Hepatoprotective Potential of Partially Hydrolyzed Guar Gum against Acute Alcohol-Induced Liver Injury in Vitro and Vivo

Abstract

Natural polysaccharides, particularly galactomannans, are potential candidates for treatment of alcoholic liver diseases (ALD). However, applications are restricted due to the physicochemical properties associated with the high molecular weight. In this work, guar gum galactomannans were partially hydrolyzed by β-mannanase, and the molecular mechanisms of hepatoprotective effects were elucidated both in vitro and in vivo. Release of lactate dehydrogenase and cytochrome C were attenuated by partially hydrolyzed guar gum (PHGG) in HepG2 cells, due to protected cell and mitochondrial membrane integrity. PHGG co-administration decreased serum amino transaminases and cholinesterase levels of acute alcohol intoxicated mice, while hepatic pathologic morphology was depleted. Activity of superoxide dismutase, catalase, and glutathione peroxidase was recovered to 198.2, 34.5, 236.0 U/mg protein, respectively, while malondialdehyde level was decreased by 76.3% (PHGG, 1000 mg/kg∙day). Co-administration of PHGG induced a 4.4-fold increment of p-AMPK expression, and lipid metabolism was mediated. PHGG alleviated toll-like-receptor-4-mediated inflammation via the signaling cascade of MyD88 and IκBα, decreasing cytokine production. Moreover, mediated expression of Bcl-2 and Bax was responsible for inhibited acute alcohol-induced apoptosis with suppressed cleavage of caspase 3 and PARP. Findings gained suggest that PHGG can be used as functional food supplement for the treatment of acute alcohol-induced liver injury.

Regulation of NOX/p38 MAPK/PPARα pathways and miR-155 expression by boswellic acids reduces hepatic injury in experimentally-induced alcoholic liver disease mouse model: novel mechanistic insight

“…Collectively, this perturbed redox status and hepatic inflammation led to hepatotoxicity via increased release of cytochrome C and activation of the apoptotic signaling cascade (Namachivayam and Valsala Gopalakrishnan 2021 ). This was supported by the reported increase in BAX to BCL2 ratio and caspase-3 activity in ethanol-fed mice both in our study and previous works (Wu et al 2019 ). On the contrary, BAs exerted a notable anti-apoptotic activity in ethanol-fed mice, evidenced by restriction of caspase-3 activity and BAX/BCL2 ratio, which comes in agreement with recent research on BAs’ antiapoptotic properties in various injury models (Ahmed et al 2020 ; Rajabian et al 2020 ).…”

Oenothein B ameliorates hepatic injury in alcoholic liver disease mice by improving oxidative stress and inflammation and modulating the gut microbiota

“…Levels of hepatotoxicity biomarkers LDH, ALT, and AST correlate with hepatocyte membrane integrity and organelle damage ( 25 ). Thus, to further evaluate the protective effect of OEB, LDH, ALT, and AST levels in each experimental group were quantified.…”

The in vitro and in vivo Antioxidant and Immunomodulatory Activity of Incomplete Degradation Products of Hemicellulosic Polysaccharide (Galactomannan) From Sesbania cannabina

“…Consistent with our findings, Bozkurt et al (2016) revealed that the usage of yeast cell wall MOS to the diet of laying hens has no significant effect on MDA content in the liver. Another report involving acute alcohol-intoxicated mice found that partially hydrolyzed guar gum had a significant effect on the reduction of MDA content in the serum (Wu et al, 2019). Unfortunately, in the same tissue or organ, the scavenger roles of these antioxidative enzymes for preventing oxidative damage did not play a significant role in reducing MDA content.…”