Morin

Morin activates the Nrf2-ARE pathway and reduces oxidative stress-induced DNA damage in pancreatic beta cells.[Pubmed: 28216051 ]

Eur J Pharmacol. 2017 Apr 15;801:9-18.

Oxidative stress is an important factor contributing to the pathogenesis of diabetes and its complications. In our earlier study, we demonstrated the antidiabetic efficacy of Morin by regulating key enzymes of carbohydrate metabolism in diabetic rats. The present study was designed to assess the antigenotoxic potential of Morin in pancreatic β-cells, using the COMET assay.
METHODS AND RESULTS:
To explore its potential mechanisms of action, three genotoxic agents, H2O2 which induces DNA damage by the generation of reactive oxygen species, streptozotocin (STZ) by RNS and Methyl methanesulfonate (MMS) by DNA alkylation was used. We found that STZ and H2O2- induced genotoxicity was dose dependently reduced by Morin as assessed by DNA tail length, tail moment, DNA content and olive moment. Since the protective property was found to be specific against oxidative DNA damage, we explored the molecular mechanism underlying Morin-induced Nuclear factor erythroid 2-related factor 2 (Nrf2) activation in pancreatic β-cells as assessed by ARE-driven downstream target genes with Luciferase reporter assay. In addition, Morin inhibited intracellular free radical generation as assessed by using DCFDA and increased the intra cellular antioxidants viz, superoxide dismutase and catalase in INS-1E cells. In addition, Morin attenuated glucose-stimulated insulin secretion following exposure to oxidative stress by STZ (P<0.05).
CONCLUSIONS:
Collectively, our data provide evidence that Morin protects pancreatic β-cells against oxidative stress-induced DNA damage by activating the Nrf2 signaling pathway.

Morin Inhibits Proliferation, Migration, and Invasion of Bladder Cancer EJ Cells via Modulation of Signaling Pathways, Cell Cycle Regulators, and Transcription Factor-Mediated MMP-9 Expression.[Pubmed: 28176369]

Drug Dev Res. 2017 Mar;78(2):81-90.

Preclinical Research Previous studies have shown that Morin exerts diverse pharmacological activities. In this study, we investigated the inhibitory activity of Morin on bladder cancer EJ cells.
METHODS AND RESULTS:
Morin significantly inhibited EJ cell proliferation, which was related to the G1-phase cell cycle arrest together with the reduced expression of cyclin D1, cyclin E, CDK2, and CDK4 via increased expression of p21WAF1. Morin also increased ERK1/2 phosphorylation and decreased JNK and AKT phosphorylation without altering the p38MAPK phosphorylation levels. Morin treatment suppressed the migration and invasion of EJ cells in wound-healing and transwell cell invasion assays. Zymographic and electrophoretic mobility shift assays showed that Morin suppressed the expression of matrix metalloproteinase-9 (MMP-9) via repression of the binding activity of AP-1, Sp-1, and NF-κB.
CONCLUSIONS:
Collectively, these results demonstrate that Morin reduced cyclin D1, cyclin E, CDK2 and CDK4 expression via the induction of p21WAF1 expression, increased ERK1/2 phosphorylation and decreased JNK, and AKT phosphorylation, and prevented MMP-9 expression via the inhibition of transcription factors AP-1, Sp-1, and NF-κB, thereby resulting in the inhibition of growth, migration, and invasion of bladder cancer EJ cells. These results provide a novel insight into the use of Morin in the prevention of bladder cancer.

Protective effects of morin on lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting TLR4/NF-κB and activating Nrf2/HO-1 signaling pathways.[Pubmed: 28213269 ]

Int Immunopharmacol. 2017 Apr;45:148-155.

Morin, a bioactive flavonoid extracted from the bark of Moraceae plants and many medicinal herbs, has anti-inflammatory and antioxidative effects. In this research, we explored the protective effects of Morin against lipopolysaccharide (LPS) and d-galactosamine (D-GalN) induced acute liver injury in mice.
METHODS AND RESULTS:
Mice were given an intraperitoneal injection of Morin before LPS and D-GalN treatment and the HepG2 cells were only given Morin to investigate its effects. The results showed that Morin markedly inhibited the production of serum alanine transaminase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), tumor necrosis factor (TNF-α) and hepatic TNF-α, IL-6, and myeloperoxidase (MPO) induced by LPS/D-GalN. In order to evaluate Morin effect in the future, we investigated the expression of nuclear factor E2 related factor 2 (Nrf2), nuclear factor-kappaB (NF-κB), toll like receptor 4 (TLR4) on liver injury.
CONCLUSIONS:
Taken together, these results suggested that Morin could exert the anti-inflammatory and anti-oxidative effects against LPS/D-GalN-induced acute liver injury by activating Nrf2 signal pathways and inhibiting NF-κB activation.

Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway.[Pubmed: 28035409 ]

Int J Mol Med. 2017 Feb;39(2):399-406.

In the present study, we investigated the cytoprotective efficacy of Morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts.
METHODS AND RESULTS:
Our results indicated that Morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and γH2AX phosphorylation were also markedly suppressed by Morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that Morin prevented H2O2-induced cellular DNA damage. Furthermore, Morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keap1) expression. Notably, these events were eliminated by transient transfection with Nrf2‑specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by Morin was mediated by the extracellular signal‑regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK.
CONCLUSIONS:
Collectively, these results demonstrated that Morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO‑1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity.

Food Funct. 2016 Sep 14;7(9):3953-63.

Inhibitory mechanism of morin on α-glucosidase and its anti-glycation properties.[Pubmed: 27549567]

It is important to investigate the inhibition of α-glucosidase due to its correlation with type 2 diabetes.
METHODS AND RESULTS:
Morin was found to exert significant inhibition activity on α-glucosidase in a reversible mixed-type manner with an IC50 value of (4.48 ± 0.04) μM. Analyses of fluorescence and circular dichroism spectra indicated that the formation of the Morin-α-glucosidase complex was driven mainly by hydrophobic forces and hydrogen bonding, and caused the conformational changes of α-glucosidase. The phase diagrams of fluorescence showed that the conformational change process was monophasic without intermediates.
CONCLUSIONS:
Molecular docking indicated that Morin mainly interacted with amino acid residues located close to the active site of α-glucosidase, which may move to cover the active pocket to reduce the binding of the substrate and then inhibit the catalytic activity. Morin was also found to exhibit inhibition in the generation of advanced glycation end products which was related to the long term complications of diabetes.