Screening of the Active Substances for the Assessment of Walnut Kernel in the Treatment of Scopolamine-Induced AD Animals.

SCOPE: Alzheimer's disease (AD) has been a challenge and hotspot in the field of neuroscience research due to the high morbidity. As we all know, walnut kernel (WK) ingestion has been linked to benefits to brain health and has the function of improving memory. This study follows the AD model induced by scopolamine to reveal the active fractions and substances of walnut in the treatment of AD. METHODS AND RESULTS: The histopathological analysis and brain tissue biochemistry assay are revealed the active fractions of WK, and this result determines that walnut kernel organic acids have significant therapeutic effect on AD. The strategy of studying ingredients pointed at lesions is integrated to ascertain the selected brain-targeted effective substances of WK for blood-brain barrier by ultra-performance liquid chromatography-quadrupole/electrostatic field orbitrap mass spectrometry, and a total of eight organic acids are figured out definite absorptivity in rat brains. Finally, the binding interaction between the effective substances and target proteins is analyzed by molecular docking, and the main function related active markers are ascertained as glansreginin A, glansreginic acid, ellagic acid, and ellagic acid 4-O-xyloside. CONCLUSIONS: The comprehensive process is helpful to the clinical application of WK as a promising cholinesterase inhibitors for nutritional intervention.

The attenuation effect of licorice on the hepatotoxicity of Euodiae Fructus by inhibiting the formation of protein conjugates and GSH depletion.

ETHNOPHARMACOLOGICAL RELEVANCE: As a traditional Chinese medicine and food, Euodiae Fructus (EF) is widely used in clinics to relieve pain and prevent vomiting and for making tea for more than a thousand years. In recent years, hepatotoxic reactions to EF have been reported. The intermediates produced by evodiamine and rutaecarpine metabolism in vitro were captured by glutathione (GSH), suggesting that the toxicity of EF may be related to metabolic activation. Whether licorice can inhibit the metabolic activation of EF has not been reported, which needed an effective strategy to clarify the correlation between protein conjugates and hepatotoxicity and the attenuation mechanism of licorice processing. AIM OF THE STUDY: This study aimed to explore the toxic components and mechanisms of EF based on metabolic activation and the detoxification of licorice. MATERIALS AND METHODS: The content and toxicity index of protein conjugates in the liver were determined by orally administering mice and rats with EF. The attenuation mechanism of licorice was examined in cell and enzymology experiments. RESULTS: The change in evodiamine-cysteinylglycine (EVO-Cys-Gly) and evodiamine-cysteine (EVO-Cys) levels was consistent with the change in hepatotoxicity. Licorice inhibited the formation of the protein conjugates of EF and increased the content of GSH in L02 cells. CONCLUSION: EF mediated by P450 enzymes produced toxic intermediates, which combined with cysteine residues in animal liver and inactivate them, leading to hepatotoxicity. Interestingly, licorice can alleviate the GSH depletion caused by EF and inhibit the production of protein conjugates by inhibiting P450 enzymes.

Large-scale microbiome analysis reveals bacterial community characteristics in typical Chinese herbal slices.

Chinese herbal slices (CHSs) are closely associated to microorganisms, whether they are endophytic or epiphytic in plants, or introduced during processing. In this study, the structures and predicted functions of microbial communities in 150 batches of samples from five types of CHSs were investigated by combining pure culture and 16 S rDNA amplicon sequencing. Bile-salt-tolerant gram-negative bacteria were detected in 56.0% of samples, and Salmonella was detected in two batches of Glycyrrhiza slices and in one batch of Rheum slices. The main genera from the Enterobacteriaceae, Bacillaceae, Fibrobacteraceae, and Pseudomonadaceae families were assessed in typical colonies. Amplicon sequencing identified 1200 bacterial genera, including some pharmacopeial-controlled bacteria and many beneficial endophytes of medicinal plants. Around 65% of the genera co-occurred in all five CHSs. In clustering based on different algorithms, the samples from each CHS type were relatively clustered, with some overlap. Ranked from highest to lowest diversity, the CHSs were Rheum, Angelica, Astragalus, Codonopsis, and Glycyrrhiza. Each CHS had its indicator species. Functional annotations suggest that potential microbial transformation uses CHSs as substrates and microbial communities as transformants. Overall, it was demonstrated that, based on their complementary advantages, high-throughput sequencing technology and traditional pure-culture technology together can fully assess the microbial load of CHSs and reduce the misdetection rate. We observed large microbial communities in typical CHSs, demonstrating differences and similarities among different CHS types. These results provide a reference for establishing new microbial limit criteria for CHSs and highlight the importance of further correlating CHS microbial community structure and function. Supplementary Information: The online version contains supplementary material available at 10.1007/s11756-022-01199-0.