Morin attenuates L-arginine induced acute pancreatitis in rats by downregulating myeloperoxidase and lipid peroxidation

Objective:To explore the therapeutic role of morin against L-arginine-induced acute pancreatitis in rats. Methods:The group 1 received two intraperitoneal injections of normal saline, and groups 2-4 were given two intraperitoneal injections of L-arginine (250 mg/100 g body weight) at 1 h interval to induce acute pancreatitis. Subsequently, group 2 received no further treatment while groups 3 and 4 were treated with morin (30 mg/kg) and diclofenac sodium (30 mg/kg), respectively. Blood glucose and serum levels of insulin, α-amylase, malondialdehyde, myeloperoxidase, alanine aminotransferase, aspartate aminotransferase and cholesterol were measured. Moreover, histopathological study was carried out to investigate the effect of morin treatment on physiology of the pancreas. Results:L-arginine significantly altered the level of blood glucose and serum levels of insulin, α-amylase, malondialdehyde, myeloperoxidase, alanine aminotransferase, aspartate aminotransferase and cholesterol. Treatment with morin or diclofenac sodium significantly improved the levels of these biomarkers. Furthermore, morin showed more significant effect than diclofenac sodium. Histopathological analysis verified that morin protected the pancreas from deleterious effects of L-arginine. Conclusions:Morin plays a protective role against L-arginine-induced acute pancreatitis via reducing lipid peroxidation and tissue inflammation, and attenuating acute pancreatitis-associated alteration in insulin secretion and glucose metabolism.

A validated HPTLC method for quantitative analysis of morin in Maclura cochinchinensis heartwood / 中草药·英文版

Objective: The study was conducted to develop and validate a high performance thin-layer chromatography (HPTLC)-densitometric method for the quantitative analysis of morin in Maclura cochinchinensis heartwood collected from different locations in Thailand. Methods: HPTLC analysis was performed on an aluminium sheet of silica gel 60 F254 using toluene: ethyl acetate: formic acid (36:12:7, volume percent) as a mobile phase. The densitometric scanning was performed at the wavelength 410 nm. HPTLC method was validated according to ICH guideline. Results: The proposed HPTLC method showed acceptable validation parameters. The content of morin in M. cochinchinensis heartwood collected from eight different provinces in Thailand were in the ranges of 1.53%−2.73%. Conclusion: The simple and sensitive HPTLC method was successfully developed and validated for determination of morin in M. cochinchinensis heartwood. The proposed HPTLC method was found to be simple, fast and inexpensive, and can be used for the routine quality control of raw materials.

Preparation of morin-Cu2+ complex imprinted polymer and its application in solid phase extraction / 中草药

Objective: To prepare morin-Cu2+ complex imprinted polymer (CIP) and use the polymer to extract morin from mulberry branch. Methods: Morin-Cu2+ CIPs were prepared in water-methanol polar solvent in the presence of Cu2+, acrylamide as the functional monomer. The CIPs were used as the solid phase extraction sorbent for extracting morin from mulberry branch. Results: The prepared CIPs had specific and selective adsorption on morin, the maximum adsorption capacity was 82 μmol/g, which was much higher than that of the traditional imprinted polymers relying on hydrogen bond and non-imprinted polymers. The separation factors of CIPs to daidzein and catechin were 4.81 and 4.02, respectively. CIPs had a significant enrichment effect on morin in the composition of the mulberry branch solid phase extraction elution solution. Conclusion: Morin-Cu2+ CIPs are excellent material used for the separation and enrichment of morin, the material has good selective adsorption ability and environmental adaptability.

Effects of Locally Delivered Morin Hydrate on Iodoacetate-induced Temporomandibular Joint Osteoarthritis in Rats / Efeitos locais da indução de Hidrato de Morina na articulação temporomandibular de ratos com osteoartrite induzida por Iodoacetato

Objectives: morin hydrate has been reported to possess many beneficial pharmacological potentialities including antioxidant and anti-osteoarthritic effects. The anti-osteoarthritic properties of locally administrated morin have not been investigated. The objective of this study is to evaluate the locally delivered morin on the temporomandibular joint osteoarthritis in rat. Materials and methods: thirty young adult female Sprague Dawley rats were randomly arranged into three groups; control, osteoarthritis and osteoarthritis with morin. Both the iodoacetate for osteoarthritis induction and morin hydrate therapy were delivered unilaterally via intra-articular route. Results: morin reduced osteoarthritis manifestations with prominent thickening of both condylar fibrous layer and articular disc accompanied with discal cells hypertrophy that ultimately acquired chondrocytes features. The condylar cartilage matrix showed enhancement of extracellular matrix production with morin administration. Discussion: the present studyhas elucidated antiosteoarthritic effect of intra articular injection of morin hydrate. Although morin has managed to prevent the propagation and advancing some of the recorded osteoarthritic manifestations; however, it showed some failure in managing others. The administration of morin hydrate modulated the structure of the joint rather than restore it back to its typical configuration. Conclusion: the morin hydrate administration to osteoarthritic animals showed relieve in some of osteoarthritic features and modulated the structure of some joint components to compensate the unhandled manifestations (AU)

Objetivo: Relata-se que o Hidrato de Morina possui diversas potencialidades farmacológicas benéficas, incluindo efeitos antioxidantes e anti-osteoartríticos. As propriedades antiosteoartríticas da morina administrada localmente não foram investigadas. O objetivo deste estudo é avaliar a Morina administrada localmente sobre a osteoartrite da articulação temporomandibular em ratos. Material e métodos: Trinta ratos adultos jovens de linhagem Sprague Dawley foram dispostos aleatoriamente em três grupos: grupo controle, grupo com osteoartrite e grupo com osteoartrite e Morina. Tanto o Iodoacetato para a indução da osteoartrite como a terapia com Hidrato de Morina foram administrados unilateralmente por via intra-articular. Resultados: A Morina reduziu as manifestações da osteoartrite com espessamento proeminente tanto da camada fibrosa condilar como do disco articular acompanhado de hipertrofia das células discais que acabaram por adquirir características condrócitas. A matriz da cartilagem condilar mostrou um aumento da produção de matriz extracelular com administração de Morina. Discussão: O presente estudo elucidou o efeito antiosteoartrítico da injeção intra-articular de Hidrato de Morina. Apesar da Morina ter impedido a propagação e o avanço de algumas das manifestações osteoartríticas registadas, mostrou algumas falhas na manipulação de outras. A administração de Hidrato de Morina modulou a estrutura da articulação em vez de restaurar à sua configuração típica. Conclusão: A administração de Hidratode Morina em animais osteoartríticos mostrou alívio em algumas das características osteoartríticas e modulou a estrutura de alguns componentes da articulação em compensação às manifestações não tratadas. (AU)

Morin Prevents Granule Cell Dispersion and Neurotoxicity via Suppression of mTORC1 in a Kainic Acid-induced Seizure Model

An abnormal reorganization of the dentate gyrus and neurotoxic events are important phenotypes in the hippocampus of patients with temporal lobe epilepsy (TLE). The effects of morin, a bioflavonoid constituent of many herbs and fruits, on epileptic seizures have not yet been elucidated, though its beneficial effects, such as its anti-inflammatory and neuroprotective properties, are well-described in various neurodegenerative diseases. In the present study, we investigated whether treatment with morin hydrate (MH) can reduce the susceptibility to seizures, granule cell dispersion (GCD), mammalian target of rapamycin complex 1 (mTORC1) activity, and the increases in the levels of apoptotic molecules and inflammatory cytokines in the kainic acid (KA)-induced seizure mouse model. Our results showed that oral administration of MH could reduce susceptibility to seizures and lead to the inhibition of GCD and mTORC1 activity in the KA-treated hippocampus. Moreover, treatment with MH significantly reduced the increased levels of apoptotic signaling molecules and pro-inflammatory mediators in the KA-treated hippocampus compared with control mice, suggesting a neuroprotective role. Therefore, these results suggest that morin has a therapeutic potential against epilepsy through its abilities to inhibit GCD and neurotoxic events in the in vivo hippocampus.

Anti-epileptic effect of morin against experimental pentylenetetrazol-inducedseizures via modulating brain monoamines and oxidative stress

Objective: To evaluate the protective effect of morin against pentylenetetrazol (PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice (18-22 g) was used to induce convulsions by intraperitoneal (i.p.) administration of PTZ (90 mg/kg). Mice were either pretreated with morin (10, 20 and 40 mg/kg) or vehicle (distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production (P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin (20 and 40 mg/kg) administration. The PTZ-induced decrease in brain GABA, dopamine and Na+K+ATPase levels and increase in xanthine oxidase activity were inhibited significantly by morin (20 and 40 mg/kg) treatment. The increased levels of malondialdehyde and nitric oxide level were significantly decreased by morin (20 and 40 mg/kg) treatment. Also, reduced levels of superoxide dismutase and glutathione were increased significantly by morin treatment. Conclusions: Results of the present study indicate that morin showed its anti-convulsant effect via modulating the levels of brain GABA, Na+K+ATPase, and oxido-nitrosative stress. Thus, morin can be a potential candidate for further clinical evaluations as an anti-epileptic agent.

Anti-epileptic effect of morin against experimental pentylenetetrazol-induced seizures via modulating brain monoamines and oxidative stress

Objective: To evaluate the protective effect of morin against pentylenetetrazol (PTZ)-induced tonic-clonic convulsions in mice. Methods: Swiss albino mice (18-22 g) was used to induce convulsions by intraperitoneal (i.p.) administration of PTZ (90 mg/kg). Mice were either pretreated with morin (10, 20 and 40 mg/kg) or vehicle (distilled water, 10 mg/kg) 45 min before PTZ administration. Various behavioral and biochemical parameters were assessed. Results: PTZ administration resulted in significant production (P<0.001) of tonic-clonic conclusion and mortality in mice. PTZ-induced increase in the duration of convulsion, onset of convulsion and mortality was inhibited significantly by morin (20 and 40 mg/kg) administration. The PTZ-induced decrease in brain GABA, dopamine and Na

Effects of co-administration with morin and acetyl-resveratrolon pharmacokinetics of saquinavir in rats / 中国药理学通报

Aim To assess the impact of morin and acetyl-resveratrol on the oral bioavailability and pharmacokinetics of saquinavir (SQV), a substrate of P-glycoprotein (P-gp), in rats.Methods Twenty rats were randomized into four groups of equal size, including a control group, two intervention groups and a positive control group, and administered orally 30 mg·kg-1 SQV with or without 40 mg·kg-1 morin or acetyl-resveratrol or verapamil (as positive control).The plasma concentrations of saquinavir were determined using a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method, and the PK of SQV was assessed using non-compartmental analysis.Results The PK parameters values of SQV, SQV+morin, SQV+acetyl-resveratrol, SQV+verapamil were as follows: AUC0-t, 381.53 μg·h·L-1,185.53 μg·h·L-1, 360.43 μg·h·L-1, 529.95 μg·h·L-1;AUC0-∞, 409.48 μg·h·L-1, 228.52 μg·h·L-1,446.67 μg·h·L-1, 552.41 μg·h·L-1;Cmax, 110.80 μg·L-1, 86.44 μg·L-1, 139.84 μg·L-1, 423.60 μg·L-1;Tmax, 0.25 h, 0.25 h, 0.25 h, 0.50 h;T1/2, 5.72 h, 5.94 h, 6.78 h, 3.78 h;MRT0-∞, 10.30 h, 9.61 h, 12.30 h, 4.89 h;CL/F, 7.59 mL·kg-1·h-1, 13.88 mL·kg-1·h-1, 7.28 mL·kg-1·h-1, 5.52 mL·kg-1·h-1.Conclusions Multiple peak phenomenon can be observed in the plasma SQV profiles.Morin can significantly reduce the SQV oral bioavailability and affect SQV PK profiles while acetyl-resveratrol cannot significantly affect the SQV oral bioavailability and SQV PK profiles in rats.

Fabrication and Application of a Molecularly Imprinted Sensor for Morin Detection / 分析化学

Based on the intermolecular interaction, a molecularly imprinted polymer electrochemical sensor with specific identification of cavity on gold electrode surface was proposed with o-aminophenol as functional monomers and morin as template molecule. The performance and effect of MIP were investigated by cyclic voltammetry ( CV) and differential pulse voltammetry ( DPV) . Factors affecting the properties of sensor, such as polymeric membrane ratio, scanning cycles, elution time and adsorption time were investigated. Substances which had a similar structure to morin was used to compared the selective response. The result showed that the sensor had a good selectivity to morin. Under the optimized experiment conditions, the current response of the imprinted sensor was linear to the concentration of morin in the range of 0 . 05-1 . 7 μmol/L with linear equation as follows: I(μA)= 1. 0800lgc(mol/L)+ 9. 3599(R=0. 9934), and the detection limit of 0. 1 μmol/L. The sensor was used to determine the content of morin in black tea samples, and the recoveries of standard addition were between 104 . 0% and 108 . 0%.

Effect of morin on LPS induced acute lung injury and its mechanism / 重庆医学

Objective To study the effect of morin on LPS induced acute lung injury mouse model and its mechanism .Meth‐ods Thirty male C57B/L mice were randomly divided into control group ,LPS group and LPS+ morin group ,with 10 in each group .5 mg/kg LPS was instilled into the lung from an trachea intubation in LPS group and LPS+morin group .Then the mice in LPS+morin group received an intraperitoneal injection of morin (40 mg/kg) every day for the next 3 d .Others received an equal a‐mount of saline .After 72 h ,the mice were sacrificed .The bronchoalveolar lavage fluid (BALF) was collected and centrifuged;the sediments were stained with Wright‐Giemsa for total cell and neutrophil count and the supernates were prepared for ELISA .The wet and dry weight of lung was weighed to calculate the wet/dry weight ratio .HE staining was performed to examine the pathologi‐cal change of lung .Western blot was used to determined the expression of TLR4 ,IKK and NF‐κB .Results Intratracheal instillation of LPS successfully established ALI model in mouse .LPS caused significant pathological changes including inflammatory cells infil‐tration ,alveolar septa thickness ,hemorrhage and edema .The wet/dry weight ratio ,the total cell count ,neutrophil count ,TNF and IL‐1βlevel in BALF ,and the expression of TLR4 ,NF‐κB ,and IKK were all increased significantly (P<0 .05) ,which were allevia‐ted by intraperitoneal injection of morin .Conclusion Morin can dampen the inflammatory response during LPS induced ALI in mouse ,which is potentially attributed to its inhibitory effect on the activation of NF‐κB .

Ação antiproliferativado flavonoide morina e do extrato da folha de oliveira (Oleaeuropaea L. ) contra a linhagem de célula H460 / The antiproliferative action of morin flavonoid and olive leaf extract (Olea europaea L. ) against the cell line H460

RESUMO O presente estudo investigou a indução de morte celular por apoptose pelo flavonóide morina e pelo extrato da folha de oliveira (Oleaeuropaea L.) em linhagens de células de câncer de pulmão do tipo não pequenas (H460). O tratamento com morina e o extrato de oliveira em células H460 resultou na redução do crescimento tumoral e indução de morte celular avaliados pelos ensaios de MTT e lactato desidrogenase (LDH) e a morte celular por apoptose confirmada por microscopia de fluorescência e análise por citometria de fluxo. Os dados indicaram que o flavonóide morina e o extrato de oliveira diminuíram a viabilidade celular para taxas percentuais de 7,22± 1,54% e 62,37± 2,85% nas concentrações de 800µM e µg/mL, respectivamente. As maiores taxas percentuais de morte celular por apoptose foram100% para morina na concentração de 800µM e 70,49 ± 5,91% para o extrato de oliveira na concentração de 800 µg/mL. Estes resultados foram associados com a alteração do potencial de membrana mitocondrial, cujos valores são de 54,91% para morina na concentração de 400µM e 42,2% para o extrato de oliveira na concentração de 800 µg/mL sugerindo envolvimento da via intrínseca da morte celular por apoptose. Portanto, morina e o extrato de oliveira afetaram a viabilidade celular da linhagem H460 induzindo morte celular por apoptose.

ABSTRACT This study investigates possible apoptosis induction mechanism by the flavonoid morin and the olive leaf extract (Olea europaea L.) in non-small lung cancer cells (H460). The treatment with morin and olive leaves extract resulted in growth inhibition and induction of apoptosis in H460 cells lines measured by the MTT assay methods and confirmed by fluorescence microscopy, flow cytometry analysis. The data indicated that themurin and the extract of olive decreased the cell viability percentage rates of 7.22 ± 1,54% and 62.37 ± 2,85% in the concentrations of 800 µM and µg/mL, respectively. The highest percentage rates of cell death by apoptosis were 100% for themorin in a concentration of 800 µM and 70.49 ± 5.91% for the olive extract in a concentration of 800 µg/mL. These findings were associated with altered mitochondrial membrane potential, whose value is 54.91% for the murin concentration of 400 µM and 42.2% for the olive extract in a concentration of 800 mg / mL, suggesting involvement of the intrinsic pathway of cell death by apoptosis. Therefore, the morin and the olive extract affect the cell viability of H460 cell lines inducing cell death by apoptosis.

Ergonomia e complexidade: o trabalho do gestor na agricultura orgânica na região de Campinas - SP / Complexity and ergonomy: the manager work at the organic agriculture in Campinas - SP Brazil

A lacuna de pesquisas sobre o trabalho humano na agricultura orgânica motivou este estudo, que teve por objetivos caracterizar e compreender o trabalho do gestor no manejo orgânico da produção agrícola. A pesquisa de campo, realizada em duas etapas, permitiu investigar o trabalho dos gestores em Unidades de Produção Agrícola Orgânica (UPAO) do interior de São Paulo, por meio da adaptação do método da Análise Ergonômica do Trabalho (AET) e de entrevistas estruturadas. Os dados de campo foram posteriormente interpretados à luz da Teoria da Complexidade (TC). Constatou-se que o gestor da agricultura orgânica é responsável por um macrossistema (produção vegetal, produção animal, processamento e serviços), atuando concomitantemente como administrador e executor do trabalho. A grande variedade de produtos oferecidos pela agricultura orgânica gera a necessidade de expertise do gestor no trato com as diferentes espécies vegetais e na sua integração com os demais sistemas de produção. Concluiu-se que o trabalho executado pelos gestores é caracterizado pela diversidade de atividades que precisam ser realizadas e integradas dentro do macrossistema, em associação com os determinantes do processo de certificação num contexto de falta de tecnologia adequada e de cenários incertos e variados. Cabe ao gestor incorporar e transformar em práticas de trabalho os preceitos ecológicos, econômicos e sociais de sustentabilidade, que podem ser contraditórios entre si, integrar essas múltiplas dimensões, por meio do desenvolvimento e da conexão de variados saberes e competências, e elaborar estratégias para superar as diversas dificuldades relacionadas com os aspectos tecnológicos, financeiros e humanos na agricultura orgânica.

The lack of research about the human work at the Organic agriculture stimulated this study, which purpose was to characterize and understand the manager's job in managing organic farming. The field research was carried out in two stages, and allowed to investigate managers' work at organic agricultural production units (UPAO) from the interior of Sao Paulo state, through an adaptation of the ergonomics' analysis method (AET) and structured interviews. The data collected were further interpreted in the light of the complexity theory (TC). It was possible to infer that the organic agricultural manager is accountable for a macro production system (vegetable, animal, processing and services), where the manager acts simultaneously as the administrator and also as the job performer. The wide products variety offered by the organic agriculture demands an expertise from the manager in order to deal with the different vegetable specimens and their integration with the remaining production systems. It was concluded that the work performed by the managers is characterized by the diversity of activities, that need to be prepared and integrated within a macro system, associated with the certification process determinants, in absence of suitable technology context and uncertain and multiple scenarios. It comes to the manager to incorporate and to transform into work practices the ecological, economical and social sustainability principles, which can be contradictory among each other. They can integrate these multiple dimensions through the development and connection of several competences and knowledge, as well as elaborate strategies to overcome multiple difficulties related to the organic agriculture's technological, financial and human aspects.

Protective Effect of Morin Hydrate on Reactive Oxygen Injury in Rabbit Corneal Epithelium

PURPOSE: Free radicals are responsible for tissue injury in corneal preservation and transplantation. Morin hydrate, a flavonoid from Brazil wood, has been shown to be cytoprotective in several types of cells. The aim of this study was to investigate the effectiveness of morin hydrate on rabbit cornea against damage induced by oxyradicals and nitric oxide. METHODS: The rabbit cornea was studied in modified Ussing chambers to determine the effects of hydrogen peroxide (H2O2) or sodium nitroprusside (SNP) by measuring the bioelectrical properties (short-circuit current (Isc), tissue resistance (Rt) and potential difference (PD)). RESULTS: 1.0 mM H2O2 markedly increased the Isc at the tear side (T-side), but not at stromal side (S-side), suggesting the site of action of H2O2 was the apical membrane (T-side). After pretreatment with morin hydrate (T-side, 1.0 mM), H2O2-induced increase of Isc and PD was markedly reduced. In addition adding morin hydrate with H2O2 simultaneously, the increase of Isc and PD was also markedly reduced. Exposure of cornea to SNP at the T-side increased nitric oxide, and increased the bioelectrical properties (PD and Isc). This effect was attenuated by the treatment with morin hydrate. CONCLUSIONS: This study demonstrated that morin hydrate behaved as a antioxidant. This property of morin hydrate may help prevent protect cornea in preservative solutions from free radical damage.