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Raw gypsum (RG) and calcined gypsum (CG) are widely used in traditional Chinese medicine (TCM). RG is usually taken orally to resolve heat and diminish inflammation, while CG is only used externally to treat ulcerations and empyrosis. Calcination at different temperatures, three phase CG structures, namely, bassanite, anhydrite III, and anhydrite II, may be generated. We herein investigated the relationship between the phase structure and the efficacy of CG and the optimum phase structure for CG. RG has a compact structure, small pore size, weak anti-inflammatory effect, but no antibacterial effect, and has almost no effect on the repair of scalds. CG150 (bassanite) has a loose texture, large pore size and specific surface area, and certain antibacterial and anti-inflammatory effects, but it has a poor repair effect on scalds. CG750 (anhydrite II) has a compact structure, small pore size and specific surface area, and low antibacterial and anti-inflammatory effects, but it has a certain repair effect on scalds. Only CG350 (anhydrite III) has good performance in texture, pore size, specific surface area, antibacterial, anti-inflammatory, and scald repair. Our research has proved that the mineral properties and biological activities of CG are different due to different phase structures. CG350, namely, anhydrite III, is considered by our research to be the optimal phase structure as CG. [ABSTRACT FROM AUTHOR]

Objective: Remote limb ischemic post-conditioning (RLIPostC) has been shown to be neuroprotective in cerebral ischemia, whereas the effect of RLIPostC on synaptogenesis remains elusive. In the present study, we investigated the effects of RLIPostC on synaptogenesis in an experimental stroke rat model. Methods: Sprague-Dawley rats were subjected to left middle cerebral artery occlusion (MCAO) and were randomly divided into a control group, an RLIPostC group and a sham group. The RLIPostC group received three cycles of RLIPostC treatment immediately after reperfusion (ten minutes ischemia and ten minutes reperfusion in bilateral femoral artery). The neurological function was assessed by neurological deficit scores and the foot fault test at days 7 and 14 after MCAO. At day 14 after MCAO, the infarct volume and oedema were determined by cresyl violet (CV) staining and by measuring brain water content, respectively. Synaptogenesis was evaluated by western blotting and immunofluorescence staining. Results: Our results showed that RLIPostC treatment significantly promoted the recovery of behavioural function, reduced infarct volume and brain oedema, and increased the expressions of SYN1, PSD95 and GAP43. Conclusions: These results confirmed that RLIPostC treatment for cerebral ischemia was safe and effective. A possible molecular mechanism of the beneficial effects of RLIPostC treatment may be the promotion of synaptogenesis. [ABSTRACT FROM AUTHOR]

Background. Zuo Gui Wan (ZGW) is a classic formula in traditional chinese medicine (TCM). Previous studies have shown that it is beneficial for impaired glucose tolerance (IGT) of adults and the offspring as well. This study aimed to understand the molecular mechanisms of the efficacy of ZGW on IGT. Methods. We used high-glucose loaded 2-cell stage mouse embryos as a model and took advantage of single-cell RNA sequencing technology to analyze the transcriptome of the model with or without ZGW. Differential gene expression analysis was performed with DESeq2. Results. High glucose can downregulate genes in the ribosome pathway, while ZGW can reverse this inhibition and as a result prevent embryo cell death caused by high glucose. Furthermore, high glucose can affect sugar metabolism and influence mitochondrial function, but ZGW can promote sugar metabolism via the tricarboxylic acid cycle mainly through upregulating the genes in the respiratory chain and oxidative phosphorylation. Conclusions. ZGW had a protective effect on embryonic cell death caused by glucose loading. The reversion of inhibition of ribosome pathway and regulation of mitochondrial energy metabolism are main effects of ZGW on high-glucose loaded embryos. This research not only revealed the global gene regulation changes of high glucose affecting 2-cell stage embryos but also provided insight into the potential molecular mechanisms of ZGW on the IGT model. [ABSTRACT FROM AUTHOR]

In this experiment, we used streptozotocin (STZ) to establish a model of gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats. After pregnancy, offspring rats were divided into 4 groups: control group, high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were fed with high fat and sugar diet. Rats in control group were fed the basic diet. The means of 2hPG were higher than 7.8 mmol·L−1 and lower than 11.1 mmol·L−1 on the rats of GDM group on week 15, and IGT models were successful. Body weight, abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM group. The level of adiponectin in Zuogui Wan GDM group was significantly higher than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a preventive effect on the offsprings’ IGT induced by high fat and sugar diet. [ABSTRACT FROM AUTHOR]

Ziziphi Spinosae Semen and Polygalae Radix (ZSS-PR) constitute a traditional Chinese herbal combination with notable applications in clinical and experimental settings due to their evident sedative and calming effects. Aligned with traditional Chinese medicine principles, Ziziphi Spinosae Semen supports cardiovascular health, nourishes the liver, and induces mental tranquillity. Simultaneously, Polygalae Radix elicits calming effects, fosters clear thinking, and reinstates proper coordination between the heart and kidneys. ZSS-PR is commonly employed as a therapeutic intervention for various insomnia types, demonstrating distinct clinical efficacy. Our previous study findings provide evidence that ZSS-PR administration significantly reduces sleep onset latency, increases overall sleep duration, and improves abnormal neurotransmitter levels in a murine insomnia model. This investigation aimed to scrutinize the intrinsic regulatory mechanism of ZSS-PR in managing insomnia using gut microbiota and serum metabolomics techniques. Mice were given DL-4-Chlorophenylalanine to induce insomnia and then treated with ZSS-PR. The open-field test assessed the animals' spontaneous activity. Concentrations of neurotransmitters, endocrine hormones, and cytokines in the duodenum were measured using enzyme linked immunosorbent assay, and brain histopathology was evaluated with H&E staining. The impact of ZSS-PR on the metabolic profile was examined by liquid chromatography couped to high resolution mass spectrometry, and 16S rDNA sequencing was used to study the influence of ZSS-PR on the gut microbiota. Additionally, the content of short-chain fatty acids (SCFAs) was analyzed by GC-MS. Finally, correlation analysis investigated relationships between biochemical markers, metabolites, SCFAs, and gut microbiota. ZSS-PR treatment significantly increased movement time and distance in mice with insomnia and improved pathological impairments in the cerebral cortex and hippocampus. It also restored abnormal levels of biochemical markers in the gut of insomnia-afflicted mice, including 5-hydroxytryptamine , dopamine, gastrin, melatonin, tumour necrosis factor-α, and interleukin-1β. Metabolomics findings showed that ZSS-PR had a significant restorative effect on 15 endogenous metabolites in mice with insomnia. Furthermore, ZSS-PR primarily influenced five metabolic pathways, such as phenylalanine, tyrosine, and tryptophan biosynthesis, glutamine, and glutamate metabolism. Additionally, gut microbiota analysis revealed notable alterations in both diversity and microbial composition after ZSS-PR treatment. These changes were primarily attributed to the relative abundances of microbiota, including Firmicutes, Bacteroidota, Fusobacteriota, Muribaculaceae_unclassified , and Ligilactobacillus. The results of SCFAs analysis demonstrated that ZSS-PR effectively restored abnormal levels of acetic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, and valeric acid in insomniac mice. Subsequent correlation analysis revealed that microbiota show obvious correlations with both biochemical markers and metabolites. The results provide compelling evidence that ZSS-PR effectively mitigates abnormal activity, reduces cerebral pathological changes, and restores abnormal levels of neurotransmitters, endocrine hormones, and cytokines in mice with insomnia. The underlying mechanism is intricately linked to the modulation of gut microbiota and endogenous metabolic pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

Yuanzhi Powder is a commonly used traditional Chinese medical formulae for its potency in enhancing memory and learning. In clinical practice, Yuanzhi Powder is a classic formula in TCM to treat amnesia of the type "deficiency of Qi, turbid phlegm harasses the head and eyes, and stagnation of phlegm converting into the fire". Our previous study showed that Yuanzhi Power, used together with Codonopsis Radix (Dangshen Yuanzhi Power, DYP), could improve learning and memory ability in animals with memory disorder (MD) and its efficacy is superior or equivalent to that of the Yuanzhi Power. This study aimed to explore the regulatory mechanism of DYP through the "bacteria-gut-brain axis". The SD rats were divided randomly into control, model, positive, DYP-L, and DYP-H groups. Except for the control group, the rats were intraperitoneally injected with D-Gal (400 mg/kg) and gavaged with aluminum chloride (200 mg/kg) every day for 50 days. The rats in the DYP group were gavaged with DYP (6.67 and 13.34 g/kg, respectively) from the 15th day, once a day. The rats in the positive group were similarly administrated with piracetam (0.5 g/kg). The rats' bodyweight was recorded from the 16th day. The learning and memory ability of animals was tested by Morris water maze. The levels of MCP-1, NF-L, NSE, and TNF-α in serum were determined by Elisa kit, while the histopathology of duodenum and colon tissues was examined by H & E staining. The diversity of intestinal flora was sequenced and analyzed. In order to reveal the role of intestinal flora in DYP treatment of MD, the intestinal flora composition and the correlation analysis of intestinal flora and the above biochemical indexes were investigated. The intestinal flora function and biological metabolic pathways were predicted and analyzed by the KEGG database. The MD animals' learning and spatial memory ability decreased significantly, compared with the normal group, accompanied by weight increase and intestinal flora disorder. DYP can improve the learning and memory ability of MD animals, and its efficacy may exert through the following ways: (i) callback the abnormal biochemical indexes of MCP-1, NF-L, NSE, and TNF-α; (ii) decreasing the relative ratio of Firmicutes/Bacteroidetes and repairing the pathology of MD animal intestinal mucosa; and (iii) the regulation of DYP on biochemical blood indexes of MD animals was significantly correlated with the regulation of intestinal flora; (iv) DYP rats showed a strong correlation between cognitive ability improvement and bodyweight loss; (v) besides, DYP could also regulate the metabolic pathways of carbohydrate, amino acid, nucleotide, and energy by affecting related biological functions. The results supported that DYP can improve MD animals' learning and memory ability by restoring the intestinal flora disorder and callback the abnormal biochemical indexes in serum, closely related to the "bacteria-gut-brain axis". [Display omitted] [ABSTRACT FROM AUTHOR]

To explore the effective components, potential targets and neuroprotective related mechanisms of Mijianchangpu decoction (MJCPD), a well-known TCM used by the Chinese Hui minorities to treat stroke, on the prevention and treatment of ischemic stroke (IS) by using experimental models combined with network pharmacology. The neuroprotective efficacy of MJCPD was estimated by applying the middle cerebral artery occlusion (MCAO) induced cerebral ischemia rats, and the neurological deficits score, TTC and HE staining as well as behavioral evaluation tests were employed to evaluate the beneficial effects. Meanwhile, the bioactive components of MJCPD responsible for the neuroprotective effects were identified by detecting the constituents in the brain of the MCAO rats with UHPLC-QTOF-MS/MS techniques, and these compounds were then underwent for network pharmacology analysis. Firstly, the targets of the bioactive compounds of MJCPD were predicted using Pharmmapper database, and simultaneously, the targets of IS disease were obtained from disease databases including DisGenet, OMIM, and GeneCards. Secondly, the protein-protein interaction (PPI) network between the targets and diseases were established to give the possible therapeutic targets for IS. Thirdly, the go function and KEGG pathway enrichment analysis were carried out and the compound-target-pathway network was constructed by Cytoscape software. Finally, the effective compounds, core targets and possible pathways were obtained by analyzing the connectivity of the network. More importantly, the core targets were verified by western blot experiments to validate the reliability of this study. MJCPD exhibited significant neuroprotective effect on IS, and 16 bioactive components of MJCPD were identified in the brain of the MCAO rats. 59 and 1982 targets related with IS disease were explored from Pharmapper and disease databases, respectively, and 32 intersecting targets were obtained as hypothetical therapeutic targets. Based on the results of the compound-target-pathway and PPI network with the degree was greater than the median, 8 effective compounds (suberic acid, epishyobunone, crocetin monomethyl ester, sfaranal, (Z)-6-octadccenoic acid, nerolidol and gurjunene) and 5 hub targets (SRC, MAPK8, MAPK14, EGFR and MAPK1) as well as 12 pathways were predicted. Western blot results showed that EGFR, p38, ERK and SRC proteins were expressed significantly different after MJCPD treatment as compared with the model group. The present study employed network pharmacology, pharmacodynamics and molecular biology techniques to predict and validate the core potential targets and signaling pathways as well as the bioactive components of MJCPD responsible for the treatment of IS. All of which are very helpful to clarify the neuroprotective mechanism of MJCPD, and obviously, the active compounds and targets in this study can also provide clues for the treatment of IS. [Display omitted] [ABSTRACT FROM AUTHOR]