Determination and tissue distribution comparisons of gentiopicroside after oral administration of raw and wine-Processed Gentiana Radix.

Gentiana Radix is one of the most often used drugs in traditional Chinese medicine. Stir frying with yellow wine is the most common processing method. To clarify the principle of processing, an experiment was carried out to compare the tissue distribution of the typical constituent after oral administration of raw G. Radix and wine-processed one. To compare the tissues distribution of gentiopicroside oral administration of raw and wine-processed G. Radix, High-performance liquid chromatogram with ultraviolet detection was developed and validated for the determination of gentiopicroside in heart, liver, spleen, lung, kidney, stomach, small intestine and large intestine tissues. The gentiopicroside in raw and wine-processed G. Radix was distributed in all tissues involved in this study. Compared with the rats administration of raw G. Radix, the proportions of gentiopicroside in heart, liver and lung tissues increased in rats with administration of wine-processed one. The proportion of gentiopicroside in upper-JIAO and liver tissue can be increased by wine-processing.

Hepatoprotective effect and metabonomics studies of radix gentianae in rats with acute liver injury.

CONTEXT: As a well-known traditional Chinese medicine for protecting the liver, the mechanism of Radix Gentianae (RG) remains unclear. OBJECTIVE: The hepatoprotective effect and metabonomics of RG were studied to explore the molecular and metabolic mechanisms of RG protecting the liver. MATERIALS AND METHODS: Sprague-Dawley rats were divided into control and model group (n = 10, orally given distilled water), intervention group (4 subgroups, n = 10, prophylactically and orally given 0.63, 2.5 and 5.6 g/kg RG and 0.2 g/kg bifendatatum for 7 d). On day 7 of the intervention, all rats except the control were injected intraperitoneally with 2.5% carbon tetrachloride vegetable oil solution (1.5 mL/kg) to induce liver injury. After 24 h of carbon tetrachloride injection, rat serum and liver tissue were collected for determining AST, ALT, TNF-α, MCP-1, IL-6, SOD, MDA, GSH, and GSH-PX. Rat serum was used for analysing endogenous metabolism by UPLC-Q-TOF-MS. RESULTS: Different doses of RG can significantly decrease the levels of AST, ALT, TNF-α, MCP-1, IL-6 and MDA, and increase the levels of SOD, GSH, and GSH-PX in rats with liver injury (p < 0.05; TNF-α, and IL-6, p < 0.05 only at 5.6 g/kg dose). Eight biomarkers of liver injury were obtained in serum metabonomics, involving five significant metabolic pathways. RG can improve steroid biosynthesis, linoleic acid metabolism, porphyrin and chlorophyll metabolism, and fatty acid biosynthesis. CONCLUSION: RG demonstrated a good ability to protect the liver and improving endogenous metabolism in rats with liver injury. This can help us understand the mechanism of RG and more clinical verifications were inspired.

Efficacy of bevacizumab combined with chemotherapy in the treatment of HER2-negative metastatic breast cancer: a network meta-analysis.

BACKGROUND: It is not known what combination of bevacizumab and chemotherapy agents is the best therapeutic regimen. Comparative study results among the efficacies of bevacizumab plus chemotherapy remain controversial in patients with HER2-negative metastatic breast cancer. METHODS: We searched Pubmed, Embase, and Cochrane Library Central Resister of Controlled Trials through were July 2019 for randomized controlled trials that evaluated the efficacy of bevacizumab plus chemotherapy in HER2-negative metastatic breast cancer. Data on included study characteristics, outcomes, and risk of bias were abstracted by two reviewers. RESULTS: A total of 16 RCT studies involving 5689 patients were included. The results showed that bevacizumab (Bev) - taxanes (Tax) - capecitabine (Cap) has highest-ranking and is probably more effective for prolonging progression-free survival (PFS) than Tax, Cap, Bev-Tax and Bev-Cap, which was no convincing differences among Bev-Cap-vinorelbine, Bev-Tax-everolimus, Bev-Tax-trebananib, Bev-exemestane, Bev-Cap-cyclophosphamide in Bev-containing regimens. For overall response rate (ORR), Bev-Tax-Cap is superior to Tax, Cap and Bev-Cap, while Bev-Tax-trebananib is superior to Cap. The cumulative probability ranking showed that Bev-Tax-Cap or Bev-Tax-trebananib may have best pathological response rate in HER2-negative metastatic breast cancer. CONCLUSION: Our results provide moderate quality evidence that bevacizumab-taxanes-capecitabine maybe the most effective bevacizumab plus chemotherapy on PFS and ORR in HER2-negative metastatic breast cancer, however it should be also considered that bevacizumab may add toxicity to chemotherapy and whether improve overall survival (OS) or not.

UPLC-MS/MS of Atractylenolide I, Atractylenolide II, Atractylenolide III, and Atractyloside A in Rat Plasma after Oral Administration of Raw and Wheat Bran-Processed Atractylodis Rhizoma.

Atractylodis Rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2⁻350, 4⁻500, 4⁻500, and 3.44⁻430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.

Rapid Characterization and Identification of Chemical Constituents in Gentiana radix before and after Wine-Processed by UHPLC-LTQ-Orbitrap MSn.

Gentiana radix is used in traditional Chinese medicine and has functions of clearing heat and drying dampness, as well as purging liver and gallbladder fire. A highly sensitive and effective strategy for rapid screening and identification of target constituents has been developed by using ultra high-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry (UHPLC-LTQ-Orbitrap) in crude and wine-processed Gentiana radix. Based on the accurate mass measurement (<5 ppm), retention times, and MS fragmentation ions, 52 constituents were unambiguously or tentatively characterized from Gentiana radix, including 21 iridoids, 11 flavonoids, 19 xanthones, and a triterpenoid. This study demonstrated that the established method could be a rapid, effective analytical tool for screening and characterization of compounds in the complex systems of Gentiana radix. By comparing the structure and peak areas of chemical constituents in crude and wine-processed Gentiana radix, we found that some compounds in crude and wine-processed Gentiana radix were significantly different.