in vivo dengan meningkatkan absorbsi senyawa. Kata Kunci : Antihiperkolesterolemia, Bawang putih tunggal, Flavonoid, Molecular docking. Anti hypercholesterolemic Potential Flavonoid (Quercetin, Isoquercetin, and Kaempferol) of Single Clove Garlic (Allium sativum) Against the Lanosterol Synthase Using Molecular Docking Technique Maghfiroh Gesty Maharani1, Sri Rahayu Lestari1, Betty Lukiati1 1Biology Departement, Faculty Mathematics and Science State University of Malang, St. Semarang 5 Malang, 65145, Indonesia Corresponding author :srirahayulestari@um.ac.id Abstract: Heart and stroke are the biggest cause of death in the world with the highest risk factors due to hypercholesterolemia. The use of herbs as hypercholesterolemia drug increases with increasing side effects of synthetic drugs and recommendations by WHO. Indonesian medicinal plants, one of which is single clove garlic. The main content of single clove garlic beside organosulfur compounds is flavonoids. The final stage of cholesterol synthesis involving the enzyme lanosterol synthase, is the most appropriate stage for drug inhibition. The purpose of this study was to predict the potential of single clove garlic flavonoids (quercetin, isoquercetin, and kaempferol) in inhibiting the enzyme lanosterol synthase as antihypercholesterolemia. This research is through molecular docking techniques with Pyrx, Pymol software, Discovery studios and web server predictors of potential and pharmacokinetic properties. The results showed that single garlic flavonoids had potential as APOA1 and HMOX1 enhancers, Lipid Peroxidase inhibitors, cardioprotectant and hepatoprotectant, had high distribution volumes (> 0.45 logL / kg), low clearance and toxicity. The docking result shows RO bond energy 48-8071 (-10.3 kcal / mol), kaempferol (-9.9 kcal / mol), quercetin (-9.8 kcal / mol), isoquercetin (-6.8 kcal / mol ), flavonoid compounds have hydrogen bonds and hydrophobic interactions, with bonding distances that are more stable than controls. Based on various parameters, flavonoids have the potential to be antihypercholesterolemic. Predicted results in the study can be continued to test single garlic flavonoids in vitro and in vivo by increasing the absorption of compounds. Keywords : Antihypercholesterolemia, Single Clove Garlic, Flavonoids, Molecular docking. 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Potensi Antihiperkolesterolemik Senyawa Flavonoid (Quercetin, Isoquercetin, dan Kaempferol) Bawang Putih Tunggal (Allium sativum) Terhadap Target Enzim Lanosterol Synthase Menggunakan Teknik Molecular Docking
SKRIPSI Jurusan Biologi - Fakultas MIPA UM, 2019Co-Authors: Maghfiroh Gesty MaharaniAbstract:Potensi Anti hiperkolesterolemik Senyawa Flavonoid (Quercetin, Isoquercetin, dan Kaempferol) Bawang Putih Tunggal (Allium sativum) Terhadap Target Enzim Lanosterol Synthase MenggunakanTeknik Molecular DockingMaghfiroh Gesty Maharani1, Sri Rahayu Lestari1, Betty Lukiati1 1Jurusan Biologi, FakultasMatematikadanIlmuPengetahuanAlam UniversitasNegeri Malang, Jalan Semarang No 5 Malang, 65145, IndonesiaEmail koresponden :srirahayulestari@um.ac.id Abstrak: Jantung dan stroke merupakan penyakit penyebab kematian terbesar di duniadengan faktor risiko tertinggi karena hiperkolesterolemia. Penggunaan tanaman herbal sebagai obat hiperkolesterolemia meningkat seiring dengan bertambahnya efek samping obat sintetis dan rekomendasi oleh WHO. Tanaman obat Indonesia, salah satunya adalah bawang putih tunggal. Kandungan utama bawang putih tunggal selain senyawa organosulfur adalah flavonoid. Tahap akhir sintesis kolesterol yang melibatkan enzim lanosterol synthase, merupakan tahapan paling tepat untuk penghambatan obat. Tujuan penelitian ini adalah memprediksi potensi senyawa flavonoid bawang putih tunggal (quercetin, isoquercetin, dan kaempferol) dalam menghambat enzim lanosterol synthase sebagai antihiperkolesterolemia. Penelitian ini melalui teknik molecular docking dengan software Pyrx, Pymol, Discovery studio serta webserver prediksi potensi dan sifat farmakokinetik. Hasil penelitian menunjukkan senyawa flavonoid bawang putih tunggal memiliki potensi sebagai APOA1 dan HMOX1 enhancer, Lipid Peroxidase inhibitor, cardioprotectant serta hepatoprotectant, memiliki volume distribusi tinggi (> 0,45 logL/kg), nilai clearance dan toksisitas rendah. Hasil docking menunjukkan energi ikatan RO 48-8071 (-10,3 kcal/mol), kaempferol (-9,9 kcal/mol), quercetin (-9,8 kcal/mol), isoquercetin (-6,8 kcal/mol), senyawa flavonoid memiliki ikatan hidrogen dan interaksi hidrofobik, dengan jarak ikatan yang lebih stabil dibandingkan kontrol. Berdasarkan berbagai parameter, senyawa flavonoid memiliki potensi sebagai antihiperkolesterolemia. Hasil prediksi pada penelitian dapat dilanjutkan untuk menguji senyawa flavonoid bawang putih tunggal secara in vitro dan in vivo dengan meningkatkan absorbsi senyawa. Kata Kunci: Antihiperkolesterolemia, Bawang putih tunggal, Flavonoid, Molecular docking. Anti hypercholesterolemic Potential Flavonoid (Quercetin, Isoquercetin, and Kaempferol) of Single Clove Garlic (Allium sativum) Against the Lanosterol Synthase Using Molecular Docking TechniqueMaghfiroh Gesty Maharani1, Sri Rahayu Lestari1, Betty Lukiati1 1Biology Departement, Faculty Mathematics and Science State University of Malang, St. Semarang 5 Malang, 65145, IndonesiaCorresponding author :srirahayulestari@um.ac.id Abstract: Heart and stroke are the biggest cause of death in the world with the highest risk factors due to hypercholesterolemia. The use of herbs as hypercholesterolemia drug increases with increasing side effects of synthetic drugs and recommendations by WHO. Indonesian medicinal plants, one of which is single clove garlic. The main content of single clove garlic beside organosulfur compounds is flavonoids. The final stage of cholesterol synthesis involving the enzyme lanosterol synthase, is the most appropriate stage for drug inhibition. The purpose of this study was to predict the potential of single clove garlic flavonoids (quercetin, isoquercetin, and kaempferol) in inhibiting the enzyme lanosterol synthase as antihypercholesterolemia. This research is through molecular docking techniques with Pyrx, Pymol software, Discovery studios and web server predictors of potential and pharmacokinetic properties. The results showed that single garlic flavonoids had potential as APOA1 and HMOX1 enhancers, Lipid Peroxidase inhibitors, cardioprotectant and hepatoprotectant, had high distribution volumes (> 0.45 logL / kg), low clearance and toxicity. The docking result shows RO bond energy 48-8071 (-10.3 kcal / mol), kaempferol (-9.9 kcal / mol), quercetin (-9.8 kcal / mol), isoquercetin (-6.8 kcal / mol ), flavonoid compounds have hydrogen bonds and hydrophobic interactions, with bonding distances that are more stable than controls. Based on various parameters, flavonoids have the potential to be antihypercholesterolemic. Predicted results in the study can be continued to test single garlic flavonoids in vitro and in vivo by increasing the absorption of compounds. Keywords: Antihypercholesterolemia, Single Clove Garlic, Flavonoids, Molecular docking
Meekyung Cha - One of the best experts on this subject based on the ideXlab platform.
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Disulfide between Cys392 and Cys438 of human serum albumin is redox-active, which is responsible for the thioredoxin-supported Lipid Peroxidase activity
Archives of biochemistry and biophysics, 2006Co-Authors: Meekyung Cha, Ilhan KimAbstract:Human serum albumin (HSA) is an abundant protein found in blood plasma and extracellular fluids. Previously, we found that HSA has a distinct thioredoxin (Trx)-dependent Lipid Peroxidase activity in the presence of palmitoyl-CoA. In this paper, we identified the redox-active disulfide, which can be specifically reduced by Trx, responsible for the Trx-dependent Lipid Peroxidase activity. The IIB-III fragment of HSA (Pro299-Leu585) sustained the Trx-dependent Lipid Peroxidase activity. Chemical modification of the Trx-reduced IIB-III with a thiol-specific modification agent resulted in a complete loss of the Peroxidase activity. The analysis of tryptic-peptides derived from the inactivated HSA and IIB-III revealed that Cys392 and Cys438, which exist as an intramolecular disulfide bond in HSA, were preferentially modified in both HSA and IIB-III. Taken together, these results suggested that HSA has a capability to reduce Lipid hydroperoxide with the use of Trx as an in vivo electron donor, and that the redox-active disulfide between Cys392 and Cys438 acts as a primary site of the catalysis for the Trx-linked Lipid Peroxidase activity.
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vibrio cholerae thiol Peroxidase glutaredoxin fusion is a 2 cys tsa ahpc subfamily acting as a Lipid hydroperoxide reductase
Journal of Biological Chemistry, 2004Co-Authors: Meekyung Cha, Seungkeun Hong, Dongsuk Lee, Ilhan KimAbstract:Recently, novel hybrid thiol Peroxidase (TPx) proteins fused with a glutaredoxin (Grx) were found from some pathogenic bacteria, cyanobacteria, and anaerobic sulfur-oxidizing phototroph. The phylogenic tree analysis that was constructed from the aligned sequences showed two major branches. Haemophilus influenzae TPx·Grx was grouped in one branch as a 1-Cys subfamily of the thiol-specific antioxident protein/AhpC family. Most TPx·Grx proteins, including Vibrio cholerae TPx·Grx, were grouped in the 2-Cys subfamily. To explain the existence of two subgroups in novel hybrid TPx proteins, we have compared the kinetics given by V. cholerae TPx·Grx, H. influenzae TPx·Grx, their separated TPx domains, and a set of mutants devoid of the redox-active cysteines. The kinetic study described here demonstrates clearly that V. cholerae TPx·Grx is a 2-Cys TPx subfamily. For the first time, we also demonstrate the Lipid Peroxidase activity of V. cholerae TPx·Grx fusion and suggest the in vivo function of 2-Cys TPx·Grx fusion serving as a Lipid Peroxidase.
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escherichia coli periplasmic thiol Peroxidase acts as Lipid hydroperoxide Peroxidase and the principal antioxidative function during anaerobic growth
Journal of Biological Chemistry, 2004Co-Authors: Meekyung Cha, Woncheol Kim, Changjin Lim, Kanghwa Kim, Ilhan KimAbstract:To clarify the enzymatic property of Escherichia coli periplasmic thiol Peroxidase (p20), the specific Peroxidase activity toward peroxides was compared with other bacterial thiol Peroxidases. p20 has the most substrate preference and Peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the most potent Lipid Peroxidase activity. Despite that the mutation of p20 caused the highest susceptibility toward organic hydroperoxide and heat stress, the cellular level of p20 did not respond to the exposure of oxidative stress. Expression level of p20 during anaerobic growth was sustained at the approximately 50% level compared with that of the aerobic growth. Viability of aerobic p20Delta without glucose was reduced to the approximately 65% level of isogenic strains, whereas viability of aerobic p20Delta with 0.5% glucose supplement was sustained. The deletion of p20 resulted in a gradual loss of the cell viability during anaerobic growth. At the stationary phase, the viability of p20Delta was down to approximately 10% level of parent strains. An analysis of the protein carbonyl contents of p20Delta as a marker for cellular oxidation indicates that severe reduction of viability of anaerobic p20Delta was caused by cumulative oxidative stress. P20Delta showed hypersensitivity toward membrane-soluble organic hydroperoxides. An analysis of protein carbonyl and Lipid hydroperoxide contents in the membrane of the stress-imposed p20Delta demonstrates that the severe reduction of viability was caused by cumulative oxidative stress on the membrane. Taken together, present data uncover in vivo function for p20 as a Lipid hydroperoxide Peroxidase and demonstrate that, as the result, p20 acts as the principal antioxidant in the anaerobic habitats.
Noorlidah Abdullah - One of the best experts on this subject based on the ideXlab platform.
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effect of clausena excavata burm f rutaceae leaf extract on wound healing and antioxidant activity in rats
Drug Design Development and Therapy, 2015Co-Authors: Shaymaa Fadhel Abbas Albaayit, Yusuf Abba, Abdullah Rasedee, Noorlidah AbdullahAbstract:Clausena excavata is a well-known plant used in folkloric medicine for the treatment of different ailments. This study aimed to determine the in vitro cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT (keratocyte) and Vero cell lines were used for evaluation of the in vitro cytotoxic effects, while the in vivo wound healing and antioxidant activities were determined in skin wounds inflicted on rats. Twenty adult male Sprague-Dawley rats were divided into five groups of four animals each. Approximately 3.14 cm2 excisional wound was inflicted on the nape of each rat following anesthesia. The treatment groups received topical application of MECE at 50 mg/mL (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD [high dose]), while the negative control group was treated with gum acacia in normal saline and the positive control group with intrasite gel. Wound contraction was evaluated on days 5, 10, and 15 after wound infliction, and tissue from wound area was collected at day 15 post-wound infliction for antioxidant enzyme evaluation and histopathological analyses. Generally, Vero cells were more resistant to the cytotoxic effects of the solvent extracts as compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C. excavata were toxic to HaCaT cells at 200 and 400 µg/mL, but the same concentrations showed higher (P<0.05) viability in Vero cells. There was significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound infliction in all the treatment groups than in the control groups. Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05) lesser inflammatory cell proliferation, degeneration, and distribution of granulation tissue than other groups. Similarly, the degree of collagen maturation, angiogenesis, and collagen distribution were significantly (P<0.05) lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite treatment groups showed a significantly (P<0.05) higher number of VEGF-positive and TGF-β1-positive cells in the skin wound than the control groups. The activities of superoxide dismutase and catalase were significantly (P<0.01) higher in the MECE-HD and intrasite treatment groups than in the other groups. Lipid Peroxidase activity of the treated groups was significantly (P<0.01) lower than that in the control group. The study showed that MECE is a potent wound healing agent through anti-inflammatory and antioxidant effects that enhanced the rate of wound contraction, re-epithelialization, and collagen deposition. The effect of MECE is suggested to be due to its high polyphenolic compound content.
Andrew J. Aguirre - One of the best experts on this subject based on the ideXlab platform.
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Dependency of a therapy-resistant state of cancer cells on a Lipid Peroxidase pathway
Nature, 2017Co-Authors: Vasanthi S. Viswanathan, Matthew J Ryan, Harshil Dhruv, Shubhroz Gill, Ossia M. Eichhoff, Brinton Seashore-ludlow, Samuel D. Kaffenberger, John K Eaton, Kenichi Shimada, Andrew J. AguirreAbstract:Cancer cells can assume different biological states, which can affect their resistance to therapies. A mesenchymal phenotype has been associated with drug resistance but the mechanism behind this state is not well understood. Stuart Schreiber and colleagues now show that tumour cells with a mesenchymal phenotype are selectively sensitive to inhibition of GPX4, an enzyme that alters Lipid metabolism. GPX4 dissipates Lipid peroxides and therefore prevents the iron-mediated reactions which induce ferroptotic cell death. These findings offer new perspectives on targeting cancers that have undergone a transition to a mesenchymal state to evade other therapeutic agents.