Sodium acetate/sodium butyrate alleviates lipopolysaccharide-induced diarrhea in mice via regulating the gut microbiota, inflammatory cytokines, antioxidant levels, and NLRP3/Caspase-1 signaling.

Diarrhea is a word-widely severe disease coupled with gastrointestinal dysfunction, especially in cattle causing huge economic losses. However, the effects of currently implemented measures are still not enough to prevent diarrhea. Previously we found that dropped short-chain fatty acids in diarrhea yaks, and butyrate is commonly known to be related to the epithelial barrier function and intestinal inflammation. However, it is still unknown whether sodium acetate/sodium butyrate could alleviate diarrhea in animals. The present study is carried out to explore the potential effects of sodium acetate/sodium butyrate on lipopolysaccharide-induced diarrhea in mice. Fifty ICR mice were randomly divided into control (C), LPS-induced (L), and sodium acetate/sodium butyrate (D, B, A)-treated groups. Serum and intestine samples were collected to examine inflammatory cytokines, antioxidant levels, relative gene expressions via real-time PCR assay, and gut microbiota changes through high-throughput sequencing. Results indicated that LPS decreased the villus height (p < 0.0001), increased the crypt depth (p < 0.05), and lowered the villus height to crypt depth ratio (p < 0.0001), while sodium acetate/sodium butyrate supplementation caused a significant increase in the villus height (p < 0.001), decrease in the crypt depth (p < 0.01), and increase in the villus height to crypt depth ratio (p < 0.001), especially. In mice treated with LPS, it was found that the serum level of IL-1ß, TNF-α (p < 0.001), and MDA (p < 0.01) was significantly higher; however, sodium acetate/sodium butyrate supplementation significantly reduced IL-1ß (p < 0.001), TNF-α (p < 0.01), and MDA (p < 0.01), respectively. A total of 19 genera were detected among mouse groups; LPS challenge decreased the abundance of Lactobacillus, unidentified F16, unidentified_S24-7, Adlercreutzia, Ruminococcus, unclassified Pseudomonadales, [Ruminococcus], Acetobacter, cc 1, Rhodococcus, unclassified Comamonadaceae, Faecalibacterium, and Cupriavidus, while increased Shigella, Rhodococcus, unclassified Comamonadaceae, and unclassified Pseudomonadales in group L. Interestingly, sodium acetate/sodium butyrate supplementation increased Lactobacillus, unidentified F16, Adlercreutzia, Ruminococcus, [Ruminococcus], unidentified F16, cc 115, Acetobacter, Faecalibacterium, and Cupriavidus, while decreased Shigella, unclassified Enterobacteriaceae, unclassified Pseudomonadales, Rhodococcus, and unclassified Comamonadaceae. LPS treatment upregulated the expressions of ZO-1 (p < 0.01) and NLRP3 (p < 0.0001) genes in mice; however, sodium acetate/sodium butyrate solution supplementation downregulated the expressions of ZO-1 (p < 0.05) and NLRP3 (p < 0.05) genes in treated mice. Also, the LPS challenge clearly downregulated the expression of Occludin (p < 0.001), Claudin (p < 0.0001), and Caspase-1 (p < 0.0001) genes, while sodium acetate/sodium butyrate solution supplementation upregulated those gene expressions in treated groups. The present study revealed that sodium acetate/sodium butyrate supplementation alleviated LPS-induced diarrhea in mice via enriching beneficial bacterium and decreasing pathogens, which could regulate oxidative damages and inflammatory responses via NLRP3/Caspase-1 signaling. The current results may give insights into the prevention and treatment of diarrhea.

De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2-Hydroxy-1,4-diones with Nucleophiles.

Herein, a divergent synthesis of a variety of 2α- and 5α-substituted furan derivatives from 2-hydroxy-1,4-diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6-conjugate addition or cyclization/Friedel-Crafts-type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6-conjugate addition for 5α substitution and >20 types for the Friedel-Crafts-type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity-oriented synthesis of α-substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4-hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea, respectively.

De novo synthesis of benzofurans via trifluoroacetic acid catalyzed cyclization/oxidative aromatization cascade reaction of 2-hydroxy-1,4-diones.

A facile, one-pot method for the de novo synthesis of benzofurans from 2-hydroxy-1,4-diones is described. Using trifluoroacetic acid (TFA) as the catalyst and N-bromobutanimide (NBS) as the oxidant, 2-hydroxy-1,4-diones underwent a cyclization/oxidative aromatization cascade reaction to afford a variety of benzofuran derivatives in moderate to good yields. This is a practically useful method for the synthesis of benzofuran derivatives starting from 2-hydroxy-1,4-diones which is also a supplement of the Paal-Knorr furan synthesis. A preliminary mechanism study was undertaken to support the proposed mechanism during which a novel 1,6-conjugate addition reaction was revealed.

Synthesis of 1 H-Pyrrol-3(2 H)-ones via Three-Component Reactions of 2,3-Diketo Esters, Amines, and Ketones.

An efficient one-pot, three-component reaction of 2,3-diketo esters with amines and ketones has been developed for the synthesis of 1 H-pyrrol-3(2 H)-ones. By using trifluoroacetic acid (TFA) as the additive and acetonitrile (MeCN) as the solvent, this convenient method provides a library of 1 H-pyrrol-3(2 H)-ones in moderate to good yields. The simple protocol features readily available starting materials, a straightforward process, good functional group tolerance, and broad substrate scope.

Displacement of Dinitrogen by Oxygen: A Methodology for the Catalytic Conversion of Diazocarbonyl Compounds to Ketocarbonyl Compounds by 2,6-Dichloropyridine-N-oxide.

Dirhodium(II) catalyzed dinitrogen extrusion from diazocarbonyl compounds by 2,6-dichloropyridine-N-oxide forms ketocarbonyl compounds in near-quantitative yields. Reactions occur at room temperature, and the pyridine product does not coordinate with dirhodium(II) to inhibit catalysis. Anhydrous tricarbonyl compounds, as well as dicarbonyl compounds, are conveniently prepared by this methodology, and they have been used in situ for catalytic ene and aldol transformations.

Acetic Acid Mediated Sulfonylation of Allenylphosphine Oxides: Divergent Synthesis of Bifunctionalized 1,3-Butadienes and Allenes.

An acetic acid-mediated sulfonylation of allenylphosphine oxides with sodium sulfinates is disclosed. This new methodology involves tandem (Ar)O-C(sp3) bond cleavage and C(sp2)/C(sp3)-SO2 formation toward divergent synthesis of sulfonyl- and phosphinyl-bifunctionalized 1,3-butadienes or allenes, depending on the substitution at the terminal carbon atoms of allenylphosphine oxides. The reaction mechanism is explained via an acid-accelerated synergistic process.

Asymmetric synthesis of 1H-pyrrol-3(2H)-ones from 2,3-diketoesters by combination of aldol condensation with benzilic acid rearrangement.

An efficient two-step protocol for the asymmetric synthesis of 1H-pyrrol-3(2H)-one derivatives in 99% ee from conveniently accessed 2,3-diketoesters has been developed.

Three-Component Cascade Reactions with 2,3-Diketoesters: A Novel Metal-Free Synthesis of 5-Vinyl-pyrrole and 4-Hydroxy-indole Derivatives.

5-Vinyl-pyrrole and 4-hydroxy-indole derivatives are synthesized by metal-free aldol/cyclization/aromatization cascade reactions of in situ generated enamines with 2,3-diketoesters. This convenient atom-economical process produces multifunctional pyrrole and indole products in moderate to good yields.

One-pot synthesis of S-alkyl dithiocarbamates via the reaction of N-tosylhydrazones, carbon disulfide and amines.

A new, convenient and efficient transition metal-free synthesis of S-alkyl dithiocarbamates through one-pot reaction of N-tosylhydrazones, carbon disulfide and amines is reported. Tosylhydrazones derived from various aromatic and aliphatic ketones or aldehydes were tested and gave dithiocarbamates in good to excellent yields. The tosylhydrazones can be generated in situ without isolation, which provides a simpler one-pot method to synthesize dithiocarbamates via the reaction of carbonyl compounds, carbon disulfide and amines in the presence of 4-methylbenzenesulfonohydrazide.