Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats

Prasath, Gopalan Sriram; Subramanian, S.

doi:10.1016/j.fct.2013.05.062

Cited by 58 publications

(21 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Parallel studies in other systems however, indicate that fisetin attenuates hydrogen peroxide-induced cell damage by scavenging ROS and activating protective functions of cellular glutathione system (33). Fisetin improved the antioxidant competence in hepatic tissues of diabetic rats and protected hepatocellular ultrastructure from hyperglycemia mediated oxidative stress (34). We speculate that lower ROS levels in fisetin treated cells may predispose to inhibited cell growth due to decreased signaling mediated by pro-survival pathways such as PI3K/AKT/ mTOR, or the NF-KB.…”

Section: Discussionmentioning

confidence: 99%

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Syed

Lall

Chamcheu

et al. 2014

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up- regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16 days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMPK-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

show abstract

Section: Discussionmentioning

confidence: 99%

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Syed

Lall

Chamcheu

et al. 2014

Archives of Biochemistry and Biophysics

View full text Add to dashboard Cite

show abstract

“…2 Chronic hyperglycemia in the course of DM contributes to the oxidative stress, causing the redox balance of the body to change with excessive production of reactive oxygen species. 3 Oxidative stress leads to an increase in protein, lipid, carbohydrate and DNA oxidation. Accordingly, it causes tissue and organ damage 4 .…”

Section: Introductionmentioning

confidence: 99%

Histopathological and Immunohistochemical Study of Antidiabetic Effects of Heracleum persicum Extract İn Experimentally Diabetic Rats

Yaman¹,

Uyar²,

Çelik³

et al. 2017

IJPER

View full text Add to dashboard Cite

Objective: This study aims to investigate the antioxidant properties and protective effects of Heracleum persicum (HP) extract in streptozotocin (STZ)-induced diabetic rats. Material and Methods: Forty-two Wistar albino male rats were divided into six groups including Control (C); Diabetes mellitus (DM); DM+Akarboz 20 mg/kg; DM+100 mg/kg HP extract (HP1); DM+200 mg/kg HP extract (HP2) and DM+400 mg/kg HP extract (HP3). Experimental diabetes was established by a single-dose [45 mg/kg, intra-peritoneal (i.p)] STZ injection. Essential dosages of HP extracts and Akarboz were applied with gastric gavage for 21 day. Results: In histopathological evaluation of the stained liver and kidney sections of diabetic rats showed degeneration and necrosis of hepatocytes, inflammatory cell infiltration and hydropic degeneration and necrosis in tubulus epithelial cells, disorder of glomerular structure and lymphocyte infiltration. These histopathological changes were ameliorated in the HP-treated rats depending on the dose level. Glutathione peroxidase 1 (GPx-1) immunoreactivity was detected in hepatocytes of liver and tubule epithelial cells of kidney. We have shown that treatment with extracts of HP modulates GPx-1 expression in HP-treated rats. STZ-induced degenerative changes in beta-cells caused decreases in the number of functioning beta-cells and insulin immunoreactivity in the pancreas of the diabetic rats. The pancreas of HP-treated rats were improved and the number of immunoreactive β cells were significantly increased. Conclusion: Our data suggests that the STZ-induced immunohistochemical and histopathological alterations could be prevented by HP extract probably due to possess the ability to regenerate β-cells.

show abstract

“…30 Structures were solved by direct methods using SHELXS-2013 31 and refined by a full-matrix least squares technique with SHELXL-2013, 31 with anisotropic thermal parameters for all non-H atoms. All H atoms were found in difference Fourier maps, but in the final refinement cycles they were repositioned in their calculated positions and refined using a riding model, with C-H = 0.94-0.98 Å, N-H = 0.87 Å, O-H = 0.83-0.84 Å and with U iso ĲH) = 1.2U eq (C,N) for CH and NH 2 or 1.5U eq (C,O) for CH 3 and OH. SHELXLE 32 was used as refinement GUI and DIAMOND 33 was used for creation of figures.…”

Section: Raman Spectroscopymentioning

confidence: 99%

Improving solubility of fisetin by cocrystallization

2014

View full text Add to dashboard Cite

Fisetin, a naturally occurring polyphenolic compound, has a proven record of in vitro demonstrated anti-carcinogenic, anti-inflammatory and antiviral properties, yet similarly to many promising APIs, its in vivo administration is complicated by low aqueous solubility and unfavourable pharmacokinetics. The presented study was focused on obtaining and characterizing cocrystals of fisetin, with the aim of improving its solubility. Solvent-drop grinding experiments, combined with FT-Raman and XRPD, were conducted to identify new cocrystalline phases, which were afterwards isolated as single-crystals and characterized structurally and in terms of thermal stability and solubility. Dissolution studies of pure fisetin and four cocrystals, namely fisetin-isonicotinamide 1 : 1 (FisInam), fisetin-nicotinamide 1 : 2 hemiethanolate (FisNam), fisetin-nicotinamide 1 : 1 (FisNam2) and fisetin-caffeine 1 : 2 (FisCaf), showed that a 2.5-fold increase of fisetin solubility was achieved for FisNam and to a smaller extent for FisCaf and FisInam (ca. 1.8-and 1.5-fold, respectively).

show abstract

Fisetin, a tetra hydroxy flavone recuperates antioxidant status and protects hepatocellular ultrastructure from hyperglycemia mediated oxidative stress in streptozotocin induced experimental diabetes in rats

Cited by 58 publications

References 49 publications

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Histopathological and Immunohistochemical Study of Antidiabetic Effects of Heracleum persicum Extract İn Experimentally Diabetic Rats

Improving solubility of fisetin by cocrystallization

Contact Info

Product

Resources

About