ABSTRACT
Objective:To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology. Method:Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes, and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis, 48 SD female rats were randomly divided into blank control group, model group, eszopiclone tablets group (0.2 mg·kg-1·d-1), modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg-1·d-1). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency, time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8), RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus. Result:A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes, including MAPK3, MAPK8, Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times, time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3, MAPK8, Akt1 and IL-6 in hippocampus（P<0.01）, while the low dose group had no significant effect. Conclusion:The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3, MAPK8, Akt1 and IL-6 genes.
ABSTRACT
Objective: To explore the curative effect and partial mechanism of modified Guipitang combined with Xingnao Kaiqiao acupuncture in the treatment of non-dementia vascular cognitive impairment (VCIND). Method: Totally 122 patients with VCIND admitted to the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine (TCM) from May 2017 to October 2018 were randomly divided into modified decoction group (39 cases), acupuncture group (42 cases) and combination group (41 cases). All of the three groups were orally given routine anticoagulants and lipid-lowering drugs. The decoction group was orally given modified Guipitang 150 mL/times, 2 times/day, in addition to the routine treatment, the acupuncture group was treated with Xingnao Kaiqiao acupuncture method in addition to the routine treatment, involving Shuigou, Neiguan (bilateral), Sanyinjiao (bilateral), Sishencong, Xuanzhong (bilateral) and Taixi (bilateral) acupoints, 2 times/day, for six days a week, the combined group was treated with Xingnao Kaiqiao acupuncture in addition to modified Guipitang. All of the three groups were treated for 8 weeks. The Montreal cognitive assessment scale (MoCA scale, Beijing version) and activity of daily life (ADL) scale, TCM symptoms and clinical efficacy were scored before treatment, 4 weeks after treatment and 8 weeks after treatment in three groups. Serum levels of calcitonin gene-related peptide (CGRP) and cone-like protein-1 (VILIP-1) were measured by enzyme-linked immunosorbent assay at different time points. Result: Compared with decoction group and acupuncture group, MoCA score, ADL score and TCM syndrome score of the combined group were decreased, the total effective rate was increased significantly after 4 and 8 weeks of treatment, the serum CGRP content was increased, and the VILIP-1 content was decreased. Conclusion: Modified Guipitang combined with Xingnao Kaiqiao acupuncture has a definite curative effect on VCIND with heart and spleen insufficiency syndrome. Its mechanism may be related to the expansion of blood vessels, the alleviation of blood supply of brain and the reduction of neuron injury.
