Fucoidan Improves D-Galactose-Induced Cognitive Dysfunction by Promoting Mitochondrial Biogenesis and Maintaining Gut Microbiome Homeostasis.

Recent studies have indicated that fucoidan has the potential to improve cognitive impairment. The objective of this study was to demonstrate the protective effect and possible mechanisms of fucoidan in D-galactose (D-gal)-induced cognitive dysfunction. Sprague Dawley rats were injected with D-galactose (200 mg/kg, sc) and administrated with fucoidan (100 mg/kg or 200 mg/kg, ig) for 8 weeks. Our results suggested that fucoidan significantly ameliorated cognitive impairment in D-gal-exposed rats and reversed histopathological changes in the hippocampus. Fucoidan reduced D-gal-induced oxidative stress, declined the inflammation level and improved mitochondrial dysfunction in hippocampal. Fucoidan promoted mitochondrial biogenesis by regulating the PGC-1α/NRF1/TFAM pathway, thereby improving D-gal-induced mitochondrial dysfunction. The regulation effect of fucoidan on PGC-1α is linked to the upstream protein of APN/AMPK/SIRT1. Additionally, the neuroprotective action of fucoidan could be related to maintaining intestinal flora homeostasis with up-regulation of Bacteroidota, Muribaculaceae and Akkermansia and down-regulation of Firmicutes. In summary, fucoidan may be a natural, promising candidate active ingredient for age-related cognitive impairment interventions.

Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.

Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD.

Fucoidan alleviated autoimmune diabetes in NOD mice by regulating pancreatic autophagy through the AMPK/mTOR1/TFEB pathway.

Objectives: The present study investigated the effect and its underlying mechanisms of fucoidan on Type 1 diabetes mellitus (T1DM) in non-obese diabetic (NOD) mice. Materials and Methods: Twenty 7-week-old NOD mice were used in this study, and randomly divided into two groups (10 mice in each group): the control group and the fucoidan treatment group (600 mg/kg. body weight). The weight gain, glucose tolerance, and fasting blood glucose level in NOD mice were detected to assess the development of diabetes. The intervention lasted for 5 weeks. The proportions of Th1/Th2 cells from spleen tissues were tested to determine the anti-inflammatory effect of fucoidan. Western blot was performed to investigate the expression levels of apoptotic markers and autophagic markers. Apoptotic cell staining was visualized through TdT-mediated dUTP nick-end labeling (TUNEL). Results: The results suggested that fucoidan ameliorated T1DM, as evidenced by increased body weight and improved glycemic control of NOD mice. Fucoidan down-regulated the Th1/Th2 cells ratio and decreased Th1 type pro-inflammatory cytokines' level. Fucoidan enhanced the mitochondrial autophagy level of pancreatic cells and increased the expressions of Beclin-1 and LC3B II/LC3B I. The expression of p-AMPK was up-regulated and p-mTOR1 was inhibited, which promoted the nucleation of transcription factor EB (TFEB), leading to autophagy. Moreover, fucoidan induced apoptosis of pancreatic tissue cells. The levels of cleaved caspase-9, cleaved caspase-3, and Bax were up-regulated after fucoidan treatment. Conclusion: Fucoidan could maintain pancreatic homeostasis and restore immune disorder through enhancing autophagy via the AMPK/mTOR1/TFEB pathway in pancreatic cells.

Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota.

Maternal dietary patterns during pregnancy have been demonstrated to impact the structure of the gut microbiota in offspring, altering their susceptibility to diseases. This study is designed to elucidate whether the impact of folic acid supplementation during pregnancy on hepatic steatosis in male offspring of rat dams exposed to a high-fat diet (HFD) is related to gut-liver axis homeostasis. In this study, female rats were administered a HFD and simultaneously supplemented with 5 mg/kg folic acid throughout their pregnancy. Histopathological examination showed that folic acid supplementation effectively ameliorated hepatic lipid accumulation and inflammatory infiltrate in male offspring subjected to a maternal HFD. Maternal folic acid supplementation reduced the abundance of Desulfobacterota and the Firmicutes/Bacteroidota (F/B) ratio in male offspring. The expression of tight junction proteins in the colon was significantly upregulated, and the serum LPS level was significantly reduced. Furthermore, there was a notable reduction in the hepatic expression of the TLR4/NF-κB signaling pathway and subsequent inflammatory mediators. Spearman's correlation analysis revealed significant associations between hepatic inflammation-related indices and several gut microbiota, particularly Desulfobacterota and Lactobacillus. With a reduction in hepatic inflammation, the expression of PPAR-α was upregulated, and the expression of SREBP-1c and its downstream lipid metabolism-related genes was downregulated. In summary, folic acid supplementation during pregnancy modulates gut microbiota and enhances intestinal barrier integrity in male offspring of HFD dams. This helps reduce the LPS leakage and suppress the expression of TLR4/NF-κB pathway in the liver, thereby improving lipid metabolism disorders, and alleviating hepatic steatosis.

Folic Acid Protects against Ethanol-Induced Hepatic Mitophagy Imbalance by ROS Scavenging and Attenuating the Elevated Hcy Levels.

Ample evidence indicates that ethanol-induced oxidative stress and mitochondrial dysfunction are central to the pathogenesis of alcoholic liver disease (ALD). As an adaptive quality control mechanism, mitophagy removes dysfunctional mitochondria to avert hepatic lesions in ALD. Folic acid exhibits potential radical scavenging properties and has been proven to ameliorate mitochondrial disorder in oxidative stress-related diseases. In this study, we aimed to uncover the mitophagy regulatory effects of folic acid in a 10w alcohol C57BL/6J mice feeding model (56% v/v) and L02 cells model cultured with ethanol (2.5% v/v). The results showed that folic acid alleviates ethanol-induced liver injury, decreasing oxidative stress and restoring liver enzyme. Furthermore, folic acid improved the mitochondrial function and inhibited ethanol-activated mitophagy through decreasing PINK1-Parkin and Drp1 expression, which inhibited the release of mitochondrial cytochrome C to the cytoplasm, preventing hepatocyte apoptosis. Intriguingly, folic acid attenuates the elevated hepatic homocysteine (Hcy) level. Additionally, the pretreatment of L02 cells with folic acid also ameliorated Hcy-induced oxidative damage, mitochondrial fission, and mitophagy. In summary, these results suggest that folic acid has beneficial effects in mitophagy remodeling by ROS scavenging and facilitating Hcy metabolism and could be developed as a potential therapeutic agent against ALD.

Influence of intestinal microecology in the development of gout or hyperuricemia and the potential therapeutic targets.

Gout and hyperuricemia are common metabolic diseases. Patients with purine metabolism disorder and/or decreased uric acid excretion showed increased uric acid levels in the blood. The increase of uric acid in the blood leads to the deposition of urate crystals in tissues, joints, and kidneys, and causes gout. Recent studies have revealed that imbalance of the intestinal microecology is closely related to the occurrence and development of hyperuricemia and gout. Disorder of the intestinal flora often occurs in patients with gout, and high purine and high fructose may induce the disorder of intestinal flora. Short-chain fatty acids and endotoxins produced by intestinal bacteria are closely related to the inflammatory response of gout. This article summarizes the characteristics of intestinal microecology in patients or animal models with hyperuricemia or gout, and explores the relationship between intestinal microecology and gout or hyperuricemia from the aspect of the intestinal barrier, intestinal microorganisms, intestinal metabolites, and intestinal immune system. We also review the current status of hyperuricemia treatment by targeting intestinal microecology.

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway.

Fucoidan is a native sulfated polysaccharide mainly isolated from brown seaweed, with diverse pharmacological activities, such as anti-inflammatory and antifibrosis. Hyperuricemia (HUA) is a common metabolic disease worldwide and mainly causes hyperuricemic nephropathy, including chronic kidney disease and end-stage renal fibrosis. The present study investigated the protective function of fucoidan in renal fibrosis and its pharmacological mechanism. The renal fibrotic model was established with the administration of potassium oxonate for 10 weeks. The protein levels of related factors were assessed in HUA mice by an enzyme-linked immunosorbent assay (ELISA) and western blotting. The results showed that fucoidan significantly reduced the levels of serum uric acid, blood urea nitrogen (BUN), α-smooth muscle actin (α-SMA), and collagen I, and improved kidney pathological changes. Furthermore, renal fibrosis had been remarkably elevated through the inhibition of the epithelial-to-mesenchymal transition (EMT) progression after fucoidan intervention, suppressing the Janus kinase 2 (JAK2) signal transducer and activator of transcription protein 3 (STAT3) signaling pathway activation. Together, this study provides experimental evidence that fucoidan may protect against hyperuricemia-induced renal fibrosis via downregulation of the JAK2/STAT3 signaling pathway.

Long Noncoding RNA MIATNB Regulates Hyperosmotic Stress-induced Corneal Epithelial Cell Injury by Inhibiting Autophagy in Dry Eye Disease.

PURPOSE: Dry eye disease (DED) has a complex etiology and the roles of long noncoding RNAs (lncRNAs) in its pathophysiology are not completely understood. Autophagy is a self-eating process important for cell survival and homeostasis. The present study explored the role of myocardial infarction-associated transcript neighbor (MIATNB) long non-coding RNA in hyperosmolarity-induced autophagy and apoptosis in human corneal epithelial cell (HCEC)-based model of dry eye disease. METHODS: In vitro assays were performed with a human SV40 immortalized corneal epithelial cell line. Different concentrations of NaCl were used to create hyperosmolarity. HCECs were cultured in presence of 70-120 mM NaCl for 24 h to create an in vitro model of dry eye. RT-qPCR was performed to assess the expression of dry eye related LC3B, ATG16L, BECN1, ATG1, ATG7, ATG13, ATG5, ATG10, and ATG101 mRNAs and western blot analysis of LC3B and P62 and RFP -GFP-tagged LC3. Flow cytometry and western blot analysis of caspase 3, BCL2 and BAX were performed to detect apoptosis. Chloroquine (CQ) was used to inhibit autophagy pharmacologically. RESULTS: Autophagy flux was activated in HCECs subjected to hyperosmotic stress. Hyperosmolarity activated apoptosis and inhibited HCEC migration and autophagy. Hyperosmolarity upregulated MIATNB expression, while MIATNB knockdown inhibited autophagosome degradation and promoted HCEC apoptosis. Under hyperosmolar conditions, MIATNB knockdown also inhibited the degradation of autophagolysosomes and stimulated HCEC apoptosis. CONCLUSION: MIATNB plays a vital role in dry eye pathogenesis and serves as a bridge between autophagy and apoptosis. Targeting MIATNB for DED treatment should be further evaluated.

Protective effect of fucoidan against iron overload and ferroptosis-induced liver injury in rats exposed to alcohol.

This study was aimed to explore the effects of fucoidan on iron overload and ferroptosis-induced liver injury, and the underlying mechanisms in rats exposed to alcohol. Sprague-Dawley rats were used to establish alcoholic liver injury model by intragastric administration with alcohol for 16 weeks. The results showed that fucoidan treatment reversed alcohol-induced increases in reactive oxygen species and malondialdehyde levels, and increased glutathione peroxidase and glutathione levels, thus protecting against liver damage. Long-term alcohol feeding resulted in abnormal increase of serum ferritin, liver total iron and the "free" iron levels. Fucoidan treatment reduced serum ferritin level and alleviated liver iron deposition. Fucoidan reversed the reduction of hepcidin induced by alcohol exposure and decreased divalent metal transporter 1 (DMT1) and ferroportin1 (FPN1) expressions in the duodenum. Electron microscope observation of liver tissues showed that alcohol exposure induced ferroptosis changes in the liver. However, fucoidan treatment could alleviate alcohol-induced ferroptosis via upregulating the expressions of p62, Nrf2, SLC7A11 and GPX4. The liver endogenous metabolites analysis by liquid chromatography and mass spectrometry showed that after fucoidan intervention, mineral absorption, biosynthesis of amino acids pathways and lipid metabolism were changed. Fucoidan intervention reduced the levels of oxidized glutathione and regulated the levels of phosphatidylethanolamines in liver tissues. Our data showed that fucoidan supplementation could inhibit iron load via regulating hepcidin-intestinal DMT1/FPN1 axis, alleviate the liver oxidative damage and protect hepatocytes from ferroptosis induced by long-term alcohol exposure through upregulating p62/Nrf2/SLC7A11 pathway in rats.

Antarctic krill oil ameliorates liver injury in rats exposed to alcohol by regulating bile acids metabolism and gut microbiota.

Bile acids (BAs) metabolism plays an important role in alcohol liver disease through the gut microflora-bile acids-liver axis. Antarctic Krill Oil (AKO) has protective effects on the liver, while whether AKO can protect against liver injury caused by alcohol is unclear. This study investigated the effects of AKO on BAs metabolism and intestinal microbiota in a rat model of alcohol-induced liver disease. Sprague-Dawley rats were randomly divided into five groups: control group, model group, low-dose AKO-treatment group (100 mg/kg/d), high-dose AKO-treatment group (200 mg/kg/d), and AKO control group (200 mg/kg/d). Administration of alcohol (8 to 10 mL/kg/d) for 16 weeks induced liver injury in rats. We found that AKO supplementation significantly protected the liver against alcohol-induced injury, evidenced by allayed hepatic histopathological changes, and inhibited the alcohol-induced elevation of serum biochemical indices. Furthermore, AKO could regulate BAs metabolism by activating the intestinal-hepatic FXR-FGF15-FGFR4 signaling axis with subsequently decreased cholesterol 7α-hydroxylase (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) levels, reduced hepatic BAs production, decreased serum BAs level and increased fecal excretion of BAs. Additionally, 16S rDNA sequencing revealed that the gut microbiome richness and composition were altered in alcohol-treated rats in comparison to the control and AKO-administrated rats. Spearman's correlation analysis showed that differential gut bacterial genera correlated with the levels of BAs profiles in the serum, liver, and feces. These findings suggested that AKO dietary supplementation may protect against alcohol-induced liver injury through modulating BAs metabolism and altering the gut microbiome.

Folic acid intervention changes liver Foxp3 methylation and ameliorates the damage caused by Th17/Treg imbalance after long-term alcohol exposure.

Folic acid, as a key source of methyl donor in DNA methylation, has been proved to play a beneficial role in inflammation modulation, which is usually impaired in alcoholic liver disease (ALD). However, the role of folic acid in alcoholic liver inflammation and injury remain elusive. In this study, we sought to uncover the potential protective mechanism by which folic acid ameliorates alcoholic liver injury. 100 male C57BL/6J mice were randomly divided into 5 groups: normal saline group, folic acid control group (5 mg per kg BW), ethanol model group (56% v/v, 10 mL per kg BW), folic acid + ethanol group, and 5-Aza + ethanol group (0.1 mL per 20 g BW). Liquor (10 mL per kg BW) was orally administered 1 h after the folic acid treatment for 10 consecutive weeks. The results showed that folic acid-inhibited ethanol-induced serum TG, TC, and LDL elevation attenuated hepatic fat accumulation and maintained ALT at a normal level. 10 weeks of ethanol administration simultaneously upregulated the hepatic proportion of Th17 and Treg cells to different extents and broke the homeostasis of liver immunization. Folic acid limited ethanol-induced inflammatory injury by increasing the frequency of hepatic Treg cells. Importantly, this effect may be caused by decreased DNMT3a, which in turn downregulates the methylated levels of CPG2 and CPG3 in the Foxp3 promoter region, changing the abundance of Foxp3 expression and improving the Th17/Treg imbalance. In summary, our findings demonstrated that folic acid supplementation may relieve ethanol-induced Th17/Treg disbalance through altering Foxp3 promoter methylation patterns, suggesting that folic acid may be a feasible preventive strategy for ALD.

Propolis Ameliorates Alcohol-Induced Depressive Symptoms in C57BL/6J Mice by Regulating Intestinal Mucosal Barrier Function and Inflammatory Reaction.

Accumulating evidence points to a critical role of the brain gut axis as an important paradigm for many central nervous system diseases. Recent studies suggest that propolis has obvious neuroprotective properties and functionality in regulating intestinal bacteria flora, hinting at a potential key effect at both terminals of this axis regulation. However, currently no clear evidence confirms the effects of propolis on alcohol-induced depression. Here, we establish an alcoholic depression model with C57BL/6J mice and demonstrate that treatment with propolis protects against alcohol-induced depressive symptoms by behavioral tests. In addition, propolis attenuates the injury of nerve cells in the hippocampal region and restores the serum levels of brain-derived neurotrophic factor (BDNF) and dopamine (DA) in mice with alcohol-induced depression. Pathology and biotin tracer assays show that propolis repairs the intestinal leakage caused by alcohol. Additionally, propolis treatment increases the expression levels of intestinal intercellular tight junctions' (TJs') structural proteins Claudin-1, Occludin and zona occludens-1 (ZO-1), as well as the activation state of the liver kinase B1/AMP-activated protein kinase (LKB1/AMPK) signaling pathway, which is closely related to the intestinal permeability. Furthermore, propolis can reduce the levels of pro-inflammatory, lipopolysaccharide (LPS) and fatty-acid-binding protein 2 (FABP2), suggesting the significance of the inflammatory response in alcoholic depression. Collectively, our findings indicate that propolis exerted an improving effect on alcohol-induced depressive symptoms by ameliorating brain gut dysfunction.

Fucoidan as an Autophagy Regulator: Mechanisms and Therapeutic Potentials for Cancer and Other Diseases.

Fucoidan, a natural polysaccharide with a variety of classical bioactivities mainly sourced from brown algae, has been extensively studied owing to its favorable pharmacological effects, including anti-inflammatory, anti-tumor, anticoagulant and liver protection. Recently it has been found to play a regulatory role in the processes of autophagy. Autophagy is an important cellular process that effectively protects cells and organisms from stimulating factors such as nutrient deficiency, low cellular ATP levels, metabolic stress, growth factor deprivation and hypoxic conditions. In recent years, many studies have shown that fucoidan can treat human diseases by regulating autophagy process though cell signaling pathways. In this review, we summarize the latest progress in the discovery of natural autophagy regulator of fucoidan for the therapeutic application in cardiac diseases, cancers and liver diseases, aiming to provide the new pharmacological application that fucoidan may treat human diseases by regulating autophagy. Furthermore, we look forward to seeing more diseases that would be treated by autophagy modulator of fucoidan and the discovery of more elaborate autophagy regulation mechanism.

Inhibition of fucoidan on breast cancer cells and potential enhancement of their sensitivity to chemotherapy by regulating autophagy.

Fucoidan is a marine-origin sulfated polysaccharide that has gained attention for its anticancer activities. However, the inhibitory effect of fucoidan on breast cancers by regulating autophagy and its mechanism are not clear, and the chemotherapeutic sensitization of fucoidan is largely unknown. In the present study, the anticancer potential of fucoidan was revealed in MCF-7 and MDA-MB-231 cells. Additionally, we also studied the chemotherapeutic sensitization of fucoidan by combining chemotherapeutic drugs doxorubicin (ADM) and cisplatin (DDP) with fucoidan on breast cancer cells. In the two kinds of human breast cancer cells, cell viability was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was examined with flow cytometry. Transfection assay was used to examine autophagy flow. Western blot was used to examine the expressions of related proteins. Results suggested that fucoidan could induce autophagy and might enhance the sensitivity of breast cancer cells to chemotherapeutic drugs. Mechanistically, fucoidan induced autophagy in breast cancer cells by down-regulating m-TOR/p70S6K/TFEB pathway. In conclusion, our research revealed that fucoidan could induce autophagy of breast cancer cells by mediating m-TOR/p70S6K/TFEB pathway, thus inhibiting tumor development. Furthermore, fucoidan might enhance the sensitivity of breast cancer cells to ADM and DDP, and this enhancement was related to autophagy.

Effect of fucoidan on ethanol-induced liver injury and steatosis in mice and the underlying mechanism.

BACKGROUND: Alcoholic liver disease is caused as a result of chronic alcohol consumption. In this study, we used an alcoholic liver injury mouse model to investigate the effect of fucoidan on ethanol-induced liver injury and steatosis and the underlying mechanisms. METHODS: All mice were randomly divided into four groups: 1) control group, 2) model group, 3) diammonium glycyrrhizinate treatment group (200 mg/kg body weight), and 4) fucoidan treatment group (300 mg/kg body weight). Administration of ethanol for 8 weeks induced liver injury and steatosis in mice. RESULTS: Fucoidan treatment decreased serum alanine aminotransferase activity, serum total cholesterol levels, and hepatic triglyceride levels, and improved the morphology of hepatic cells. Fucoidan treatment upregulated the expression of AMPKα1, SIRT1, and PGC-1α and inhibited the expression of ChREBP and HNF-1α. The levels of hepatic IL-6 and IL-18 were significantly decreased in the fucoidan group. Further, the levels of cytochrome P450-2E1 (CYP2E1), glucose-regulated protein (GRP) 78, and 3-nitrotyrosine (3-NT) in hepatic tissues were reduced in the fucoidan group as compared to the model group. Fucoidan significantly reversed the reduction of ileac Farnesoid X receptor (FXR) and fibroblast growth factor 15 (FGF15) levels induced by alcohol-feeding and reduced CYP7A1 (cholesterol 7α-hydroxylase) expression and total bile acid levels in the liver tissue. In addition, fucoidan regulated the structure of gut flora, with increased abundance of Prevotella and decreased abundance of Paraprevotella and Romboutsia as detected by 16S rDNA high-throughput sequencing. CONCLUSION: Fucoidan inhibited alcohol-induced steatosis and disorders of bile acid metabolism in mice through the AMPKα1/SIRT1 pathway and the gut microbiota-bile acid-liver axis and protected against alcohol-induced liver injury in vivo.

Protective effects of fucoidan against ethanol-induced liver injury through maintaining mitochondrial function and mitophagy balance in rats.

For alcoholic liver disease (ALD), mitophagy has been reported as a promising therapeutic strategy to alleviate the hepatic lesion elicited by ethanol. This study was conducted to investigate the regulatory effects of fucoidan on mitophagy induced by chronic ethanol administration in rats. Here, 20 male rats in each group were treated with fucoidan (150 and 300 mg per kg body weight) by gavage once daily. Up to 56% liquor (7 to 9 mL per kg body weight) was orally administered 1 h after the fucoidan treatment for 20 weeks. The results showed that chronic ethanol consumption elevated the levels of hepatic enzymes (ALT, AST, and GGT) and triglyceride (TG) contents, with liver antioxidant enzymes being decreased and lipid peroxidation products increased and thus initiating the mitochondria-induced endogenous apoptotic pathway. Furthermore, ethanol-induced excessive oxidative stress inhibited the function of mitochondria and promoted damaged mitochondria accumulation which stimulated the PTEN-induced putative kinase 1 (PINK1) and Parkin associated mitophagic pathway in the liver. In contrast, the fucoidan pretreatment alleviated ethanol-induced histopathological changes, disorders of lipid metabolism, and oxidative damage with mitophagy related proteins and mitochondrial dynamics-related proteins namely mitochondrial E3 ubiquitin ligase 1 (Mul1), mitofusin2 (Mfn2) and dynamin-related protein 1 (Drp1) being restored to a normal level. In summary, our findings suggest that fucoidan pretreatment protects against ethanol-induced damaged mitochondria accumulation and over-activated mitophagy, which plays a pivotal role in maintaining mitochondrial homeostasis and ensuring mitochondrial quality.

Metabolic regulation mechanism of fucoidan via intestinal microecology in diseases.

The intestinal microecology is an extremely complex ecosystem consisting of gut microbiota, intestinal mucosa and the intestinal immune system. The intestinal microecology performs several important functions and is considered to be an essential 'organ' because it plays an important role in regulating human metabolism. Fucoidan contains a large amount of fucose and galactose residues, as well as various other neutral and acidic monosaccharides. Fucoidan particularly effects tumors, inflammatory bowel disease, diabetes and obesity by repairing intestinal mucosal damage and improving the intestinal microecological environment. It has been proposed that fucoidan could be used as a prebiotic agent for pharmaceutical and functional foods. In this review, we elucidate the potential mechanisms of the metabolic regulation of fucoidan with respect to the intestinal microecology of diseases. © 2021 Society of Chemical Industry.

Effect of nicotinamide riboside on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice.

Alcoholic liver disease (ALD) is the most common complication of alcohol abuse, while we lack safe and effective treatment for ALD. This study aimed to explore the effects of nicotinamide riboside (NR) on lipid metabolism and gut microflora-bile acid axis in alcohol-exposed mice. NR significantly improved liver histopathological damage and abnormal liver function. NR as a provider of nicotinamide adenine dinucleotide (NAD+) increased the NAD+/NADH ratio. Meanwhile, NR inhibited the activation of the protein phosphatase 1 signaling pathway, decreased the liver triglyceride and total bile acid levels, and reduced lipid accumulation. According to the results of gut microflora species analysis, NR intervention changed the microbial community structure at the phylum, family and genus levels, and the species abundances returned to a level similar to these of the normal control group. Besides, the results of high-performance liquid chromatograph-mass spectrometry showed that NR intervention resulted in fecal bile acid levels tending to be normal with decreased chenodeoxycholic acid level and increased deoxycholic acid and hyocholic acid levels. Spearman's correlation analysis showed a correlation between gut microflora and bile acids. Therefore, NR supplementation has the potential to prevent ALD, and its mechanism may be related to regulating lipid metabolism disorders and the gut microflora-bile acid axis.

Aplysin Retards Pancreatic Necrosis and Inflammatory Responses in NOD Mice by Stabilizing Intestinal Barriers and Regulating Gut Microbial Composition.

Aplysin is a brominated sesquiterpene with an isoprene skeleton and has biological activities. The purpose of this study is to investigate the inhibitory effect of aplysin on spontaneous pancreatic necrosis in nonobese diabetic (NOD) mice and its potential mechanisms. Results showed that NOD mice at 12 weeks of age showed obvious spontaneous pancreatic necrosis, damaged tight junctions of intestinal epithelia, and widened gaps in tight and adherens junctions. Aplysin intervention was able to alleviate spontaneous pancreatic necrosis in NOD mice, accompanied with decreased serum endotoxin levels and downregulated expressions of Toll-like receptor 4 and its related molecules MyD88, TRAF-6, NF-κB p65, TRIF, TRAM, and IRF-3, as well as protein levels of interleukin-1ß and interferon-ß in pancreatic tissues. In addition, we observed obvious improvements of intestinal mucosal barrier function and changes of gut microbiota in the relative abundance at the phylum level and the genus level in aplysin-treated mice compared with control mice. Together, these data suggested that aplysin could retard spontaneous pancreatic necrosis and inflammatory responses in NOD mice through the stabilization of intestinal barriers and regulation of gut microbial composition.

Effect of B vitamins supplementation on cardio-metabolic factors in patients with stable coronary artery disease: A randomized double-blind trial.

BACKGROUND AND OBJECTIVES: This study aimed to evaluate whether B vitamins supplementation would improve dyslipidemia, alleviate inflammatory state of patients with stable coronary artery disease (SCAD). METHODS AND STUDY DESIGN: We conducted a randomized, double-blind, 12-week, placebo-controlled trial involving adults with SCAD, and who were randomly divided into B vitamins group (folic acid and VB-6) and control group (placebo tablet). Blood tests had also been performed at baseline and endpoint. RESULTS: After 12 weeks of intervention, B vitamins supplementation significantly improved the concentration of serum TG, TC and HDL-C (p<0.05). Changes of serum homocysteine in B vitamins treatment were significantly different compared to placebo by the multivariate-adjusted analysis (3.02±2.35 vs 1.55±1.58 p<0.001). Meanwhile, the levels of IL-1ß and IL-10, significant difference were observed between two groups after adjustment for confounding factors. CONCLUSIONS: Supplementation with B vitamins significantly improves lipid metabolism, alleviate inflammation and serum homocysteine concentration in patients with SCAD.