Chaiqin Chengqi Decoction as an adjuvant treatment for mild/moderately severe hypertriglyceridemic acute pancreatitis: A retrospective study

Hypertriglyceridemia is the third leading cause of acute pancreatitis(AP),and its incidence is increasing.Due to its relatively insidious etiology,it is easy to be ignored in the early stages.In China,Chaiqin Chengqi Decoction(CQCQD)has long been employed for treating AP.AIM To evaluate the effectiveness of CQCQD in patients diagnosed with mild/moderately severe hypertriglyceridemic AP(HTG-AP).METHODS In this study,the clinical data of 39 patients with HTG-AP admitted from January 2019 to November 2022 were collected.The changes of blood lipids,gastrointestinal symptoms,and abdominal pain before and after treatment were analyzed and compared between the two groups.RESULTS Twenty patients were treated with the conventional HTG-AP regimen,and 19 patients were additionally treated with CQCQD.After receiving treatment,the triglycerides(TG)level of the CQCQD group was lower than that of the CQCQD group(3.14±0.25 mmol/L vs 4.96±0.47 mmol/L,P<0.01).After 3 d of treatment,the patients in the CQCQD group had more bowel movements than the control group(2.51±0.25 times vs 1.00±0.17 times,P=0.01).The gastrointestinal function of most patients returned to normal,and the acute gastrointestinal injury score was significantly lower than that of the control group(0.11±0.07 vs 0.42±0.11,P<0.01).CONCLUSION In patients with HTG-AP,CQCQD can significantly reduce the TG level,shorten the recovery time of defecation,significantly improve the gastrointestinal function.

The Study of Molecular Mechanisms of Xuanbai Chengqi Decoction(宣白承气汤)in the Treatment of Coronavirus Disease 2019 Based on Network Pharmacology and Molecular Docking Method

Objective:To explore the molecular mechanism of Xuanbai Chengqi Decoction(宣白承气汤)in the treatment of Coronavirus Disease 2019(COVID-19)based on network pharmacology,and to verify by molecular docking technology.Methods:The components and targets of Xuanbai Chengqi Decoction(宣白承气汤)were obtained by TCMSP,targets’information was corrected based on the databases such as UniP rot and DrugBank,and the software Cytoscape3.7.1 was adopted to construct TCM-Component-Target and Component-Target network.The main targets were mapped to the KEGG pathway and the GO biological process with the help of DAVID to further elucidate the potential relationship between the main targets and Xuanbai Chengqi Decoction(宣白承气汤)therapy for COVID-19.In the end,the Swiss Dock platform was adopted for the molecular docking verification of key components and targets.Results:The Component-Target network consists of 35 components and 106 corresponding targets,the main targets include COX-2,NCOA2,PTGS1,HSP90 AB1,PRKACA and PGR,etc.There are 561 GO entries of target mapping(P 0.05),including 155 entries for Biological Processes(BP),147 entries for Cell Composition(CC),and 259 entries for Molecular Function(MF).There are 38 KEGG mapping pathways(P 0.05),including many aspects of infectious disease,immune system and endocrine system,as well as Calcium signaling pathway,VEGF signaling pathway,PI3K-Akt signaling pathway and other processes.Conclusion:The result of molecular docking shows that the affinity of the key components such as beta-sitosterol and stigmasterol are similar to recommended medications for COVID-19.Its effect in the treatment of middle stage of COVID-19 may be related to the blocking of the binding of COVID-19 virus and ACE2,antivirus,and relieving inflammatory storm.

Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology

The current study was designed to explore the brain protection mechanism of Xinglou Chengqi Decoction(XCD)based on gut microbiota analysis and network pharmacology. A transient middle cerebral artery occlusion(MCAO) model of mice was established, followed by behavioral evaluation, TTC and TUNEL staining. Additionally, to investigate the effects of gut microbiota on neurological function after stroke, C57BL/6 mice were treated with anti-biotic cocktails 14 days prior to ischemic stroke(IS) to deplete the gut microbiota. High-throughput 16S rDNA gene sequencing, metabonomics technique, and flow multifactor technology were used to analyze bacterial communities, SCFAs and inflammatory cytokines respectively. Finally, as a supplement, network pharmacology and molecular docking were applied to fully explore the multicomponent-multitarget-multichannel mechanism of XCD in treating IS, implicated in ADME screening, target identification, network analysis, functional annotation, and pathway enrichment analysis.We found that XCD effectively improved neurological function, relieved cerebral infarction and decreased the neuronal apoptosis.Moreover, XCD promoted the release of anti-inflammatory factor like IL-10, while down-regulating pro-inflammatory factors such as TNF-α, IL-17A, and IL-22. Furthermore, XCD significantly increased the levels of short chain fatty acids(SCFAs), especially butyric acid. The mechanism might be related to the regulation of SCFAs-producing bacteria like Verrucomicrobia and Akkermansia, and bacteria that regulate inflammation like Paraprevotella, Roseburia, Streptophyta and Enterococcu. Finally, in the network pharmacological analysis, 51 active compounds in XCD and 44 intersection targets of IS and XCD were selected. As a validation, components in XCD docked well with key targets. It was obviously that biological processes were mainly involved in the regulation of apoptotic process, inflammatory response, response to fatty acid, and regulation of establishment of endothelial barrier in GO enrichment. XCD can improve neurological function in experimental stroke mice, partly due to the regulation of gut microbiota. Besises, XCD has the characteristic of "multi-component, multi-target and multi-channel" in the treatment of IS revealed by network pharmacology and molecular docking.

Changes of Neuronal Acetylcholine Receptor Alpha 7 of Peritoneal Macrophage in Experimental Acute Pancreatitis Treated by Chaiqin Chengqi Decoction(柴芩承气汤)

Objective：To investigate effect of Chaiqin Chengqi Decoction（柴芩承气汤,CQCQD） on changes of neuronal acetylcholine receptor alpha 7（nAChRα7） of peritoneal macrophages in acute pancreatitis（AP）.Methods：Eighteen Kunming mice were equally randomized into the control group,AP group and CQCQD treatment group.AP was induced by two intraperitoneal injections of 4 g/kg L-arginine at 1 h apart,while control mice received saline injections.At 72 h after the first injection of L-arginine,mice in the treatment group were intragastrically administered 0.1 mL/10 g CQCQD every 2 h for 3 times,whilst mice in the other two groups received the same amount of saline feeding.Mice were sacrificed by cervical dislocation 2 h after the last feeding of either CQCQD or saline.Peritoneal macrophages were collected for determination of nAChRα7 mRNA and protein expression.Serum was collected for detection of interleukin-6（IL-6）,IL-10 and acetylcholine（ACh）levels,and pancreas was for histopathology analysis.Results：The CQCQD treatment significantly ameliorated the severity of AP as evidenced by reducing the pancreatic histopathology score（4.5 ± 0.5 vs.6.2 ± 1.7,P〈0.05）and the serum IL-6 levels（1228.31419.2 pg/mL vs.1589.6 ±337.3 pg/mL,P〈0.05）.The mRNA and protein expression of nAChRα7 of the peritoneal macrophages in the AP group were similar to the control group（P〉0.05）,but were significantly up-regulated after the CQCQD treatment（P〈0.05）.The serum ACh levels in the AP group were significantly lower than those in the control group（3.1 ± 0.6 μg/mL vs 4.8 ± 0.7 μg/mL P〈0.05）,but were significantly increased after the CQCQD treatment（5.6±1.5 μg/mL vs 3.1 ±0.6 μg/mL,P〈0.05）.Conclusion：CQCQD is protective against L-arginine-induced AP through mechanisms involving nAChR α 7 of peritoneal macrophages.

Xuanbai Chengqi decoction(宣白承气汤) plus Western Medicine in treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung:a Meta-analysis

OBJECTIVE: To evaluate the effectiveness and safety of Xuanbai Chengqi decoction(宣白承气汤, XBCQD) plus Western Medicine(WM) in treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung.METHODS: Randomized controlled trials(RCTs) investigating the effect of XBCQD on severe pneumonia with symptom pattern of phlegm-heat obstructing lung, were included in this study. Seven electronic databases were searched up to March 2019.Meta-analysis was conducted by Review Manager5.3 software. Risk ratio(RR) and mean difference(MD) with 95% confidence interval(CI) were used as effect estimation.RESULTS: Eleven RCTs were included, involving992 participants. Meta-analysis showed that XBCQD combined with WM achieved better effectiveness than WM alone in terms of total effective rate[RR = 1.23, 95%CI(1.16, 1.30)], clinical pulmonary infection score [CPIS, MD =-2.02, 95%CI(-2.42,-1.63)], acute physiology and chronic health evaluation Ⅱ [APACHE Ⅱ, MD =-6.81, 95% CI(-8.26,5.37)], mechanical ventilation time [MD =-101.41,95%CI(-140.47,-62.34)], and lactic acid content in arterial blood [MD =-2.41, 95%CI(-2.64,-2.18)].CONCLUSION: XBCQD combined with WM had better benefit than WM alone to the patients of severe pneumonia with the symptom pattern of phlegm-heat obstructing lung. However, due to low quality of the included studies, more rigorously designed studies were required to further evaluate the effectiveness and safety of XBCQD in the treatment of severe pneumonia with symptom pattern of phlegm-heat obstructing lung.

The Effect of Chaiqin Chengqi Decoction(柴芩承气汤) on Modulating Serum Matrix Metalloproteinase 9 in Patients with Severe Acute Pancreatitis

Objective： To investigate the effect of Chaiqin Chengqi Decoction （柴芩承气汤, CQCQD） on regulating serum matrix metalloproteinase 9 （MMP-9） in patients with severe acute pancreatitis （SAP）. Methods： Thirty-five SAP patients hospitalized in West China Hospital from September 1, 2008 to February 28, 2009 were randomly assigned to two groups using a computer-derived random number sequence in a ratio of 1：1, treatment group （18 patients） and the placebo control group （17 patients）. The patients in the treatment group were administered with CQCQD by gastric parfusion （50 mL/2 h） and retention enema （200 mL/6 h） for 7 days. The two groups had similar baseline information. The clinical indicators, including the initial Balthazar＇s computed tomography （CT） score, acute physiology and chronic health evaluation I1 （APACHE II） scores on 1st, 3rd, 5th and 7th day, incidences and durations of complications and the serum C-reactive protein （CRP）, levels of MMP-9 on the 1st, 3rd, 5th and 7th day, were recorded and compared between the two groups. Resalts： The serum MMP-9, CRP and the APACHE I1 scores on the 3rd, 5th and 7th day in the treatment group were lower than those in the control group （P〈0.05）. The serum MMP-9 was positively correlated with the APACHE II score on the 1st day （r=0.430, P=0.01）. The durations of acute respiratory distress syndrome （5.4± 2.4 vs. 2.9± 1.3）, acute hepatitis （4.6± 0.8 vs. 1.9 ± 0.6） and acute heart failure （3.9 ± 1.6 vs. 1.3 ± 0.6, P〈0.05） in the control group were longer than those in the treatment group. Conclusion： CQCQD could decrease the serum MMP-9 to relieve the severity of clinical symptoms and prevent the development of multiple organ dysfunction syndrome in patients with SAP.

Effect of Chaiqin Chengqi Decoction(柴芩承气汤) on Cholecystokinin Receptor 1-Mediated Signal Transduction of Pancreatic Acinar Cells in Acute Necrotizing Pancreatitis Rats

Objective： To investigate the effect of Chaiqin Chengqi Decoction （柴芩承气汤,CQCQD） on cholecystokinin receptor 1 （CCKR1）-mediated signal transduction of pancreatic acinar cell in rats with acute necrotic pancreatitis （ANP）. Methods： Twenty-seven Sprague-Dawley rats were randomized into three groups： the control group, the ANP group, and the CQCQD group （9 in each group）. ANP rats were induced by two intraperitoneal injections of 8% L-arginine （pH=7.0, 4.4 g/kg） over a 2-h period. Rats were treated with 1.5 mL/100 g body weight of CQCQD （CQCQD group） or physiological saline （control and ANP groups） at 2 h interval. And 6 h after induction, pancreatic tissues were collected for histopathological examination. Pancreatic acinar cells were isolated for determination of CCKR1 mRNA and protein expression, phospholipase C （PLC） and inositol-1,4,5-triphosphate （IP3）, and determination of fluorescence intensity （FI） as a measure of intracellular calcium ion concentration [Ca2＋]i. Results： The pancreatic histopathological score （6.2± 1.1） and the levels of PLC （1,187.2±228.2μg/mL） and IP3 （872.2±88.4 μg/mL） of acinar cells in the ANP group were higher than those in the control （2.8± 0.4, 682.5± 121.8 μ g/mL, 518.4 ± 115.8 μ g/mL） and the CQCQD （3.8± 0.8, 905.3± 78.5 μ g/mL, 611.0±42.5μ g/mL） groups （P〈0.05）. [Ca2＋]i FI for the ANP group （34.8± 27.0） was higher than that in the control （5.1 ± 2.2） and CQCQD （12.6± 2.5） groups （P〈0.05）. The expression of pancreatic acinar cell CCKR1 mRNA in the ANP group was up-regulated （expression ratio=1.761; ,0=0.024） compared with the control group. The expression of pancreatic acinar cell CCKR1 mRNA in the CQCQD group was down-regulated （expression ratio=0.311; P=0.035） compared with the ANP group. The ratio of gray values of the CCKR1 and β-actin in the ANP group （1.43±0.17） was higher than those in the control （0.70 ± 0.15） and CQCQD （0.79± 0.11） groups （P〈0.05）. Conclusions： Pancreatic acinar ceil calcium overload of ANP induced by L-arginine was related to the up-regulated expressions of pancreatic acinar cell CCKR1 mRNA and protein. CQCQD can down-regulate expressions of pancreatic acinar cell CCKR1 mRNA and protein to reduce the PLC and IP3 of pancreatic acinar cells, relieving the calcium overload and reducing the pathological changes in rats with ANP.

Effects of Supplemented Taohe Chengqi Decoction (桃核承气汤) in Treating Insulin Resistance in Rats with Non-Insulin Dependent Diabetes Mellitus

Objective: To investigate the effect of supplemented Taohe Chengqi Decoction (桃核承气汤,STHCQD) in treating non-insulin dependent diabetes mellitus (NIDDM). Methods: The model of rats withNIDDM was formed with injection of streptozotocin and fed on high calorie diet to study the effects of STHCQDon the release of insulin sensitivity. Results: (l ) Fasting serum glucose, serum insulin, intake of food and waterwere significantly decreased (P < 0. 05 -- 0. 01 ) in STHCQD-treated diabetic rats as compared with untreated diabetic rats, while the insulin sensitivity was significantly increased (P < 0. 05 ). (2) The liver cell membranesfrom STHCQD-treated diabetic rats released the quantity of insulin receptor which inhibited adenylate cyclaseactivity, but this effect was blunted in untreated diabetic rats (P < 0. 05). (3) A significantly increased glucoseoxidation in adipocyte of STHCQD-treated diabetic rats was found as compared with those of untreated diabeticrats (P< 0. 05). Conclusions: STHCQD therapy Increased sensitivity and responsiveness of target cells to insulin, i. e. it might decrease insulin resistance at receptor sites and POst--receptor sites in rats with NIDDM, butcould not.reverse the insulin resistance.

Effect of Chishao Chengqi Decoction (赤芍承气汤) on Endotoxin and TNF-α in Patients with Severe Hepatic Diseases

Objective: To observe the effect of Chishao Chengqi decoction (CCD ) in treating severe hepatopathy and its influence on serum endotoxin(ET) and tu mor necrosis factor α (TNF-α), in order to explore the possible mechanism o f CCD in protecting liver cells and in preventing liver failure.Methods: Sixty patients suffering from hepatopathy were divided into the treated group and control group randomly, 30 in each group. They were treated with comprehensive treatment, including hepatocyte growth-promoting factors, thymosin, Transmetil and albumin. CCD was given to the treated group ad ditionally. The therapeutic effects were observed and the changes of some bioch emical criteria, including alanine transaminase (ALT), aspartate aminotransferas e (AST), total bilirubin (TB), albumin (ALB) as well as such parameters as proth rombin activity (PTA), serum levels of ET and TNF-α were all detected respec tively before treatment and after treatment.Results: In the treated group, 8 patients was clinically cured af ter treatment, 11 were markedly alleviated, 7 improved and 4 remained unchanged, while in the control group, the respective numbers were 5, 8, 8 and 9. The tota l effective rate of the treated group was significantly better than that of the control group by( P <0.05). ET and TNF-α levels in patients were signific antly higher than the normal range before treatment, and they were lowered after treatment. Comparison of the effect between the two groups showed significant d ifference ( P <0.05 ) , with that in the treated group better than that in t he control group.Conclusion: CCD decoction could reduce the production and releasi ng of ET and TNF-α in severe hepatopathy patients, which might be one of its therapeutic mechanisms.