1.The rule of Traditional Chinese Medicine compounds for acute pancreatitis analyzed based on the National Patent Database
Caixing XIE ; Guozhong CHEN ; Xiaoxia CHEN ; Rihui ZHENG ; Xin YANG ; Yifeng LIANG
International Journal of Traditional Chinese Medicine 2022;44(7):796-800
Objective:Based on the Ancient and Modern Medical Record Cloud Platform, we aimed to analyze the rules of TCM compound patents for the treatment of acute pancreatitis.Methods:Compound patents for acute pancreatitis were retrieved from the National Patent Database. After the steps of data screening, data entry, and data specification, a database of compound patents treated for acute pancreatitis was established. The frequency analysis, attribute analysis, association analysis, cluster analysis, and complex network analysis were performed by using the Ancient and modern medical record cloud platform.Results:A total of 87 compound patents were obtained, comprising 213 herbs, of which the core drugs were Rhei radix et rhizoma, Bupleuri radix, Aurantii fructus immaturus, Glycyrrhizae radix et rhizoma, Magnoliae officinalis cortex, Corydalis rhizoma, Scutellariae radix, Aucklandiae radix, Natrii sulfas, Coptidis rhizoma. The drugs were mainly warm, cold and slightly cold, and the drugs taste mostly bitter and spicy, and the drugs mainly belonged to the spleen meridian and liver meridian. The cluster analysis results contained 5 categories. The associations of drugs included Bupleuri radix - Rhei radix et rhizoma, Aurantii fructus immaturus - Rhei radix et rhizoma, Magnoliae officinalis cortex - Rhei radix et rhizoma, for which complex network analysis yielded a core composition of Rhei radix et rhizoma, Bupleuri radix, Glycyrrhizae radix et rhizoma, Natrii sulfas, Aurantii fructus immaturus, Corydalis rhizoma, Scutellariae radix, Magnoliae officinalis cortex. Conclusion:The eliminating stasis by purging for acute pancreatitis is dominated by Rhei radix et rhizoma, channeling Fu Qi method is based on Aurantii fructus immaturus and Bupleuri radix, and eliminating stasis by purging combined with channeling Fu Qi methods can be used with Magnoliae officinalis cortex, Natrii sulfas, etc.
2.Study on the molecular mechanism of Qifang Weitong granules in treating gastric cancer based on network pharmacology
Xiaoxia CHEN ; Guozhong CHEN ; Yifeng LIANG ; Caixing XIE ; Xin YANG ; Rihui ZHENG
International Journal of Traditional Chinese Medicine 2022;44(8):925-930
Objective:To analyze the potential mechanism of Qifang Weitong granules in the treatment of gastric cancer based on network pharmacology and molecular docking method.Methods:TCMSP, TCMID, and Swiss Target Prediction databases were used to screen out the chemical components and related targets of Qifang Weitong Granules. GeneCards and OMIM databases were used to screen out the gastric cancer targets to obtain common targets of this disease and Qifang Weitong Granules and upload them to STRING database to form a PPI network, and obtain the key targets and analyze the correlation between the key targets and gastric cancer in Oncomine tumor database. In addition, the regulatory network of gastric cancer and Qifang Weitong Granules was constructed by using Cytoscape software, and the CluoGO plug-in and R language of Cytoscape software were used to perform GO and KEGG enrichment analysis on the key targets. The possibility of the binding between the molecules of this medicine and targeted molecules is verified by molecular docking.Results:There were 168 medicinal chemical components obtained in Qifang Weitong Granules, 2 803 gastric cancer targets, and 49 common targets. In the regulatory network of gastric cancer and Qifang Weitong Granules, β-sitosterol, formononet, stigmasterol have higher values of chemical composition. The key targets in the PPI network are MAPK8, FOS, AR, etc. The GO enrichment analysis focused on the positive regulation of mitochondrial outer membrane permeability in the apoptosis signaling pathway, while the KEGG enrichment analysis is significantly enriched in apoptosis access. The result of molecular docking showed good binding and stable conformation.Conclusion:Qifang Weitong Granules can induce the expression of genes and proteins related to gastric cancer, show its effect by affecting the level of hormones, cell apoptosis and other biological processes, and activating the apoptosis signal pathway.
3.Clinical observation of Qingjie Huagong Decoction combined with western medicine in the treatment of severe acute pancreatitis complicated with cholelithiasis (bile duct stones)
Rihui ZHENG ; Guozhong CHEN ; Xiping TANG ; Tiechao YUAN ; Xin YANG ; Baijun QIN ; Caixing XIE
International Journal of Traditional Chinese Medicine 2022;44(2):145-149
Objective:To evaluate the clinical efficacy of TCM Qingjie Huagong Decoction combined with routine internal medicine in the treatment of severe acute pancreatitis with cholelithiasis (bile duct stones) in the early stage.Methods:Thirty-two patients with severe acute pancreatitis combined with cholelithiasis in the first affiliated Hospital of GuangXi University of Traditional Chinese Medicine were selected and randomly divided into two groups with 16 in each, both groups were treated for 14 days. Serum amylase (AMS) was detected by iodine-starch colorimetry, GOT and GPT were detected by continuous monitoring method, and CRP, IL-6 and procalcitonin (PCT) were detected by immune transmission turbidimetry. Acute Physiological and Chronic Health Score Ⅱ (APACHE Ⅱ), CT Severity Index Score (CTSI) and Modified Marshall Score were used to evaluate the severity of SAP. The recovery time of body temperature, the relief time of abdominal distension pain, the recovery time of bowel sounds and the total hospital stay were observed and recorded to evaluate the clinical effect.Results:The total effective rate was 93.8% (15/16) in the treatment group and 75.0% (12/16) in the control group. There was significant difference between the two groups ( χ2=8.19, P=0.042). After treatment, the level of AMS, WBC, CRP, PCT, AST, ALT and IL-6 in the treatment group were lower than those in the control group ( t values were 14.3, 7.24, 9.63, 5.48, 7.05, 7.33, 28.34, respectively, all Ps<0.05); After treatment, the time for body temperature to return to normal [(2.91±0.12)d vs. (3.78±0.38)d, t=8.76], the time for relief of abdominal distension pain [(4.77±0.68)d vs. (7.13±1.55)d, t=9.52], the time for recovery of bowel sounds [(3.90±1.80)d vs. (4.89±1.38)d, t=2.98] and the total hospital stay [(22.60±2.80)d vs. (30.37±3.89)d, t=7.88] in the treatment group were all significantly shorter than those in the control group ( P<0.01); APACHE Ⅱ, CTSI and the Modified Marshall Score in the treatment group were lower than those in the control group ( t values were 11.82, 12.72, 7.71, respectively, all Ps<0.01). Conclusion:Qingjie Huagong Decoction combined with ERCP and conventional western medicine therapy can reduce the level of inflammation in patients with cholelithiasis in the early stage of SAP, relieve clinical symptoms and improve clinical efficacy.
4.Effect of Five Huoxue Huayu Prescriptions on Blood Lipid Metabolism, Liver Tissue and ABCA1 and PPARγ Expression in New Zealand Rabbits with Blood Stasis Syndrome
Lina LAI ; Jinxia LI ; Caixing ZHENG ; Ling LI ; Xiaoqing ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(15):78-84
ObjectiveTo observe the effects of five Huoxue Huayu prescriptions on blood lipid metabolism, liver tissue and adenosine triphosphate binding cassette transporter A1 (ABCA1) and peroxisome proliferator-activated receptor γ(PPARγ) expression in New Zealand rabbits with blood stasis syndrome, and to compare their differences in order to provide laboratory evidence for clinical selection of prescriptions and drugs. MethodSeventy New Zealand rabbits were randomly divided into normal group (n=10) and model group (n=60). The blood stasis syndrome was modeled by the method of starvation+high-fat feed+adrenaline. After the models were successfully established, they were randomly divided into Xuefu Zhuyutang(3.55 g·kg-1·d-1) group, Danshenyin(1.962 g·kg-1·d-1) group, Shixiaosan(0.56 g·kg-1·d-1) group, Huoluo Xiaolingdan(2.80 g·kg-1·d-1) group, and Taohong Siwutang(2.66 g·kg-1·d-1) group, and were given corresponding compound prescriptions by gavage. The normal group and model group were given the same dose of distilled water. After the treatment of 30 consecutive days, blood was taken from the abdominal aorta to detect the content of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol(LDL-C) and apolipoprotein A1 (ApoA1). Hematoxylin-eosin(HE) staining was used to observe the changes in liver tissue. Real-time polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression of ABCA1 and PPARγ in liver tissue, respectively. ResultCompared with the conditions in the normal group, increased mRNA and protein levels of HDL-C, LDL-C, TG, TC, and PPARγ (P<0.01), decreased ApoA1 level (P<0.05) and decreased mRNA and protein levels of ABCA1 (P<0.01) were found in the model group. Compared with the conditions in the model group, the HDL-C level in the five Huoxue Huayu prescriptions was lowered (P<0.05), and lowered TG level in Xuefu Zhuyutang group and Shixiaosan group (P<0.05), decreased LDL-C and TC levels in Shixiaosan group (P<0.05), and increased ApoA1 level in the Huoluo Xiaolingdan group (P<0.01) and Taohong Siwutang group (P<0.05) were observed. Furthermore, the mRNA and protein levels of ABCA1 in Xuefu Zhuyutang group, Shixiaosan group, Huoluo Xiaolingdan group and Taohong Siwutang group were elevated (P<0.05, P<0.01), and the elevated levels were higher than that of Danshenyin group (P<0.05). The mRNA level of PPARγ in the five Huoxue Huayu prescriptions was reduced (P<0.01), and its protein level was also decreased in Xuefu Zhuyutang group, Shixiaosan group, Huoluo Xiaolingdan group and Taohong Siwutang group (P<0.01). ConclusionThe five Huoxue Huayu prescriptions had a certain therapeutic effect on dyslipidemia,which might be achieved by up-regulating the expression of ApoA1 and ABCA1 to promote the production of HDL-C and strengthen the excretion of dysfunctional HDL-C. And Xuefu Zhuyutang had the optimal effect in lowering lipid.
5.Mechanism of Ferroptosis in Cerebral Ischemia-reperfusion and Interventional Mechanism of Huoxue Huayu Jiedu Prescription Based on "Blood Stasis and Toxin" Pathogenesis
Jiayue HAN ; Danyi PAN ; Jiaxuan XIAO ; Yuchen LIU ; Jiyong LIU ; Yidi ZENG ; Jinxia LI ; Caixing ZHENG ; Hua LI ; Wanghua LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):51-60
ObjectiveTo explore the material basis of the "interaction of blood stasis and toxin" mechanism in cerebral ischemia-reperfusion injury, as well as the protective role of Huoxue Huayu Jiedu prescription (HXHYJDF) against ferroptosis. MethodsSixty SPF-grade male SD rats were randomly divided into six groups: sham group, model group, deferoxamine (DFO) group (100 mg·kg-1), low-dose HXHYJDF group (4.52 g·kg-1), medium-dose HXHYJDF group (9.04 g·kg-1), and high-dose HXHYJDF group (18.07 g·kg-1), with ten rats in each group. Except for the sham group, the other groups were used to replicate the model of focal cerebral ischemia-reperfusion in the middle cerebral artery of rats by the reforming Longa method. Neurological function was assessed at 1st, 3rd, 5th, and 7th days post-reperfusion using the modified neurological severity scores (m-NSS). Brain tissue pathology and the morphology of mitochondria were observed using hematoxylin-eosin (HE) staining and transmission electron microscopy. The contents of malondialdehyde (MDA), glutathione (GSH), divalent iron ions (Fe2+), and reactive oxygen species (ROS) in the ischemic cerebral tissue were detected using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry and Western blot (WB) were used to detect the expression of iron death marker proteins glutathione peroxidase 4 (GPX4), ferroportin-1 (FPN1), transferrin receptor protein 1 (TfR1), and ferritin mitochondrial (FtMt) in brain tissue. ResultsCompared with the sham group, the mNSS score of the model group was significantly increased (P<0.01). HE staining showed that the number of neurons in the cortex of brain tissue was seriously reduced, and the intercellular space was widened. The nucleus was fragmented, and the cytoplasm was vacuolated. The results of transmission electron microscopy showed that the mitochondria in the cytoplasm contracted and rounded, and the mitochondrial cristae decreased. The matrix was lost and vacuolated, and the density of the mitochondrial bilayer membrane increased. The results of ELISA showed that the content of GSH decreased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS increased significantly (P<0.01). The results of immunohistochemistry and WB showed that the expression of GPX4 and FPN1 proteins was significantly decreased (P<0.01), and the expression of FtMt and TfR1 proteins was significantly increased (P<0.01). Compared with those of the model group, the m-NSS scores of the high-dose and medium-dose HXHYJDF groups began to decrease on the 3rd and 5th days, respectively (P<0.05, P<0.01). The results of HE and transmission electron microscopy showed that the intervention of HXHYJDF improved the pathological changes of neurons and mitochondria. The results of ELISA showed that the content of GSH in the medium-dose and high-dose HXHYJDF groups increased significantly (P<0.01), and the contents of MDA, Fe2+, and ROS decreased significantly (P<0.05, P<0.01). The content of GSH in the low-dose HXHYJDF group increased significantly (P<0.01), and the contents of MDA and ROS decreased significantly (P<0.01). The results of immunohistochemistry showed that the expression of GPX4 and FPN1 in the high-dose HXHYJDF group increased significantly (P<0.01), and the expression of FtMt and TfR1 decreased significantly (P<0.01). The expression of GPX4 and FPN1 in the medium-dose HXHYJDF group increased significantly (P<0.05), and the expression of TfR1 decreased significantly (P<0.01). WB results showed that the expression levels of FPN1 and GPX4 proteins in the high-dose, medium-dose, and low-dose HXHYJDF groups were significantly up-regulated (P<0.01), and the expression levels of FtMt and TfR1 proteins were significantly down-regulated (P<0.01). ConclusionHXHYJDF can significantly improve neurological dysfunction symptoms in rats with cerebral ischemia-reperfusion injury, improve the pathological morphology of the infarcted brain tissue, and protect the brain tissue of rats with cerebral ischemia-reperfusion injury to a certain extent. Neuronal ferroptosis is involved in cerebral ischemia-reperfusion injury, with increased levels of MDA, Fe2+, ROS, and TfR1 and decreased levels of FtMt, FPN1, GPX4, and GSH potentially constituting the material basis of the interaction of blood stasis and toxin mechanism in cerebral ischemia-reperfusion injury. HXHYJDF may exert brain-protective effects by regulating iron metabolism-related proteins, promoting the discharge of free iron, reducing brain iron deposition, alleviating oxidative stress, and inhibiting ferroptosis.