Wen-Fu Tang

Simultaneous determination of the 10 major components of Da-Cheng-Qi decoction in dog plasma by liquid chromatography tandem mass spectrometry.

A liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the 10 major components of Da-Cheng-Qi decoction (rhein, emodin, aloe-emodin, chrysophanol, rheochrysidin, naringin, naringenin, hesperidin, magnolol and honokiol) in dog plasma. Plasma samples were spiked with internal standard (ibuprofen), acidified with HCl and extracted twice by liquid-liquid extraction using ethyl acetate. Separation was performed on a YMC-Pack ODS-A C(18) column (5 microm, 150 mm x 4.6 mm) and a C(18) guard column (5 microm, 4.0 mm x 2.0 mm) with methanol-water (92:8, v/v) at a flow rate of 0.3 mL/min. The LC/MS system was operated under the multiple reaction monitoring mode using electrospray ionization in the negative ion mode. All analytes showed good linearity over a wide concentration range (r>0.99). The linear range of the calibration curves was 5000-19.53 ng/mL for rhein; 400-3.13 ng/mL for emodin; 800-3.13 ng/mL for aloe-emodin, chrysophanol, naringin, naringenin, hesperidin, magnolol and honokiol; 160-0.63 ng/mL for rheochrysidin. The lower limit of quantification was: 19.53 ng/mL for rhein; 3.13 ng/mL for emodin, aloe-emodin, chrysophanol, naringin, naringenin, hesperidin, magnolol and honokiol; 0.6 3 ng/mL for rheochrysidin. The overall mean accuracy for the 10 major components of Da-Cheng-Qi decoction was 90.40-108.60%. Intra-day and inter-day precision was < or =12.43% and < or =11.32%, respectively. We conclude that this method is appropriate for simultaneous determination of the 10 major components of Da-Cheng-Qi decoction in dog plasma and the investigation of the pharmacokinetics of Da-Cheng-Qi decoction in dog.

Early oral refeeding wisdom in patients with mild acute pancreatitis.

Objectives To evaluate the safety and efficacy of early oral refeeding (EORF) in patients with mild acute pancreatitis (AP) and to investigate the optimal duration to commence EORF. Methods A prospective, randomized, controlled trial was conducted in patients with mild AP. Patients with EORF (started oral feeding once they subjectively felt hungry) were compared with patients receiving routine oral refeeding (RORF) for time interval between disease onset and initiation of oral refeeding, total length of hospitalization (LOH), postrefeeding LOH, and adverse gastrointestinal events. Results There were 75 and 74 patients in the EORF group and the RORF group, respectively, with comparable baseline characteristics. Patients in the EORF group started refeeding significantly earlier than those in the RORF group (4.56 ± 1.53 vs 6.75 ± 2.29 days; P < 0.05). Moreover, patients in the EORF group had significantly shorter total (6.8 ± 2.1 vs 10.4 ± 4.1 days; P < 0.01) and post refeeding LOH (2.24 ± 0.52 vs 3.27 ± 0.61 days; P < 0.01). There was no significant difference in adverse gastrointestinal events between the 2 groups. Conclusion In patients with mild AP, EORF, with the subjective feeling of hunger, is safe, feasible, and reduces LOH.

Amelioration of experimental acute pancreatitis with Dachengqi decoction via regulation of necrosis-apoptosis switch in the pancreatic acinar cell

Severity of acute pancreatitis contributes to the modality of cell death. Pervious studies have demonstrated that the herb medicine formula “Dachengqi Decoction” (DCQD) could ameliorate the severity of acute pancreatitis. However, the biological mechanisms governing its action of most remain unclear. The role of apoptosis/necrosis switch within acute pancreatitis has attracted much interest, because the induction of apoptosis within injured cells might suppress inflammation and ameliorate the disease. In this study, we used cerulein (10−8 M)-stimulated AR42J cells as an in vitro model of acute pancreatitis and retrograde perfusion into the biliopancreatic duct of 3.5% sodium taurocholate as an in vivo rat model. After the treatment of DCQD, cell viability, levels of apoptosis and necrosis, reactive oxygen species positive cells, serum amylase, concentration of nitric oxide and inducible nitric oxide syntheses, pancreatic tissue pathological score and inflammatory cell infiltration were tested. Pretreatment with DCQD increased cell viability, induced apoptosis, decreased necrosis and reduced the severity of pancreatitis tissue. Moreover, treatment with DCQD reduced the generation of reactive oxygen species in AR42J cells but increased the concentration of nitric oxide of pancreatitis tissues. Therefore, the regulation of apoptosis/necrosis switch by DCQD might contribute to ameliorating the pancreatic inflammation and pathological damage. Further, the different effect on reactive oxygen species and nitric oxide may play an important role in DCQD-regulated apoptosis/necrosis switch in acute pancreatitis.

Effects of food and gender on the pharmacokinetics of rhein and emodin in rats after oral dosing with Da-Cheng-Qi decoction

Da‐Cheng‐Qi decoction (DCQD), a traditional Chinese medicine preparation used to treat digestive diseases, is composed of dahuang (Rheum officinale Baill, Polygonaceae), houpu (Magnolia officinalis Rehd., Magnoliaceae), zhishi (Citrus aurantium L, Rutaceae) and mangxiao (sodium sulphate). Rhein and emodin are the major active components of Rheum officinale Baill. To investigate the effects of food and gender on the plasma concentrations of rhein and emodin after oral administration of DCQD, a rapid high‐performance liquid chromatographic method was developed and validated. A reversed phase C18 column (150 × 4.6 mm) and a mobile phase of methanol and 0.2% acetic acid (78:22, v/v) were employed with ultraviolet detection at 254 nm. Feeding was observed to decrease the absorption of rhein and emodin in rats receiving DCQD orally. No evidence for gender‐based differences in the pharmacokinetics of rhein was observed. However, the half‐life and area under the concentration–time curve for emodin differed significantly between male and female rats. Because food intake and gender are anticipated to influence the pharmacokinetics of DCQD in human subjects, it is recommended that oral doses of DCQD be reduced in fasting subjects and that female patients receive lower oral doses compared with male patients. Copyright

Effect of Formula Compatibility on the Pharmacokinetics of Components from Dachengqi Decoction （大承气汤） in Rats

ObjectiveTo investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, 大承气汤) in rats.MethodsTwenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study.ResultsThe area under the curve (AUC), mean retention time (MRT), the peak concentration (Cmax) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, Cmax, and the absorption of Dahuang’s component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang’s component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, Cmax and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T1/2α), the drug eliminated half-life time (T1/2β), MRT, and time of peak concentration (Tmax) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer.ConclusionsThe compatibility in Chinese medicine could affect the drug’s pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.

Classification and Management of Pancreatic Pseudocysts

AbstractThis article aims to elucidate the classification of and optimal treatment for pancreatic pseudocysts.Various approaches, including endoscopic drainage, percutaneous drainage, and open surgery, have been employed for the management of pancreatic pseudocysts. However, no scientific classification of pancreatic pseudocysts has been devised, which could assist in the selection of optimal therapy.We evaluated the treatment modalities used in 893 patients diagnosed with pancreatic pseudocysts according to the revision of the Atlanta classification in our department between 2001 and 2010. All the pancreatic pseudocysts have course of disease >4 weeks and have mature cysts wall detected by computed tomography or transabdominal ultrasonography. Endoscopic drainage, percutaneous drainage, or open surgery was selected on the basis of the pseudocyst characteristics. Clinical data and patient outcomes were reviewed.Among the 893 patients, 13 (1.5%) had percutaneous drainage. Eighty-three (9%) had type I pancreatic pseudocysts and were treated with observation. Ten patients (1%) had type II pseudocysts and underwent the Whipple procedure or resection of the pancreatic body and tail. Forty-six patients (5.2%) had type III pseudocysts: 44 (4.9%) underwent surgical internal drainage and 2 (0.2%) underwent endoscopic drainage. Five hundred six patients (56.7%) had type IV pseudocysts: 297 (33.3%) underwent surgical internal drainage and 209 (23.4%) underwent endoscopic drainage. Finally, 235 patients (26.3%) had type V pseudocysts: 36 (4%) underwent distal pancreatectomy or splenectomy and 199 (22.3%) underwent endoscopic drainage.A new classification system was devised, based on the size, anatomical location, and clinical manifestations of the pancreatic pseudocyst along with the relationship between the pseudocyst and the pancreatic duct. Different therapeutic strategies could be considered based on this classification. When clinically feasible, endoscopic drainage should be considered the optimal management strategy for pancreatic pseudocysts.

Effect of somatostatin on immune inflammatory response in patients with severe acute pancreatitis.

OBJECTIVE:  Somatostatin regulates immune inflammatory response via apoptosis and adhesion of leukocytes in many diseases. This article reported a study that aimed to observe the mechanism and effect of somatostatin on the immune inflammatory response through apoptosis and adhesion of leukocytes in severe acute pancreatitis.

Effect of electroacupuncture on the inflammatory response in patients with acute pancreatitis: an exploratory study

Objectives To examine the effects of electroacupuncture (EA) on inflammatory responses in patients with acute pancreatitis (AP). Methods Eighty patients with mild or severe AP were randomly allocated to a control group or an EA group. All patients were managed conservatively. In addition, the EA group received acupuncture for 30 min per day for 7 days at bilateral points ST36, LI4, TE6, ST37 and LR3. Interleukin (IL)-6, IL-10 and C-reactive protein (CRP) levels were measured on admission and on day 7. The time to re-feeding and length of stay in hospital were also recorded. Results A total of 58 patients provided complete data. The characteristics of the patients in the EA and control groups were similar. After 7 days the serum concentrations of IL-10 were higher in the EA group than in the control group (mild AP: 6.2±1.2 vs 5.2±0.9 pg/mL, p<0.05; severe AP: 14.9±7.8 vs 7.9±6.3 pg/mL, p<0.05). For patients with severe AP, the CRP level in the EA group was lower than in the control group (p<0.05). Conclusions EA may reduce the severity of AP by inducing anti-inflammatory effects and reducing the time to re-feeding; however, it did not reduce the length of hospital stay. Trial Registration Number ChiCTR-TRC-13003572.

Rhein induces a necrosis-apoptosis switch in pancreatic acinar cells.

Objectives. The Chinese herbal medicine Da-Cheng-Qi decoction can regulate a necrosis-apoptosis switch in injured pancreatic acinar cells. This study investigated the effects of rhein, a component of this medicine, on a necrosis-apoptosis switch in pancreatic rat AR42J cells. Methods. Cerulein-treated AR42J cells were used. After pretreatment with 479, 119.8, or 29.9 μg/L rhein, cells were cocultured with rhein and cerulein (10−8 M) for 4, 8, or 16 h. Apoptosis and necrosis were examined using annexin V and propidium iodide costaining. Mitochondria-dependent apoptosis-associated proteins were examined using enzyme-linked immunosorbent assays and western blotting. Results. Few cells died in untreated samples. The number was significantly higher in 16-h-cerulein-treated samples and treatment with 479 μg/L rhein most effectively increased the apoptotic-to-necrotic cell ratio (P < 0.05). In cerulein-treated cells, rhein increased the concentrations of p53, cytochrome C, and caspase-3, and increased the Bax/Bcl-2 ratio in a time- and dose-dependent manner, with the maximum effect in cells treated with 479 μg/L rhein for 16 h (P < 0.05). Conclusions. Rhein induces the necrosis-apoptosis switch in injured pancreatic acinar cells in a time- and dose-dependent manner. Mitochondria-dependent apoptosis signaling pathways might play an important role in this effect.

Pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction in the liver of rats with severe acute pancreatitis

AIM To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis. METHODS Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated. RESULTS The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (P < 0.05). DCQD could reduce the pathological scores in the pancreas and liver of the rats with SAP, especially in the HDG. Compared to the SOG, the ALT and AST levels in serum were higher in the MG (P < 0.05), while there was no statistical difference in the MG and HDG. CONCLUSION DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.