Erjing pill, a Traditional Chinese Medicine (TCM) formulation composed of Polygonatum sibiricum and Lycium chinense, has an important role in the treatment of Alzheimer's disease (AD). However, the underlying mechanisms of the action of Erjing pill in AD have remained elusive. In the present study, the key ingredients of Erjing pill were investigated and the active components and their mechanisms of action on AD were analyzed based on networks pharmacology. By using the TCM and TCM Systems Pharmacology and databases, the components of Erjing pill were screened and the data were captured using Discovery Studio. The SwissTarget webserver database was used to predict the potential protein targets of Erjing pill components for pathologies related to AD. The data were further analyzed with the disease targets of AD based on analysis of the Online Mendelian Inheritance in Man, DiGSeE and Therapeutic Target Database. Subsequent analysis of mechanistic pathways of the screened components and protein targets allowed us to construct a network by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, which revealed potential molecular mechanisms of Erjing pill against AD. Finally, the protective effect of three active components on neurons was verified using an in vitro injury model of PC12 cells induced by Aβ25-35. The results indicated that 65 bioactive components of Erjing pill, including lauric acid and zederone, and 6 targets, including acetylcholinesterase, butylcholinesterase and amyloid protein precursor, were closely associated with the prevention and treatment of AD. The molecular components of Erjing pill were indicated to be involved in various biological signaling processes, mainly in synaptic signal transmission, transsynaptic signal transmission and chemical synaptic transmission. Furthermore, related pathways targeted by Erjing pill in AD included the regulation of neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, serotoninergic synapses, calcium signaling pathways and dopaminergic synapses. A cell viability assay indicated that the compounds (polygonatine A, polygonatine C and 4',5-dihydroxyflavone) assessed were able to significantly improve the survival rate and increase the Ca2+ level in a PC12 cell model of AD induced by amyloid-β25-35. The present study revealed that the mechanisms of action of Erjing pill to prevent and treat AD included a multicompound, multitarget and multipathway regulatory network.

San Pian decoction (SPD), a traditional Chinese medicine preparation composed of eight herbs, has been reported to alleviate migraine. However, its active ingredients and the potential mechanism of action remains unclear. The purpose of this study was to comprehensively analyze SPD for the treatment of chronic migraine based on pharmacological direction and to identify the active ingredients and pharmacological mechanism of SPD in the treatment of migraine.

Accumulating evidence suggests that natural medicines have notable curative effects on neurological conditions, such as migraine, that are mediated by regulating the gut microbial flora. A natural medicine pair used in traditional Chinese medicine, Gastrodia elata Blume and Uncaria rhynchophylla (Miq.) Miq. ex Havil. (GU), have shown excellent effect in treating migraine, yet the role of gut microbes in the therapeutic effect of GU in chronic migraine (CMG) is unknown. Here, we performed a 16S rRNA gene sequencing and metabolomics study of the effects of GU in a nitroglycerin (NTG)-induced rat model of CMG. Our results showed that the gut microbial community structure changed significantly and was similar to that of control rats after GU administration in CMG rats. Specifically, GU increased the relative abundance of Bacteroides and Coprococcus and reduced the abundance of Prevotella_1 and Escherichia-Shigella in CMG rats. The metabolomics profiles of the plasma and ileum contents of CMG rats obtained with an ultra-performance liquid chromatography-mass spectrometer (UPLC-MS) revealed similar biomarkers in both samples, and GU treatment reduced 3-indoxyl sulfate, glutamic acid, L-tyrosine, and L-arginine levels, and increased 5-HIAA, L-tryptophan, and linoleic acid levels in plasma. Correlation analysis showed that the affected bacteria were closely related to amino acid metabolism. Most importantly, GU treatment hardly affected biomarkers in feces samples after inhibiting the activity of gut microbes. Collectively, these findings indicate that structural changes in gut flora are closely related to host metabolism and that regulating the gut microbial community structure and function may be one of the important mechanisms underlying the therapeutic effects of GU in migraine.

Migraine is a chronic brain disease that leads to periodic neurological attacks. Parishin A and isorhynchophylline (PI) is the active monomer component extracted from the traditional antimigraine Chinese medicinal combination of Gastrodia and Uncaria, respectively. In this study, using high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) technology, we performed pharmacokinetic and lipidomic study on migraine model rats after administration of PI. For the detection of the compounds in plasma, AB Sciex Triple Quad™ 4500 was applied for quantitative analysis, and the COSMOSIL C18 column (2.1 × 100 mm, 2.6 μm) was used for separation. Isorhynchophylline (ISO: m/z 384.8-241.2) and its main metabolite rhynchophylline (RHY: m/z 384.8-160.2) were simultaneously detected under positive ion modes. Besides, parishin A (PA: m/z 995.1-726.9) and its main metabolite gastrodin (GAS: m/z 331.1-123.0) were simultaneously detected with negative ion modes. For the analysis of endogenous lipid components, Dionex Ultimate 3000 (UHPLC) Thermo Orbitrap Elite was applied for the detection, and the Waters UPLCRBEH C18 column (1.7 μm 100 ∗ 2.1 mm) was used for separation. Chloroform/methanol (2 : 1, v : v) was used for extraction. The results demonstrated that PI exists significant difference in metabolism between single- and coadministration and can regulate lipid levels associated with migraine.

Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear.