Xanthones from Calophyllum Polyanthum Wallich ex Choisy with CYP1 Enzymes Inhibitory Activity.

Three new xanthone compounds, 1,3,5-trihydroxy-2-(2-hydroxy-3-methylbut-3-enyl)-4-(3-methylbut-2-enyl)xanthone (1), toxyloxanthone E (2), dehydrocycloguanandin B (3) along with 15 known xanthones (4-18) were isolated from the aerial parts of Calophyllum polyanthum Wall. ex Choisy. Their structures were fully characterised using spectroscopic data, as well as comparison with the previous literature data. All isolated compounds had inhibitory effects against CYP1A1, CYP1A2 and CYP1B1 enzymes at working concentration of 10 µM, 1 µM and 10 µM, respectively. Among them, compounds 10, 11, and 12 exhibited better CYP1A2 enzyme inhibitory effects than that of the positive control α-naphthoflavone, with 51.05 %, 56.82 % and 44.93 % inhibition, respectively.

Parabacteroides distasonis ameliorates hepatic fibrosis potentially via modulating intestinal bile acid metabolism and hepatocyte pyroptosis in male mice.

Parabacteroides distasonis (P. distasonis) plays an important role in human health, including diabetes, colorectal cancer and inflammatory bowel disease. Here, we show that P. distasonis is decreased in patients with hepatic fibrosis, and that administration of P. distasonis to male mice improves thioacetamide (TAA)- and methionine and choline-deficient (MCD) diet-induced hepatic fibrosis. Administration of P. distasonis also leads to increased bile salt hydrolase (BSH) activity, inhibition of intestinal farnesoid X receptor (FXR) signaling and decreased taurochenodeoxycholic acid (TCDCA) levels in liver. TCDCA produces toxicity in mouse primary hepatic cells (HSCs) and induces mitochondrial permeability transition (MPT) and Caspase-11 pyroptosis in mice. The decrease of TCDCA by P. distasonis improves activation of HSCs through decreasing MPT-Caspase-11 pyroptosis in hepatocytes. Celastrol, a compound reported to increase P. distasonis abundance in mice, promotes the growth of P. distasonis with concomitant enhancement of bile acid excretion and improvement of hepatic fibrosis in male mice. These data suggest that supplementation of P. distasonis may be a promising means to ameliorate hepatic fibrosis.

Synthesis, Characterization, and Pharmacodynamics Study of Enrofloxacin Mesylate.

INTRODUCTION: Enrofloxacin is used in the treatment of a wide variety of bacterial infections in mammals. However, its poor solubility limits the clinical use. METHODS: In order to improve the solubility of enrofloxacin, the enrofloxacin mesylate (EM) were obtained by a chemical synthesis method. The characterization of EM was carried out using ultraviolet scan (UV), synchronous thermal analysis (SDT), fourier transform infrared spectrometer (FTIR) and mass spectrometry (MS), nuclear magnetic resonance (NMR) and X-ray powder diffraction analysis (XRPD). Acute toxicity of EM in Kunming mice was studied. Besides, pharmacokinetic studies were performed in New Zealand rabbits at a single oral dose of 10 mg/kg, and the antibacterial activity of EM was also evaluated. RESULTS: EM was successfully synthesized and purified. The stoichiometric ratio of mesylate to enrofloxacin was 1:1 and the aqueous solubility of EM was 483.01±4.06 mg/mL, the solubility of EM was about 2000 times higher than enrofloxacin. The oral lethal dose (LD50) of EM was 1168.364 mg/kg, and the pharmacokinetics indicated that the oral relative bioavailability of EM was about 1.79 times and 1.48 times higher than that of enrofloxacin and enrofloxacin hydrochloride, respectively. In addition, the in vitro antibacterial activity of EM was not significantly changed compared with enrofloxacin and enrofloxacin hydrochloride. CONCLUSION: EM has higher solubility, low toxicity for oral use, and increases the oral bioavailability in rabbit. This study may be of benefit for the development of new enrofloxacin drugs.

Isobologram Analysis: A Comprehensive Review of Methodology and Current Research.

Drug combination is a common method for clinical disease treatment. Whether the combination of drugs is reasonable often affects the result of the disease treatment. Many methods have been used to evaluate interaction between drugs to date. Isobologram analysis has been mathematically proven and widely used to evaluate drug interactions. In this paper, the principle of isobologram analysis and its application in drug interaction evaluation are summarized. The applications of the similar cotoxicity coefficient and fractional inhibitory concentration index in the evaluation of drug interaction are also reviewed. This work is expected to evaluate the effect of formulations scientifically and provide scientific judgment standards for the development of formulations and clinical drug compatibility.