Dachengqi Decoction Research Articles

Dachengqi Decoction Ameliorated Liver Injury in Liver Fibrosis Mice by Maintaining Gut Vascular Barrier Integrity

Dachengqi Decoction Ameliorated Liver Injury in Liver Fibrosis Mice by Maintaining Gut Vascular Barrier Integrity

Dachengqi decoction dispensing granule ameliorates LPS-induced acute lung injury by inhibiting PANoptosis in vivo and in vitro

Ethnopharmacological relevanceAcute lung injury (ALI) is a serious health-threatening syndrome of intense inflammatory response in the lungs, with progression leading to acute respiratory distress syndrome (ARDS). Dachengqi decoction dispensing granule (DDG) has a pulmonary protective role, but its potential modulatory mechanism to alleviate ALI needs further excavation. Aim of the studyThis study aims to investigate the effect and potential mechanism of DDG on lipopolysaccharide (LPS)-induced ALI models in vivo and in vitro. Materials and methodsLPS-treated Balb/c mice and BEAS-2B cells were used to construct in vivo and in vitro ALI models, respectively. Hematoxylin-eosin (HE), Wet weight/Dry weight (W/D) calculation of lung tissue, and total protein and Lactic dehydrogenase (LDH) assays in BALF were performed to assess the extent of lung tissue injury and pulmonary edema. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in BALF, serum, and cell supernatant. The qRT-PCR was used to detect inflammatory factors, Z-DNA binding protein 1 (ZBP1), and receptor-interacting protein kinase 1 (RIPK1) expression in lung tissues and BEAS-2B cells. Double immunofluorescence staining and co-immunoprecipitation were used to detect the relative expression and co-localization of ZBP1 and RIPK1. The effects of LPS and DDG on BEAS-2B cell activity were detected by Cell Counting Kit-8 (CCK-8). Western blot (WB) was performed to analyze the expression of PANoptosis-related proteins in lung tissues and BEAS-2B cells. ResultsIn vivo, DDG pretreatment could dose-dependently improve the pathological changes of lung tissue in ALI mice, and reduce the W/D ratio of lung, total protein concentration, and LDH content in BALF. In vitro, DDG reversed the inhibitory effect of LPS on BEAS-2B cell viability. Meanwhile, DDG significantly reduced the levels of inflammatory factors in vitro and in vivo. In addition, DDG could inhibit the expression levels of PANoptosis-related proteins, especially the upstream key regulatory molecules ZBP1 and RIPK1. ConclusionDDG could inhibit excessive inflammation and PANoptosis to alleviate LPS-induced ALI, thus possessing good anti-inflammatory and lung-protective effects. This study establishes a theoretical basis for the further development of DDG and provides a new prospect for ALI treatment by targeting PANoptosis.

Da-Cheng-Qi decoction improves severe acute pancreatitis capillary leakage syndrome by regulating tight junction-associated proteins.

To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome. In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2h pre-modeling and 2 and 4h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD. Serum levels of amylase, TNF-α, IL-1β, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (p < 0.05). DCQD treatment significantly attenuated rat pancreas damage (p < 0.05) and reduced tissue capillary permeability compared to the SAP group (p < 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (p < 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (p < 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression in vitro (p < 0.05). DCQD can improve capillary permeability in both in vivo and in vitro models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.

Analysing pharmacodynamic interactions of traditional Chinese medicine in treating acute pancreatitis based on OPLS method.

Acute pancreatitis (AP) is a surgical abdominal disease for which the Dachengqi Decoction (DCQD) of traditional Chinese medicine (TCM) is widely used in China. This study aims to analyse the pharmacodynamic interactions and quantitative relationship of DCQD in the treatment of AP based on orthogonal partial least squares (OPLS) analysis. The experimental data show organic chemical components as candidate pharmacodynamic substances (PS) in the blood and include pharmacodynamic indicators (PIs). Taking each PI as the target and using OPLS method to construct three types of mathematical equations, including the mathematical relationship between the pharmacodynamic substances and each target pharmacodynamic indicator (PS-TPI); the mathematical relationship between the pharmacodynamic substances, the pharmacodynamics indicators and each target pharmacodynamic indicator (PS, PI-TPI); and the mathematical relationship between the pharmacodynamic indicators and each target pharmacodynamic indicator (PI-TPI). Through analysis, we find that the R2Y(cum) values and VIP values indicate that PS and PI are the follow-up factors of TPI; the coefficient value indicates that there is a quantitative relationship between the PS and the TPI; and there also is a quantitative relationship between PI and TPI. The results demonstrated that PS and other PIs are the important influencing factors of TPI, and that there are interactions and quantitative relationships among the PIs.

Effect of Somatostatin Combined with Modified Dachengqi Decoction on Intestinal Function and Inflammatory Factors (TNF-α, IL-6, and IL-8) in Acute Pancreatitis

Effect of Somatostatin Combined with Modified Dachengqi Decoction on Intestinal Function and Inflammatory Factors (TNF-α, IL-6, and IL-8) in Acute Pancreatitis

Dachengqi decoction alleviates acute lung injury by suppressing HIF-1α-mediated glycolysis

Ethnopharmacological relevanceAcute lung injury (ALI) is an aggressive inflammatory disease of the lungs characterized by a high mortality rate. More and more researchers have found that herbal medicines are highly effective in preventing and treating inflammatory lung diseases. Among them, Dachengqi Decoction (DCQD) is considered to be the representative prescription of “lung-intestine combined treatment” in traditional Chinese medicine, and its potential protective mechanism against ALI is worthy of further study. Aim of the studyBased on the theory of “lung-intestine combined treatment”, the protective effect and molecular mechanism of DCQD in alleviating ALI were verified by network pharmacology and experiments. Materials and methodsThe active ingredients of DCQD were obtained by UPLC-MS. Network pharmacology and molecular docking techniques were used to screen the active ingredient-target pathway of DCQD for ALI treatment. Additionally, the ALI model was constructed and verified in vivo according to the predicted results. Results34 active components and 570 potential targets of DCQD were selected by network pharmacological analysis. In addition, 950 target genes of ALI and 2095 target genes related to sepsis were obtained, and 570 interlinked target genes of the two were identified. We finally screened out 199 common target genes critical to DCQD treatment of ALI and sepsis, and then enriched them with GO and KEGG. In the ALI model, studies have found that DCQD alleviates the inflammatory response of ALI, possibly by inhibiting HIF-1α-mediated glycolysis. ConclusionThis study confirmed the preventive effect of DCQD on ALI, and found that DCQD can improve the protective mechanism of ALI by regulating the expression of HIF-1α, down-regulating glycolysis and reducing inflammation.

Clinical study of evaluating the clinical effect of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area measured by bedside ultrasound

To evaluate the clinical value of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area (CSA) measured by bedside ultrasound. A parallel group randomized controlled trial was conducted. A total of 80 patients with sepsis with gastrointestinal dysfunction admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2021 to October 2022 were enrolled. According to whether patients agree to use Dachengqi decoction after admission, all patients were divided into Dachengqi decoction group (observation group) and conventional treatment group (control group) by 1 : 1 randomization, each group has 40 patients. Both groups were treated with fluid resuscitation, anti-infection, maintaining stable respiratory circulation, early nourishing feeding, promoting gastrointestinal motility, and regulating intestinal flora. The observation group was treated with Dachengqi decoction on the basis of western medicine, 30 mL decoction was taken in the morning and evening. Both groups were treated for 7 days. The CSA of the two groups was measured by bedside ultrasound before and after treatment. The gastric residual volume (GRV1 and GRV2) were calculated by formula and traditional gastric tube withdrawal method. The gastrointestinal dysfunction score, acute physiology and chronic health evaluation II (APACHE II), intraperitoneal pressure (IAP), serum preprotein (PA), albumin (Alb), white blood cell count (WBC), procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP), length of intensive care unit (ICU) stay and incidence of aspiration were detected to evaluate the clinical efficacy of Dachengqi decoction, the correlation and advantages and disadvantages between CSA measured by bedside ultrasound and other evaluation indicators of gastrointestinal dysfunction in sepsis were also analyzed. There were no significant differences in the indicators before treatment between the two groups, which were comparable. In comparison with the pre-treatment period, CSA, GRV, gastrointestinal dysfunction score, APACHE II score, IAP, WBC, PCT, and hs-CRP of the two groups after treatment were significantly decreased, PA and Alb were significantly increased, and the observation group decreased or increased more significantly than the control group [CSA (cm2): 4.53±1.56 vs. 6.04±2.52, GRV1 (mL): 39.85±8.21 vs. 53.05±11.73, GRV2 (mL): 29.22±5.20 vs. 40.91±8.97, gastrointestinal dysfunction score: 0.87±0.19 vs. 1.35±0.26, APACHE II score: 11.54±3.43 vs. 14.28±3.07, IAP (cmH2O, 1 cmH2O ≈ 0.098 kPa): 9.79±2.01 vs. 13.30±2.73, WBC (×109/L): 9.35±1.24 vs. 12.35±1.36, PCT (μg/L): 3.68±1.12 vs. 6.43±1.45, hs-CRP (mg/L): 24.76±5.41 vs. 46.76±6.38, PA (mg/L): 370.29±45.89 vs. 258.33±34.58, Alb (g/L): 38.83±5.64 vs. 33.20±4.98, all P < 0.05]. The length of ICU stay (days: 10.56±3.19 vs. 14.24±3.45) and incidence of aspiration (12.5% vs. 25.0%) were lower than those in the control group (both P < 0.05). Correlation analysis showed that CSA measured by bedside ultrasound was positively correlated with GRV2, gastrointestinal dysfunction score, APACHE II score, and IAP (r values were 0.84, 0.78, 0.75, 0.72, all P < 0.01) and negatively correlated with PA and Alb (r values were -0.64 and -0.62, both P < 0.01). The Dachengqi decoction can significantly improve the clinical symptoms of septic patients with gastrointestinal dysfunction, reduce systemic inflammatory response, improve nutritional status, and shorten ICU hospital stay. Bedside ultrasound monitoring of CSA is a simple, accurate and effective means to evaluate gastrointestinal dysfunction, which is worthy of further clinical promotion.

Dachengqi decoction ameliorates sepsis-induced liver injury by inhibiting the TGF-β1/Smad3 pathways

BackgroundSepsis-induced acute liver injury (ALI) is a major contributor to mortality in septic patients. Exploring the pathogenesis and developing effective treatment strategies for sepsis-induced ALI is critical for improving patient outcomes. Dachengqi decoction (DCQD), which is a classic Chinese herbal medicine, has been shown to possess potent anti-inflammatory properties. However, the protective effects and underlying mechanisms of DCQD against sepsis-induced ALI remain unclear. This study aimed to investigate the protective effect of DCQD on sepsis-induced ALI and elucidate the involvement of the TGF-1β/Smad3 pathways. MethodsA septic mouse model was established using caecal ligation and puncture (CLP) to evaluate the protective effect of DCQD on sepsis-induced ALI in vivo. An in vitro cellular inflammation model was established using LPS-stimulated LO2 cells to further investigate the underlying mechanism. ResultsDCQD (2.5, 5.0, and 10.0 g/kg body weight) was administered twice daily for 2 days and exerted a dose-dependent protective effect against sepsis-induced ALI. DCQD treatment significantly inhibited inappropriate inflammatory responses and oxidative stress in liver tissue. Moreover, DCQD maintained liver homeostasis by inhibiting hepatocyte apoptosis and improving sepsis-induced liver damage. In vivo and in vitro studies indicated that the TGF-β1/Smad3 signalling pathway played an important role in sepsis-induced ALI, and DCQD treatment significantly inhibited the activation of this pathway. ConclusionsDCQD can effectively suppress excessive inflammatory responses and oxidative stress, leading to a substantial reduction in hepatocyte apoptosis in sepsis-induced ALI.

Dachengqi Decoction alleviates intestinal inflammation in ovalbumin-induced asthma by reducing group 2 innate lymphoid cells in a microbiota-dependent manner.

Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study aimed to reveal the mechanisms of DCQD on the intestinal complications of asthma mediated by group 2 innate lymphoid cells (ILC2) and intestinal microbiota. Ovalbumin (OVA) was used to construct asthmatic murine models. IgE, cytokines (e.g., IL-4, IL-5), fecal water content, colonic length, histopathologic appearance, and gut microbiota were evaluated in asthmatic mice treated with DCQD. Finally, we administered DCQD to antibiotic-treated asthmatic mice to measure the ILC2 in the small intestine and colon. DCQD decreased pulmonary IgE, IL-4, and IL-5 levels in asthmatic mice. The fecal water content, the colonic length weight loss, and the epithelial damage of jejunum, ileum, and colon of asthmatic mice were ameliorated by DCQD. Meanwhile, DCQD greatly improved intestinal dysbiosis by enriching Allobaculum, Romboutsia and Turicibacter in the whole intestine, and Lactobacillus gasseri only in the colon. However, DCQD caused less abundant Faecalibaculum and Lactobacillus vaginalis in the small intestine of asthmatic mice. A higher ILC2 proportion in different gut segments of asthmatic mice was reversed by DCQD. Finally, significant correlations appeared between DCQD-mediated specific bacteria and cytokines (e.g., IL-4, IL-5) or ILC2. These findings indicate that DCQD alleviated the concurrent intestinal inflammation in OVA-induced asthma by decreasing the excessive accumulation of intestinal ILC2 in a microbiota-dependent manner across different gut locations.

Da-Cheng-Qi decoction improves severe acute pancreatitis-associated acute lung injury by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response in rats

Context Da-Cheng-Qi Decoction (DCQD) has a significant effect on Severe Acute Pancreatitis-Associated Acute Lung Injury (SAP-ALI). Objective To explore the mechanism of DCQD in the treatment of SAP-ALI based on intestinal barrier function and intestinal lymphatic pathway. Materials and methods Forty-five Sprague-Dawley rats were divided into three groups: sham operation, model, and DCQD. The SAP model was induced by a retrograde infusion of 5.0% sodium taurocholate solution (1 mg/kg) at a constant rate of 12 mL/h using an infusion pump into the bile-pancreatic duct. Sham operation and model group were given 0.9% normal saline, while DCQD group was given DCQD (5.99 g/kg/d) by gavage 1 h before operation and 1, 11 and 23 h after operation. The levels of HMGB1, RAGE, TNF-α, IL-6, ICAM-1, d-LA, DAO in blood and MPO in lung were detected using ELISA. The expression of HMGB1, RAGE, NF-κB p65 in mesenteric lymph nodes and lung were determined. Results Compared with SAP group, DCQD significantly reduced the histopathological scoring of pancreatic tissue (SAP, 2.80 ± 0.42; DCQD, 2.58 ± 0.52), intestine (SAP, 3.30 ± 0.68; DCQD, 2.50 ± 0.80) and lung (SAP, 3.30 ± 0.68; DCQD, 2.42 ± 0.52). DCQD reduced serum HMGB1 level (SAP, 134.09 ± 19.79; DCQD, 88.05 ± 9.19), RAGE level (SAP, 5.05 ± 1.44; DCQD, 2.13 ± 0.54). WB and RT-PCR showed HMGB1-RAGE pathway was inhibited by DCQD (p < 0.01). Discussion and conclusions DCQD improves SAP-ALI in rats by interfering with intestinal lymphatic pathway and reducing HMGB1-induced inflammatory response.

Analysis of the Characteristics of Zheng's Laryngology in Treating Constipation

Constipation is a common clinical disease and often occurs as a concomitant symptom of other diseases. It often happens to children, the elderly and the frail. Doctors have always used Dachengqi Decoction and its addition or subtraction to treat hot constipation; The method of warming yang is used to treat cold constipation. At the same time, rhubarb and other laxative drugs are needed to assist. The medicinal properties of rhubarb are bitter cold, severe, and easy to damage yin and consume qi. It is not suitable for children and the elderly and infirm. Zheng's laryngology advocates the treatment of hot constipation with cool and moist, and the treatment of cold constipation with warm and moist, which reflects the academic thought of Zheng's laryngology to protect vitality and yin. The warm and moist method for treating constipation has distinctive characteristics and definite curative effect, which is worthy of clinical promotion and application. What’s more, it is especially suitable for children and the elderly and infirm.

Prediction of the mechanism of Dachengqi Decoction treating colorectal cancer based on the analysis method of " into serum components -action target-key pathway"

Ethnopharmacological relevanceColorectal cancer (CRC) is a common digestive tract malignant tumor that its morbidity and mortality seriously affect human health. At present, Dachengqi Decoction (DCQ), a traditional Chinese medicine formula, has been clinically used as an adjuvant therapy for CRC. However, pharmacodynamic substance basis and therapeutic mechanism are still unclear. Aim of the studyThe main constituents absorbed in the blood and possible active targets after DCQ administration were explored based on the analysis method of “into serum components, action target and key pathway”, which may provide reference for the study of the pharmacodynamic material basis and action mechanism of Dachengqi Decoction in the treatment of CRC. Material and methodsBased on the serum pharmacochemistry of traditional Chinese medicine (TCM), the prescription prototype ingredients of DCQ in mice serum samples were identified by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry technology (UPLC-Q-TOF-MSE). Taking the prototype ingredients absorbed into serum as the research object, the possible targets and key pathways of DCQ in vivo were demonstrated by network pharmacology. Finally, using molecular docking verified the binding activity of prototype components and potential action targets. ResultsA total of 46 prototype components of DCQ were identified in mice serum, most of which were derived from flavonoids and anthraquinones in Citrus aurantium L. and Rheum palmatum L. Network pharmacology prediction results indicated that the drug prototype components entering the serum may mainly regulate targets including mitogen-activated protein kinase (MAPK), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), etc. and main pathways such as (phosphatidylinositol 3-kinase/protein kinase B) PI3K-AKT signaling pathway, advanced glycation end products-receptor for AGE (AGE-RAGE) signaling pathway and IL-17 signaling pathway, etc. Molecular docking showed that the prototype active components had strong binding activity to VEGF, Harvey rat sarcoma viral oncogene homolog (HRAS) and MAPK1. ConclusionsThis study elucidated that most of the direct acting substances of DCQ in vivo were flavonoids and anthraquinones, which may play a role in regulating cell reproduction and apoptosis and inhibiting inflammation, providing a reference for the research of pharmacodynamic material basis and mechanism of DCQ in the treatment of CRC.

Observation and analysis on clinical efficacy of Dachengqi decoction for acute pancreatitis

To observe the clinical efficacy of Dachengqi decoction combined with octreotide in the treatment of patients with acute pancreatitis (AP). From March 2018 to February 2021, a total of 68 patients with mild acute pancreatitis (MAP) and moderately severe acute pancreatitis (MSAP) admitted to Shanghai Traditional Chinese Medicine-Integrated Hospital were included, and they were randomly divided into western medicine treatment group and Dachengqi decoction group. The patients in the western medicine treatment group received conventional western medicine (octreotide+symptomatic treatment); in the Dachengqi decoction group, 100 mL of Dachengqi decoction was taken orally on the basis of conventional western medicine, twice a day; the observation time for both groups was 7 days. The levels of inflammation parameters [white blood cell count (WBC), interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP)] and serum amylase (Amy) before and after treatment of patients between the two groups, as well as the occurrence of clinical efficacy indicators and adverse reactions were compared. Among the 68 included patients, 4 were excluded because the specimen was not obtained or the patient gave up the treatment. A total of 64 patients were finally enrolled in the analysis, including 32 cases in the Dachengqi decoction group and 32 cases in the western medicine treatment group respectively. There was no statistically significant difference in inflammation parameters or serum Amy levels before treatment between the two groups. At 7 days of treatment, the inflammatory parameters and serum Amy levels of the two groups were significantly lower than those before treatment [western medicine treatment group: WBC (×109/L) was 5.94±2.08 vs. 11.81±3.66, IL-6 (ng/L) was 7.22 (5.72, 14.23) vs. 30.13 (15.77, 85.37), PCT (μg/L) was 0.068 (0.052, 0.128) vs. 0.290 (0.231, 0.428), CRP (mg/L) was 26.0 (18.3, 35.8) vs. 112.0 (62.0, 126.0), Amy (U/L) was 77 (57, 116) vs. 352 (162, 1 576); Dachengqi decoction group: WBC (×109/L) was 5.56±2.04 vs. 12.22±2.85, IL-6 (ng/L) was 5.70 (3.26, 11.06) was 50.30 (23.99, 88.32), PCT (μg/L) was 0.038 (0.028, 0.808) vs. 0.308 (0.129, 0.462), CRP (mg/L) was 11.0 (3.5, 24.0) vs. 150.0 (75.0. 193.0), Amy (U/L) was 78 (57, 104) vs. 447 (336, 718); all P < 0.05], and the levels of IL-6, PCT, and CRP decreased more significantly after treatment in the Dachengqi decoction group (all P < 0.05). The total clinical effective rate of patients in the Dachengqi decoction group was significantly higher than that of the western medicine treatment group [93.75% (30/32) vs. 71.88% (23/32), P < 0.05]. There was no obvious adverse event during the treatment and observation period in the two groups. Dachengqi decoction combined with octreotide therapy could improve the clinical efficacy of AP patients, and its mechanism might be related to reducing the level of inflammatory factors, thereby inhibiting the inflammatory response, and regulating the level of serum Amy.

Mechanism of lung and intestine combination therapy in treatment of acute lung injury by inhibiting inflammatory response based on NF-κB/NLRP3 signaling pathway and alveolar macrophage activation

Lung and intestine combination therapy(LICT) is effective in the treatment of acute lung injury(ALI). In this study, the combination of Mahuang Decoction and Dachengqi Decoction(hereinafter referred to as the combination), a manifestation of LICT, was employed to explore the effect of nuclear factor kappaB(NF-κB)/nucleotide binding oligomerization domain-like receptors-3(NLRP3) pathway and alveolar macrophage activation on the lung inflammation in rats with ALI, for the purpose of elucidating the mechanism of LICT in treating ALI. After the modeling of ALI with limpolysaccharide(LPS, ip), rats were respectively given(ig) the combination at 10, 7.5, and 5 g·kg~(-1)(high-dose, medium-dose, and low-dose LICT groups, separately), once every 8 h for 3 times. Haematoxylin-eosin(HE) staining was used to observe the histopathological changes of lung tissue, followed by the scoring of inflammation. Immunohistochemistry was applied to detect alveolar macrophage activation, enzyme-linked immunosorbent assay(ELISA) was applied to detect the serum content of tumor necrosis factor-α(TNF-α) and interleukin-18(IL-18), Western blot was applied to detect the protein expression of phosphorylated-nuclear factor kappaB p65(p-NF-κB p65), nuclear factor kappaB p65(NF-κB p65), phosphorylated-inhibitor kappaB alpha(p-IκBα), inhibitor kappaB alpha(IκBα), and NLRP3 in lung tissue, and quantitative reverse transcription-PCR(qRT-PCR) was applied to detect the mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. The results showed that LICT groups demonstrated lung injury relief, decrease in inflammation score, alleviation of alveolar macrophage activation, significant decline in serum content of inflammatory factors TNF-α and IL-18, and decrease of the protein expression of p-NF-κB p65/NF-κB p65, p-IκBα/IκBα, and NLRP3, and mRNA expression of TNF-α, IL-18, NLRP3, and NF-κB p65 in lung tissue. In summary, LICT has definite therapeutic effect on ALI. The mechanism is that it inhibits alveolar macrophage activation by suppressing NF-κB/NLRP3 signaling pathway, thereby reducing the activation and release of inflammatory factors and finally inhibiting inflammation.

Dachengqi Decoction Ameliorated the Sepsis-Induced Liver Injury by Inhibiting the TGF-β1/Smad3 Pathways

Dachengqi Decoction Ameliorated the Sepsis-Induced Liver Injury by Inhibiting the TGF-β1/Smad3 Pathways

Protective effect of Dachengqi decoction on the pancreatic microcirculatory system in severe acute pancreatitis by down-regulating HMGB-TLR-4-IL-23-IL-17A mediated neutrophil activation by targeting SIRT1.

Dachengqi decoction (DCQD), one of classic prescription of Chinese herbal medicine has been widely used in clinic to treat severe acute pancreatitis (SAP). The damage of pancreatic microcirculation plays key pathogenesis of SAP. However, little is known about the molecular pharmacological activity of DCQD on pancreatic microcirculation in SAP. Sodium taurodeoxycholate and cerulein were used to establish model of SAP in vitro and in vivo, respectively. The pancreatic pathological morphology, wet weight ratio, myeloperoxidase (MPO) activity, cell viability and microcirculatory function of the pancreas, as well as serum lipase and amylase expressions were evaluated. The expression levels of SIRT1, acety-HMGB1, TLR-4, HMGB1, IL-23, IL-17A, neutrophil chemokines (KC, LIX, and MIP-2), and inflammation-related factors (IL-6, IL-1β, and TNF-α), the translocation of HMGB1 and the interaction of SIRT-HMGB1 in the pancreas and serum were determined by ELISA real-time PCR, western blotting and immunoprecipitation. In vivo studies showed that DCQD or neutralizing antibody (anti-23p19 or anti-IL-17A) could all significantly decrease lipase, amylase activity, down-regulate the expression of CD68, Myeloperoxidase (MPO), wet/weight, IL-1β, IL-6, TNF-α, and neutrophil chemokines (KC, LIX, MIP-2), alleviate pathological injury and improve pancreatic microcirculatory function in rats with SAP. Furthermore, DCQD remarkably increased SIRT1 expression, promoted SIRT1 and HMGB1 combination, reduced HMGB1 translocation from nuclear to cytoplasm, and alleviated the expression of acetyl-HMGB1, HMGB1, IL-17A, TLR-4, and IL-23 in vitro and in vivo with SAP. However, the intervention with EX527 (SIRT1 inhibitor) or r-HMGB1 (recombinant HMGB1) obliviously reverses the above mentioned influence mentioned above of DCQD in SAP. In vitro, we confirmed that DCQD could decrease HMGB1 acetylation, migration, and release, and improve the decline of cell viability, SIRT1 expression and SIRI-HMGB1 combination induced by cerulean with promoting macrophage to release IL-23 by relying on the HMGB1/TLR-4 way. DCQD treatment improves SAP-induced pancreatic microcirculatory dysfunction by inhibiting neutrophil-mediated inflammation via inactivating HMGB1-TLR-4-IL-23-IL-17A signaling by targeting SIRT1.

Mechanism and experimental verification of Dachengqi Decoction in treatment of sepsis based on network pharmacology

This study aims to predict the material basis and mechanism of Dachengqi Decoction in the treatment of sepsis based on network pharmacology. The chemical constituents and targets of Dachengqi Decoction were retrieved from TCMSP, UniPot and DrugBank and the targets for the treatment of sepsis from OMIM and GeneCards. The potential targets of Dachengqi Decoction for the treatment of sepsis were screened by OmicShare. STRING database and Cytoscape 3.7.2 were used to construct the Chinese medicinal-active component-target-disease, active component-key target-key pathway, and protein-protein interaction(PPT) networks. The gene ontology(GO) term enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were performed by DAVID(P&lt;0.05). Finally, the animal experiment was conducted to verify some targets and pathways. A total of 40 active components and 157 targets of the Dachengqi Decoction, 2 407 targets for the treatment of sepsis, and 91 common targets of the prescription and the disease were also obtained. The key targets were prostaglandin G/H synthase 2(PTGS2), prostaglandin G/H synthase 1(PTGS1), protein kinase cAMP-dependent catalytic-α(PRKACA), coagulation factor 2 receptor(F2 R), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic gamma subunit(PIK3 CG), dipeptidyl peptidase 4(DPP4), etc. A total of 533 terms and 125 pathways were obtained for the 91 targets. The main terms were the response to drug, negative regulation of apoptotic process, positive regulation of nitric oxide biosynthetic process and lipopolysaccharide-mediated signaling pathway, and the pathways included pathways in cancer, hepatitis B, and phosphatidylinositol 3-kinase and protein kinase B(PI3 K/Akt) signaling pathway. The animal experiment confirmed that Dachengqi Decoction can down-regulate inflammatory cytokines interleukin-1β(IL-1β), IL-6 and tumor necrosis factor α(TNF-α)(P&lt;0.01). It could also reduce the wet/dry weight ratio of lung tissue, the level of myeloperoxidase(MPO) and the phosphorylation of PI3 K and Akt(P&lt;0.01). These results indicated that Dchengqi Decoction could act on inflammation-related targets and improve sepsis by inhibiting PI3 K/Akt signaling pathway. The animal experiment supported the predictions of network pharmacology. Dachengqi Decoction intervenes sepsis via multiple components, multiple targets, and multiple pathways. The result lays a foundation for further research on the mechanism of Dachengqi Decoction in the treatment of sepsis.

Da Cheng Qi Decoction Alleviates Cerulein-Stimulated AR42J Pancreatic Acinar Cell Injury via the JAK2/STAT3 Signaling Pathway.

Background Acute pancreatitis (AP) is a common acute abdomen inflammation, characterized by the dysregulation of digestive enzyme production and secretion. Many studies have shown that Da Cheng Qi Decoction (DCQD) is a secure, effective prescription on AP. In this study, cerulein-stimulated AR42J cells damage model was established to further explore the feasibility and underlying mechanism of DCQD as a potential inhibitor of JAK2/STAT3 pathway for the treatment of AP. Methods Cell viability of DCQD was measured using a cell counting Kit-8 assay. Pancreatic biochemical markers such as amylase, lipase, and C-reactive protein production were measured by assay kits, respectively. Cytokines (TNF-α, IL-6, IL-10, and IL-1β) were assayed by ELISA. Protein location and protein expression were detected by immunofluorescence staining and Western blotting, respectively. Gene expression was assessed by real-time PCR. For mechanistic analysis of the effect of DCQD on JAK2/STAT3 signaling pathway, selective JAK2 inhibitor (Fedratinib) and STAT3 inhibitor (Stattic) as well as STAT3 activator (Garcinone D) were used. Results DCQD protected cells by regulating cerulein-induced inflammation and reducing the secretion of pancreatic biochemical markers. Moreover, DCQD could not only inhibit the nuclear translocation of p-STAT3, but also decrease the mRNA expression of JAK2 and STAT3 as well as the ratio of p-JAK2/JAK2 and p-STAT3/STAT3 in protein level. Additionally, DCQD could regulate the mRNA and protein expression of JAK2/STAT3 downstream effectors, Bax and Bcl-XL. The activated effect of cerulein on JAK2/STAT3 pathway was also reversed by JAK2 inhibitor Fedratinib or STAT3 inhibitor Stattic. And the overexpression of JAK2/STAT3 pathway, via STAT3 activator Garcinone D, did exert damage on cells, which bore a resemblance to cerulein. Conclusion The activation of JAK2/STAT3 pathway may play a key role in the pathogenesis of cerulein-stimulated AR42J pancreatic acinar cell injury. DCQD could improve inflammatory cytokines and cell injury, which might be mediated by suppressing the activation of JAK2/STAT3 signaling pathway.

Virtual Screening of the Multi-pathway and Multi-gene Regulatory Molecular Mechanism of Dachengqi Decoction in the Treatment of Stroke Based on Network Pharmacology.

Stroke is ranked second among diseases that cause mortality worldwide. Owing to its complicated pathogenesis, no satisfactory treatment strategies for stroke are available. Dachengqi decoction (DCQD), a traditional Chinese herbal medicine, has been widely used in China for a long time, as it has a good effect on stroke. However, the molecular mechanism underlying this effect of DCQD is unclear. In the present study, we aimed to reveal and explore the multi-pathway and multi-gene regulatory molecular mechanism of Dachengqi decoction in the treatment of stroke. In this study, a network pharmacology method, in combination with oral bioavailability prediction and drug-likeness evaluation, was employed to predict the active ingredients of DCQD. The target genes of the active components and the traced pathways related to these target genes were predicted. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using clusterProfiler software package on the R platform and ClueGo+CluePedia plug-ins. Finally, the key DCQD targets were verified using the Gene Expression Omnibus (GEO) dataset. According to the ADME model, 52 active components were screened from 296 active components of DCQD. After prediction and screening, 215 stroke-related targets were obtained and analyzed via GO and KEGG analyses. GO analysis showed that DCQD targets were mainly involved in the regulation of oxidative stress, lipid metabolism, inflammation, and other biological processes. KEGG pathway analysis further revealed pathways involved in stroke, such as arachidonic acid metabolic, HIF-1 signaling pathway, estrogen signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, platelet activation pathway, VEGF signaling pathway, and cAMP signaling pathway. Network analysis revealed that DCQD might be involved in the regulation of lipid metabolism, blood pressure, inflammation, angiogenesis, neuroprotection, platelet aggregation, apoptosis, and oxidation in stroke treatment. GEO dataset analysis showed that DCQD's therapeutic effects might be exerted via the bidirectional regulation principle. Based on the methods of network pharmacology and GEO analysis, it was found that, during stroke treatment, DCQD regulates and controls multiple genes and multiple pathways in a synergistic manner, providing a new strategy for stroke treatment.

Chaiqin chengqi decoction alleviates severity of acute pancreatitis via inhibition of TLR4 and NLRP3 inflammasome: Identification of bioactive ingredients via pharmacological sub-network analysis and experimental validation

BackgroundChaiqin chengqi decoction (CQCQD) is a Chinese herbal formula derived from dachengqi decoction. CQCQD has been used for the management of acute pancreatitis (AP) in the West China Hospital for more than 30 years. Although CQCQD has a well-established clinical efficacy, little is known about its bioactive ingredients, how they interact with different therapeutic targets and the pathways to produce anti-inflammatory effects. PurposeToll-like receptor 4 (TLR4) and the nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated pro-inflammatory signaling pathways, play a central role in AP in determining the extent of pancreatic injury and systemic inflammation. In this study, we screened the bioactive ingredients using a pharmacological sub-network analysis based on the TLR4/NLRP3 signaling pathways followed by experimental validation. MethodsThe main CQCQD bioactive compounds were identified by UPLC-QTOF/MS. The TLR4/NLRP3 targets in AP for CQCQD active ingredients were confirmed through a pharmacological sub-network analysis. Mice received 7 intraperitoneal injections of cerulein (50 μg/kg; hourly) to induce AP (CER-AP), while oral gavage of CQCQD (5, 10, 15 and 20 g/kg; 3 doses, 2 hourly) was commenced at the 3rd injection of cerulein. Histopathology and biochemical indices were used for assessing AP severity, while polymerase chain reaction, Western blot and immunohistochemistry analyses were used to study the mechanisms. Identified active CQCQD compounds were further validated in freshly isolated mouse pancreatic acinar cells and cultured RAW264.7 macrophages. ResultsThe main compounds from CQCQD belonged to flavonoids, iridoids, phenols, lignans, anthraquinones and corresponding glycosides. The sub-network analysis revealed that emodin, rhein, baicalin and chrysin were the compounds most relevant for directly regulating the TLR4/NLRP3-related proteins TLR4, RelA, NF-κB and TNF-α. In vivo, CQCQD attenuated the pancreatic injury and systemic inflammation of CER-AP and was associated with reduced expression of TLR4/NLRP3-related mRNAs and proteins. Emodin, rhein, baicalin and chrysin significantly diminished pancreatic acinar cell necrosis with varied effects on suppressing the expression of TLR4/NLRP3-related mRNAs. Emodin, rhein and chrysin also decreased nitric oxide production in macrophages and their combination had synergistic effects on alleviating cell death as well as expression of TLR4/NLRP3-related proteins. ConclusionsCQCQD attenuated the severity of AP at least in part by inhibiting the TLR4/NLRP3 pro-inflammatory pathways. Its active ingredients, emodin, baicalin, rhein and chrysin contributed to these beneficial effects.