Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

[The protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion injury and coagulopathy after excision of liver cancer].

OBJECTIVE: To observe the protective effect of Xuebijing injection pretreatment on hepatic ischemia reperfusion (I/R) injury and coagulopathy in liver cancer patients undergoing excision of hepatic cancer after occlusion of hepatic blood flow. METHODS: A prospective randomly controlled study was conducted. Sixty patients with liver cancer classified as Child-Pugh class A undergoing hepatectomy in the Department of Hepatobiliary Surgery of Sun Yat-sen University Cancer Center from October 2011 to March 2013 were enrolled. The patients were randomized into control group and Xuebijing group (each patient received 100 mL Xuebijing injection added to 0.9% saline as a preoperative treatment for 3 days). Complete blood count, coagulation function, hepatic function, serum pro-inflammatory cytokines and alpha-fetoprotein (AFP) levels were determined before and after operation. RESULTS: Forty-five out of 60 patients were enrolled eventually, with 23 patients in control group and 22 in Xuebijing group, and among them 43 patients were positive for hepatitis B surface antigen (HBsAg) at admission. Compared with those before operation, the postoperative levels of alanine transaminase (ALT), aspartate transaminase (AST) and lactate dehydrogenase (LDH) in control and Xuebijing groups were significantly elevated, prothrombin time (PT) and activated partial prothrombin time (AfYIT) were significantly prolonged, and white blood cells (WBC) , proportion of neutrophils (N) and C-reactive protein (CRP) were significantly increased (P<0.05 or P<0.01 ). Although the above indexes in Xuebijing group after operation were lower than those in control group in different degrees [ALT (U/L): 213.1 (80.4-796.6) vs. 265.8 (15.6-882.3), AST (UIL): 194.1 (65.4-914.2) vs. 264.3 (15.4-475.9), LDH (lg,U/L): 5.69 ± 0.72 vs. 5.71 ± 0.72, PT (s): 15.24 ± 2.16 vs. 14.41 ± 1.33, AfYIT (s): 31.51 ± 7.04 vs. 29.47 ± 4.90, WBC (x 109/L) : 13.4 7 ± 4.66 vs. 14.58 ± 4.40, N: 0.87 ± 0.06 vs. 0.87 ± 0.04, CRP (mg/L): 40.64 (16.93-189.59) vs. 45.64 ( 1.65-349.40) J, no statistical significance was found between the groups (all P>0.05 ). The preoperative levels of tumor necrosis factor-a (TNF -a) and interleukin-6 OL-6) were both less than 1.0 ng/L, and the postoperative levels of TNF-a showed no significant change, and IL-6 was increased to 485.10 (104.00-837.50) ng/L and 193.26 (95.10-385.20) ng/L in control and Xuebijing groups respectively (P<0.01). The serum high mobility group box-1 ( HMGB1 ) protein levels after operation were higher than those of preoperative in both groups (both P<0.01), but the postoperative HMGB1 in Xuebijing group were significantly lower than those in control group (j.Lg/L: 268.73 ± 5.56 vs. 277.12 ± 2.92, P<0.01). Acute physiology and chronic health evaluation ll (APACHE ll) score in Xuebijing group was significantly lower than that in control group (4.18 ± 3.75 vs. 4.53 ± 2.34, t=5.328, P=0.027), and the first passage of flatus and defecation after operation in Xuebijing group were significantly earlier than those in control group [exhaust time (days): 3 (2-4) vs. 3 (2-4), U=-2.023, P=0.043; defecation time (days): 4 (2-6) vs. 5 (3-8), U =-2.926, P=0.003 J. However, no difference was found between two groups in the postoperative and total hospital days. Spearman rank correlation analysis showed there were positive correlations between hepatitis B virus (HBV)-DNA levels and preoperative ALT (r=0.414, P=0.044) and AST (r=0.405, P=0.024) in 33 HBV-DNA positive patients, but there was no significant correlation between HBV -DNA levels or other preoperative liver function indicators. CONCLUSIONS: Hepatic I/R injury and coagulopathy may occur in liver cancer patients undergoing resection of cancer with occlusion of hepatic blood flow. Xuebijing injection may inhibit the release of serum pro-inflammatory cytokines, thereby alleviate hepatic I/R injury and promote the recovery of intestinal function. But it does not offer protective effect on coagulopathy.