Pei Ma

The long-term high-fat and high-fructose diet (HFFD) exacerbates cognitive decline and gut microbiota disorder. Coreopsis tinctoria flower (CTF), grown at high altitudes, has been revered as a popular health-enhancing tea modulating glycolipid metabolism in Chinese. However, the neuroprotective effects of CTF against HFFD-induced cognitive decline remain to be elucidated. The present study investigated the hypothesis that the neuroprotective benefits of CTF are mediated by tryptophan metabolism derived from gut microbiota. The phytochemical characterization of CTF was performed by LC-MS/MS-assisted feature-based molecular networking method. Behavioral, neurophysiological and metabolic evaluations demonstrated CTF improved glycolipid metabolic disorders and cognitive decline in HFFD-fed mice. Integrative 16S rRNA sequencing and metabolomics analysis revealed CTF modulated the abundance of specific gut microbial genera (e.g., Colidextribacter) and enhanced gut bacteria-dependent tryptophan metabolites (especially indole-3-lactic acid and indole-3-carboxylic acid) levels in the hippocampus. Notably, antibiotic-induced depletion of microbiota abolished these metabolite changes and the neuroprotective effects of CTF, confirming the crucial role of the intestinal microbiota. Additionally, the protective effects of ICA and ILA on D-glucose induced synaptic damage in SH-SY5Y cells have been identified directly. These findings highlight the importance of microbiota-regulated tryptophan metabolism as a key mechanism behind the cognitive benefits of CTF, demonstrating its potential for managing metabolic disorder–related neurodegenerative conditions.

Background: This work aims to systematically investigate the formulation rules and potential mechanisms of Salviae Miltiorrhizae Radix et Rhizoma (SM)-containing health products to support healthy blood lipid levels.Materials and methods: Data on SM-containing health products were retrieved from official databases. Formulation patterns were analyzed using frequency statistics and association rule mining. An integrated network pharmacology strategy was then used to explore potential regulatory mechanisms, including active compound screening, target prediction, protein–protein interaction (PPI) network construction, and functional enrichment analysis. Results were further validated using molecular docking.Results: A total of 477 approved products were analyzed, with “helping maintain blood lipid levels” as the primary health function claim. These products contained 160 compatible medicinal herbs, which are mainly mild-cold in nature and sweet in flavor. They are commonly used for “deficiency tonification” and “blood-activating and stasis-resolving” in traditional Chinese medicine (TCM). A total of 267 compounds and 181 key targets were identified for the lipid-regulating function of SM. These targets were enriched in peroxisome proliferator-activated receptor (PPAR) signaling, Lipid and Atherosclerosis, and the Regulation of Lipolysis in adipocytes. Eight targets, including AKT1 and peroxisome proliferator-activated receptor gamma (PPARG), were identified as core targets. Finally, molecular docking results suggested potential binding affinities between primary active components and core targets.Conclusion: This study demonstrated that SM exerts its lipid-regulating effects via multi-component, multi-target, and multi-pathway mechanisms. These findings provided a theoretical basis for the rational development and application of relevant health products.

The fruits of Schisandra chinensis (SCF) and Schisandra sphenanthera (SSF) are traditional Chinese herbal medicines classified as medicinal and food homologous materials, known for their significant neuroprotective efficacy. However, the differences in their therapeutic effects and active components for the treatment of vascular cognitive impairment (VCI) remain unclear. This study aimed to elucidate the neuroprotective activities of SCF and SSF on VCI and investigate the compositional disparities between the two. The lipopolysaccharide-induced and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced BV2 cell models were used to evaluate the protective effects of SCF and SSF against neuroinflammation and mitochondrial damage, respectively. The therapeutic effects were further validated using a bilateral common carotid artery stenosis mouse model. Compositional differences were analyzed using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and drug-like properties of their constituents were assessed. In vitro experiments showed that SCF and SSF at concentrations of 6.4, 16, and 40 μg/mL reduced nitric oxide, tumor necrosis factor-alpha, and interleukin-6 levels in a dose-dependent manner. Notably, at the same concentrations, SCF significantly mitigated OGD/R-induced mitochondrial damage, whereas SSF showed no significant effect. Compared with SSF, SCF exhibited stronger anti-neuroinflammatory and antioxidant properties. In vivo experiments further demonstrated that SCF, administered at 400 mg/kg, was more effective in improving learning ability, spatial learning and memory, cerebral blood flow, and nerve fiber repair than SSF. Moreover, 71 and 64 compounds were identified in SCF and SSF, respectively, using UPLC-Q-TOF/MS. Drug-like property analysis of these compounds revealed that the superior therapeutic effects of SCF may be attributed to differences in biphenylcyclooctene-type lignans. Our data support the conclusion that SCF possesses significantly superior neuroprotective activity compared to SSF, providing a theoretical basis for its clinical application in VCI.

Background and purpose Isookanin, an important antioxidant component in Coreopsis tinctoria Nutt., has shown remarkable hypolipidemic, hypoglycemic, and hypotensive effects. However, the neuroprotective effect of isookanin has not been reported yet. Here, the neuroprotective effects and relevant molecular mechanisms of isookanin are explored for the first time. Methods The SH-SY5Y cells were exposed to neurotoxic H₂O₂, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and Aβ_25-35, respectively. Cell viability and apoptosis were evaluated by MTT, lactate dehydrogenase (LDH), and TUNEL assays. Intercellular ROS and mitochondrial membrane potential were assessed by DCFH-DA and JC-1 assay. Western blot and qRT-PCR were used to explore the perturbed signaling at the gene and protein levels. Molecular docking analysis and in vitro assay were further applied to confirm potential target. Results Among the three in vitro models, isookanin showed the best neuroprotection against MPTP-induced damage. Isookanin attenuated the levels of LDH, intracellular ROS, and mitochondrial membrane potential. Isookanin upregulated phosphorylation of AKT and PI3K, and increased BCL2/BAX ratio. Isookanin possessed a powerful affinity toward AKT. Besides, the protective effects of isookanin disappeared when cells were co-treated with an AKT inhibitor (AZD5363). Conclusion Isookanin regulated BCL2/BAX and PI3K/AKT pathways to reduce mitochondrial damage and cellular apoptosis. Isookanin may be a new protector for neurodegenerative diseases. Graphical Abstract