The Therapeutic Mechanisms of Propolis Against CCl4-Mediated Liver Injury by Mediating Apoptosis of Activated Hepatic Stellate Cells and Improving the Hepatic Architecture through PI3K/AKT/mTOR, TGF-β/Smad2, Bcl2/BAX/P53 and iNOS Signaling Pathways

Badr, Gamal; Sayed, Eman A.; Waly, Hanan; Hassan, Khadiga Abdel-Hameed; Mahmoud, Mohamed H.; Selamoğlu, Zeliha

doi:10.33594/000000140

Cited by 45 publications

(12 citation statements)

References 80 publications

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“…Supplementation of propolis is successfully recovered the changes induced by CCl 4 injection. 65 The present study showed decreases in Bcl-2 mRNA expres-…”

Section: Detection Of Caspase-9 and Bcl-2 In Liver And Kidney Tissuessupporting

confidence: 53%

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Izzularab

Megeed

Yehia

2020

Environmental Toxicology

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This study assessed the use of emulsion-produced propolis nanoparticles for treating carbon tetrachloride (CCl 4)-induced liver fibrosis and nephropathy on albino rat model. The evaluation of hepatotoxicity, nephrotoxicity, and the treatment outcomes involved biochemical investigations of blood samples as well as molecular analysis, and histopathological assessment for liver and kidney tissue samples. CCl 4 treatment caused elevated biochemical indicators of hepatotoxic and nephrotoxic effects as detected by liver and kidney functions tests, which improved gradually with propolis nanoparticles treatment. The molecular studies showed an increase in transforming growth factor β (TGF-β), Nephrin, and Caspase-9, while Bcl-2 levels dropped in both liver and kidney tissue samples; such changes were normalized after treatment. The histological findings confirm both biochemical and molecular studies. Our results indicated that propolis nanoparticles had an anti-inflammatory effect as proved by decreased expression of TGF-β in liver tissue and Nephrin in kidney tissue. The propolis nanoparticles showed an anti-apoptotic effect on liver and kidney tissue increasing the expression of Bcl-2 and decreasing the expression of Caspase-9.

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“…Supplementation of propolis is successfully recovered the changes induced by CCl 4 injection. 65 The present study showed decreases in Bcl-2 mRNA expres-…”

Section: Detection Of Caspase-9 and Bcl-2 In Liver And Kidney Tissuessupporting

confidence: 53%

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Izzularab

Megeed

Yehia

2020

Environmental Toxicology

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“…Nowadays, numerous functional foods and their ingredients are involved in the amelioration of the chemical's toxicity due to their antioxidant and anti-inflammatory roles 13 – 17 , 18 . Acacia Senegal (AS) gum (Gum Arabic), which is a naturally occurring exudate derived from the trunk and branches of AS and Acacia seyal trees, is one of these functional foods that have numerous medicinal effects.…”

Section: Introductionmentioning

confidence: 99%

Acacia senegal gum attenuates systemic toxicity in CCl4-intoxicated rats via regulation of the ROS/NF-κB signaling pathway

Abu‐Serie

Hamouda

Habashy

2021

Sci Rep

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Acacia senegal (AS) gum (Gum Arabic) is a natural emulsifier exudate from the branches and trunk of Acacia trees and it is recognized by the Food and Drug Administration (FDA) agency as a secure dietary fiber. The present research evaluated the systemic oxidative and necroinflammatory stress induced by CCl4 administration and the alleviating effect of AS gum aqueous extract (ASE, 7.5 g/Kg b.w.). The results demonstrated the presence of certain phenolic compounds in ASE, as well as its in vitro potent scavenging ability against ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), NO, and lipid peroxide radicals. Also, the outcomes revealed an improvement in the CCl4-induced liver, lung, brain, and spleen toxicity by reducing the levels of ROS, lipid peroxidation, NO, and the gene expression of NF-κB and its relevant ROS-mediated inflammatory genes. In contrast, the total antioxidant capacity (TAC), as well as the enzymatic and non-enzymatic antioxidants, were significantly upregulated in these organs after the treatment with ASE. These results were confirmed by improving the morphological features of each organ. Therefore, ASE can ameliorate the systemic toxicity caused by CCl4 via regulation of the ROS/NF-κB signaling pathway in the rat organs, which is owed to its phytochemical composition.

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“…Moreover, we related effects of EGCG to signalling pathways of AKT and mTOR as an index to HSCs activations. 20 Assessing these pathways were performed through western blot analysis by choosing ECGC with the concentration of 50 µM. Online supplemental figure 3B, C showed less phosphorylated AKT and mTOR in the LX2 NTCP+ cells following incubations with the EGCG.…”

Section: Resultsmentioning

confidence: 99%

Sodium⁺/taurocholate cotransporting polypeptide as target therapy for liver fibrosis

Salhab

Amer

et al. 2021

Gut

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ObjectiveSodium+/ taurocholate cotransporting polypeptide (NTCP) is a membrane transporter affecting the enterohepatic circulation of bile acids (BAs). We aimed to evaluate NTCP’s roles in humans and animal models of liver fibrosis (LF).DesignPrimary hepatic stellate cells (pHSCs) isolated from livers biopsies of patients with LF with different fibrosis grading were stained for NTCP. NTCP gene silencing, taurocholic acid (TCA), obeticholic acid (OCA), epigallocatechin gallate (EGCG) and HA-100 dihydrochloride (HA-100) were used as tools to modulate NTCP expression on human HSC line (LX2). BA trafficking/uptake were assessed extracellularly (LX2 culture medium) and intracellularly following treatment with/without NTCP neutralizing antibody. LF models of C57/BL6 mice of carbon tetrachloride (CCl4) and leptin-deficient (Ob/Ob) fed with high-fat diet (Ob/Ob HFD) were evaluated for pHSCs-NTCP expressions, metabolic and LF profiles following intraperitoneal injections of NTCP neutralizing antibody.ResultspHSCs from F3/F4-scored patients of LF exhibit threefold increased NTCP expressions compared with F0-scored patients (p<0.0001). Sorted-activated HSCs (LX2αSMA+) showed high expressions of NTCP and high TCA uptake in vitro and triggered a further increase in their activations. This phenomenon was inhibited with NTCP small interfering RNA and the NTCP neutralizing antibody. Sorted LX2NTCP+ (high alpha smooth muscle actin (αSMA)/high NTCP) cells showed high phosphorylated pathways of AKT/mTOR and protein kinase C (PKC) accompanied with a decrease in farnesoid X receptor expression. Moreover, LX2NTCP+ cells treated with EGCG, OCA and PKC inhibitor HA-100 significantly decreased NTCP and αSMA. NTCP neutralizing antibody inhibited NTCP (less TCA uptake); it attenuated LF in both CCl4 and Ob/Ob HFD animal models with ameliorated metabolic profile.ConclusionNTCP expression is linearly correlated with fibrosis severity. Modulated BA trafficking could be an important step in LF pathogenesis. Antagonising BA uptake may suggest a therapeutic strategy for preventing disease progression.

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The Therapeutic Mechanisms of Propolis Against CCl4-Mediated Liver Injury by Mediating Apoptosis of Activated Hepatic Stellate Cells and Improving the Hepatic Architecture through PI3K/AKT/mTOR, TGF-β/Smad2, Bcl2/BAX/P53 and iNOS Signaling Pathways

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 45 publications

References 80 publications

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Acacia senegal gum attenuates systemic toxicity in CCl4-intoxicated rats via regulation of the ROS/NF-κB signaling pathway

Sodium⁺/taurocholate cotransporting polypeptide as target therapy for liver fibrosis

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The Therapeutic Mechanisms of Propolis Against CCl4-Mediated Liver Injury by Mediating Apoptosis of Activated Hepatic Stellate Cells and Improving the Hepatic Architecture through PI3K/AKT/mTOR, TGF-β/Smad2, Bcl2/BAX/P53 and iNOS Signaling Pathways

Abstract: This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.

Cited by 45 publications

References 80 publications

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Propolis nanoparticles modulate the inflammatory and apoptotic pathways in carbon tetrachloride‐induced liver fibrosis and nephropathy in rats

Acacia senegal gum attenuates systemic toxicity in CCl4-intoxicated rats via regulation of the ROS/NF-κB signaling pathway

Sodium+/taurocholate cotransporting polypeptide as target therapy for liver fibrosis

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Sodium⁺/taurocholate cotransporting polypeptide as target therapy for liver fibrosis