Sanhua Tang protects against ischemic stroke by preventing blood-brain barrier injury: a network pharmacology and experiments.

OBJECTIVE: To assess the effect and mechanism of Sanhua Tang (, SHT) in treating ischemic stroke (IS) through the "Kaitong Xuanfu" theory by using network pharmacology and animal experiments. METHODS: The active ingredients and targets of SHT and IS were screened by public databases such as Traditional Chinese Medicine systems pharmacology, GeneCards, and online mendelian inheritance in man. Visual network topographies were constructed using R, Cytoscape 3.6.0, AutoDockTools, a user-sponsored molecular visualization system on an open-source foundation, and other software to analyze the correlation between targets and active ingredients. The middle cerebral artery occlusion (MCAO) model was established by operation. Animals were divided into the Sham group, MCAO group (M group), aloe-emodin (AE) group (MCAO rats treated with aloe-emodin), SHT at low dosage (SL group) (MCAO rats treated with SL), SHT at medium dosage (SM group), and SHT at high dosage (SH group). 2,3,5-triphenyl tetrazolium chloride staining was used to detect the volume of cerebral infarction; Nissl staining was used to observe the morphology of neuronal cells; transmission electron microscopy was used to observe the integrity of the blood-brain barrier (BBB); enzyme-linked immunosorbent assay was used to detect the content of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α) in serum. Western blot was used to detect the expression of vascular endothelial growth factor A (VEGFA) protein in the cerebral ischemic penumbra. RESULTS: Using network pharmacology and molecular docking validation, four active ingredients (lignan, naringenin, aloe-rhodopsin, and ß-sitosterol), seven target proteins (protein kinase b 1, IL-6, TNF, VEGFA, TP53, jun proto-oncogene, and cysteinyl aspartate specific proteinase 3), and inflammatory signaling pathways were identified. Animal experiments showed that the SH and AE groups had fewer neurological deficits, reduced brain infarct volumes, decreased serum inflammatory factor levels, increased expression of VEGFA protein, and less structural damage to neurons and BBB. CONCLUSION: The present study found that the therapeutic mechanism of SHT against IS may be related to the inhibition of BBB inflammatory damage, which is also the mechanism of "Kaitong Xuanfu." The high-dose group of SHT was relatively effective in regulating inflammatory factors, improving BBB permeability, and protecting neuronal cells from damage.

Qinghua decoction improves chronic nonbacterial prostatitis possibly regulating the chromogranin A/nerve growth factor/tyrosine kinase A signaling pathway mediated by inflammatory factors.

OBJECTIVE: To explore the mechanism by which Qinghua decoction regulates neuroendocrine inflammation in chronic nonbacterial prostatitis (CNP) model rats and provide an experimental basis for clinical treatment. METHODS: The rats were randomly divided into six groups: normal control, model, Qianlie Tongyu capsule, low-dose Qinghua decoction, medium-dose Qinghua decoction, and high-dose Qinghua decoction group with six rats in each group. Rats in each group were sacrificed on the 29th day of treatment, and blood and prostate tissues were collected. Serum levels of tumor necrosis factor-alpha and interleukins 1-beta, 6, 8, and 10 (TNF-α and IL-1ß, -6, -8, and -10, respectively) were measured using enzyme-linked immunosorbent assay. The pathological changes in the rat prostate tissue in each group were observed under a light microscope. The expression levels of chromogranin A (CgA), nerve growth factor (NGF), and tyrosine kinase A (TrkA) were detected using reverse transcription quantitative polymerase chain reaction. Western blotting was used to detect protein expression of CgA, NGF, and TrkA. RESULTS: In the model group, the prostate capsule membrane and stroma were significantly dilated with more inflammatory cells infiltrating the stroma and perivessels. TNF-α, IL-1ß, -6, and -8, CgA, NGF, and TrkA levels increased, whereas the content of IL-10 decreased, which was statistically significant compared to that in the normal control group ( < 0.05). Prostate tissue cells in the high-dose group were neatly arranged with no obvious inflammatory cell infiltration. When compared with the model group, the high-dose Qinghua decoction group showed a significant improvement in these indices ( < 0.05). CONCLUSION: Qinghua decoction led to inhibition of pathological changes in the prostate tissue of rats with CNP, regulation of inflammatory cytokine expression, and inhibition in the expression of CgA, NGF, and TrkA. This mechanism may be primarily related to regulation of the CgA/NGF/TrkA signaling pathway mediated by various inflammatory factors.

Scalp acupuncture Yikang therapy on Baihui (GV20), Sishencong (EX-HN1), Zhisanzhen, Niesanzhen improves neurobehavior in young rats with cerebral palsy through Notch signaling pathway.

OBJECTIVE: To investigate the efficacy of scalp acupuncture Yikang therapy on Baihui (GV20), Sishencong (EX-HN1), Zhisanzhen, Niesanzhen, on neurobehavior in young rats with cerebral palsy based on Notch signaling pathway. METHODS: Thirty 7-day-old rats were randomly divided into sham, model and acupuncture, 10 rats in each group. The cerebral palsy model was established by the accepted modeling method, the acupuncture group selected "Baihui (GV20)", "Sishencong (EX-HN1)", "Zhisanzhen" and "Niesanzhen" for intervention 24 h after the model was made. The body masses were recorded before and after the treatment, respectively. After the intervention, the rats were subjected to suspension experiment, slope experiment, tactile stimulation experiment and Morris water maze experiment. After the end of the experiment, the morphological changes of hippocampal histology were observed by hematoxylin-eosin (HE) staining under light microscope, and the expression of Notch1, Notch3 and Hes5 were detected by Western blot and quantitative real-time polymerase chain reaction (PCR). RESULTS: The changes in body mass of the rats in each group were different; in behavioral experiments, compared with the sham, the suspension time of the model was shortened, the slope experiment, tactile stimulation experiment, and escape latency time were prolonged, and the number of platform crossing was reduced in the model, compared with the model, the suspension time of the acupuncture was prolonged, the slope experiment, tactile stimulation experiment, and escape latency time were shortened, and the number of platform crossing times was increased; HE staining showed severe hippocampal damage in the model and reduced hippocampal damage in the acupuncture. Western Blot and real-time fluorescence quantitative PCR showed that the expression of Notch1, Notch3 and Hes5 were increased in the model and the expression of Notch1, Notch3, Hes5 in acupuncture were decreased. CONCLUSIONS: Scalp acupuncture Yikang therapy may improve neurobehavior and reduce brain injury in rats with cerebral palsy by downregulating the expression of Notch1, Notch3, and Hes5.