Effect of Guipitang on ERK1/2 and p38 MAPK in Rats with Myocardial Ischemia / 中国实验方剂学杂志

ObjectiveTo explore the therapeutic effect and mechanism of Guipitang on rats with myocardial ischemia. MethodFifty SD rats were divided into five groups： a control group， a model group， low and high-dose Guipitang （7.52， 15.04 g·kg-1） groups， and a trimetazidine group （0.002 g·kg-1）. By intragastric administration of vitamin D3 and feeding rats with high-fat forage and injecting isoproterenol， the rat model of myocardial ischemia was established. After drug treatment of 15 d， an electrocardiogram （ECG） was performed to analyze the degree of myocardial injury. A fully automatic biochemical analyzer was used to detect the changes in the serum levels of total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， triglyceride （TG）， and low-density lipoprotein cholesterol （LDL-C）. Hematoxylin-eosin （HE） staining and Masson staining were used to observe myocardial histopathological changes. TdT-mediated dUTP nick end labeling （TUNEL） staining was used to detect cardiomyocyte apoptosis. Western blot was adopted to detect the protein levels of extracellular signal-regulated kinase 1/2 （ERK1/2）， phospho-ERK1/2 （p-ERK1/2）， p38 mitogen-activated protein kinase （p38 MAPK）， phospho-p38 MAPK （p-p38 MAPK）， B-cell lymphoma-2 （Bcl-2）-associated X （Bax）， Bcl-2， and cleaved cysteine aspartate proteolytic enzyme （cleaved Caspase-3）. ResultCompared with the control group， the ECG S-T segment decreased in the model group. The serum levels of TC， TG， and LDL-C were increased significantly （P<0.05）. The arrangement of myocardial tissue was disordered， and the proportion of cardiomyocyte apoptosis increased. The protein levels of cleaved Caspase-3， Bax， and p-p38 MAPK in the heart were increased， and the Bcl-2 expression was decreased （P<0.05）. Compared with the model group， the S-T segment downward shift was restored in the low and high-dose Guipitang groups and trimetazidine group， and the levels of TC， TG， and LDL-C were decreased. The protein expression of cleaved Caspase-3 and Bax in the heart dropped， and p-p38 MAPK and p-ERK1/2 protein expressions increased significantly （P<0.05）. The degree of myocardial injury was alleviated， and the proportion of cardiomyocyte apoptosis decreased. Bcl-2 protein expression was increased significantly in the low-dose Guipitang group （P<0.05）. ERK1/2 and p38 MAPK proteins had no significant difference among different groups. ConclusionGuipitang could alleviate myocardial injury and inhibit cardiomyocyte apoptosis in rats by activating the expression of ERK1/2 and p38 MAPK.

Clinical Study on Modified Guipitang Combined with Xuefu Zhuyutang in Treating Mild Cognitive Impairment After Cerebral Infarction / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy and anti-inflammatory and anti-oxidant effect of modified Guipitang combined with Xuefu Zhuyutang in the treatment of mild cognitive impairment （MCI） after cerebral infarction with syndromes of heart and spleen deficiency and blood stasis blocking collateral. MethodA total of 114 eligible patients were randomly divided into a control group and an observation group，with 57 cases in each group. Patients in the control group were given red deer ginseng tablets （po），4 tablets/time，2 times/day. Patients in the observation group were given modified Guipitang combined with Xuefu Zhuyutang （po，1 dose/day）for continuous 8 weeks. This study compared the scores of montreal cognitive assessment （MoCA） scale，Rivermead behavioral memory test （RBMT），activities of daily living （ADL），trail making test B （TMT-B），neuropsychiatric inventory questionnaire （NPI） and scores of traditional Chinese medcine（TCM） syndrome with syndromes of heart and spleen deficiency and blood stasis blocking collateral before and after treatment. Then we further detected the levels of 8-hydroxydeoxyguanosine （8-OHDG），malondialdehyde （MDA），oxidized low density lipoprotein （ox-LDL），superoxide dismutase （SOD），homocysteine （Hcy），interleukin-8 （IL-8），C-reactive protein （CRP） and fibrinogen （FIB） levels before and after treatment. ResultThe total effective rate for the treatment of cognitive function impairment in the observation group was 92.98% （53/57），which was higher than 78.95% （45/57） in the control group （χ2＝4.653，P<0.05）. The recovery rate of cognitive function in the observation group was 54.39% （31/57），which was higher than 33.33% （19/57） in the control group （χ2＝5.130，P<0.05）. The MoCA，RBMT and ADL scores of the observation group were higher than those of the control group （P<0.01），and the TMT-B time of the former was shorter than that of the latter （P<0.01）. In addition， the observation group showed lower scores of TCM syndrome，NPI-1 and NPI-2 scores than the control group （P<0.01）. The SOD level of the observation group was higher than that of the control group （P<0.01），and the levels of 8-OHDG，ox-LDL，MDA，Hcy，IL-8，CRP and FIB were lower than those of the control group （P<0.01）. ConclusionModified Guipitang combined with Xuefu Zhuyutang can improve cognitive function in MCI patients after cerebral infarction with syndromes of heart and spleen deficiency and blood stasis blocking collateral， with anti-inflammatory and anti-oxidant effect， and yield superior efficacy than red deer ginseng tablets.

Modern Clinical Applications and Type of Disease Prevention and Treatment of Guipitang： A Review / 中国实验方剂学杂志

The Chinese herbal medicines contained in Guipitang （GPT） were retrieved in the databases， including traditional Chinese medicine systems pharmacology database and analysis platform （TCMSP）， encyclopedia of traditional Chinese medicine （ETCM）， bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine （BATMAN-TCM）， and database for associated traditional Chinese medicine， gene， and disease information using text mining （TCMGeneDIT）， and the compounds and their potential targets were obtained. Disease enrichment analysis on the potential targets of GPT was carried out to obtain the diseases potentially treated by GPT using MetaCore. Disease enrichment results showed that the potential diseases treated by GPT included encephalopathy， gastrointestinal diseases， nutritional/metabolic diseases， tumors/cancers， cardiovascular system diseases， endocrine system diseases， immune system diseases， drug-related side effects/adverse reactions， and congenital/hereditary diseases. On these grounds， the diseases treated by GPT were reviewed. The results of the previous research on diseases treated by GPT were consistent with analysis results of network pharmacology. The modern applications of GPT clinically went beyond its original indications， but its applications were based on the clinical manifestation of qi and blood deficiency in the heart and spleen， presenting the characteristic of "same treatment for different diseases". This study is expected to provide a reference for the further research and development of GPT.

Observe Impact Modified Guipitang Administration Combined with Hot Pressing of Traditional Chinese Medicine on Rehabilitation in Patients with Deficiency of Qi and Blood Syndrome Breast Cancer Postoperative / 中国实验方剂学杂志

Objective:To observe the rehabilitation effect of modified Guipitang administration combined with traditional Chinese medicine （TCM） hot pressing in patients with deficiency of Qi and blood syndrome breast cancer postoperative， and investigate its effect on immune function and tumor markers. Method:One hundred and fifty-four patients were divided into observation group （77 cases） and control group （77 cases） by random number table. Two groups were given comprehensive treatment measures after operation. Patients in control group additionally took Bazhen granules orally， 8 g/time， 2 times/day， for eight weeks. Patients in observation group additionally took Guipitang orally for syndrome differentiation， 1 dose/day for eight weeks. The chest， shoulders and upper limbs of the affected side were hot-pressed with TCM， 20 min/time， 2 times/ day， 5 days a week， the first 4 weeks. The occurrence of lymphedema， subcutaneous fluid， poor skin flap growth， sleep disturbance， shoulder joint dysfunction， etc. Were recorded in both groups. Before and after treatment， the scores of European organization for research and treatment of cancer quality of life questionnaire core-30（EORTC QLQ-30）， and scores of cancer-induced fatigue and Qi and blood deficiency were graded. T lymphocyte subsets （CD3⁺， CD4⁺， CD8⁺ levels and CD4⁺/CD8⁺）， regulatory T cells （Treg）， inhibitory T cells （Ts）， cytotoxic T cells （Tc）， human growth differentiation factor 3 （GDF3）， serum carbohydrate antigen 153 （CA153）， carcinoembryonic antigen （CEA） and human epidermal growth factor -2 （HER-2） levels were detected before and after treatment. Result:After treatment， the observation group incidence of lymphedema， subcutaneous effusion， poor skin flap growth， sleep disturbance and shoulder joint dysfunction was 8（10.39%）， 9（11.69%）， 11（14.29%）， 25（32.47%） and 8 （10.39%） respectively in the observation group， all lower than 18（23.38%）， 20（25.97%）， 23（29.87%）， 46（59.74%） and 19（24.68%） in the control group（<italic>P</italic><0.05， <italic>P</italic><0.01）. The scores of overall quality of life and function scores in the observation group were higher than those in the control group （<italic>P</italic><0.01）， hile symptom score was lower than that in the control group （<italic>P</italic><0.01）. The scores of cancer-induced fatigue deficiency of Qi and blood syndrome in the observation group were lower than those in the control group （<italic>P</italic><0.01）. The Tc， CD3⁺， CD4⁺， CD4⁺/CD8⁺ levels in the observation group were higher than those of the control group （<italic>P</italic><0.01）， while the Treg， Ts， CD8⁺ levels were lower than those in the control group （<italic>P</italic><0.01）. The GDF3， CA153， CEA， HER-2 levels in the observation group were lower than those in the control group （<italic>P</italic><0.01）. Conclusion:On the basis of conventional comprehensive interventions of western medicine， Guipitang combined with TCM hot pressing for breast cancer patients after surgery can reduce postoperative complications， reduce fatigue， postoperative symptoms and TCM syndromes. Besides， it can enhance the immune function of the body， improve the quality of life， promote postoperative recovery， and inhibit the expression of tumor markers， thus improving the prognosis of patients.

Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology / 中国实验方剂学杂志

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.

Effect of Modified Guipitang Combined with Xingnao Kaiqiao Acupuncture in Treatment of Heart and Spleen Insufficiency Syndrome of Non-dementia Vascular Cognitive Impairment / 中国实验方剂学杂志

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.