Background: Huai Hua San (HHS), a famous Traditional Chinese Medicine (TCM) formula, has been widely applied in treating ulcerative colitis (UC). However, the interaction of bioactives from HHS with the targets involved in UC has not been elucidated yet. Aim: A network pharmacology-based approach combined with molecular docking and in vitro validation was performed to determine the bioactives, key targets, and potential pharmacological mechanism of HHS against UC. Materials and Methods: Bioactives and potential targets of HHS, as well as UC-related targets, were retrieved from public databases. Crucial bioactive ingredients, potential targets, and signaling pathways were acquired through bioinformatics analysis, including protein–protein interaction (PPI), as well as the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Subsequently, molecular docking was carried out to predict the combination of active compounds with core targets. Lastly, in vitro experiments were conducted to further verify the findings. Results: A total of 28 bioactive ingredients of HHS and 421 HHS-UC-related targets were screened. Bioinformatics analysis revealed that quercetin, luteolin, and nobiletin may be potential candidate agents. JUN, TP53, and ESR1 could become potential therapeutic targets. PI3K-AKT signaling pathway might play an important role in HHS against UC. Moreover, molecular docking suggested that quercetin, luteolin, and nobiletin combined well with JUN, TP53, and ESR1, respectively. Cell experiments showed that the most important ingredient of HHS, quercetin, could inhibit the levels of inflammatory factors and phosphorylated c-Jun, as well as PI3K-Akt signaling pathway in LPS-induced RAW264.7 cells, which further confirmed the prediction by network pharmacology strategy and molecular docking. Conclusion: Our results comprehensively illustrated the bioactives, potential targets, and molecular mechanism of HHS against UC. It also provided a promising strategy to uncover the scientific basis and therapeutic mechanism of TCM formulae in treating diseases.

Ageing is a crucial risk factor for Alzheimer’s disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.

Background: Icariin (ICA), an active ingredient extracted fromEpimediumspecies, has shown promising results in the treatment of Alzheimer's disease (AD), although its potential therapeutic mechanism remains largely unknown. This study aimed to investigate the therapeutic effects and the underlying mechanisms of ICA on AD by an integrated analysis of gut microbiota, metabolomics, and network pharmacology (NP).Methods: The cognitive impairment of mice was measured using the Morris Water Maze test and the pathological changes were assessed using hematoxylin and eosin staining. 16S rRNA sequencing and multi-metabolomics were performed to analyze the alterations in the gut microbiota and fecal/serum metabolism. Meanwhile, NP was used to determine the putative molecular regulation mechanism of ICA in AD treatment.Results: Our results revealed that ICA intervention significantly improved cognitive dysfunction in APP/PS1 mice and typical AD pathologies in the hippocampus of the APP/PS1 mice. Moreover, the gut microbiota analysis showed that ICA administration reversed AD-induced gut microbiota dysbiosis in APP/PS1 mice by elevating the abundance ofAkkermansiaand reducing the abundance ofAlistipe. Furthermore, the metabolomic analysis revealed that ICA reversed the AD-induced metabolic disorder via regulating the glycerophospholipid and sphingolipid metabolism, and correlation analysis revealed that glycerophospholipid and sphingolipid were closely related toAlistipeandAkkermansia. Moreover, NP indicated that ICA might regulate the sphingolipid signaling pathway via the PRKCA/TNF/TP53/AKT1/RELA/NFKB1 axis for the treatment of AD.Conclusion: These findings indicated that ICA may serve as a promising therapeutic approach for AD and that the ICA-mediated protective effects were associated with the amelioration of microbiota disturbance and metabolic disorder.Graphical