Potential targets of Euodiae Fructus in treatment of insomnia based on network pharmacology / 中国中药杂志

The acupoint application of Euodiae Fructus at Yongquan(KI1) can significantly improve the sleep quality of patients with insomnia with berberine as the main effective component for the efficacy. Nineteen active compounds and 203 drug targets were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). After comparison with GeneCards and Online Mendelian Inheritance in Man(OMIM), 24 common genes of diseases and drugs were obtained. STRING 11.0 was used to construct a protein-protein interaction(PPI) network of the overlapping genes, and Matthews correlation coefficient(MCC) was employed to screen the core genes, which were then subjected to enrichment analysis with gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG). The results revealed that the main compounds of Euodiae Fructus, such as berberine and rutaecarpine, participated in the biological processes(such as neurotransmitter receptor activity) by regulating C-reactive protein(CRP), estrogen receptor 1(ESR1), 5-hydroxytryptamine(5-HT) receptor, and interleukin-6(IL-6) to exert sedative, anxiolytic, and antidepressant effects. Sixty 4-week-old SPF mice were randomly divided into a control group, a model group, a positive drug(diazepam tablets) group, and low-, medium-, and high-dose berberine groups. Medication with corresponding drugs was performed for one week. The results demonstrated that berberine was potent in reducing the activities and standing times of mice, down-regulating the levels of CRP and IL-6 mRNA in the hypothalamus, and up-regulating the expression of 5-HT(P<0.01); however, no significant effect on ESR1 was observed. The network of Euodiae Fructus in treating insomnia was constructed by network pharmacology and verified by tests. The findings indicated that the therapeutic efficacy of Euodiae Fructus in treating insomnia was achieved by participating in multiple biological processes, such as neurotransmitter receptor activity, which provided a scientific basis for its clinical application.

Effect of Modified Tongqiao Huoxuetang on Circulating Blood Flow and Wall Shear Stress Due to Blood Stasis and Channel Blockage / 中国实验方剂学杂志

Objective:To observe the effect of modified Tongqiao Huoxuetang on circulating blood flow and wall shear stress of vertebrobasilar dolichoectasia (VBD) due to blood stasis and channel blockage. Method:A total of 97 patients admitted in our department from October 2017 to August 2019 were collected. The traditional Chinese medicine (TCM) syndromes were consistent with blood stasis and channel blockage, and diagnosed as VBD by magnetic resonance angiography (MRA). The patients were divided into experimental group (48 cases) and control group (49 cases). Control group was given basic therapy and placebo of TCM, while treatment group was given basic therapy and modified Tongqiao Huoxuetang for 30 days. The degree of relief of vertigo symptoms, vertigo symptom scale (VSS), activity balance confidence (ABC), transcranial doppler (TCD) bilateral vertebral artery and basilar artery blood flow velocity [systolic blood flow velocity (Vs), mean blood flow velocity (Vm), diastolic blood flow velocity (Vd)], mean blood flow differences between (MFV), pulsatility index, resistance index (RI), and wall shear force (WSS) were observed before and after treatment. Result:Compared with control group before treatment, the score of ABC scale in control group after treatment was markedly higher, while the score of VSS was significantly lower (P<0.05). However, there was no statistical significance in the score of vertigo symptom. Compared with treatment group before treatment, the symptom grade of vertigo degree and the score of VSS in treatment group after treatment were substantially lower, while the score of ABC scale was significantly higher (P<0.05). Compared with control group, the score of vertigo degree symptoms and VSS in treatment group were markedly lower, while the score of ABC scale was significantly higher (P<0.05). Compared with control group before treatment, Vm, MFV and WSS of bilateral vertebral artery in control group after treatment were substantially higher, while RI was significantly lower (P<0.05). However, there were no statistical significances in Vs, Vd and PI in control group before and after treatment. Compared with treatment group, Vs, Vd, Vm, MFV and WSS of bilateral vertebral artery in treatment group after treatment were markedly higher, while RI was significantly lower (P<0.05). However, there was no statistical significance in PI of experimental group before and after treatment. Compared with control group after treatment, Vs, Vd, Vm, MFV and WSS of bilateral vertebral artery in treatment group after treatment were substantially higher, while there was no statistical significance in PI and RI. Before and after treatment, there were similar changes in blood flow parameters of the basilar artery and bilateral vertebral artery. Conclusion:Modified Tongqiao Huoxuetang could improve the clinical symptoms of dizziness or vertigo in patients of VBD due to blood stasis and channel blockage, and the mechanism might be related to the improvement of post-circulation hemodynamics by Tongqiao Huoxuetang.

Effect of JNK signal transduction pathway in intense noise-induced apoptosis of vestibular hair cells in guinea pigs / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the mechanism of intense noise-induced apoptosis of vestibular hair cells in guinea pigs and the effect of phosphorylated c-Jun N-terminal kinase (JNK) signal transduction pathway in intense noise-induced apoptosis of vestibular hair cells.</p><p><b>METHODS</b>Thirty-two guinea pigs were randomly and equally divided into 1, 5, and 15 d experimental groups and control group. The guinea pigs in the experimental groups were exposed to 4 kHz narrow-band noise at 120 dB SPL for 4 h and then subjected to measurement of auditory brainstem response at 1, 5, or 15 d after noise exposure. In each group, four guinea pigs were used to prepare paraffin sections of vestibular hair cells, and the rest for extraction of total protein from vestibular hair cells. The apoptosis of vestibular hair cells was detected by terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP nick-end labeling (TUNEL). The expression levels of p-JNK and pc-Jun were measured by immunohistochemistry and Western blot.</p><p><b>RESULTS</b>TUNEL-positive cells were found in the vestibular hair cells in the experimental groups, most in the 1 d experimental group and least in the 15 d experimental group, but no positive cells were found in the control group. The immunohistochemical results showed that p-JNK and pc-Jun were detected in the cell nuclei in the experimental groups, but no p-JNK- and pc-Jun-positive cells were found in the control group. The Western blot showed that p-JNK and pc-Jun were increased and activated quickly at 1d after noise exposure, reached the peak levels at 5 d after noise exposure, and were then decreased gradually, but they were still at relatively high levels at 15 d after noise exposure.</p><p><b>CONCLUSION</b>Intense noise can cause injury to vestibular hair cells by inducing cell apoptosis, and p-JNK marks the activation of JNK signal transduction pathway, suggesting that JNK signal transduction pathway plays an important role in intense noise-induced apoptosis of vestibular hair cells in guinea pigs.</p>