Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence

Okkay, Irmak Ferah; Okkay, Ufuk; Gündoğdu, Ömer Lütfi; Bayram, Cemil; Mendil, Ali Sefa; Ertugrul, Muhammed Sait; Hacımüftüoğlu, Ahmet

doi:10.1016/j.neulet.2021.136385

Cited by 26 publications

(10 citation statements)

References 60 publications

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“…SA has been shown to exert several beneficial effects. For instance, SA has antioxidant, 16 anti‐inflammatory, 17 neuroprotective, 18 hepatoprotective, 19 cardioprotective, 20 nephroprotective, 21 and anti‐cancer 22,23 properties. In the context of the liver, SA has been shown to induce apoptosis in liver cancer cells 24 .…”

Section: Introductionmentioning

confidence: 99%

Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats

Gheena

Ezhilarasan

Harini

et al. 2022

Environmental Toxicology

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Sodium valproate (SV) is a well‐known anti‐epileptic drug, also used to control convulsions, bipolar disorders and migraines. SV has been shown to induce liver toxicity in clinical subjects. Syringic acid (SA), a natural polyphenolic compound has potential antioxidant, anti‐inflammatory and several beneficial effects. Therefore, in this study, we evaluated hepatoprotective effect of SA against SV‐induced liver injury in rats. Wistar rats were treated with SV orally at a dose of 500 mg/kg, once daily, for 14 days. Another three groups of rats were administered with SV and concurrently treated with SA (40 and 80 mg/kg) and silymarin (SIL) (100 mg/kg) for 14 days. SV administration for 14 days caused significant (p < .001) elevation of liver transaminases and ALP in serum. Liver MDA level was significantly (p < .001) increased with a concomitant decrease (p < .001) in enzymic antioxidants activities in SV administered rats. SV administration also caused the upregulation of proinflammatory markers such as tumor necrosis factor α, c‐Jun N‐terminal kinase, nuclear factor kappa B, cyclooxygenase‐2 and Interleukin 6 expressions in liver tissue. Histopathological studies also revealed the presence of inflammatory cell infiltration and hepatocellular necrosis upon SV administration. At both doses, concurrent administration of SA and SIL significantly (p < .001) inhibited the liver transaminase activities in serum, oxidative stress, and proinflammatory markers expression in liver tissue. Our current results suggest that SA can be a promising herbal drug that can inhibit SV‐induced hepatotoxicity when administered together due its potential anti‐inflammatory effects.

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Section: Introductionmentioning

confidence: 99%

Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats

Gheena

Ezhilarasan

Harini

et al. 2022

Environmental Toxicology

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“…52 Furthermore, the expression of GFAP proteins in the brain tissue of swine models of HE was decreased and astroglial cells changed morphologically. 53 On the contrary, in other studies, GFAP immunoreactivity was significantly increased in hippocampal areas of thioacetamide-induced HE rats 54,55 and cerebral cortex of hyperammonemic rats, 56 whereas in BDL-induced cirrhosis and HE rats, opposite results were seen. 55 Ammonia on organotypic mice brain slice increased expression of GFAP and caused astrocyte swelling.…”

Section: Discussionmentioning

confidence: 66%

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

Sepehrinezhad

Shahbazi

Negah

et al. 2023

Bioinform Biol Insights

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Hepatic encephalopathy (HE) is a set of complex neurological complications that arise from advanced liver disease. The precise molecular and cellular mechanism of HE is not fully understood. Differentially expressed genes (DEGs) from microarray technologies are powerful approaches to obtain new insight into the pathophysiology of HE. We analyzed microarray data sets of cirrhotic patients with HE from Gene Expression Omnibus to identify DEGs in postmortem cerebral tissues. Consequently, we uploaded significant DEGs into the STRING to specify protein-protein interactions. Cytoscape was used to reconstruct the genetic network and identify hub genes. Target genes were uploaded to different databases to perform comprehensive enrichment analysis and repurpose new therapeutic options for HE. A total of 457 DEGs were identified in 2 data sets totally from 12 cirrhotic patients with HE compared with 12 healthy subjects. We found that 274 genes were upregulated and 183 genes were downregulated. Network analyses on significant DEGs indicated 12 hub genes associated with HE. Enrichment analysis identified fatty acid beta-oxidation, cerebral organic acidurias, and regulation of actin cytoskeleton as main involved pathways associated with upregulated genes; serotonin receptor 2 and ELK-SRF/GATA4 signaling, GPCRs, class A rhodopsin-like, and p38 MAPK signaling pathway were related to downregulated genes. Finally, we predicted 39 probable effective drugs/agents for HE. This study not only confirms main important involved mechanisms of HE but also reveals some yet unknown activated molecular and cellular pathways in human HE. In addition, new targets were identified that could be of value in the future study of HE.

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“…After each rat, the cage is cleaned with alcohol to remove odor and urine (Ferah Okkay et al, 2022). The Elevated Plus Maze Test is used to measure anxiety-like behaviour in rodents.…”

Section: Monitoring Behaviourmentioning

confidence: 99%

Multi-tissue network analysis reveals the effect of JNK inhibition on dietary sucrose-induced metabolic dysfunction in rats

Yang,

Zhang,

Kim

et al. 2024

Preprint

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Excessive consumption of sucrose, in the form of sugar-sweetened beverages, has been implicated in the pathogenesis of metabolic dysfunction?associated fatty liver disease (MAFLD) and other related metabolic syndromes. The c-Jun N-terminal kinase (JNK) pathway plays a crucial role in response to dietary stressors, and it was demonstrated that the inhibition of the JNK pathway could potentially be used in the treatment of MAFLD. However, the intricate mechanisms underlying these interventions remain incompletely understood given their multifaceted effects across multiple tissues. In this study, we challenged rats with sucrose-sweetened water and investigated the potential effects of JNK inhibition by employing network analysis based on the transcriptome profiling obtained from hepatic and extrahepatic tissues, including visceral white adipose tissue, skeletal muscle, and brain. Our data demonstrate that JNK inhibition by JNK-IN-5A effectively reduces the circulating triglyceride accumulation and inflammation in rats subjected to sucrose consumption. Coexpression analysis and genome-scale metabolic modelling reveal that sucrose overconsumption primarily induces transcriptional dysfunction related to fatty acid and oxidative metabolism in the liver and adipose tissues, which are largely rectified after JNK inhibition at a clinically relevant dose. Skeletal muscle exhibited minimal transcriptional changes to sucrose overconsumption but underwent substantial metabolic adaptation following the JNK inhibition. Overall, our data provides novel insights into the molecular basis by which JNK inhibition exerts its metabolic effect in the metabolically active tissues. Furthermore, our findings underpin the critical role of extrahepatic metabolism in the development of diet-induced steatosis, offering valuable guidance for future studies focused on JNK-targeting for effective treatment of MAFLD.

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Syringic acid protects against thioacetamide-induced hepatic encephalopathy: Behavioral, biochemical, and molecular evidence

Cited by 26 publications

References 60 publications

Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats

Syringic acid and silymarin concurrent administration inhibits sodium valproate‐induced liver injury in rats

New Insight Into Mechanisms of Hepatic Encephalopathy: An Integrative Analysis Approach to Identify Molecular Markers and Therapeutic Targets

Multi-tissue network analysis reveals the effect of JNK inhibition on dietary sucrose-induced metabolic dysfunction in rats

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