OBJECTIVE:To observe the efficacy and safety of mecobalamin combined with folic acid in the treatment of dia-betic peripheral neuropathy(DPN)with hyperhomocysteinemia. METHODS:Data of 40 DPN patients with high hyperhomocystein-emia were enrolled into high Hcy group and 30 DPN patients with normal Hcy were enrolled into normal Hcy group. Normal Hcy group was given diet control,hypoglycemic drugs or insulin for controlling glucose and other conventional treatment to make the fasting plasma glucose was lower than 7.0 mmol/L and 2 h postprandial glucose lower than 11.0 mmol/L;based on it,high Hcy group was given Mecobalamin injection 500 μg by intramuscular injection,once a day+Folic acid tablet 5 mg,once a day. 14 d was a treatment course and it lasted 2 courses. Clinical efficacy,Hcy level,the motor nerve conduction velocity(MNCV)and sen-sory nerve conduction velocity (SNCV) of tibial and peroneal nerve and total symptom scale (TSS) score before and after treat-ment in high Hcy group were observed and compared with normal Hcy group,and the incidence of adverse reactions in high Hcy group was recorded. RESULTS:After treatment,the total effective rate in high Hcy group was 75.0%;Hcy and TSS score in high Hcy group were significantly lower than before and higher than normal Hcy group,MNCV and SNCV of tibial and peroneal nerve were significantly higher than before and lower than normal Hcy group,the differences were statistically significant(P<0.05). Th incidence of adverse reactions of high Hcy group was 5.0%. CONCLUSIONS:Based on the conventional treatment,Mecobalamin combined with folic acid has good efficacy in the treatmen of DPN with hyperhomocysteinemia,it can significantly reduce plasma Hcy levels and improve nerve conduction velocity in patients with DPN,with good safety.

OBJECTIVETo provide a scientific basis for the drug-combination and aim to examine whether astragaloside IV has the impact on the cytochrome P450 enzymes.

METHODTolbutamide, chlorzoxazone, coumarin, nifedipine, and phenacetin were as probe substrates of rat CYP2C9, CYP2E1, CYP2A6, CYP3A4, and CYP1A2, and were incubated in rat liver microsomes with astragaloside IV. Triplicate samples were run to generate IC50 value by incubating P450 probe substrates in the presence of five concentrations of astragaloside IV in the incubation mixture. The K(i) values were determined by fitting the probe substrate at various inhibitor concentrations to the equations for competitive inhibition, noncompetitive inhibition, noncompetitive inhibition, and mixed-type inhibition.

RESULTIC50 and K(i) values were estimated, and the types of inhibition were determined. Among the five probe substrates, astragaloside IV might not significantly affect CYP2E1, CYP2A6 and CYP1A2-mediated metabolism in rats, but was a competitive inhibitor of CYP2C9 (IC50 35.40 micromol x L(-1), K(i) 42.88 micromol x L(-1)), and was a uncompetitive inhibitor of CYP3A4 (IC50 88.24 micromol x L(-1), K(i) 33.31 micromol x L(-1)).

CONCLUSIONThese results suggested that astragaloside IV inhibited CYP2C9 and CYP3A4, which provided useful information for safe and effective use of astragaloside IV.

Animals ; Cytochrome P-450 Enzyme Inhibitors ; Cytochrome P-450 Enzyme System ; chemistry ; metabolism ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Enzyme Inhibitors ; chemistry ; pharmacology ; Kinetics ; Male ; Microsomes, Liver ; chemistry ; drug effects ; enzymology ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Triterpenes ; pharmacology

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer's disease.In this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different biomatrices.The plasma pharmacokinetics,tissue distri-bution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were system-atically investigated.Despite its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were indiscriminate.Sodium oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavail-ability in rats(0.6％-1.6％)and dogs(4.5％-9.3％).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major tissues.So-dium oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a con-stant area under the concentration-time curve ratio(CSF/plasma)of approximately 5％.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated rats.Moreover,only 33.7％(male)and 26.3％(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.