Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted β-Sitosterol against CCl4 induced hepatotoxicity in rats

Abdou, Ebtsam M; Fayed, Marwa A. A.; Helal, Doaa A.; Ahmed, Kawkab A.

doi:10.1038/s41598-019-56320-2

Cited by 49 publications

(26 citation statements)

References 72 publications

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“…The animal models exposed to CCl 4 and D-gal/LPS have been extensively applied for investigating the underlying mechanisms of acute liver injury. CCl 4 is a widely used chemical toxicant and causes severe liver tissue damage by the cytochrome P450 enzymes to form reactive intermediates, such as trichloromethylfree radicals and peroxyl radical, which results in lipid peroxidation and hepatocyte necrosis [24][25][26]. Lipopolysaccharide (LPS), also known as endotoxin, is a major component of the outer membrane of Gramnegative bacteria, which induces a strong inflammatory response [27,28].…”

Section: Discussionmentioning

confidence: 99%

The dynamics of cell death patterns and regeneration during acute liver injury in mice

Shao

et al. 2022

FEBS Open Bio

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Acute liver injury is a serious clinical syndrome with multiple causes and unclear pathological process. Here, CCl4‐ and D‐galactosamine/lipopolysaccharide (D‐gal/LPS)‐induced acute liver injury was established to explore the cell death patterns and determine whether or not liver regeneration occurred. In CCl4‐induced hepatic injury, three phases, including the early, progressive, and recovery phase, were considered based on alterations of serum transaminases and liver morphology. Moreover, in this model, cytokines exhibited double‐peak fluctuations; apoptosis and pyroptosis persisted throughout all phases; autophagy occurred in the early and the progressive phases; and sufficient and timely hepatocyte regeneration was observed only during the recovery phase. All of these phenomena contribute to mild liver injury and subsequent regeneration. Strikingly, only the early and progressive phases were observed in the D‐gal/LPS model. Slight pyroptosis occurred in the early phase but diminished in the progressive phase, while apoptosis, reduced autophagy, and slight but subsequently diminished regeneration occurred only during the progressive phase, accompanied by a strong cytokine storm, resulting in severe liver injury with high mortality. Taken together, our work reveals variable modes and dynamics of cell death and regeneration, which lead to different consequences for mild and severe acute liver injury, providing a helpful reference for clinical therapy and prognosis.

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Section: Discussionmentioning

confidence: 99%

The dynamics of cell death patterns and regeneration during acute liver injury in mice

Shao

et al. 2022

FEBS Open Bio

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“…Moreover, integrated miRNAomics, proteomics and metabolomics analysis found that geniposide could upregulate the protein levels of isocitrate dehydrogenase (IDH) 1 and 2 through downregulating the expression of miR-144-5p and then modulate energy metabolism in ethanol-induced apoptosis hepatocyte model in vitro ( Qiu et al, 2017 ). Lipid peroxidation induced by CCl 4 treatment can alter the permeability of the cell membrane, resulting in damage to the intracellular organelle membrane structures, such as mitochondria, endoplasmic reticulum, and Golgi apparatus, etc., which further triggers the metabolic disorders in hepatocytes ( Abdou et al, 2019 ). Untargeted metabolomics were used to analyze the metabolic regulatory effects of geniposide on CCl 4 -induced liver fibrosis model.…”

Section: Discussionmentioning

confidence: 99%

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Yang

Jin

et al. 2021

Front. Pharmacol.

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Liver fibrosis is a progressive liver damage condition caused by various factors and may progress toward liver cirrhosis, and even hepatocellular carcinoma. Many studies have found that the disfunction in metabolism could contribute to the development of liver fibrosis. Geniposide, derived from Gardenia jasminoides J. Ellis, has been demonstrated with therapeutic effects on liver fibrosis. However, the exact molecular mechanisms of such liver-protection remain largely unknown. The aim of this study was to explored the effect of geniposide on metabolic regulations in liver fibrosis. We used carbon tetrachloride (CCl4) to construct a mouse model of liver fibrosis and subsequently administered geniposide treatment. Therapeutic effects of geniposide on liver fibrosis were accessed through measuring the levels of hepatic enzymes in serum and the pathological changes in liver. We also investigated the effects of geniposide on inflammatory response, oxidative stress and apoptosis in liver. Furthermore, serum untargeted metabolomics were used to explore the metabolic regulatory mechanisms behind geniposide on liver fibrosis. Our results demonstrated that geniposide could reduce the levels of hepatic enzymes in serum and ameliorate the pathological changes in liver fibrosis mice. Geniposide enhanced the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and decreased methane dicarboxylic aldehyde (MDA) levels in liver. Geniposide treatment also decreased the levels of interleukin (IL)-6, IL-1β, and tumor necrosis factor-alpha (TNF-a) in liver tissue homogenate. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay (TUNEL) staining demonstrated that geniposide could reduce the apoptosis of hepatocytes. Geniposide increased the protein expression of B-cell lymphoma-2 (Bcl-2) and downregulated the protein expression of Bcl-2 Associated X (Bax), cleaved-Caspase 3, and cleaved-Caspase 9. Serum untargeted metabolomics analysis demonstrated that geniposide treatment improved the metabolic disorders including glycerophospholipid metabolism, arginine and proline metabolism, and arachidonic acid (AA) metabolism. In conclusion, our study demonstrated the protective effects of geniposide on liver fibrosis. We found that geniposide could treat liver fibrosis by inhibiting oxidative stress, reducing inflammatory response and apoptosis in the liver, and modulating glycerophospholipid, and arginine, proline, and AA metabolism processes.

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“…For β-sitosterol, it is a regarded as a safe nutritional supplement that can be sold commercially in the market [ 22 ]. It was recognized to possess several bioactivities including anti-nociceptive [ 23 ], anxiolytic & sedative effects [ 24 ], analgesic [ 25 ], immune modulatory [ 26 ], antimicrobial [ 27 ], anti-inflammatory [ 28 ], protective effect against non-alcoholic fatty liver disease [ 29 ], lipid lowering [ 30 ], hepatoprotective [ 31 ], protective effect on respiratory diseases [ 32 ], wound healing [ 33 ], antidiabetic [ 34 ], antioxidant [ 35 ], and anticancer [ 36 ]. As an anticancer, it could inhibit the growth of HeLa, HT-29, KB, and MCF-7 cell lines with moderate IC 50 values ranging from 0.099 to 1.49 μg/mL [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative, antibacterial, and antioxidant activities of Bauhinia strychnifolia Craib aqueous extracts in gut and liver perspective

Phonghanpot

Jarintanan

2021

BMC Complement Med Ther

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Background Bauhinia strychnifolia Craib is an herb in Thai traditional medicine. Its decoction is traditionally used as an anticancer, antidiarrheal, and hangover remedy for centuries. Several studies described bioactivities of its organic solvent extracts, however, only few demonstrated the usefulness of the decoction. Here, we aimed to determine the bioactivities of Bauhinia strychnifolia Craib root and stem aqueous extracts in gut and liver perspective. Methods To achieve the goal, we performed MTT test, microscopic analyses, disc diffusion assay, broth microdilution assay, free radicals scavenging assays, and LC-MS analysis. Results We found that the extracts inhibited the growth of human hepatocellular carcinoma (HepG2) and colon adenocarcinoma (HT-29) cell lines. Moreover, they also inhibited the growth of gram-positive bacteria Staphylococcus aureus and Bacillus cereus but not inhibited the growth of gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa. Furthermore, the extracts exhibited moderate antioxidant activity and increased GSH production in HepG2 cell line when compared with untreated. Our LC-MS analysis confirmed the existence of anticancer and antioxidant; 3,5,7,3′,5′-pentahydroxyflavanonol-3-O-α-L-rhamnopyranoside and β-sitosterol, in the extracts. Conclusion The results from our study supported that the administration of Bauhinia strychnifolia Craib root and stem decoction would really aid colon or liver cancer patients and detoxify the alcoholic drunkard as it is claimed in Thai traditional medicine.

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Assessment of the hepatoprotective effect of developed lipid-polymer hybrid nanoparticles (LPHNPs) encapsulating naturally extracted β-Sitosterol against CCl4 induced hepatotoxicity in rats

Cited by 49 publications

References 72 publications

The dynamics of cell death patterns and regeneration during acute liver injury in mice

The dynamics of cell death patterns and regeneration during acute liver injury in mice

Geniposide Ameliorates Liver Fibrosis Through Reducing Oxidative Stress and Inflammatory Respose, Inhibiting Apoptosis and Modulating Overall Metabolism

Antiproliferative, antibacterial, and antioxidant activities of Bauhinia strychnifolia Craib aqueous extracts in gut and liver perspective

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