N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats

Chunchai, Titikorn; Keawtep, Puntarik; Arinno, Apiwan; Saiyasit, Napatsorn; Prus, Dillon; Apaijai, Nattayaporn; Pratchayasakul, Wasana; Chattipakorn, Nipon

doi:10.18632/aging.101989

Cited by 20 publications

(9 citation statements)

References 65 publications

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“…Previous research found that oligofructose-enriched inulin in the diet (5%, w/w) produced relaxing-like effects and improved learning functions in animal models . A combination of N -acetyl cysteine and inulin has been reported to help with cognitive decline in a testosterone-deprived rat model . Recent studies also demonstrated that inulin could reduce HFD-induced neuroinflammation and anxiety .…”

Section: Discussionmentioning

confidence: 99%

High-Dietary Fiber Intake Alleviates Antenatal Obesity-Induced Postpartum Depression: Roles of Gut Microbiota and Microbial Metabolite Short-chain Fatty Acid Involved

Liu

et al. 2020

J. Agric. Food Chem.

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Antenatal obesity increases the risk of postpartum depression. Previous research found that dietary fiber supplementation could alleviate mental behavioral disorders. The present study aims to uncover the effects of high-dietary fiber intake on high-fat diet (HFD)-induced depressive-like behaviors and its underlying mechanism. Female C57BL6/J mice were fed with HFD to establish an antenatal obese model. A high-dietary fiber intake (inulin, 0.037 g/kcal) significantly attenuated cognitive deficits and depressive-like behaviors in the maternal mice after the offspring weaning. High-dietary fiber intake upregulated the expression of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) and suppressed neuroinflammation. Furthermore, high-dietary fiber intake restructured the gut microbiome and elevated the formation of short-chain fatty acids (SCFAs). Correlation analysis indicated that the increase in microbes such as Lactobacillus and S24-7, and SCFAs’ levels were positively correlated with behavioral improvements. In conclusion, high-dietary fiber intake is a promising nutritional intervention strategy to prevent antenatal obesity-induced behavioral disorders via a microbiota–gut–brain axis.

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Section: Discussionmentioning

confidence: 99%

High-Dietary Fiber Intake Alleviates Antenatal Obesity-Induced Postpartum Depression: Roles of Gut Microbiota and Microbial Metabolite Short-chain Fatty Acid Involved

Liu

et al. 2020

J. Agric. Food Chem.

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“…It has been shown that inulin improves mood as well as memory and digestion in humans [ 17 ]. Inulin also ameliorates castration-induced cognitive decline [ 18 ]. Unexpectedly, although long-term (6 months) supplementation of inulin (7.5%) improves metabolic syndrome in toll-like receptor 5 (TLR5)-knockout mice, many of these mice develop icteric hepatocellular carcinoma (HCC) [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Dysregulated bile acid receptor-mediated signaling and IL-17A induction are implicated in diet-associated hepatic health and cognitive function

et al. 2020

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Background Chronic consumption of high sugar and high fat diet associated with liver inflammation and cognitive decline. This paper tests a hypothesis that the development and resolution of diet-induced nonalcoholic fatty liver disease (NAFLD) has an impact on neuroplasticity and cognition. Methods C57BL/6 wild-type mice were fed with either a healthy control diet (CD) or a fructose, palmitate, and cholesterol (FPC)-enriched diet since weaning. When mice were 3-months old, FPC diet-fed mice were randomly assigned to receive either FPC-enriched diet with or without 6% inulin supplementation. At 8 months of age, all three groups of mice were euthanized followed by analysis of inflammatory signaling in the liver and brain, gut microbiota, and cecal metabolites. Results Our data showed that FPC diet intake induced hepatic steatosis and inflammation in the liver and brain along with elevated RORγ and IL-17A signaling. Accompanied by microglia activation and reduced hippocampal long-term potentiation, FPC diet intake also reduced postsynaptic density-95 and brain derived neurotrophic factor, whereas inulin supplementation prevented diet-reduced neuroplasticity and the development of NAFLD. In the gut, FPC diet increased Coriobacteriaceae and Erysipelotrichaceae, which are implicated in cholesterol metabolism, and the genus Allobaculum, and inulin supplementation reduced them. Furthermore, FPC diet reduced FXR and TGR5 signaling, and inulin supplementation reversed these changes. Untargeted cecal metabolomics profiling uncovered 273 metabolites, and 104 had significant changes due to FPC diet intake or inulin supplementation. Among the top 10 most affected metabolites, FPC-fed mice had marked increase of zymosterol, a cholesterol biosynthesis metabolite, and reduced 2,8-dihydroxyquinoline, which has known benefits in reducing glucose intolerance; these changes were reversible by inulin supplementation. Additionally, the abundance of Barnesiella, Coprobacter, Clostridium XIVa, and Butyrivibrio were negatively correlated with FPC diet intake and the concentration of cecal zymosterol but positively associated with inulin supplementation, suggesting their benefits. Conclusion Taken together, the presented data suggest that diet alters the gut microbiota and their metabolites, including bile acids. This will subsequently affect IL-17A signaling, resulting in systemic impacts on both hepatic metabolism and cognitive function.

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“…In rodents, the hippocampus is a critical structure for memory formation (Denninger et al, 2018;Vogel-Ciernia & Wood, 2014). We have found that HFD-induced prediabetes impaired hippocampaldependent cognitive function (Chunchai et al, 2019;Jinawong et al, 2020). As the aim of this study is to determine the effect of L6H21 and metformin on hippocampal-dependent cognitive function at different time points, it is important to select the effective cognitive function test that must reflect the hippocampal-dependent cognitive function in a short time period.…”

Section: Determination Of Cognitive Function By Nol Test In Combinati...mentioning

confidence: 99%

“…Sample sizes subjected to statistical analysis included eight rats per group, which were estimated from G*Power program (Version 3.1.9.4). The effect size calculation was determined on the basis of our previous study (Chunchai et al, 2019). The group size in this study represents independent values, and the statistical analysis was done using these independent values.…”

Section: Data and Statistical Analysismentioning

confidence: 99%

L6H21 protects against cognitive impairment and brain pathologies via toll‐like receptor 4–myeloid differentiation factor 2 signalling in prediabetic rats

Sumneang

Ongnok

et al. 2021

British J Pharmacology

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Background and Purpose: Chronic high-fat diet (HFD) intake instigates prediabetes and brain pathologies, which include cognitive decline and neuroinflammation. The myeloid differentiation factor 2 (MD-2)/toll-like receptor 4 (TLR4) complex plays a pivotal role in neuroinflammation. The MD-2 inhibitor (L6H21) reduces systemic inflammation and metabolic disturbances in HFD-induced prediabetes. However, the potential role of L6H21, and its comparison with metformin, on brain pathologies in HFD-induced prediabetes has never been investigated.Experimental Approach: Male Wistar rats were given either a normal diet (ND) (n = 8) or a HFD (n = 104) for 16 weeks. At the 13th week, ND-fed rats were given a vehicle, whereas HFD-fed rats were randomly divided into 13 subgroups. Each subgroup was given vehicle, L6H21 (three doses) or metformin (300-mgÁkg À1 Áday À1 ) for 1, 2 or 4 weeks. Metabolic parameters, cognitive function, brain mitochondrial function, brain TLR4-MD-2 signalling, microglial morphology, brain oxidative stress, brain cell death and dendritic spine density were investigated.Key Results: HFD-fed rats developed prediabetes, neuroinflammation, brain pathologies and cognitive impairment. All doses of L6H21 and metformin given to HFD-fed rats at 2 and 4 weeks attenuated metabolic disturbance. Conclusion and Implications:In rats, L6H21 and metformin restored cognition and attenuated brain pathologies dose and time-dependently. These results indicate a neuroprotective role of MD-2 inhibitor in a model of prediabetes.

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N-acetyl cysteine, inulin and the two as a combined therapy ameliorate cognitive decline in testosterone-deprived rats

Cited by 20 publications

References 65 publications

High-Dietary Fiber Intake Alleviates Antenatal Obesity-Induced Postpartum Depression: Roles of Gut Microbiota and Microbial Metabolite Short-chain Fatty Acid Involved

High-Dietary Fiber Intake Alleviates Antenatal Obesity-Induced Postpartum Depression: Roles of Gut Microbiota and Microbial Metabolite Short-chain Fatty Acid Involved

Dysregulated bile acid receptor-mediated signaling and IL-17A induction are implicated in diet-associated hepatic health and cognitive function

L6H21 protects against cognitive impairment and brain pathologies via toll‐like receptor 4–myeloid differentiation factor 2 signalling in prediabetic rats

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