A series of indole-fused medium-sized N-heterocyclic systems 10a–h were prepared from laboratory-synthesized
indole-based esters 9a–h via intramolecular Friedel–Crafts cyclizations induced by both trifluoromethanesulfonic acid
and AlCl3/CH3NO2 catalysts under suitable conditions. The synthetic sequence to precursors 9a–h that started from simple
N-methylindole-2-carboxylic acid involved conversion to aminoindoles 2a, b, reaction with a,b-unsaturated acid
chlorides to yield acyclic amides 5a–d, ring closure to tricyclic lactams 6a–d, and carbonyl reduction to respective
pyrido and azepino tricyclic amines 7a–d, which finally underwent N-alkylations with a- or b-haloesters to produce the
required ester precursors. The structures of synthesized compounds without stereochemical implications are established
using both spectral and analytical data.

A series of indole-fused medium-sized N-heterocyclic systems 10a–h were prepared from laboratory-synthesized
indole-based esters 9a–h via intramolecular Friedel–Crafts cyclizations induced by both trifluoromethanesulfonic acid
and AlCl3/CH3NO2 catalysts under suitable conditions. The synthetic sequence to precursors 9a–h that started from simple
N-methylindole-2-carboxylic acid involved conversion to aminoindoles 2a, b, reaction with a,b-unsaturated acid
chlorides to yield acyclic amides 5a–d, ring closure to tricyclic lactams 6a–d, and carbonyl reduction to respective
pyrido and azepino tricyclic amines 7a–d, which finally underwent N-alkylations with a- or b-haloesters to produce the
required ester precursors. The structures of synthesized compounds without stereochemical implications are established
using both spectral and analytical data.

BACKGROUND/AIMS:

Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis.
METHODS:

Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA.
RESULTS:

We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-β followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice.
CONCLUSION:

Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

BACKGROUND/AIMS:

Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis.
METHODS:

Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA.
RESULTS:

We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-β followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice.
CONCLUSION:

Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

BACKGROUND/AIMS:

Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis.
METHODS:

Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA.
RESULTS:

We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-β followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice.
CONCLUSION:

Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

BACKGROUND/AIMS:

Propolis is one of the most promising natural products, exhibiting not only therapeutic but also prophylactic actions. Propolis has several biological and pharmacological properties, including hepatoprotective activities. The present study aimed to investigate the underlying molecular mechanisms of propolis against CCl4-mediated liver fibrosis.
METHODS:

Three groups of male BALB/c mice (n=15/ group) were used: group 1 comprised control mice; groups 2 and 3 were injected with CCl4 for the induction of liver fibrosis. Group 3 was then orally supplemented with propolis (100 mg/kg body weight) for four weeks. Different techniques were used to monitor the antifibrotic effects of propolis, including histopathological investigations using H&E, Masson's trichrome and Sirius red staining; Western blotting; flow cytometry; and ELISA.
RESULTS:

We found that the induction of liver fibrosis by CCl4 was associated with a significant increase in hepatic collagen and α-smooth muscle actin (α-SMA) expression. Moreover, CCl4-treated mice also exhibited histopathological alterations in the liver architecture. Additionally, the liver of CCl4-treated mice exhibited a marked increase in proinflammatory signals, such as increased expression of HSP70 and increased levels of proinflammatory cytokines and ROS. Mechanistically, the liver of CCl4-treated mice exhibited a significant increase in the phosphorylation of AKT and mTOR; upregulation of the expression of BAX and cytochrome C; downregulation of the expression of Bcl2; a significant elevation in the levels of TGF-β followed by increased phosphorylation of SMAD2; and a marked increase in the expression of P53 and iNOS. Interestingly, oral supplementation of CCl4-treated mice with propolis significantly abolished hepatic collagen deposition, abrogated inflammatory signals and oxidative stress, restored CCl4-mediated alterations in the signaling cascades, and hence repaired the hepatic architecture nearly to the normal architecture observed in the control mice.
CONCLUSION:

Our findings revealed the therapeutic potential and the underlying mechanisms of propolis against liver fibrosis.

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The kinetics of oxidation of methyl cellulose polysaccharide by acidic permanganate at a constant ionic strength of
2.0 mol dm−3 has been investigated, spectrophotometrically. Pseudo-first-order plots showed two distinct stages. The first stage
was found to be relatively slow which corresponded to the formation of the substrate radical and Mn3+ or Mn4+ species as initial
oxidation products, followed by an increase in the reaction rate at longer time periods. The reaction kinetics showed first-order
dependence in permanganate and fractional second-order kinetics with respect to methyl cellulose concentration. The hydrogen
ion dependence of the reaction rates indicated that the oxidation process is acid catalyzed. The induced polymerization of
acrylonitrile indicated the intervention of free-radical mechanism. A kinetic evidence for the formation of 1:2 intermediate
complex between the oxidant and the reductant, respectively, was revealed. The activation parameters have been evaluated, and a
tentative reaction mechanism consistent with the kinetic results obtained is discussed.

The kinetics of oxidation of methyl cellulose polysaccharide by acidic permanganate at a constant ionic strength of
2.0 mol dm−3 has been investigated, spectrophotometrically. Pseudo-first-order plots showed two distinct stages. The first stage
was found to be relatively slow which corresponded to the formation of the substrate radical and Mn3+ or Mn4+ species as initial
oxidation products, followed by an increase in the reaction rate at longer time periods. The reaction kinetics showed first-order
dependence in permanganate and fractional second-order kinetics with respect to methyl cellulose concentration. The hydrogen
ion dependence of the reaction rates indicated that the oxidation process is acid catalyzed. The induced polymerization of
acrylonitrile indicated the intervention of free-radical mechanism. A kinetic evidence for the formation of 1:2 intermediate
complex between the oxidant and the reductant, respectively, was revealed. The activation parameters have been evaluated, and a
tentative reaction mechanism consistent with the kinetic results obtained is discussed.

The kinetics of oxidation of methyl cellulose polysaccharide by acidic permanganate at a constant ionic strength of
2.0 mol dm−3 has been investigated, spectrophotometrically. Pseudo-first-order plots showed two distinct stages. The first stage
was found to be relatively slow which corresponded to the formation of the substrate radical and Mn3+ or Mn4+ species as initial
oxidation products, followed by an increase in the reaction rate at longer time periods. The reaction kinetics showed first-order
dependence in permanganate and fractional second-order kinetics with respect to methyl cellulose concentration. The hydrogen
ion dependence of the reaction rates indicated that the oxidation process is acid catalyzed. The induced polymerization of
acrylonitrile indicated the intervention of free-radical mechanism. A kinetic evidence for the formation of 1:2 intermediate
complex between the oxidant and the reductant, respectively, was revealed. The activation parameters have been evaluated, and a
tentative reaction mechanism consistent with the kinetic results obtained is discussed.