Mechanism of Xiangsha Liujunzi Tang in Regulation of RhoA/ROCK2/MYPT1 Pathway to Improve Gastric Motility in Rats with Functional Dyspepsia / 中国实验方剂学杂志

ObjectiveTo explore the intervention mechanism of Xiangsha Liujunzi Tang in rats with functional dyspepsia （FD） based on the Ras homolog gene family member A （RhoA）/Rho-associated coiled-coil containing protein kinase 2 （ROCK2）/Myosin phosphatase target Subunit 1 （MYPT1） pathway. MethodSixty male SD suckling rats in SPF grades were randomly divided into blank group （n=10） and model group （n=50）. The comprehensive modeling method （gavage administration of iodoacetamide+exhaustion of swimming+disturbance of hunger and satiety） was used to replicate the rat model of FD. After successful replication of the model， the rats in the model group were randomly divided into model group， mosapride group， and high， middle， and low-dose Xiangsha Liujunzi Tang groups， with 10 rats in each group. Rats in the blank group and model group were given 10 mL kg-1·d-1 normal saline， those in the mosapride group were given 1.35 mg·kg-1·d-1 mosapride， and those in the high， middle， and low-dose Xiangsha Liujunzi Tang groups were given 12， 6， and 3 g·kg-1·d-1 Xiangsha Liujunzi Tang， respectively. The intervention lasted 14 days. The general living conditions of rats were observed before and after modeling and administration， and the 3-hour food intake and body mass of rats were measured. After intervention， the intestinal propulsion rate of rats was measured， and the pathological changes in the gastric tissue were observed by hematoxylin-eosin （HE） staining. The content of choline acetyl transferase （ChAT） and vasoactive intestinal peptide （VIP） in the medulla oblongata and gastric tissue homogenate was determined by enzyme-linked immunosorbent assay （ELISA）， the distribution of adenosine triphosphate （ATP） enzyme in gastric antrum smooth muscle was observed by frozen section staining， and the protein expression levels of RhoA， ROCK2， and phosphorylated-myosin phosphatase target subunit 1 （p-MYPT1） in the gastric tissue were detected by Western blot. ResultCompared with the blank group， the model group had withered hair， lazy movement， slow action， poor general living condition， lower 3-hour food intake， body mass， and lower intestinal propulsion rate （P<0.05）， whereas no obvious abnormality in gastric histopathology. In the model group， the content of ChAT in the medulla oblongata and gastric tissue decreased， the content of VIP in gastric tissue increased， the distribution of ATP enzyme in gastric antrum smooth muscle decreased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue decreased significantly （P<0.05）. As compared with the model group， the general living condition of rats in each intervention group was significantly improved， and the 3-hour food intake， body mass， and intestinal propulsion rate were significantly increased （P<0.05）. There was no significant difference in gastric pathology in the intervention groups. The content of ChAT in the medulla oblongata and gastric tissue increased significantly， the content of VIP in the gastric tissue decreased， the distribution of ATP enzyme in gastric antrum smooth muscle increased significantly， and the protein expression levels of RhoA， ROCK2， and p-MYPT1 in the gastric tissue increased significantly （P<0.05）. The intervention effect of Xiangsha Liujunzi Tang group on the above indexes was dose-dependent. ConclusionXiangsha Liujunzi Tang can effectively improve the general living condition and gastric motility of rats with FD， and its specific mechanism may be related to the activation of the RhoA/ROCK2/MYPT1 pathway in the gastric tissue to regulate smooth muscle relaxation and contraction and promote gastric motility.

Clinical Observation of Effects of Modified Xiangsha Liujunzi Tang Application on Adverse Reaction of Moderately/Highly Emetogenic Chemotherapy for Gastrointestinal Tumors / 中国实验方剂学杂志

Objective:To investigate the effects of external application of modified Xiangsha Liujunzi Tang in improving gastrointestinal reaction，immune function， and quality of life in patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy. Method:A total of 140 inpatients （from January 2018 to May 2021） with gastrointestinal malignancies diagnosed by the Oncology Department of Integrated Traditional Chinese and Western Medicine of China-Japan Friendship Hospital and treated with moderately/highly emetogenic chemotherapy were randomly divided into an experimental group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70） according to the Good Clinical Practice （GCP）. Participants were given routine antiemetic treatment once 20 minutes before chemotherapy （tropisetron 5 mg + dexamethasone 5 mg or methylprednisolone 40 mg）. On this basis， the patients in the experimental group were treated with external application of modified Xiangsha Liujunzi Tang for 1 week on the second day after chemotherapy （the selected points were Zhongwan， Neiguan and Zusanli， 6 hours a day， and the application was changed every day）， and the patients in the control group were applied with comfort patch at the same time. The gastrointestinal reaction grade， subset concentration of lymphocytes， and Karnofsky score in two groups before and one week after chemotherapy were recorded， and all data were analyzed by SPSS 19.0 statistical software. Result:The grades of chemotherapy-related gastrointestinal reaction in two groups after treatment decreased as compared with that before treatment （<italic>P</italic><0.05）. The experimental group was superior to the control group after treatment in terms of grade decrease （<italic>P</italic><0.05）. The total response rate of the experimental group was 81.43% （57/70）， higher than 62.86% （44/70） in the control group （<italic>χ</italic>²=9.73， <italic>P</italic><0.05）. Stratified analysis was performed on the experimental group. Compared with the conditions before treatment， the grade of gastrointestinal reaction in patients with esophageal cancer and colorectal cancer of the experimental group decreased after treatment （<italic>P</italic><0.05）， and that in patients of different genders decreased after treatment （<italic>P</italic><0.05）. The results of immune function showed that there was no significant difference in the concentrations of CD3⁺， CD4⁺， CD8⁺， and NK cell subsets of the control group before and after treatment， while the concentrations of CD3⁺， CD4⁺， and NK cell subsets of the experimental group were higher than those before treatment and even superior to those in the control group （<italic>P</italic><0.05）. The Karnofsky score of quality of life in the experimental group was higher than that in the control group， with quality of life improved （<italic>P</italic><0.05）. Conclusion:External application of modified Xiangsha Liujunzi can improve the gastrointestinal reaction，immune function， and quality of life of patients with gastrointestinal tumors after moderately/highly emetogenic chemotherapy.

Effect and Mechanism of Xiangsha Liujunzi Tang on Lipid Deposition in Liver of ApoE-/- AS Mice by Affecting Long Noncoding RNA-HC/miR-130b and to Regulate Cholesterol Metabolism / 中国实验方剂学杂志

Objective:To investigate the mechanism of Xiangsha Liujunzi Tang in improving liver lipid deposition in ApoE^-/- atherosclerotic （AS） mice by affecting long noncoding RNA-HC （Lnc-HC）/microRNA-130b （miR-130b） in the regulation of cholesterol metabolism. Method:Totolly 10 C57BL/6J mice were selected as normal controls， and 30 healthy ApoE^-/- mice fed with high fat diet for 12 weeks were then randomly divided into the model group， Xiangsha Liujunzi Tang group（19.12 g·kg^-1·d^-1） and simvastatin group（2.275 mg·kg^-1·d^-1）， with gavage administration for 4 weeks. The serum lipid level of mice was detected by automatic biochemistry analyzer， and the histopathological changes of liver cells were observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect expression of long noncoding RNA-HC， and miR-130b. Real-time PCR and Western blot assay were used to detect gene and protein expression of peroxisome proliferator-activated receptor gamma （PPAR<italic>γ</italic>）， liver X receptor （LXR）， ATP-binding cassette transporters A1 （ABCA1）， ATP-binding cassette transporters G1 （ABCG1）， ATP-binding cassette transporters G5 （ABCG5）， and ATP-binding cassette transporters G8 （ABCG8）. Result:Compared with the normal control group， the mice in the model group showed abnormal blood lipids， larger liver cells， obvious fat vacuoles， significantly increased expression of Lnc-HC， miR-130b in liver， and significantly decreased gene and protein expression of PPAR<italic>γ</italic>， LXR， ABCA1， ABCG1， ABCG5， and ABCG8 in mice liver （<italic>P</italic><0.05，<italic>P</italic><0.01）. Compared with the model group， the abnormal blood lipid levels of the mice in the Xiangsha Liujunzi Tang group and the simvastatin group were improved， and the number of fatty vacuoles of liver cells was significantly reduced， the expression of liver Lnc-HC， miR-130b in Xiangsha Liujunzi Tang group decreased significantly （<italic>P</italic><0.05，<italic>P</italic><0.01）， the gene and protein levels of liver PPAR<italic>γ</italic>， ABCA1， ABCG1， ABCG5， ABCG8 in mice of the Xiangsha Liujunzi Tang group and the simvastatin group showed an upward trend. Among them， the gene and protein expression of LXR protein in the liver of the Xiangsha Liujunzi Tang group was significantly up-regulated （<italic>P</italic><0.05）. Conclusion:Xiangsha Liujunzi Tang may improve the lipid deposition in the liver of ApoE^-/-AS mice by affecting Lnc-HC/miR-130b to regulate the cholesterol metabolism process mediated by PPAR<italic>γ</italic>， thus playing a role in preventing and treating AS.