[Progress on historical evolution, clinical application, and pharmacological effects of Dachaihu Decoction and predictive analysis of its quality markers].

Dachaihu Decoction is a classic prescription with the function of harmonizing Shaoyang and purging away internal stasis of heat, which was specially developed by Master ZHANG Zhongjing for the concurrent disease of Shaoyang and Yangming. A large number of international studies have shown that Dachaihu Decoction has liver protection, gallbladder benefit, anti-inflammatory, and other pharmacological effects and is mostly used in modern clinical treatment of acute pancreatitis, acute cholecystitis, cholelithiasis, and other digestive diseases. This paper combined bibliography and statistics and selected the ancient book database and CNKI database to search the relevant literature on Dachaihu decoction, verify the composition and dosage, processing method, main diseases, and modern clinical application, and predict its quality markers(Q-markers) based on the "five principles" of Q-markers. The results suggest that saikosaponin a, baicalin, and 6-gingerol can be selected as potential Q-markers for Dachaihu Decoction, so as to provide a basis for the clinical research of traditional Chinese medicine and the development and application of compound preparations.

[Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review].

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

Preliminary exploration of method for screening efficacy markers compatibility in TCM prescriptions based on Q-markers: Anti-inflammatory activity of Dachaihu decoction as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DD), a classic Chinese herbal prescription, is composed of radix of Bupleurum chinense DC. (Chaihu), radix of Scutellaria baicalensis Georgi (Huangqin), radix of Paeonia lactiflora Pall. (Baishao), rhizoma of Pinellia ternata (Thunb.) Breit. (Banxia), fructus of Citrus aurantium L. (Zhishi), rhizoma of Zingiber officinale Rosc. (Shengjiang), fructus of Ziziphus jujuba Mill. (Dazao) and rhizoma of Rheum officinale Baill. (Dahuang). DD has the traditional effects of soothing the liver, relieving depression and clearing heat from the stomach, and is mainly used to treat heat stagnation in the liver and stomach. AIM OF THE STUDY: Dachaihu decoction (DD), a classic prescription commonly used in clinical practice for the treatment of pancreatitis and cholecystitis. Although its pharmacological effects are clear, the efficacy components and mechanism of action remain intricate and difficult to clarify. MATERIALS AND METHODS: The action targets and components of the anti-inflammatory activity of DD were predicted by network pharmacology; the effective components and targets were verified by HPLC and qPCR; the efficacy markers of DD were further screened by in vitro experiments; the pharmacological value of DD and its components compatibility were evaluated by in vitro experiments. RESULTS: The key targets MMP9, JAK2, MAP2K1 and NR3C1 were screened by network pharmacology; HPLC analysis showed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were identified as potential efficacy markers of DD; molecular docking combined with qPCR verification suggested that baicalin, naringin, neohesperidin, hesperidin and baicalein and wogonoside had certain ability to regulate above targets; in vitro studies revealed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 could inhibit the release of NO, pancreatic lipase and α-glucosidase; after comprehensive comparison and analysis, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were selected as the efficacy markers of DD; in vivo studies indicated that DD and its efficacy markers (components compatibility) had definite therapeutic effects on guinea pigs with cholecystitis. CONCLUSIONS: The efficacy markers of DD including naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 can be used as components compatibility to exert anti-inflammatory activity. In addition, a method for obtaining the compatibility of efficacy markers by simplifying the prescription is initially established.

Dachaihu decoction ameliorates septic intestinal injury via modulating the gut microbiota and glutathione metabolism as revealed by multi-omics.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu decoction (DCH), a classic formula for Yangming and Shaoyang Syndrome Complex recorded in "Treatise on Cold Damage", has been widely used in treating intestinal disorders and inflammatory diseases with few side effects in China. However, the mechanism of DCH on septic intestinal injury (SII) remains to be explored. AIM OF THE STUDY: This study aimed to clarify the mechanism of DCH on SII. MATERIALS AND METHODS: SII model of rat, established by cecal ligation and puncture (CLP), was used to study the effect of DCH on SII. 24 h mortality was recorded. Histological changes were observed by H&E staining. The expression of tight junction protein ZO-1 (ZO-1) and mucin2 (MUC2) was determined by immunohistochemical analysis. Secretory IgA (sIgA), diamine oxidase (DAO) and intestinal fatty acid binding protein (iFABP) were determined by enzyme-linked immunosorbent assay (ELISA). IL-1ß, IL-6 and TNF-α were measured by ELISA and quantitative Real-time PCR (RT-qPCR). The gut microbiota was analyzed by 16S rRNA sequencing. The potential targets and pathways of DCH in treating SII were analyzed by integrative analysis of transcriptomic and metabolomic methods. Total glutathione (T-GSH), GSH, GSSG (reduced form of GSH), GSH peroxidase (GPX), superoxide dismutase (SOD), malonaldehyde (MDA) and indicators of hepatic and renal function were measured by biochemical kits. RESULTS: Medium dose of DCH improved 24 h mortality of SII rats, reduced the pathological changes of ileum, and increased the expression levels of ZO-1, MUC2 and sIgA. DCH decreased DAO, iFABP of serum and IL-1ß, IL-6, TNF-α of ileum. DCH improved α- and ß-diversity and modulated the structure of gut microbiota, with Escherichia_Shigella decreased and Bacteroides and Ruminococcus increased. GSH metabolism was identified as the key pathway of DCH on SII by integrative analysis of transcriptome and metabolome. GSH/GSSG and the most common indicators of oxidative stress, were validated. Antioxidative T-GSH, GSH, GPX and SOD were increased, while MDA, the mark of lipid peroxidation was downregulated by DCH. Eventually, DCH was proved to be safe and hepato- and nephro-protective. CONCLUSION: DCH ameliorated septic intestinal injury possibly by modulating the gut microbiota and enhancing glutathione metabolism of SII rats, without hepatotoxicity and nephrotoxicity.

Study on the Mechanism of Dachaihu Decoction in the Treatment of Acute Pancreatitis Based on Artificial Intelligence Combined with in vivo Experiments.

BACKGROUND AND AIM: To explore the possible mechanism of Dachaihu Decoction (DCHD) in the treatment of AP, and use in vivo experiments to verify. METHODS: The targets and active ingredients of DCHD in the treatment of AP were obtained through network pharmacology, and the preliminary verification was carried out by molecular docking. Caerulein was used to develop the AP rat model. H&E staining was performed to observe variations in pancreatic tissue. Western blot and RT-qPCR were conducted to evaluate the associated proteins and mRNA. RESULTS: The network pharmacology and molecular docking results showed that the key targets (EGFR, TNF, SRC, VEGFA and CTNNB1) and key active components (beta-sitosterol, stigmasterol, baicalein, quercetin, and kaempferol) of DCHD in the treatment of AP had good binding. H&E staining revealed that rat pancreatic tissues considerably damaged post caerulein intervention, and it has also been suggested that DCHD ameliorates damage to pancreatic tissue. Simultaneously, EGFR, TNF, SRC, VEGFA protein, and mRNA expression levels were increased in the model group compared to the blank group (P < 0.01), whereas CTNNB1 expression was found to be decreased in the model group (P < 0.01). Compared with the model group, the protein expression levels of EGFR, TNF, SRC, and VEGFA in the treatment group were down-regulated (P < 0.01), and CTNNB1 was up-regulated (P < 0.05). CONCLUSION: DCHD protects pancreatic tissues and improves symptoms in AP rats by upregulating CTNNB1 protein and mRNA while inhibiting EGFR, TNF, SRC, and VEGFA protein and mRNA expression.

Dachaihu decoction inhibits hypernutrition-induced liver metastasis from colorectal cancer by maintaining the gut vascular barrier.

Background: Colorectal cancer (CRC) is the third most common malignancy and the second deadliest cancer worldwide. Metastasis to the liver, the most common metastatic site in CRC, is the leading cause of death in patients with CRC. Hyperlipidemia, which is common in patients with CRC, promotes CRC progression and metastasis. Hyperlipidemia is commonly observed in obese patients and is often induced by hypernutrition. The underlying mechanism of hypernutrition-induced hyperlipidemia in promoting CRC liver metastasis remains unclear, and there is an unmet need for effective and low-cost treatments for patients with CRC. Methods: A mouse cecum orthotopic CRC model combined with high-fat diet (HFD) feeding, was established to mimic liver metastasis in CRC in obese patients. The effects of Dachaihu decoction (DCHD), a traditional herbal medicine used to treat inflammation and nonalcoholic fatty liver disease, and of the conventional prescription medicine obeticholic acid (OCA) were evaluated. HFD-induced obesity, hyperlipidemia, and CRC liver metastasis were assessed, along with the histology and pathology of the liver and intestine and the expression of metabolic genes in these tissues. The effects of DCHD and OCA on HFD-induced outcomes were evaluated, and human umbilical vein endothelial cells (HUVECs) treated with bile acids (BAs) and DCHD were used to study the underlying mechanisms in vitro. Results: HFD-mediated obesity and hyperlipidemia promoted CRC metastasis, accompanied by disruption of the gut vascular barrier (GVB) and altered bile acid (BA) metabolism. DCHD decreased HFD-induced hyperlipidemia and liver metastasis in CRC, improving overall survival. Those effects of DCHD were equivalent to or better than those of OCA. DCHD regulated the expression of genes of BA metabolism and tight junctions (TJ) to prevent HFD-induced disruption of the GVB. In HUVECs, DCHD prevented the increases in intracellular Ca2+ and accumulation of reactive oxygen species induced by primary conjugated BAs, assisting in the maintenance of redox homeostasis and preventing the downregulation of TJ proteins, thereby maintaining the integrity of the endothelial barrier. Conclusions: The data provide a link between hypernutrition and GVB disruption, which contributes to high liver metastasis in patients with CRC. DCHD may represent a novel therapy in CRC, and targeting abnormal lipid metabolism could be a promising therapeutic strategy for avoiding hypernutrition-associated CRC metastasis.

Mechanism of heat-clearing prescriptions in alleviating type 2 diabetes mellitus:a review / 中国中药杂志

Type 2 diabetes mellitus(T2DM), a common chronic metabolic disease, is often accompanied by internal heat syndrome. Heat-clearing prescriptions are widely used to treat different heat syndromes of T2DM from the aspects of clearing stagnant heat, excess heat, damp heat, phlegm heat, and heat toxin, demonstrating remarkable effects. The mechanism of blood sugar-lowering agents has always been a hotspot of research. Recently, the basic studies of heat-clearing prescriptions from different perspectives have been increasing year by year. To clarify the mechanisms of heat-clearing prescriptions and find specific mechanisms, we systematically reviewed the basic studies of heat-clearing prescriptions commonly used for the treatment of T2DM in the past decade, intending to provide a reference for related research.

The efficacy and safety of dachaihu decoction in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

Background: Type 2 diabetes mellitus (T2DM) is a clinical metabolic syndrome characterized by persistent hyperglycemia, which is caused by defective insulin secretion and decreased function in regulating glucose metabolism. Dachaihu Decoction (DCHD) is a traditional Chinese medicine formula that has been gradually used in T2DM treatment. A comprehensive analysis on the efficacy and safety of DCHD in T2DM treatment is necessary. Objective: This meta-analysis aimed to systematically assess the clinical efficacy and safety of DCHD in the T2DM treatment and provide a reference for subsequent research and clinical practice. Methods: Both Chinese and English databases were searched from their inceptions to November 2021. All retrieved studies were screened according to inclusion and exclusion criteria and randomized controlled trials about DCHD on T2DM were enrolled. The quality of the literature was assessed using the bias risk assessment tool in the Cochrane Handbook. Data extraction was performed on the selected studies. Review Manager 5.4 and Stata 16.0 were used for meta-analysis. Sources of heterogeneity were also explored by using meta-regression and subgroup analysis. Funnel plot and Egger's test were used to assess publication bias and the evidence quality was assessed by GRADE. Results: 17 eligible studies, involving 1,525 patients, were included in this study. Compared with conventional treatment, combined treatment with DCHD was significantly better in improving HbA1c (MD = -0.90%, 95%CI: -1.20 to -0.60, p < 0.01), FBG (MD = -1.08 mmol/L, 95%CI: -1.28 to -0.87, p < 0.01), 2hPG (MD = -1.25 mmol/L, 95%CI: -1.42 to -1.09, p < 0.01), TC (MD = -0.50 mmol/L, 95%CI: -0.70 to -0.30, p < 0.01), TG (MD = -0.44 mmol/L, 95%CI: -0.61 to -0.26, p < 0.01), LDL-C (MD = -0.58 mmol/L, 95%CI: -0.85 to -0.31, p < 0.01), HOMA-IR (SMD = -2.04, 95%CI: -3.09 to -0.99, p < 0.01), HOMA-ß (SMD = 2.48, 95%CI: 2.20 to 2.76, p < 0.01) and BMI (MD = -1.52 kg/m2, 95%CI: -2.55 to -0.49, p < 0.01). When DCHD used alone, it had a similar efficacy to conventional treatment in HbA1c (MD = -0.04%, 95%CI: -0.17 to 0.09, p = 0.57) and FBG (MD = 0.13 mmol/L, 95%CI: -0.09 to 0.36, p = 0.24). It can also reduce 2hPG, even if not as effective as conventional treatment (MD = 0.54 mmol/L, 95%CI: 0.19 to 0.89, p < 0.01). Due to the small number of included studies, it is unclear whether DCHD used alone has an improving effect on lipid metabolism, BMI, HOMA-IR and HOMA-ß. Analysis of adverse events showed DCHD was relatively safe. No obvious publication bias was detected by Funnel plot and Egger's test. Conclusion: Based on this meta-analysis, we found that the combination with DCHD in the T2DM treatment has more advantages than conventional treatment alone, which can further regulate the glucose and lipid metabolism, reduce insulin resistance, improve islet function and lower BMI. DCHD alone also plays a certain role in regulating glucose. Meanwhile, DCHD is relatively safe. However, limited by the quality and quantity of included studies, the efficacy and safety of DCHD remain uncertain. More high-quality studies are still needed to provide more reliable evidence for the clinical application of DCHD. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021296718, identifier CRD42021296718.

[Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism].

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

Study on discovery of efficacy markers for Dachaihu Decoction and its action mechanism / 中国中药杂志

Dachaihu Decoction is a classical Chinese herbal prescription that is effective in harmonizing lesser yang and purging internal accumulated heat. At present, it has been widely used in clinical practice, and the resulting outcomes are satisfactory. However, its quality indicators and action mechanism are still not clear. Therefore, this paper explored the efficacy markers of Dachaihu Decoction and its action mechanism based on literature mining, molecular biology, and network pharmacology, so as to better control its quality and ensure its clinical efficacy. The efficacy markers of Dachaihu Decoction were predicted and analyzed according to the "five principles" for Q-markers of Chinese herbs. Then the anti-inflammatory activity of the efficacy markers of Dachaihu Decoction was evaluated with Griess reagent after the establishment of RAW264.7 cell inflammation model in vitro with lipopolysaccharide(LPS). The potential targets of efficacy markers were predicted by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), ChEMBL, and SwissTargetPrediction, followed by the construction of the protein-protein interaction(PPI) network of the efficacy markers of Dachaihu Decoction. Topological, GO, and KEGG enrichment analysis was carried out to construct the "key target-signaling pathway-biological process" network, thus elucidating the action mechanism of the efficacy markers of Dachaihu Decoction. Saikosaponin B_2, baicalin, baicalein, wogonoside, neohesperidin, naringin, hesperidin, and paeoniflorin were considered as the potential efficacy markers of Dachaihu Decoction. The anti-inflammatory activity evaluation showed that the potential efficacy markers effectively inhibited the release of NO, exhibiting good anti-inflammatory activities. As demonstrated by network pharmacology, the efficacy markers of Dachaihu Decoction regulated the inflammatory response by acting on MAPK and NF-κB signaling pathways, the carbohydrate metabolism by HIF-1 and PI3 K-AKT signaling pathways, and the lipid metabolism by AMPK and PI3 K-AKT signaling pathways. This study discovered the efficacy markers of Dachaihu Decoction based on literature mining combined with molecular biological experiments and explored its action mechanism at the molecular level based on network pharmacology, which would provide reference for the quality control of Dachaihu Decoction and scientific basis for its clinical application.

Study on effective components and mechanism of Dachaihu Decoction in treatment of pancreatitis (syndrome of liver depression and qi stagnation) / 中草药

Objective: To study the effective components and mechanism of action of Dachaihu Decoction (DCHD) in the treatment of pancreatitis (syndrome of liver depression and qi stagnation). Methods: The PPI network and the multi-dimensional relationship network of “Chinese material medica prescription active ingredient key target” of DCHD in the treatment of pancreatitis with stagnation of liver qi. Based on network pharmacology, the software such as Cytoscape 3.6.0 was firstly used to construct the PPI interaction network of key targets in the Chinese material medica with the effect of soothing liver and regulating qi (“Shugan Liqi” in Chinese) and DCHD “Chinese material medica prescription-effective components-key target” multi-dimensional network for the treatment of pancreatitis, and then treat the two networks as an intersection to obtain the network of DCHD for the treatment of pancreatitis (syndrome of liver depression and qi stagnation) “Chinese material medica prescription-effective components-key target”, and finally analyzed with relevant software. Results: A total of 59 key targets for Shugan Liqi were obtained such as AKT1, VEGFA, and PRSS1; A total of 83 main active ingredients such as quercetin, kaempferol and baicalein were collected from DCHD. The treatment of pancreatitis (syndrome of liver depression and qi stagnation) involved 18 targets of Ganyu Qizhi such as PTGS2, DPP4, PRSS1, and 30 related biological processes and signaling pathways such as extracellular matrix degeadation, IL-17 signaling pathway, and AGE-RAGE signaling pathway in diabetic complications. Conclusion: The multi-component and multi-target in DCHD are the basis for its efficacy. It is worthwhile to deeply think about the use of network pharmacology in the context of syndrome research.

Clinical Study on Effects of Modified Dachaihu Decoction on Treatment of Constipation in Hemodialysis Patients / 中国中医药信息杂志

Objective To observe the clinical efficacy of modified Dachaihu Decoction on the treatment of constipation in hemodialysis patients. Methods Totally 60 hemodialysis patients were divided into treatment group and control group through random number table method, with 30 cases in each group. Both groups received Western basic treatment. The treatment group was given modified Dachaihu Decoction on the basis of Western medicine treatment,one dosage 100 mL per day,morning and evening after dinner,orally.The control group received Maren Runchang Pills, one pill each time, twice a day, orally. The treatment cycle for both groups was one month. The clinical efficacy, constipation symptoms, incidence of hypotension during dialysis, incidence of muscle spasm and Kt/V were compared between the two groups. Results The total effective rate was 93.33% (28/30) in the treatment group and 66.67% (20/30) in the control group. The treatment group was significantly better than the control group (P<0.05). Compared with before treatment, the number of defecation per week increased after treatment in both groups, and the squatting time decreased; Comparing the two groups after treatment, the number of defecation per week and squatting time in the treatment group were significantly better than those in the control group (P<0.05). Compared with before treatment, the incidence of hypotension rate in the treatment groups of dialysis were significantly reduced (P<0.05); After treatment, the incidence of hypotension in the treatment group was significantly lower than those in the control group (P<0.05). Compared with before treatment, Kt/V in both groups increased significantly (P<0.05); After treatment, the improvement of Kt/V in the treatment group was significantly better than that in the control group(P<0.05).Conclusion Modified Dachaihu Decoction can effectively improve the symptoms of hemodialysis patients with constipation and improve the dialysis adequacy.

Clinical observation on therapeutic effect of Dachaihu decoction for treating stroke-associated pneumonia in senile patients with excess-heat syndrome / 中国中西医结合急救杂志

Objective To observe the clinical efficacy of Dachaihu decoction in treatment of stroke-associated pneumonia (SAP) in the elderly patients with excess-heat syndrome and acute ischemic stroke (AIS). Methods One hundred elderly patients with excess-heat syndrome and SAP admitted to the Department of Neurology of Tianjin Nankai Hospital from August 2015 to September 2016 were enrolled, and they were divided into a control group and an observation group according to the random number table, 50 cases in each group. Both groups were given conventional neurological treatment, while the observation group additionally received Dachaihu decoction (the ingredients of the decoction: bupleurum 15 g, scutellariae 10 g, pinellia 10 g, fructus aurantii immaturus 15 g, radix paeoniae alba 10 g, rhubarb 5 g, ginger 10 g, jujube 2), and according to the individual's symptoms and signs, the above ingredients can be added and/or subtracted, 1 dose per day, divided into two parts, 1 part taken in the morning and 1 part in the evening orally, 14 days as a therapeutic course. The body temperature recovery time, the duration of antibiotic treatment, the changes of Clinical Pulmonary Infection Score (CPIS) and National Institutes of Health Stroke Scale (NIHSS) score before and after treatment of the two groups were observed and the therapeutic effects in the two groups were evaluated. Results The body temperature recovery time (days: 6.56±2.70 vs. 8.08±3.23) and the duration of antibiotic treatment (days: 8.78±2.80 vs. 10.02±2.90) in the observation group were significantly shorter than those in the control group (both P ＜ 0.05); with the prolongation of treatment, after treatment, the CPIS and NIHSS score were decreased significantly in both groups, reaching the lowest levels on the 14th day, and the degrees of score descent in observation group were more significant than those of the control group (CPIS score: 0.68±0.59 vs. 1.12±0.96, NIHSS score: 6.38±2.31 vs. 7.44±2.74, both P ＜ 0.05); the total effective rate in the observation group was significantly higher than that in the control group [92% (46/50) vs. 76% (38/50), P ＜ 0.05]. Conclusion The therapeutic effect of Dachaihu decoction used for treatment of SAP in elderly patients with excess-heat syndrome is favorably effective and safe.

Dachaihu decoction ameliorates pancreatic fibrosis by inhibiting macrophage infiltration in chronic pancreatitis.

AIM: To explore the role of macrophages in chronic pancreatitis (CP) and the effect of Dachaihu decoction (DCHD) on pancreatic fibrosis in mice. METHODS: KunMing mice were randomly divided into a control group, CP group, and DCHD group. In the CP and DCHD groups, mice were intraperitoneally injected with 20% L-arginine (3 g/kg twice 1 d/wk for 6 wk). Mice in the DCHD group were administered DCHD intragastrically at a dose of 14 g/kg/d 1 wk after CP induction. At 2 wk, 4 wk and 6 wk post-modeling, the morphology of the pancreas was observed using hematoxylin and eosin, and Masson staining. Interleukin-6 (IL-6) serum levels were assayed using an enzyme-linked immunosorbent assay. Double immunofluorescence staining was performed to observe the co-expression of F4/80 and IL-6 in the pancreas. Inflammatory factors including monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and IL-6 were determined using real time-polymerase chain reaction. Western blot analysis was used to detect fibronectin levels in the pancreas. RESULTS: Compared with the control group, mice with 20% L-arginine-induced CP had obvious macrophage infiltration and a higher level of fibrosis. IL-6 serum concentrations were significantly increased. Double immunofluorescence staining showed that IL-6 and F4/80 were co-expressed in the pancreas. With the administration of DCHD, the infiltration of macrophages and degree of fibrosis in the pancreas were significantly attenuated; IL-6, MCP-1 and MIP-1α mRNA, and fibronectin levels were reduced. CONCLUSION: The dominant role of macrophages in the development of CP was mainly related to IL-6 production. DCHD was effective in ameliorating pancreatic fibrosis by inhibiting macrophage infiltration and inflammatory factor secretion in the pancreas.

[Effect of DaChaiHu Decoction on pancreatic fibrosis induced by DBTC combined with alcohol and the mechanism of TGF-beta/Smad signaling pathway].

OBJECTIVE: To investigate the effects of transforming growth factor-ß (TGF-ß) and Smad in chronic pancreatitis (CP) induced by dibutyltin dichloride (DBTC) combined with ethanol, and the effect for prevention and treatment of pancreatic fibrosis by DaChaiHu Decoction (tradeiional Chinese medicine). METHODS: Ninety-six healthy male Kunming mice were randomly divided into control group (Con group), chronic pancreatitis (CP group) group, Dachai Hu decoction treatment group (DCHD group) (n=32). Then the mice were treated with DBTC 8 mg/kg by tail vein injection and fed with 10% ethanol replacing the normal drinking water to replicate mouse CP model. After three days of modeling the mice were randomly divided into CP group and DCHD group. The mice in DCHD group were administered intragastrically with DaChaiHu Decoction (1 g/ml, 6 g/kg·d) at the following 8 weeks. After modeling for 1 week, 2 weeks, 4 weeks and 8 weeks, the mice were anesthetized and sacrificed(n=8). The morphology and the degree of fibrosischanges of pancreatic tissue were detected by HE staining. The protein expressions of type I collagen and TGF beta R I, p-Smad 2/3 and Smad 7 in pancreatic tissue were detected by Western blot assay. The expressions of MMP-1/TIMP-1 mRNA inpancreatic tissue were detected by RT-PCR. RESULTS: Compared with control group, DBTC combined with ethanol induced CP with increased activity of serum amylase and hyaluronic acid level. While in DCHD group, the activity of amylase and hyaluronic acid level were decreased significantly. Compared with control group, the protein expressions of COLA1, TGF beta R I, p-Smad 2/3 in CP Group were elevated,but the expression of Smad 7 was significantly reduced; In DCHD treatment group,the expression of TGF beta R I, p-Smad 2/3 and COLA1 were reduced, and the protein expression of Smad 7 was increased. In 2w and 4w, the level of MMP-1mRNA continued to decrease, while TIMP-1mRNA expression was increased significantly (P<0.01). At each time point of DCHD group, the expression of MMP-1 were markedly increased and TIMP-1 were reduced, compared with those of the CP group (P<0.05). CONCLUSIONS: DaChaiHu Decoction play a role in the prevention and treatment of chronic pancreatitis and the development of fibrosis, the mechanism may related to inhibit the activation of TGF beta/Smad signaling pathway, and regulate the balance between synthesis and degradation of extracellular matrix.

Combined effect of octreotide and Dachaihu decoction on treatment of se-vere acute pancreatitis / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the combined effect of octreotide and Dachaihu decoction on the treatment of severe acute pancreatitis (SAP).METHODS:Wistar rats (n=50) were randomly divided into sham group, SAP group, octreotide group, Dachaihu decoction group and combination group.The quantity of ascites was measured.The levels of amylase, alanine aminotransferase and creatinine in the serum were examined.The morphological changes of the pancreatic tissues were observed by HE staining.The activation of NF-κB and IκBαexpression were determined by Western blot.The mRNA expression with ICAM-1 and IL-1 was detected by qPCR.RESULTS: Combined treatment with octreotide and Dachaihu decoction effectively reduced the quantity of ascites and the levels of amylase, alanine aminotransferase and creat-inine in the serum in SAP rats.Moreover, combined treatment significantly inhibited SAP-induced activation of NF-κB and decrease in IκBαprotein expression, accompanied by a decrease in ICAM-1 and IL-1 mRNA expression.CONCLU-SION:Combination of octreotide with Dachaihu decoction effectively attenuates SAP by inhibiting NF-κB signaling pathway and ICAM-1 and IL-1 expression.

Research on the effect of Dachaihu decoction on plasma inflammatory cytokines of acute pancreatitis patient / 国际中医中药杂志

ObjectiveTo observe effect of Dachaihu decoction on plasma inflammatory cytokines of acute pancreatitis patients.Methods186 cases of acute pancreatitis were randomly recruited into TCM group and control group.The control group was given routine treatment.On the basis of the control group,the TCM group was given Dachaihu decoction for enema additionally,twice daily,7 days.Then plasma inflammatory cytokines level was tested in both groups.ResultsTCM group had lower levels of TNF-α [ (42.18 ± 20.57) mg/L、(22.06± 10.73) mg/L,(9.88 ±4.62)mg/L],IL-1β[ (0.28 ±0.11) μg/L,(0.19±0.02) μg/L,(0.18 ±0.06)μg/L],and IL-6[(87.90±49.41)ng/L,(16.59±10.24) ng/L,(14.96±11.42) ng/L] at 2/5/7 days than the control group.There were statistical difference (P＜0.05).ConclusionEnema with Dachaihu decoction was effective on reducing plasma inflammatory cytokines level.It was probably the key to cure acute pancreatitis.