morin and Disease-Models--Animal

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in the world. Mitophagy has been implicated in PD etiology for decades and its pharmacological activation is recognized as a promising treatment strategy for PD. For mitophagy initiation, low mitochondrial membrane potential (ΔΨm) is essential. We identified a natural compound morin that could induce mitophagy without affecting ΔΨm. Morin is a flavonoid that can be isolated from fruits like mulberry.. To reveal the effect of morin on the PD mice model and their potential underlying molecular mechanism.. Mitophagy process induced by morin in N2a cells meditation were measured using flow cytometry and immunofluorescence. JC-1 fluorescence dye used to detect the mitochondrial membrane potential (ΔΨm). The TFEB nuclear translocation were examined by immunofluorescence staining and western blot assay. The PD mice model was induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) intraperitoneal administration.. We found that morin also promoted nuclear translocation of the mitophagy regulator TFEB and activated the AMPK-ULK1 pathway. In MPTP-induced PD in vivo models, morin protected DA neurons from MPTP neurotoxicity and ameliorated behavioral deficit.. Although morin was previously reported to be neuroprotective in PD, the detailed molecular mechanisms remain to be elucidated. For the first time, we report morin served as a novel and safe mitophagy enhancer underlying AMPK-ULK1 pathway and exhibited anti-Parkinsonian effects indicating its potential as a clinical drug for PD treatment.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; AMP-Activated Protein Kinases; Animals; Disease Models, Animal; Dopaminergic Neurons; Flavonoids; Mice; Mice, Inbred C57BL; Mitophagy; Neuroprotective Agents; Parkinson Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder affecting both motor and non-motor functions. It is well reported that the neuropathological process leading to PD starts from the gut before spreading to the CNS affirming the role of environmental toxicants such as rotenone. Morin (3, 5, 7, 2', 4'-pentahydroxyflavone) possesses neuroprotective and anti-oxidant activities which could be beneficial in PD. This study was designed to investigate the ameliorative influence of morin on rotenone-induced PD in mice. Male albino mice (18-23 g) were randomly divided into groups (n = 15) and treated for 28 consecutive days as follows: group 1: normal saline (10 ml/kg, p.o); group 2: rotenone (1 mg/kg, p.o, 0.5%w/v in CMC); groups 3-5: morin (5, 20 or 80 mg/kg, i.p.) + rotenone (1 mg/kg, p.o.), respectively, group 6: morin (20 mg/kg only, i.p.). Behavioural tasks were carried out weekly 1 h after treatments. Mice were euthanized on day 28 and discreet brain regions were assayed for oxidative stress parameters and immunohistochemical analysis. Morin reversed rotenone-induced behavioural deficits (motor incoordination, working memory deficit and depressive-like behaviour). Moreso, rotenone-induced lipid peroxidation (MDA), with a concomitant decrease in glutathione (GSH), superoxide dismutase (SOD) and acetylcholinesterase (AchE) activities in discreet regions of the brain were attenuated by the pre-treatment of mice with morin. Rotenone caused significant increase in the expression of iba-1, glial fibrillary acidic protein (GFAP), toll-like receptor 4 (TLR-4), and α-synuclein with a decrease in tyrosine hydroxylase positive neurons (TH) expression which were ameliorated by the pretreatment of mice with morin. Furthermore, rotenone-induced colon necrosis was reversed by morin administration. This study lend credence to the neuroprotective action of morin on rotenone-induced PD through enhancement of antioxidant defense and anti-inflammatory mechanisms.

Topics: Acetylcholinesterase; Animals; Antioxidants; Brain-Gut Axis; Disease Models, Animal; Flavonoids; Glutathione; Male; Mice; Neuroprotective Agents; Oxidative Stress; Parkinson Disease; Rotenone

Neurodegenerative diseases such as Parkinson's disease (PD) are known to be related to oxidative stress and neuroinflammation, and thus, modulating neuroinflammation offers a possible means of treating PD-associated pathologies. Morin (2',3,4',5,7-pentahydroxy flavone) is a flavonol with anti-oxidative and anti-inflammatory effects found in wines, herbs, and fruits. The present study was undertaken to determine whether a morin-containing diet has protective effects in an MPTP-induced mouse model of PD. Mice were fed a control or morin diet for 34 days, and then MPTP (30 mg/kg, i.p.) was administered daily for 5 days to induce a PD-like pathology. We found that dietary morin prevented MPTP-induced motor dysfunction and ameliorated dopaminergic neuronal damage in striatum (STR) and substantia nigra (SN) in our mouse model. Furthermore, MPTP-induced neuroinflammation was significantly reduced in mice fed morin. In vitro studies showed that morin effectively suppressed glial activations in primary microglia and astrocytes, and biochemical analysis and a docking simulation indicated that the anti-inflammatory effects of morin were mediated by blocking the extracellular signal-regulated kinase (ERK)-p65 pathway. These findings suggest that morin effectively inhibits glial activations and has potential use as a functional food ingredient with therapeutic potential for the treatment of PD and other neurodegenerative diseases associated with neuroinflammation.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Anti-Inflammatory Agents; Disease Models, Animal; Dopaminergic Neurons; Extracellular Signal-Regulated MAP Kinases; Flavones; Flavonols; Food Ingredients; Mice; Mice, Inbred C57BL; Microglia; MPTP Poisoning; Neuroprotective Agents; Parkinson Disease

The special features of cyclodextrins (CDs), hydrophilic outer surfaces and hydrophobic inner surfaces, allow for development of inclusion complexes. The two bioactive strong antioxidant hepatoprotective compounds, Morin and vitamin E, are water insoluble. The present study aimed to prepare Morin-vitamin E-β-cyclodextrin inclusion complex loaded chitosan nanoparticles (M-Vit.E-CD-CS NPs) and to examine their hepatoprotective efficacy against arsenic-induced toxicity in a murine model. The NPs were characterized by FTIR, DLS, NMR, DSC, XRD, AFM, and a TEM study. The NPs were spherical in shape, 178 ± 1.5 nm in size with a polydispersity index (PDI) value of 0.18 and a zeta potential value of −22.4 ± 0.31 mV, with >50% encapsulation and drug loading efficacy. Mice were exposed to arsenic via drinking water, followed by treatment without or with the NPs on every alternate day up to 30 days by oral gavaging. Administration of NPs inhibited the arsenic-induced elevation of liver function markers, inflammatory and proapoptotic factors, reactive oxygen species (ROS) production, alteration in the level of blood parameters and antioxidant factors, and liver damage, which was measured by different biochemical assays, ELISA, Western blot, and histological study. Organ distribution of nanoparticles was measured by HPLC. M-Vit.E-CD-CS NPs showing potent hepatoprotective activity may be therapeutically beneficial.

Topics: Animals; Antioxidants; Arsenic; beta-Cyclodextrins; Chitosan; Disease Models, Animal; Drinking Water; Drug Carriers; Flavones; Mice; Nanoparticles; Reactive Oxygen Species; Vitamin E; Vitamins

Morin (MRN), a known natural flavonol, has demonstrated its shielding aptitude against ischemia/reperfusion (I/Re) lesion in various organs. Nonetheless, its potential influence on hepatic I/Re-induced injury modulation has not been fully elucidated. Consequently, the current study strived to investigate the mechanistic maneuvering of MRN against hepatic I/Re. Furthermore, the effects of MRN on Nrf2, TLR4, and NLRP3 proteins were evaluated via molecular docking studies.. For fulfilling this aim, Sprague-Dawley rats were allotted into 4 groups; Sham-operated (ShG), hepatic I/Re (30 min/24 h), and 10 days orally pre-treated MRN (50 and 100 mg/kg).. MRN mechanistic maneuver disclosed its ability to safeguard the hepatocytes partially due to antioxidant aptitude through intensifying the expression/content of Nrf2/HO-1 trajectory accompanied by total antioxidant capacity boosting besides MDA lessening. In addition, MRN anti-inflammatory attribute was affirmed by downsizing the expression/content of TLR4/NF-κB trajectory accompanied by a sequent lessening of TNF-α, IL-1β, IL-6, and ICAM-1 content. Moreover, MRN action entangled NLRP3 inhibitory character with subsequent MPO rebating. Furthermore, MRN anti-apoptotic trait verified by diminishing the pro-apoptotic and the executioner markers; Bax and caspase-3 levels, respectively. On the other hand, MRN administration proved its shielding action by improving the histopathological deterioration and lessening the serum ALT and AST levels. Finally, in silico studies exhibited moderate to promising binding affinities of MRN with the selected proteins ranging from -4.23 to -6.09 kcal mol. Higher and lower doses of MRN purveyed plausible defensive mechanisms and abated episodes concomitant with hepatic I/Re mischief in part, by modifying oxidative status and inflammation by the impact on Nrf2/HO-1, TLR4/ NF-κB, and NLRP3 pathway.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Disease Models, Animal; Flavonoids; Inflammation Mediators; Liver; Liver Diseases; Male; Molecular Docking Simulation; NF-E2-Related Factor 2; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Protein Binding; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4

When Zika virus emerged as a public health emergency there were no drugs or vaccines approved for its prevention or treatment. We used a high-throughput screen for Zika virus protease inhibitors to identify several inhibitors of Zika virus infection. We expressed the NS2B-NS3 Zika virus protease and conducted a biochemical screen for small-molecule inhibitors. A quantitative structure-activity relationship model was employed to virtually screen ∼138,000 compounds, which increased the identification of active compounds, while decreasing screening time and resources. Candidate inhibitors were validated in several viral infection assays. Small molecules with favorable clinical profiles, especially the five-lipoxygenase-activating protein inhibitor, MK-591, inhibited the Zika virus protease and infection in neural stem cells. Members of the tetracycline family of antibiotics were more potent inhibitors of Zika virus infection than the protease, suggesting they may have multiple mechanisms of action. The most potent tetracycline, methacycline, reduced the amount of Zika virus present in the brain and the severity of Zika virus-induced motor deficits in an immunocompetent mouse model. As Food and Drug Administration-approved drugs, the tetracyclines could be quickly translated to the clinic. The compounds identified through our screening paradigm have the potential to be used as prophylactics for patients traveling to endemic regions or for the treatment of the neurological complications of Zika virus infection.

Topics: Animals; Antiviral Agents; Artificial Intelligence; Chlorocebus aethiops; Disease Models, Animal; Drug Evaluation, Preclinical; High-Throughput Screening Assays; Immunocompetence; Inhibitory Concentration 50; Methacycline; Mice, Inbred C57BL; Protease Inhibitors; Quantitative Structure-Activity Relationship; Small Molecule Libraries; Vero Cells; Zika Virus; Zika Virus Infection

Angiogenesis, disturbance in redox homeostasis, and deregulated redox signaling are considered as common hallmarks of cancer progression and chemo resistance. In this context, PERK (protein kinase PKR-like ER kinase) branch of the unfolded protein response (UPR), an adaptive mechanism triggered by endoplasmic reticulum (ER) stress to cope with protein misfolding and perturbed proteostasis, has shown to regulate angiogenesis and oxidative stress. This study aimed to investigate the impact of morin, a poly phenolic compound from the family of

Topics: 1,2-Dimethylhydrazine; Angiogenesis Inhibitors; Animals; Antioxidants; Colon; Disease Models, Animal; eIF-2 Kinase; Flavonoids; Gene Expression; Male; Moraceae; Neovascularization, Pathologic; NF-E2-Related Factor 2; Oxidative Stress; Random Allocation; Rats; Rats, Wistar; Signal Transduction; Unfolded Protein Response

Acrylamide (ACR) is a heat-induced carcinogen substance that is found in some foods due to cooking or other thermal processes. The aim of present study was to assess the probable protective effects of morin against ACR-induced hepatorenal toxicity in rats. The rats were treated with ACR (38.27 mg/kg b.w., p.o.) alone or with morin (50 and 100 mg/kg b.w., p.o.) for 10 consecutive days. Morin treatment attenuated the ACR-induced liver and kidney tissue injury by diminishing the serum AST, ALP, ALT, urea and creatinine levels. Morin increased activities of SOD, CAT and GPx and levels of GSH, and suppressed lipid peroxidation in ACR induced tissues. Histopathological changes and immunohistochemical expressions of p53, EGFR, nephrin and AQP2 in the ACR-induced liver and kidney tissues were decreased after administration of morin. In addition, morin reversed the changes in levels of apoptotic, autophagic and inflammatory parameters such as caspase-3, bax, bcl-2, cytochrome c, beclin-1, LC3A, LC3B, p38α MAPK, NF-κB, IL-1β, IL-6, TNF-α and COX-2 in the ACR-induced toxicity. Morin also affected the protein levels by regulating the PI3K/Akt/mTOR signaling pathway and thus alleviated ACR-induced apoptosis and autophagy. Overall, these findings may shed some lights on new approaches for the treatment of ACR-induced hepatotoxicity and nephrotoxicity.

Topics: Acrylamide; Acute Kidney Injury; Animals; Autophagy; bcl-2-Associated X Protein; Beclin-1; Biomarkers; Caspase 3; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Cytochromes c; Cytokines; Disease Models, Animal; Flavonoids; Kidney; Lipid Peroxidation; Liver; Male; Microtubule-Associated Proteins; Mitogen-Activated Protein Kinase 14; NF-kappa B; Oxidative Stress; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; TOR Serine-Threonine Kinases

Sepsis-associated encephalopathy (SAE) often leads to cognitive impairments in the rest life of septic survivors. The potential pathological changes of SAE are complicated and have not been fully understood. Morin, a flavone compound exhibiting neuroprotective activity and anti-inflammation effect, was employed to treat with CLP-induced septic mice in our study. The data from a novel object recognition test and tail suspension test indicated that morin treatment reversed cognitive dysfunction and relieved depressive-like behaviors in septic mice. Morin down-regulated the expressions of IL-6, MCP-1, TNF-α and IL-10 in serum and diminished microglia activation in septic mice. Additionally, Western blot results showed that morin reduced the phosphokinase GSK3β activity and elevated the phosphatase PP2A activity, which led to lower tau phosphorylation. Morin reduced Aβ deposition and protected the synapse integrity, which might be the possible mechanism of protecting cognitive functions in septic mice. In conclusion, we identified that morin exerted anti-inflammation and anti-neurodegeneration effects in septic mice, and prevented further cognitive impairments.

Topics: Animals; Antioxidants; Cognitive Dysfunction; Disease Models, Animal; Flavonoids; Inflammation Mediators; Male; Mice; Mice, Inbred BALB C; Neuroprotective Agents; Sepsis; Sepsis-Associated Encephalopathy

Listeria monocytogenes (L. monocytogenes) is a global opportunistic intracellular pathogen that can cause many infections, including meningitis and abortion in humans and animals; thus, L. monocytogenes poses a great threat to public safety and the development of the aquaculture industry. The isolation rate of Listeria monocytogenes in fishery products has always been high. And the pore-forming toxin listeriolysin O (LLO) is one of the most important virulence factors of L. monocytogenes. LLO can promote cytosolic bacterial proliferation and help the pathogen evade attacks from the host immune system. In addition, L. monocytogenes infection can trigger a series of severe inflammatory reactions.. Here, we further confirmed that morin lacking anti-Listeria activity could inhibit LLO oligomerization. We also found that morin can effectively alleviate the inflammation induced by Listeria in vivo and in vitro and exerted an obvious protective effect on infected cells and mice.. Morin does not possess anti-Listeria activity, neither does it interfere with secretion of LLO. However, morin inhibits oligomerisation of LLO and morin does reduce the inflammation caused during Listeria infection.

Topics: Animals; Bacterial Toxins; Cell Line; Disease Models, Animal; Flavonoids; Gene Expression Regulation, Bacterial; Heat-Shock Proteins; Hemolysin Proteins; Humans; Listeria monocytogenes; Listeriosis; Mice; Protein Multimerization; Virulence

Depression is a common mental illness that possesses a noteworthy effect on patients' lives. Many theories are recently studied for their plausible involvement in depression pathogenesis, especially oxidative stress and inflammation. Morin (2',3,4',5,7-pentahydroxyflavone), a natural flavonoid, is characterized by its potent anti-inflammatory, and anti-oxidant activities. Accordingly, the aim of the current study was to investigate its potential protective anti-depressant effect in the model of chronic unpredictable mild stress (CUMS) in experimental rats. Moreover, the conceivable neuro-protective mechanisms, especially those related to the inflammasome pathway, were explored. Several, mild, unpredictable stressors were applied for 4 weeks concomitantly with the oral administration of morin (15 and 30 mg/Kg). Morin hydrate supplementations exhibited a significant improvement in the scores of the forced swimming and sucrose preference tests. In addition, it prompted a marked elevation in the ambulation, rearing as well as grooming scores of the open field test. The morin-treated groups showed a great improvement in the biochemical parameters in both the cortex and hippocampus, where it significantly elevated the serotonin, epinephrine, and norepinephrine levels. Also, it significantly increased reduced glutathione levels and decreased malondialdehyde levels. Regarding the inflammasome pathway, morin significantly decreased the tissue levels of tumor necrosis factor-alpha, toll-like receptor-4, interleukin-1beta, NOD-like receptor pyrin domain-containing protein-3, and caspase-1 levels. Morin also significantly decreased the level of the key apoptotic marker, caspase-3. In conclusion, these findings propose that morin might show a promising anti-depressant effect.

Topics: Animals; Antidepressive Agents; Behavior, Animal; Cerebral Cortex; Depression; Disease Models, Animal; Flavonoids; Hippocampus; Inflammasomes; Male; Rats, Sprague-Dawley; Signal Transduction; Stress, Psychological

This study aimed to investigate the effects of morin on cerebral damage and blood-brain barrier (BBB) integrity in a middle cerebral artery occlusion (MCAO) and reperfusion model. Wistar rats were exposed to MCAO for 2 h, followed by reperfusion. Thirty mg/kg of morin was administered via intraperitoneal injection at the different time points: before ischemia, during ischemia, and at reperfusion. The rats were divided into five groups, including sham, vehicle, and three groups of morin. Twenty-four hours after reperfusion, the rats were tested for neurological deficits, and the brains were harvested to assess brain damage. In addition, brains were harvested 72 h to determine BBB disruption. We found that morin significantly reduced reactive oxygen species production and lipid peroxidation. It also decreased inflammation via reducing the expression of Toll-like receptor 4, nuclear factor kappa-beta. Morin ameliorated cerebral damage and reduced apoptosis through decreasing the cerebral infarct size, including apoptotic cell death. Moreover, morin decreased the BBB damage via reducing Evans blue extravasation, neutrophil infiltration, and increasing tight junction protein expression. Therefore, morin protected against cerebral and BBB damage by attenuating oxidative stress, inflammation, and apoptosis in MCAO and reperfusion models.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Blood-Brain Barrier; Brain Ischemia; Disease Models, Animal; Flavonoids; Inflammation; Injections, Intraperitoneal; Lipid Peroxidation; Male; Neutrophil Infiltration; NF-kappa B; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Reperfusion Injury; Toll-Like Receptor 4

There is a major clinical need for new therapies for the treatment of chronic itch. Many of the molecular components involved in itch neurotransmission are known, including the neuropeptide NPPB, a transmitter required for normal itch responses to multiple pruritogens in mice. Here, we investigated the potential for a novel strategy for the treatment of itch that involves the inhibition of the NPPB receptor NPR1 (natriuretic peptide receptor 1). Because there are no available effective human NPR1 (hNPR1) antagonists, we performed a high-throughput cell-based screen and identified 15 small-molecule hNPR1 inhibitors. Using in vitro assays, we demonstrated that these compounds specifically inhibit hNPR1 and murine NPR1 (mNPR1). In vivo, NPR1 antagonism attenuated behavioral responses to both acute itch- and chronic itch-challenged mice. Together, our results suggest that inhibiting NPR1 might be an effective strategy for treating acute and chronic itch.

Topics: Animals; Behavior, Animal; Cell-Free System; Dermatitis, Contact; Disease Models, Animal; Ganglia, Spinal; Humans; Mice, Inbred C57BL; Mice, Knockout; Neurons; Pruritus; Receptors, Atrial Natriuretic Factor; Reproducibility of Results; Signal Transduction; Small Molecule Libraries

l-Arginine-nitric oxide pathway has been reported to be involved in the mediation of the psychopharmacological effects of many psychotropic drugs. Previous studies have shown that morin, a psychotropic compound isolated from mulberry leaf produces functional psychopharmacological effects indicative of antidepressant, antipsychotic, anxiolytic and nootropic properties. However, the role of l-arginine-nitric oxide pathway in the psychotropic effects of morin has not been fully investigated, hence, the need for this study. Male Swiss mice were pretreated individually or in combination with nitric oxide precursor [l-arginine (750 mg/kg, i.p.)], competitive nonselective nitric oxide synthase (NOS) inhibitor [N(G)-nitro-l-arginine methyl ester (l-NAME, i.p) (50 mg/kg)] or selective neuronal NOS inhibitor [methylene blue (3.75 mg/kg, i.p)] prior to morin (100 mg/kg, i.p.) or saline (10 mL/kg, i.p.) treatment. Psychopharmacological activities were then evaluated 30 min later using open field, Y-maze, and forced swim tests. l-Arginine significantly reversed the effects of morin on locomotion, memory and depression in mice. The reduced motor activity and enhanced memory function produced by morin were significantly attenuated by methylene blue but augmented the antimobility activity of morin in the FST. Moreover, l-NAME potentiated the psychopharmacological effects of morin in the open field and forced swim tests but reduced its memory promoting effect. Meanwhile, morin supplementation reversed the effects of l-arginine on l-NAME-treated mice in all behavioral models. The results of this study suggest that l-arginine-nitric oxide pathway might play a role in the modulation of the antidepressant and memory promoting effects of morin in mice.

Topics: Animals; Antidepressive Agents; Arginine; Behavior, Animal; Depression; Disease Models, Animal; Flavonoids; Injections, Intraperitoneal; Male; Memory; Memory and Learning Tests; Methylene Blue; Mice; Motor Activity; NG-Nitroarginine Methyl Ester; Nitric Oxide; Signal Transduction; Swimming

Increased activity of the PI3K/AKT/mTOR pathway has been observed in chronic myeloid leukemia (CML). Morin, a kind of flavonoid, exhibits a significant anticancer activity by suppressing the PI3K/AKT signaling pathway. However, the effect of morin on CML and its underlying mechanisms is poorly understood. Here, we found that morin dose dependently inhibited the proliferation of CML cell lines K562 and KCL22 and induced their apoptosis, with a significant increase in cell apoptosis upon exposure of cells to 50 μmol/L morin. Moreover, morin significantly reduced CML xenograft growth in nude mice. Mechanically, morin attenuated phosphorylated AKT level by upregulating PTEN expression, thus leading to the inhibition of AKT signaling. Knockdown of PTEN by its siRNA completely abrogated morin-induced cell apoptosis, indicating that PTEN mediates the inductive effect of morin on CML cell apoptosis. More importantly, we found that miR-188-5p was significantly upregulated in CML patients and CML cell lines. Treating CML cells with morin markedly downregulated the miR-188-5p expression level. Further, we demonstrated that miR-188-5p repressed PTEN expression by directly targeting its 3'-UTR. miR-188-5p downregulation induced by morin enhanced CML cell apoptosis by relieving miR-188-5p repression of PTEN expression. In summary, morin exerts significant anticancer efficacy in CML by regulating the miR-188-5p/PTEN axis and thus repressing the PI3K/AKT signaling.

Topics: Animals; Antioxidants; Apoptosis; Cell Proliferation; Disease Models, Animal; Flavonoids; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mice; Mice, Nude; MicroRNAs; PTEN Phosphohydrolase

Topics: Animals; Antioxidants; Carcinogenesis; Colon; Colonic Neoplasms; Disease Models, Animal; Flavonoids; Genes, APC; In Vitro Techniques; Male; Protein Tyrosine Phosphatases; Proto-Oncogene Proteins; Rats; Rats, Inbred F344

Neuroinflammation plays a prominent role in the pathophysiology and progression of schizophrenia. Thus, suppression of neuroinflammation may retard the progression of the disease. This study was designed to investigate whether morin, a bioactive compound with antipsychotic-like activity could reduce biomarkers of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)- and ketamine (KET)-induced schizophrenic-like behavior in mice. Animals were treated once daily intraperitoneally with morin (100 mg/kg), haloperidol (1 mg/kg), risperidone (0.5 mg/kg), or saline (10 mL/kg) in combination with LPS (0.1 mg/kg) for 14 consecutive days. However, from days 8-14, overt schizophrenia-like episode was produced with i.p. injection of KET (20 mg/kg) once daily. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction and social-memory tests) and cognitive (Y-maze test) symptoms were assessed on day 14. Thereafter, the levels and expressions of biomarkers of neuroinflammation were estimated in the striatum (ST), prefrontal cortex (PFC) and hippocampus (HC) using spectrophotometry, ELISA and immunohistochemistry. The effects of morin on cortical pyramidal neurons were estimated using Golgi-impregnation staining technique. LPS in combination with KET significantly (p < 0.05) induced schizophrenia-like behaviors, which was attenuated by morin. Morin significantly (p < 0.05) decreased tumor necrosis factor-α, interleukine-6 levels and myeloperoxidase activity in the ST, PFC and HC of mice treated with LPS + KET. Moreover, morin reduced regional brain expressions of cyclooxygenase-2, inducible nitric oxide synthase and nuclear factor kappa-B, and also rescued loss of pyramidal neurons in the PFC. Taken together, these findings suggest that morin reduces schizophrenic-like symptoms induced by LPS + KET via mechanisms related to inhibition of the release of pro-inflammatory mediators and suppression of degeneration of cortical pyramidal neurons in mice.

Topics: Animals; Antioxidants; Behavior, Animal; Cerebellar Cortex; Disease Models, Animal; Flavonoids; Humans; Inflammation Mediators; Interleukin-6; Ketamine; Lipopolysaccharides; Male; Mice; Neurogenic Inflammation; Peroxidase; Pyramidal Cells; Schizophrenia; Social Behavior; Spinocerebellar Degenerations; Tumor Necrosis Factor-alpha

Morin is a naturally occurring flavonoid with strong anti-oxidant and anti-inflammatory properties. Studies have shown that flavones modulate neurotransmission through enhancement of gamma amino butyric acid activity in the central nervous system; which led to the hypothesis that they could exert tranquilizing effects in rodents. Hence, this study was designed to evaluate the antipsychotic effect of morin on experimental animal models.. The antipsychotic effect of morin (25, 50 and 100 mg/kg) administered intraperitoneally (i.p.) was assessed on novelty-induced locomotion, apomorphine-induced stereotypy, ketamine-induced stereotypy, ketamine-induced hyperlocomotion and ketamine-enhanced immobility in forced swim test (FST). Catalepsy and rota rod tests were also carried out to evaluate the extrapyramidal side effects of morin.. Morin (25, 50 and 100 mg/kg, i.p.) pretreatments significantly (p<0.05) demonstrated anti-schizophrenia-like behavior by inhibiting ketamine-induced hyperlocomotion in mice. Moreover, morin (50 and 100 mg/kg, i.p.) significantly (p<0.05) reduced spontaneous locomotor activity. Also, morin suppressed apomorphine-induced stereotypy and ketamine-induced stereotypy. The increase in immobility in FST due to ketamine administration was reduced by morin in a significant dose-dependent manner. Furthermore, the antipsychotic activity of morin was not associated with extrapyramidal side effects, as evidenced by decreased decent latency and increased motoric coordination and performance in mice.. The results of the study revealed that morin demonstrated antipsychotic-like property devoid of extrapyramidal side effects in experimental animal models and may be beneficial in the treatment of schizophrenia-like behaviors; particularly in patients with behavioral hyperactivity and negative symptoms.

Topics: Animals; Antipsychotic Agents; Apomorphine; Catalepsy; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids; Immobility Response, Tonic; Ketamine; Locomotion; Male; Mice; Rotarod Performance Test; Stereotyped Behavior

Melanoma is one of the most malignant skin tumors with high mortality rate. Morin has been reported to treat several cancers. However, whether or how Morin affects melanoma progression is still poorly understood. Either Morin treatment or miR-216a overexpression reduced cell viability, sphere formation ability and expressions of stem cell marker genes CD20, CD44, CD133 and Wnt-3A. MiR-216a was induced by Morin treatment in CD133

Topics: AC133 Antigen; Animals; Biomarkers, Tumor; Cell Proliferation; Cell Self Renewal; Depression, Chemical; Disease Models, Animal; Down-Regulation; Flavonoids; Humans; Melanoma; MicroRNAs; Tumor Cells, Cultured; Up-Regulation; Wnt3A Protein

GABAergic (Gamma-aminobutyric acid) and neurotrophic derangements have important implication in schizophrenia, a neuropsychiatric disease. Previous studies have shown that nicotinamide adenine dinucleotide phosphate oxidase (NADPH-oxidase) alters GABAergic and neurotrophic activities via inflammatory and oxidative pathways. Thus, it has been proposed that agents with anti-oxidant and anti-inflammatory properties might be beneficial for the treatment of the disease. Morin is neuroactive bioflavonoid compound, which has been reported to demonstrate antipsychotic and anti-oxidant/anti-inflammatory activities. In this study, we further evaluated its effects on the brain markers of GABAergic, neurotrophic and oxidative alterations in the preventive and reversal of schizophrenia-like behavior induced by ketamine (KET). In the prevention protocol, adult mice were treated intraperitoneally with morin (100 mg/kg/day), haloperidol (1 mg/kg/day), risperidone (0.5 mg/kg/day), or saline (10 mL/kg/day) for 14 consecutive days. In addition, the animals were administered KET (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days. From 8th to 14th days mice were additionally treated with morin, haloperidol, risperidone or saline. Schizophrenic-like behaviors consisting of positive (stereotypy test), negative (behavioral despair in forced swim test) and cognitive (novel-object recognition test) symptoms were evaluated. Afterwards, brain levels of biomarkers of GABAergic (Glutamic acid decarboxylase-67, GAD

Topics: Animals; Antioxidants; Behavioral Symptoms; Brain; Brain-Derived Neurotrophic Factor; Catalase; Disease Models, Animal; Dopamine Antagonists; Excitatory Amino Acid Antagonists; Flavonoids; Haloperidol; Ketamine; Male; Memory, Short-Term; Mice; NADPH Oxidases; Risperidone; Schizophrenia; Stereotyped Behavior; Superoxide Dismutase; Swimming

Previous studies have revealed that morin (MOR), a neuroactive bioflavonoid, with proven psychotropic and neuroprotective properties reduced schizophrenic-like behaviors in mice. This study further evaluated the ability of MOR to prevent and reverse ketamine-induced schizophrenic-like behaviors and the underlying neurochemical changes and increased oxidative/nitrergic stress in mice. In the preventive protocol, mice received intraperitoneal injection of MOR (100 mg/kg), reference antipsychotic drugs [haloperidol (1 mg/kg), risperidone (0.5 mg/kg)], or saline daily for 14 consecutive days prior to i.p. injection of ketamine (KET) (20 mg/kg/day) from the 8th to the 14th day. In the reversal protocol, the animals received KET or saline for 14 days prior to MOR, haloperidol, risperidone, or saline treatments. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction test) and cognitive (Y-maze test) symptoms were evaluated. Thereafter, the brain levels of dopamine, glutamate, 5-hydroxytryptamine and acetyl-cholinesterase, as well as biomarkers of oxidative/nitrergic stress were measured in the striatum, prefrontal-cortex (PFC) and hippocampus (HC). Morin prevented and reversed KET-induced hyperlocomotion, social and cognitive deficits. Also, MOR or risperidone attenuated altered dopaminergic, glutamatergic, 5-hydroxytryptaminergic and cholinergic neurotransmissions in brain region-dependent manner. The increased malondialdehyde and nitrite levels accompanied by decreased glutathione concentrations in the striatum, PFC and HC in KET-treated mice were significantly attenuated by MOR or risperidone. Taken together, these findings suggest that the anti-schizophrenic-like activity of MOR may be mediated via mechanisms related to attenuation of neurochemical changes and oxidative/nitrergic alterations in mice.

Topics: Animals; Antioxidants; Antipsychotic Agents; Disease Models, Animal; Flavonoids; Hippocampus; Ketamine; Maze Learning; Mice; Oxidative Stress; Schizophrenia

Doxorubicin (DOX) is an effective antineoplastic agent of the anthracycline group. However, as with most anticancer drugs, they cause some toxic effects, including major cardiotoxicity and cognitive impairment. In this study, protective effects of morin against DOX-induced cardiotoxicity and neurotoxicity in rats were investigated. Morin was orally administered to rats at a dose of 50 and 100 mg/kg body weight for 10 days. DOX was administered 40 mg/kg body weight by single dose intraperitoneal injection on the 8th day of the study. Both the levels of glutathione (GSH) and malondialdehyde (MDA) were assessed and enzyme activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were assessed to determine the protective effect of morin against oxidative stress. To determine the anti-inflammatory effect, the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), nuclear factor kappa B (NF-κB) were assessed in the heart and brain tissues. Lactate dehydrogenase (LDH) and creatine kinase isoenzyme-MB (CKMB) activities, which are cardiac function markers, and cardiac troponin-I (cTn-I) levels were also determined. Anti-apoptotic effect was determined by anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) and pro-apoptotic protein cysteine aspartate specific protease-3 (caspase-3) changes. The regulatory role of morin in signal transduction in the brain tissue was assigned with the determination of amount of acetylcholinesterase (AChE), and its healing effect on the central nervous system was determined with imuinohistochemical detection of glial fibrillar acidic protein (GFAP) level. Histopathological evaluation of heart and brain tissues was performed in all groups.

Topics: Acetylcholinesterase; Animals; Anti-Infective Agents; Antioxidants; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Brain; Brain Diseases; Cardiotoxicity; Cytokines; Cytoprotection; Disease Models, Animal; Doxorubicin; Flavonoids; Glial Fibrillary Acidic Protein; GPI-Linked Proteins; Heart Diseases; Inflammation; Inflammation Mediators; Male; Myocardium; Oxidative Stress; Rats, Wistar; Signal Transduction

Morin is a flavanoid which exhibits potent antioxidant activity in various oxidative stress related diseases. The current study was attempted to scrutinize the preclinical bio-efficacy of morin on focal ischemia.. The animal model of focal cerebral ischemic injury was done by midbrain carotid artery occlusion (MCAO) method, followed by Morin (30mg/kg) administration for seven days.. The outcome of the study showed that treatment with morin displayed positive effects in reducing the focal cerebral ischemia. This effect was evident with the improvements in neurological deficits, reduction in MDA content and elevation of antioxidant levels (SOD, GSH and Gpx). Furthermore, protein expression of Bax and caspase-3 were effectively down-regulated, whilst the expression of Bcl-2 was significantly elevated. On the other hand, the mRNA expression of proinflammatory cytokines was significantly reduced in focal cerebral ischemic rats upon morin intervention.. Thus, the beneficial effects of morin on cerebral ischemia assault may result from the reduction of oxidative stress, inhibition of apoptosis and inflammation. The neuroprotective effects of morin supplement may serve as potent adjuvant in the amelioration of ischemic stroke.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Apoptosis; Brain Ischemia; Cytokines; Disease Models, Animal; Flavonoids; Inflammation; Male; Oxidative Stress; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; RNA, Messenger; Stroke

Paclitaxel is a first-line microtubule-stabilizing drug in treating prostate cancer. However, most patients develop resistance and experience relapse. Morin (3,5,7,20,40-pentahydroxyflavone) is an anti-tumor flavonoid in a numerous types of cancer cells including breast, ovarian and lung cancers. We therefore researched the effects of morin as an adjuvant to paclitaxel in in treating DU145 and PC-3 cells in vitro and DU145 derived prostate cancers in nude mice models. The chemosensitivities of these cells to the treatments of morin and paclitaxel were tested through viability assays utilizing cell counting kit 8 (CCK-8) and apoptosis assays through flow cytometry analyses. MicroRNA (miRNA) microarray was employed to determine the changes in miRNA profile of morin treated DU145 cells. The results from microarrays were further certified by quantitative real-time reverse transcription-PCR (qRT-PCR). The underlying targets of miR-155 were verified using luciferase assays followed by Western blot assays. In the results, morin was capable of repressing the cell viabilities in the paclitaxel-treated cells. MiR-155might be an effective target that can be down-regulated in morin-treated cells. We also discovered that GATA binding protein 3 (GATA3) was directly repressed by miR-155, and the treatment of morin reversed the expression of GATA3. In conclusion, morin might be a potential adjuvant of paclitaxel in treating prostate cancer through regulating miR-155/GATA3 axis.

Topics: 3' Untranslated Regions; Animals; Apoptosis; Cell Line, Tumor; Cell Survival; Cluster Analysis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Female; Flavonoids; GATA3 Transcription Factor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Silencing; Humans; Male; Mice; MicroRNAs; Paclitaxel; Prostatic Neoplasms; RNA Interference; Xenograft Model Antitumor Assays

Parkinson's disease (PD) is one of the most common neurodegenerative disorders and is characterized by loss of dopaminergic neurons in the substantia nigra (SN). Although the causes of PD are not understood, evidence suggests that oxidative stress, mitochondrial dysfunction, and inflammation are associated with its pathogenesis. Morin (3,5,7,2',4'-pentahydroxyflavone) is a flavonol found in wine and many herbs and fruits. Previous studies have suggested that morin prevents oxidative damage and inflammation and ameliorates mitochondrial dysfunction. The present study describes the neuroprotective effects of morin in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and we report the results of our investigation into its neuroprotective mechanism in primary neurons and astrocytes. In the mouse model, morin pretreatment ameliorated motor dysfunction, protected against dopaminergic neuronal losses in SN and striatum, and alleviated MPTP-induced astrocyte activation. In vitro studies revealed that morin protected primary cultured neurons against 1-methyl-4-phenylpyridine (MPP(+) )-mediated reactive oxygen species production and mitochondrial membrane potential (MMP) disruption. In addition, morin effectively reduced MPP(+) -induced astroglial activation and nuclear translocation of nuclear factor-κB in primary cultured astrocytes. These results indicate that morin acts via multiple neuroprotective mechanisms in our mouse model and suggest that morin be viewed as a potential treatment and preventative for PD. © 2016 Wiley Periodicals, Inc.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Animals, Newborn; Anti-Inflammatory Agents; Astrocytes; Brain; Cells, Cultured; Cerebral Cortex; Disease Models, Animal; Embryo, Mammalian; Flavonoids; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Motor Activity; MPTP Poisoning; Neurons; Neuroprostanes; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

The anti-inflammatory effect of morin, a dietary bioflavanol was explored on monosodium urate (MSU) crystal-induced inflammation in rats, an experimental model for acute gouty arthritis. Morin treatment (30mg/kg b.wt) significantly attenuated the ankle swelling and the levels of lipid peroxidation, nitric oxide, serum pro-inflammatory cytokines (tumor necrosis factor (TNF) -α, interleukin (IL)-1β, and IL-6), monocyte chemoattractant protein (MCP)-1, vascular endothelial growth factor (VEGF), prostaglandin E2 (PGE2), and articular elastase along with an increased anti-oxidant status (catalase (CAT) and superoxide dismutase (SOD)) in the joint homogenate of MSU crystal-induced rats. Histological assessment revealed that morin limited the diffusion of joint space, synovial hyperplasia, and inflammatory cell infiltrations. The mRNA expression of NLRP3 (nucleotide oligomerization domain (NOD)-like receptor family, pyrin domain containing 3) inflammasome, caspase-1, pro-inflammatory cytokines, MCP-1, inflammatory enzymes (inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)), and nuclear factor-kappa B (NF-κB) p65 was found downregulated and HPRT (hypo-xanthine phospho-ribosyl transferase) mRNA expression was upregulated in morin treated MSU crystal-induced rats. In addition, morin treatment reduced the protein expression of NF-κB p65, p-NF-κB p65, iNOS, COX-2, and TNF-α. The results clearly demonstrated that morin exert a potent anti-inflammatory effect on MSU crystal-induced inflammation in rats.

Topics: Acute Disease; Animals; Antioxidants; Arthritis, Gouty; Cyclooxygenase 2; Cytokines; Diet; Disease Models, Animal; Female; Flavonoids; Gene Expression Regulation, Enzymologic; Hypoxanthine Phosphoribosyltransferase; Inflammasomes; Inflammation Mediators; Male; Nitric Oxide Synthase Type II; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Pancreatic Elastase; Rats; Rats, Wistar; Synovial Membrane; Transcription Factor RelA; Tumor Necrosis Factor-alpha; Uric Acid

Liver diseases are among the most serious health issues nowadays. Hepatocellular carcinoma, one of the most lethal types of cancer worldwide, can be caused by chemically-induced oxidative stress. In the present study, we aimed to evaluate the protective effects of morin hydrate (MH) against acrylamide (AA)-induced hepatotoxicity in male ICR mice. The mice were randomly allocated into 4 groups [the control, the group subcutaneously injected with AA alone (50 mg/kg body weight), the group subcutaneously injected with AA (50 mg/kg body weight) and MH (5 mg/kg body weight) and the group subcutaneously injected with AA (50 mg/kg body weight) and MH (15 mg/kg body weight) for 5 consecutive days]. Histopathological evaluations were performed and the levels of serum hepatic enzymes were analyzed to determine initial liver injury, and the mice in the AA-treated groups were compared with the mice receiving no treatment and with the mice administered MH in combination with AA. Furthermore, oxidative stress, hepatic inflammation and the levels of DNA damage-related markers were evaluated to determine the extent of liver damage induced by AA within a short-term period. The subcutaneous administration of AA induced severe hepatic injury, and combined treatment with AA and MH resulted in a significant improvement in all evaluated parameters. This recovery was most obvious in the group receiving AA and 15 mg/kg body weight dose of MH. The findings of our study demonstrated that MH protected mice from severe hepatic injury induced by AA. Moreover, MH is a natural polyphenolic compound, and thus it has potential for use in the treatment of severe liver diseases, in place of many synthetic drugs.

Topics: Acrylamide; Animals; Chemical and Drug Induced Liver Injury; Disease Models, Animal; Flavonoids; Male; Mice; Mice, Inbred ICR

Diabetes-induced damages in brain are known as diabetic encephalopathy, which is well characterized by cellular, molecular and functional changes in the brain of diabetic subjects and rodents. However, little is known about the mechanism of damages and the therapeutic strategies in ameliorating those damages in the diabetic brain. In this study, we utilized a flavonoid, morin which is emerging as a potent drug against a wide range of free radical-mediated as well as neurodegenerative diseases. Morin (15 and 30 mg/kg body weight/day) was orally administered to two different groups of rats after 1 week of diabetes induction, and continued for five consecutive weeks. Two other untreated groups of diabetic and non-diabetic rats were used to compare with drug-treated groups. After drug treatments, cerebral cortex of the brain harvested and analyzed for different factors. Morin supplementation especially at high dose increased the levels of insulin, reduced glutathione, superoxide dismutase and catalase activities, and decreased fasting glucose and thiobarbituric acid reactive substances in the diabetic brain compared to untreated diabetic rats (P < 0.05). Morin also significantly decreased the level of inflammatory markers (TNFα, IL1β, IL-6) in the diabetic brain compared to untreated diabetic rats. Furthermore, the drug influenced an increase in the level of neurotrophic factors (BDNF, NGF and IGF-1) in the diabetic brain compared to untreated diabetic rats (P < 0.05). Thus, our results indicate a beneficial effect of morin by decreasing oxidative stress, inflammation and increasing the neurotrophic support in the diabetic brain, which may ameliorate diabetic encephalopathy.

Topics: Animals; Antioxidants; Blood Glucose; Body Weight; Brain; Catalase; Cytokines; Diabetes Mellitus, Experimental; Disease Models, Animal; Dose-Response Relationship, Drug; Flavonoids; Glutathione; Inflammation; Male; Nerve Growth Factors; Oxidative Stress; Rats; Rats, Wistar; Superoxide Dismutase; Thiobarbituric Acid Reactive Substances

Myocardial infarction affects a large population in the world. Lipid peroxide metabolism plays an important role in the pathology of myocardial infarction.. The present study was designed to investigate the antioxidant potential of morin, a flavonoid in isoproterenol (ISO)-induced myocardial infarction (MI), in rats.. Male albino Wistar rats were pre-treated with morin (40 mg/kg), daily for a period of 30 days. After the treatment period, ISO (85 mg/kg), was subcutaneously injected in rats at an interval of 24 h for 2 days.. ISO-administered rats showed elevated levels of thiobarbituric acid reactive substances (TBARS), and lipid hydro-peroxide (LOOH), in plasma and heart. Pretreatment with morin, the above changes were significantly reduced to near normal level. ISO-administered rats showed decrease in the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione-S-transferase (GST) in heart. In addition, decrease the levels non enzymatic antioxidants such as reduced glutathione (GSH), vitamin C and vitamin E in plasma and heart while ceruloplasmin in plasma.. Pretreatment with morin, reversed these above biochemical changes towards normalcy. These findings revealed that, the morin possess antioxidant activity in experimentally induced cardiac toxicity.

Topics: Animals; Antioxidants; Disease Models, Animal; Flavonoids; Glutathione; Glutathione Peroxidase; Humans; Lipid Peroxidation; Male; Myocardial Infarction; Rats; Rats, Wistar; Superoxide Dismutase

The aim of this investigation was to evaluate the preventive role of morin, a flavonoid, on cardiac marker enzymes such as aspartate transaminase, lactate dehydrogenase, creatine kinase and creatine kinase-MB, membrane-bound enzymes such as sodium potassium-dependent adenosine triphosphatase, calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase, and glycoproteins such as hexose, hexosamine, fucose and sialic acid in isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Male albino Wistar rats were pretreated with morin (20, 40 and 80 mg/kg) daily for a period of 30 days. After the treatment period, ISO (85 mg/kg) was subcutaneously injected into the rats at an interval of 24 h for 2 days. ISO-induced rats showed significantly (P < 0.05) increased activities of cardiac marker enzymes in serum and decreased activities in the heart, and increased activities of calcium-dependent adenosine triphosphatase and magnesium-dependent adenosine triphosphatase in the heart, and the activity of sodium potassium-dependent adenosine triphosphatase decreased in the heart. ISO induction also showed a significant increase in the levels of glycoproteins in serum and the heart. Pretreatment with morin (40 mg/kg) daily for a period of 30 days exhibited significant (P < 0.05) effects and altered these biochemical parameters positively compared to the other two doses. Thus, our study shows that morin has a protective role in ISO-induced MI in rats. The observed effects might be due to the free radical-scavenging, antioxidant and membrane-stabilising properties of morin.

Topics: Adenosine Triphosphatases; Animals; Biomarkers; Disease Models, Animal; Flavonoids; Glycoproteins; Isoproterenol; Male; Myocardial Infarction; Myocardium; Protective Agents; Rats; Rats, Wistar

Morin displayed significant inhibition of chick chorioallantoic membrane (CAM) angiogenesis and was able to increase the endostatin level in human umbilical vein endothelial cells (HUVECs). Morin was shown to contain an in vivo anti-inflammatory activity using a carrageenan-induced air pouch model in mice. Antinociceptive activity of morin was also assessed using an acetic acid-induced writhing test in mice. Collectively, morin possesses antiangiogenic, in vivo anti-inflammatory, and antinociceptive activities.

Topics: Acetic Acid; Analgesics; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Behavior, Animal; Carrageenan; Cell Line; Chick Embryo; Chorioallantoic Membrane; Disease Models, Animal; Endostatins; Endothelial Cells; Flavonoids; Humans; Inflammation; Maclura; Male; Mice; Mice, Inbred ICR; Pain; Phytotherapy; Plant Extracts; Psidium; Umbilical Veins

Chemopreventive agents are used to diminish the morbidity and mortality of cancer by delaying the course of carcinogenesis. Formation of ACF and amplified activity of colon biotransforming enzymes were considered to be hallmarks of colon carcinogenesis. Morin, a bioflavonoid present in fruits and show various pharmacological and biological activities. Our present study, shows the modulatory effect of morin administration on 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci (ACF) in rat colon, and fecal and mucosal biotransforming enzyme activities. A total of 64 rats were randomized into four groups. Group 1 served as control, groups 2 and 4 received 50mg/kg b.w. of morin intragastrically for the entire period of the study (30 weeks). Groups 3 and 4 received subcutaneous injection of DMH (20mg/kg b.w.) for 15 weeks. Rats were sacrificed at the end of 30 weeks. The incidence of tumors/polyps in the colon cancer of rats and treated with morin showed reduced incidence (40%) of tumors, as compared to DMH (100%) treated rats. Morin administration significantly reduced ACF formation and lowered the activities of fecal and mucosal biotransforming enzymes. Our findings suggest that morin (50mg/kg b.w.) may be a possible chemopreventive agent against colon cancer.

Topics: 1,2-Dimethylhydrazine; Animals; Antioxidants; beta-Glucosidase; Carcinogens; Colon; Colonic Neoplasms; Disease Models, Animal; Flavonoids; Glucuronidase; Intestinal Mucosa; Male; Nitroreductases; Polysaccharide-Lyases; Precancerous Conditions; Rats; Rats, Wistar

The anti-inflammatory activities of flavonols (quercetin, rutin and morin) and flavanones (hesperetin and hesperidin) were investigated in animal models of acute and chronic inflammation. Rutin was only effective in the chronic process, principally in adjuvant arthritis. On neurogenic inflammation induced by xylene, only the flavanones were effective; besides, these compounds were the most effective on subchronic process. The most important compound in reducing paw oedema induced by carrageenan was quercetin.

Topics: Animals; Arthritis, Experimental; Carrageenan; Disease Models, Animal; Ear; Edema; Flavonoids; Hesperidin; Hindlimb; Inflammation; Mice; Molecular Structure; Quercetin; Random Allocation; Rats; Rats, Wistar; Rutin; Xylenes

Morin is a flavonoid present in fruits and Chinese herbs. Based on in vitro studies, morin has been reported to show various beneficial biological activities. However, there is growing evidence that conjugative metabolism is central to the biological fate of flavonoids. Therefore, the biological effects of morin could be primarily determined by its conjugated metabolites. In this study, the effects of morin and its sulfates/glucuronides on the production of nitric oxide (NO) and cytokines from lipopolysaccharide (LPS)-activated macrophages were individually investigated and compared. The results indicated that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by 1.25 mM morin and 1.25 microM morin sulfates/glucuronides. Meanwhile, the 50% inhibition concentration (IC50) values of morin and morin sulfates/glucuronides in activated peritoneal macrophages were 1.5 mM morin and 1.5 microM morin sulfates/glucuronides, respectively. In addition, 30% of the tumor necrosis factor-alpha (TNF-alpha) and 35% of the interleukin (IL)-12 productions from activated macrophages were inhibited by 2-2.5 mM morin and 2-2.5 microM morin sulfates/glucuronides, respectively. Furthermore, phagocyte activities in the peripheral blood of those for mice dosed with morin for two months were about 65-70% of controls. Lower NO production and reduced macrophage phagocytic activities corresponded to LPS-resistant state. These findings indicated that morin may exhibit anti-inflammatory activity and reduced the incidence of experimental septic shock through decreasing the functions of macrophages and may regulate immune response through modulating the cytokine profiles. Therefore, morin could be a promising therapeutic candidate for inflammatory disease due to the strong activity of its metabolites.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Cell Line; Disease Models, Animal; Drugs, Chinese Herbal; Flavonoids; Glucuronides; Inhibitory Concentration 50; Interleukin-12; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Mice, Inbred BALB C; Nitric Oxide; Phagocytes; Shock, Septic; Sulfates; Tumor Necrosis Factor-alpha

Morin, a bioflavonoid with antioxidant properties, shows intestinal anti-inflammatory activity in the acute phase of the trinitrobenzenesulphonic acid model of rat colitis.. To assess the anti-inflammatory activity of morin in the chronic stages of trinitrobenzenesulphonic acid-induced rat colitis.. Rats were rendered colitic by a single colonic instillation of 30 mg of the hapten trinitrobenzenesulphonic acid dissolved in 0.25 mL of 50% ethanol. A group of colitic animals was given morin orally at doses of 25 mg/kg daily. Animals were sacrificed every week for 4 weeks. Colonic damage was evaluated macroscopically and microscopically. Different biochemical markers of colonic inflammation were also assayed, including myeloperoxidase activity, leukotriene B4 and interleukin-1beta synthesis, glutathione and malonyldialdehyde levels and nitric oxide synthase activity.. The administration of morin facilitated tissue recovery during the 4 weeks following colonic insult with trinitrobenzenesulphonic acid, as demonstrated macroscopically and microscopically, as well as biochemically by a reduction in myeloperoxidase activity. The intestinal anti-inflammatory effect of morin was accompanied by a significant reduction in colonic leukotriene B4 and interleukin-1beta levels, improvement in colonic oxidative stress and inhibition of colonic nitric oxide synthase activity.. Morin exerts a beneficial anti-inflammatory effect in the chronic phase of trinitrobenzenesulphonic acid-induced rat colitis through the down-regulation of some of the mediators involved in the intestinal inflammatory response, including free radicals, cytokines, leukotriene B4 and nitric oxide.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Chronic Disease; Colitis; Disease Models, Animal; Female; Flavonoids; Interleukin-1; Intestinal Mucosa; Leukotriene B4; Nitric Oxide; Nitric Oxide Synthase; Peroxidase; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid

The flavonoid morin was tested for anti-inflammatory activity in trinitrobenzenesulfonic acid (TNBS)-induced rat colitis. Rats were pretreated orally with several doses of the flavonoid (5, 10, 25, 100 and 200 mg/kg) 48, 24 and 1 h before and 24 h after colitis induction and examined for colonic damage 48 h after colitis induction. Colonic inflammation was characterized by diffuse hemorrhagic necrosis of the mucosa, bowel wall thickening, impairment of fluid absorption, increase in myeloperoxidase (MPO) activity, enhanced leukotriene B4 (LTB4) synthesis, glutathione depletion and increased levels of malonyldialdehyde (MDA). Morin treatment, at doses ranging from 10 to 200 mg/kg, significantly reduced colonic macroscopic damage. This beneficial effect was also confirmed by inhibition of colonic MPO activity. Several mechanisms may contribute to the protective effect exerted by morin. First, inhibition of colonic LTB4 synthesis is a common feature for all the active doses of the flavonoid. Second, the antioxidant properties of morin, which partially prevented colonic glutathione depletion (at doses of 10 and 25 mg/kg) or inhibited colonic MDA production (at doses of 100 and 200 mg/kg), can collaborate in preventing TNBS-induced inflammation.

Topics: Acute Disease; Administration, Oral; Animals; Antioxidants; Colitis; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Flavonoids; Leukotriene B4; Malondialdehyde; Rats; Rats, Wistar; Trinitrobenzenesulfonic Acid