Alzheimer’s disease (AD) is a neurodegenerative brain disease and is the most common form of dementia. In recent years, many studies indicated the association of gut microbiota changes with metabolic diseases. However, the gut microbiota of AD has not been investigated. The present study aims to compare the gut microbiota in APP/PS1 transgenic mice of AD and C57/Bl6 wild-type (WT) mice by pyrosequencing the V3 and V4 regions of the bacterial 16S ribosomal RNA genes. The 3-, 6-, and 8-month-old APP/PS1 and WT mice were used to explore the effects of age on the gut microbiota. First, the results indicated that impaired spatial learning and memory appeared in 6-month-old APP/PS1 mice and was further aggravated in the 8-month-old group, which was consistent with immunohistochemical studies of amyloid plaque. Second, AD histological and behavioral manifestations in the APP/PS1 mice were found to be correlated with a specific gut microbiome state. Third, the microbiota diversity of APP/PS1 mice decreased with increased age. Fourth, further inspection showed that the abundance of Helicobacteraceae and Desulfovibrionaceae at the family level and Odoribacter and Helicobacter at the genus level increased significantly in APP/PS1 mice than in WT mice, while Prevotella abundance in WT mice was significantly higher than in APP/PS1 mice. More human studies are warranted to explore the potential of gut microbiota as diagnostic biomarkers or therapeutic target for AD.

Curcumin, the major active component of turmeric ( Curcuma longa ), is widely used as a spice and food-coloring agent, and also exhibits multiple biological activities. However, as curcumin has poor systemic bioavailability its pharmacology remains to be elucidated. Owing to the high concentration of curcumin in the gastrointestinal tract after oral administration, we hypothesize that it may exert regulative effects on the gut microbiota. We investigated the regulative effects of oral curcumin administration on the gut microbiota of C57BL/6 mice and found that curcumin significantly affected the abundance of several representative families in gut microbial communities, including Prevotellaceae, Bacteroidaceae, and Rikenellaceae. Considering the pathogenic associations between gut microbiota and many diseases, the present findings may help us to interpret the therapeutic benefits of curcumin.

With the accelerated aging of human society Alzheimer’s disease (AD) has become one of the most threatening diseases in the elderly. However, there is no efficient therapeutic agent to combat AD. Berberine is a natural isoquinoline alkaloid that possesses a wide range of pharmacological effects. In the present paper, we review the multiple activities of berberine, including antioxidant, acetylcholinesterase and butyrylcholinesterase inhibitory, monoamine oxidase inhibitory, amyloid-b peptide level-reducing and cholesterol-lowering activities, which suggest that berberine may act as a promising multipotent agent to combat AD.

The relationship between poor in vivo bioavailability and effective pharmacological activity are not yet fully clarified for many flavonoids. The analysis of flavonoids-induced alterations in the gut microbiota represents a promising approach to provide useful clues to elucidate the mechanism of action. Here, we investigate the effect of myricetin supplementation on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in rats and explore the associations with the gut microbiota through high-throughput analyses. The 12-week myricetin supplementation and fecal microbiota transplantation outcomes suggest that myricetin significantly slows the development of NAFLD. Meanwhile, the anti-NAFLD effects of myricetin are associated with the modulation of the gut microbiota composition. Myricetin reduces hepatic lipid synthesis and inflammation through modulations in fecal butyric-acid-related gut microbiota and protection of the gut barrier function. This study may facilitate the elucidation of the action mechanism of flavonoids with low bioavailability.

Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer’s disease (AD), including the superoxide anion radical (O₂^.–)-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O₂^.–-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.