Oxidative stress and neuroinflammation are considered as crucial culprits in Alzheimer’s disease (AD). Torularhodin, a carotenoid pigment, possesses powerful antioxidant activity. This study aimed to elucidate the protective effects of torularhodin in the AD-like mouse model and investigated the underlying mechanisms. Behavioral and histopathological results suggested that torularhodin relieved cognitive impairments, attenuated Aβ accumulation, and inhibited glial overactivation in d-gal/AlCl3-induced ICR mice. Simultaneously, torularhodin also markedly increased antioxidant enzyme capacities, lowered the contents of RAGE, and reduced levels of inflammatory cytokines. Western blot results showed that torularhodin ameliorated neuronal oxidative damage via activation of Nrf2 translocation, upregulation of HO-1, and inactivation of NF-κB in vivo and in vitro. Thus, torularhodin effectively ameliorated cognitive impairment, oxidative stress, and neuroinflammation, possibly through the Nrf2/NF-κB signaling pathways, suggesting torularhodin might offer a promising prevention strategy for neurodegenerative diseases.

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Maca compounds prescription (MCP) is a common botanical used in dietary supplements, primarily to treat exercise-induced fatigue. The aim of this study is to elucidate the multi-target mechanism of MCP on fatigue management via network pharmacology and gut microbiota analysis. Databases and literature were used to screen the chemical compounds and targets of MCP. Subsequently, 120 active ingredients and 116 fatigue-related targets played a cooperative role in managing fatigue, where several intestine-specific targets indicated the anti-fatigue mechanism of MCP might be closely related to its prebiotics of intestinal bacteria. Thus, forced swimming tests (FSTs) were carried and mice fecal samples were collected and analyzed by 16S rRNA sequencing. Gut microbiota were beneficially regulated in the MCP-treated group in phylum, genus and OTU levels, respectively, and that with a critical correlation included Lactobacillus and Candidatus Planktophila. The results systematically reveal that MCP acts against fatigue on multi-targets with different ingredients and reshapes the gut microbial ecosystem.