Prebiotic-like cyclodextrin assisted silybin on NAFLD through restoring liver and gut homeostasis.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with no currently approved treatment. The natural compound silybin (SLN) has versatile hepatoprotective efficacy with negligible adverse effects; however, poor absorption limits its clinical applications. Gut microbiota has been proposed to play a crucial role in the pathophysiology of NAFLD and targeted for disease control. Cyclodextrins, the cyclic oligosaccharides, were documented to have various health benefits with potential prebiotic properties. This study aimed to develop a silybin-2-hydroxypropyl-ß-cyclodextrin inclusion (SHßCD) to improve the therapeutic efficacy of SLN and elucidate the mechanisms of improvement. The results showed that SLN formed a 1:1 stoichiometric inclusion complex with HP-ß-CD. The solubility of SLN was increased by generating SHßCD, resulting in improved drug permeability and bioavailability. In high-fat diet (HFD)-fed hamsters, SHßCD modulated gut health by restoring the gut microbiota and intestinal integrity. SHßCD showed superior anti-lipid accumulation, antioxidant, and anti-inflammatory effects compared with SLN alone. Transcriptome analysis in the liver tissue implied that the improved inflammation and/or energy homeostasis was the potential mechanism. Therefore, SHßCD may be a promising alternative for the treatment of NAFLD, attributing to the dual functions of HßCD on drug absorption and gut microbial homeostasis.

Bicyclol Alleviates Atherosclerosis by Manipulating Gut Microbiota.

Atherosclerosis (AS) is associated with high morbidity and mortality, thus imposing a growing burden on modern society. Herb-derived bicyclol (BIC) is a versatile bioactive compound that can be used to treat AS. However, its efficacy in AS is not yet described. Here, it is shown that BIC normalizes gut microflora dysbiosis induced by a high fat diet in Apoe(-/-) mice. Metagenome-wide association study analysis verifies that the modulation on carbohydrate-active enzymes and short-chain fatty acid generating genes in gut flora is among the mechanisms. The gut healthiness, especially the gut immunity and integrity, is restored by BIC intervention, leading to improved systemic immune cell dynamic and liver functions. Accordingly, the endothelial activation, macrophage infiltration, and cholesterol ester accumulation in the aortic arch are alleviated by BIC to lessen the plaque onset. Moreover, it is proved that the therapeutic effect of BIC on AS is transmissible by fecal microbiota transplantation. The current study, for the first time, demonstrates the antiatherosclerotic effects of BIC and shows that its therapeutic value can at least partially be attributed to its manipulation of gut microbiota.

Design of Hepatic Targeted Drug Delivery Systems for Natural Products: Insights into Nomenclature Revision of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), recently renamed metabolic-dysfunction-associated fatty liver disease (MAFLD), affects a quarter of the worldwide population. Natural products have been extensively utilized in treating NAFLD because of their distinctive advantages over chemotherapeutic drugs, despite the fact that there are no approved drugs for therapy. Notably, the limitations of many natural products, such as poor water solubility, low bioavailability in vivo, low hepatic distribution, and lack of targeted effects, have severely restricted their clinical application. These issues could be resolved via hepatic targeted drug delivery systems (HTDDS) that boost clinical efficacy in treating NAFLD and decrease the adverse effects on other organs. Herein an overview of natural products comprising formulas, single medicinal plants, and their crude extracts has been presented to treat NAFLD. Also, the clinical efficacy and molecular mechanism of active monomer compounds against NAFLD are systematically discussed. The targeted delivery of natural products via HTDDS has been explored to provide a different nanotechnology-based NAFLD treatment strategy and to make suggestions for natural-product-based targeted nanocarrier design. Finally, the challenges and opportunities put forth by the nomenclature update of NAFLD are outlined along with insights into how to improve the NAFLD therapy and how to design more rigorous nanocarriers for the HTDDS. In brief, we summarize the up-to-date developments of the NAFLD-HTDDS based on natural products and provide viewpoints for the establishment of more stringent anti-NAFLD natural-product-targeted nanoformulations.

Functional nano-vector boost anti-atherosclerosis efficacy of berberine in Apoe (-/-) mice.

Atherosclerosis (AS) is the leading cause of heart attacks, stroke, and peripheral vascular disease. Berberine (BBR), a botanical medicine, has diversified anti-atherosclerotic effects but with poor absorption. The aim of this study was to develop an effective BBR-entrapped nano-system for treating AS in high-fat diet (HFD)-fed Apoe (-/-) mice, and also explore the possible underlying mechanisms involved. Three d-α-tocopherol polyethylene glycol (PEG) succinate (TPGS) analogues with different PEG chain lengths were synthesized to formulate BBR-entrapped micelles. HFD-fed Apoe (-/-) mice were administered with optimized formula (BBR, 100 mg/kg/day) orally for 5 months. The artery plaque onset and related metabolic disorders were evaluated, and the underlying mechanisms were studied. Our data showed that, BT1500M increased BBR deposition in liver and adipose by 107.6% and 172.3%, respectively. In the Apoe (-/-) mice, BT1500M ameliorated HFD-induced hyperlipidemia and lipid accumulation in liver and adipose. BT1500M also suppressed HFD-induced chronic inflammation as evidenced by the reduced liver and adipose levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß); and decreased plasma level of TNF-α, IL-6, IL-1ß, interferon-γ (IFN-γ), monocyte chemotactic protein (MCP), and macrophage inflammatory factor (MIP). The mechanism study showed that BT1500M changed Ampk and Nf-κb gene expression, and interrupted a crosstalk process between adipocytes and macrophages. Further investigation proved that BT1500M decreased endothelial lesion and subsequent macrophage activation, cytokines release, as well as cholesteryl ester gathering in the aortic arch, resulting in ameliorated artery plaque build-up. Our results provide a practical strategy for treating AS using a BBR-entrapped nano-system.

Ultrahigh hydrogen evolution performance of under-water "superaerophobic" MoS2 nanostructured electrodes.

The adhesion of as-formed gas bubbles on the electrode surface usually impedes mass-transfer kinetics and subsequently decreases electrolysis efficiency. Here it is demonstrated that nanostructured MoS2 films on conductive substrates show a faster hydrogen evolution reaction (HER), current increase, and a more-stable working state than their flat counterpart by significantly alleviating the adhesion of as-formed gas bubbles on the electrode. This study clearly reveals the importance of a nano-porous structure for HER, which should be general and beneficial for constructing other gas-evolution electrodes.

In situ fabrication of porous MoS2 thin-films as high-performance catalysts for electrochemical hydrogen evolution.

Amorphous MoS2 porous thin films (denoted as MoS2 PTFs) with high activity towards hydrogen evolution reaction (HER) were fabricated by in situ sulfuration of a Mo substrate. A small overpotential (~120 mV) and a low Tafel slope (~41 mV dec(-1)) can be observed and their excellent performance was ascribed to the combination of the amorphous feature, porous structure and optimized thickness.