Selenium nanoparticles (SeNPs) have attracted attention due to their favorable properties, unique bioactivities, and potential for use in nutritional supplements and nanomedicine applications. However, the application of SeNPs in the clinic has been greatly hindered by their poor stability, and their potential to protect against alcohol-induced oxidative stress has not been fully investigated. Herein, SeNPs were synthesized in the presence of chitosan (CS) or chitooligosaccharide (COS), and a mixture of SeNPs, CS, and COS was spray-dried to prepare selenium-nanoparticles-loaded chitosan/chitooligosaccharide microparticles (SeNPs-CS/COS-Ms). Their physicochemical properties, including morphology, elemental state, size distribution, surface potential, and characteristic structure, were investigated. The release of SeNPs from the vehicle and the free radical scavenging ability of SeNPs-CS/COS-Ms were also studied. Furthermore, the safety of SeNPs-CS/COS-Ms and their antioxidant activity against alcohol were evaluated in mice. The results indicate that SeNPs-CS/COS-Ms, with a novel structure characterized by their smooth or wrinkled surface, hollow core, and COS body filled with SeNPs-CS nanobeads, were able to release SeNPs and scavenge DPPH and superoxide anion radicals. SeNPs-CS/COS-Ms were found to be much safer than selenite, and they might protect mice from ethanol-induced oxidative stress by reducing lipid and protein oxidation and by boosting glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT). In conclusion, SeNPs-CS/COS-Ms offer a new way to develop stable SeNPs with higher efficacy and better biosafety, and the antioxidant potential of SeNPs-CS/COS-Ms against ethanol deserves further development.

Selenium nanoparticles (SeNPs) have attracted wide attention for their use in nutritional supplements and nanomedicine applications. However, their potential to protect against autoimmune hepatitis has not been fully investigated, and the role of their antioxidant capacity in hepatoprotection is uncertain. In this study, chitosan-stabilized SeNPs (CS-SeNPs) were prepared by means of rapid ultra-filtration, and then their antioxidant ability and free-radical scavenging capacity were evaluated. The hepatoprotective potential of a spray-dried CS-SeNPs powder against autoimmune liver disease was also studied in the concanavalin A (Con A)-induced liver injury mouse model. CS-SeNPs with size of around 60 nm exhibited acceptable oxygen radical absorbance capacity and were able to scavenge DPPH, superoxide anion, and hydroxyl radicals. The CS-SeNPs powder alleviated Con A-caused hepatocyte necrosis and reduced the elevated levels of serum alanine transaminase, aspartate transaminase, and lactic dehydrogenase in Con A-treated mice. These results suggest that the CS-SeNPs powder protected the mice from Con-A-induced oxidative stress in the liver by retarding lipid oxidation and by boosting the activities of superoxide dismutase, glutathione peroxidase, and catalase, partly because of its ability to improve Se retention. In conclusion, SeNPs present potent hepatoprotective potential against Con A-induced liver damage by enhancing the redox state in the liver; therefore, they deserve further development.

In this study, the effects of a polysaccharide derived from Laminaria japonica (LJP) on obesity were investigated in mice fed a high-fat diet (HFD). LJP significantly attenuated obesity-related features, lowering serum triglycerides, glucose, total cholesterol and low-density lipoprotein cholesterol levels. HFD-induced liver steatosis and hepatocellular ballooning were significantly attenuated by LJP. Additionally, LJP was found to significantly modulate hepatic gene expressions of AMPK and HMGCR, which are key regulators of lipid and cholesterol metabolism. We further found that LJP ameliorated HFD-induced gut microbiota (GM) dysbiosis by significantly reducing the obesity-related Firmicutes to Bacteroidetes ratio, meanwhile promoting the growth of Verrucomicrobia at the phylum level. At the genus level, propionate-producing bacteria Bacteroides and Akkermansia were elevated by LJP, which might explain the result that LJP elevated fecal propionate concentration. Taken together, these findings suggest that dietary intake of LJP modulates hepatic energy homeostasis to alleviate obesity-related nonalcoholic fatty liver disease associated with GM regulation.

Gut microbiota (GM) is considered to play an important role in obesity. Additionally, the impact of dietary fiber (DF) consumption on GM has been well established. Brown seaweeds are known to be a rich source of DF. However, the effect of insoluble DFs (IDFs) alone from brown seaweed on obesity and GM remains to be determined. This study investigated the effect of IDFs prepared from Laminaria japonica Aresch on high-fat diet (HFD)-induced obesity and GM dysbiosis in mice. Although HFD-induced body weight gain was not significantly attenuated by the IDF treatment, HFD-induced liver injury was ameliorated, and the HFD-elevated serum cholesterol concentration and glucose level of obese mice were significantly lowered. IDF treatment significantly modulated the GM composition disturbed by the HFD. It was found that 5% IDFs restored the GM to a very similar composition to that in the normal mice. The relative abundance of Akkermansia genus was decreased by >300-fold in HFD-fed mice, and it was fully restored by 5% IDF administration. Akkermansia muciniphila, a short-chain fatty acid producer, was identified as a marker species in both control and high-dose IDF groups. Furthermore, IDFs significantly restored the HFD-reduced acetate and propionate levels in the cecal content. In conclusion, the beneficial effect of IDFs derived from L. japonica on obesity was confirmed in mice, and the underlying mechanism may be associated with the modulation of GM composition, possibly through the enrichment of Akkermansia.

Background: Selenium (Se) is an indispensable trace element required for animals and human beings, whereas Se-deficiency can accelerate the development of acute gastric injury induced by over-consumption of alcohol. Selenium nanoparticles (SeNPs), as a special Se-supplement with favorable properties and unique bioactivities, are expected to play a passive role in gastroprotection. To the best of our knowledge, the gastroprotective potential of SeNPs is unknown and also, a rapid preparation of orally stable SeNPs available for prospective commercial application in the clinic is needed. Thus, SeNPs-embedded chitosan microspheres (SeNPs-CM) were developed to deliver SeNPs, and their gastroprotective potential was evaluated. Results: Herein, a rapid, eco-friendly and economic preparation process, composed of synthesis of SeNPs decorated by chitosan (CS), purification of CS-SeNPs by ultra-filtration (UF) and spray-drying of the purified CS-SeNPs, was introduced to prepare SeNPs-CM. The uniformly distributed SeNPs with a nanosize range of 60 nm were loaded into CS-microspheres, and they could be released from the microspheres in gastric conditions. In addition, SeNPs-CM were safer than selenite in terms of Se dose, with a LD₅₀ of around 8-fold of that of selenite, and it could efficiently enhance the Se retention in Se-deficient Wistar rats. Furthermore, SeNPs-CM pre-treatment might significantly attenuate the ethanol-induced gastric mucosal damage, based on histological evaluation. It might be partly attributed to the systematic antioxidant activities of SeNPs-CM, reflected by the reduction in lipid peroxidation, the augmentation in antioxidant enzymatic activity as well as decreasing aggressive nitric oxides (NO). Conclusion: SeNPs-CM could be taken into consideration as a prospective Se-supplement for the oral delivery of SeNPs, with prominent gastroprotective effect against ethanol-induced mucosal injury.

Postherpetic neuralgia (PHN) is nerve pain caused by a reactivation of the varicella zoster virus. Medications are used to reduce PHN but their use is limited by serious side effects. Tetrodotoxin (TTX) is a latent neurotoxin that can block neuropathic pain, but its therapeutic index is only 3–5 times with intravenous or intramuscular injection. Therefore, we prepared oral TTX pellets and examined their effect in a rat model of PHN induced by resiniferatoxin (RTX). Oral TTX pellets were significantly effective at preventing RTX-induced mechanical and thermal allodynia, and similar to pregabalin. Moreover, oral administration of TTX pellets dose-dependently inhibited RTX-induced PHN compared with intramuscular administration of TTX injection. We also studied the pharmacokinetic profile of TTX pellets. Our results showed that the blood concentration of TTX reached a maximum plasma concentration (C_max) at around 2 h, with an elimination half-life time (t_1/2) of 3.23 ± 1.74 h after intragastric administration. The median lethal dose (LD₅₀) of TTX pellets was 517.43 μg/kg via oral administration to rats, while the median effective dose (ED50) was approximately 5.85 μg/kg, and the therapeutic index was 88.45. Altogether, this has indicated that oral TTX pellets greatly enhance safety when compared with TTX injection.