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OBJECTIVE To investigate the effects of Compound troxerutin and poreine cerebroside injection on the activity of cytochrome P450 （CYP450） enzyme in vivo and in vitro. METHODS Human liver microsomes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） and the specific probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 for 30 min. The production of corresponding metabolites was detected by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）， and the half inhibitory concentration （IC50） was calculated. The relative mRNA expression （i.e. induction multiple） of CYP450 enzyme was determined by real-time fluorescence quantitative PCR after human primary hepatocytes were incubated with Compound troxerutin and poreine cerebroside injection （volume fraction 0.05%-10%） or 3 positive inducers of CYP1A2， CYP2B6， CYP3A4 for 48 hours. Male SD rats were randomly divided into control group （normal saline+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10， 10， 8 mg/kg） and experimental group （Compound troxerutin and poreine cerebroside injection 0.9 mL/kg+probe substrates of CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6， CYP3A4 8， 2， 1， 1， 10，10， 8 mg/kg）， with 6 rats in each group. The pharmacokinetic parameters of probe substrates were detected by UPLC-MS/MS and Cocktail probe drug method. RESULTS After the lzqpharm@126.com treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the activities of CYP2B6， CYP2C8 and CYP2C19 in human liver microsomes had no significant change， and IC50 could not be fitted； IC50 of CYP1A2， CYP2C9， CYP2D6 and CYP3A4 were 419.90%， 97.78%， 176.00%， 19.42%， respectively. After the treatment of 0.05%-10% Compound troxerutin and poreine cerebroside injection， the average induction multiple of CYP3A4 mRNA in human primary hepatocytes （No. MHK） was 4.88 （and the average induction multiples of 2 concentration points were higher than 2）. After the treatment of Compound troxerutin and poreine cerebroside injection， AUC0－t and AUC0－∞ of CYP2C8， CYP2C9 and CYP2C19 substrates were increased significantly， CL of CYP2C8 and CYP2C19 substrates were decreased significantly， while t1/2 of CYP2C9 substrate was prolonged significantly （P＜0.05）. CONCLUSIONS Compound troxerutin and poreine cerebroside injection has no obvious inhibitory effect on CYP1A2， CYP2B6， CYP2C8， CYP2C9， CYP2C19， CYP2D6 and CYP3A4 in human liver microsomes in vitro， but can induce the mRNA expression of CYP3A4 in human primary hepatocytes in vitro， and can inhibit the activities of CYP2C8， CYP2C9 and CYP2C19 in rats in vivo.
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Quercetin 3-O-glycosides (Q3Gs) are important members of quercetin glycosides with excellent pharmacological activities such as anti-oxidation, anti-inflammation, anti-cancer and anti-virus. Two representatives of Q3Gs, rutin and troxerutin, have been developed into clinical drugs, demonstrating Q3Gs have become one of the important sources of innovative drugs. However, the applications of Q3Gs in food and pharmaceutical industries are hampered by its poor bioavailability. Of the known means, selective acylation modification of Q3Gs through enzymatic catalysis to obtain Q3G esters is one of the effective ways to improve its bioavailability. Herein, the enzyme-mediated acylation of Q3Gs were reviewed in details, focusing on the four tool enzymes (acyltransferases, lipases, proteases and esterases) and the whole-cell mediated biotransformation, as well as the effect of acylations on the biological activities of Q3Gs. Furthermore, the highly efficient synthesis and diversification of acylated site for Q3G esters were also discussed. Taken together, this review provides a new perspective for further structural modifications of Q3Gs towards drug development.
Subject(s)
Acylation , Biological Availability , Glycosides , Quercetin , RutinABSTRACT
This study aimed to assess the effects of Ginkgo Biloba Extract and Troxerutin on the hippocampus of induced diabetes mellitus in adult albino rats using histological methods.50 adult male albino rats were divided into three groups; Group I (Control); Group II (diabetic): subdivided into Subgroup IIa (T1DM)), Subgroup IIb (T1DM+GBE), Subgroup IIc (T1DM+ troxerutin); Group III: subdivided into Subgroup IIIa (GBE) and Subgroup IIIb (troxerutin). The brain was removed and the cerebral hemisphere was coronally cut at the hippocampal level and used for light microscopic study (H&E staining and PCNA immunostaining). There was a statistically insignificant improvement in animal weights in subgroup IIb and subgroup IIc. Subgroup IIb showed a statistically significant reduction of blood glucose levels while the subgroup IIc showed insignificant reduction of blood glucose levels. Diabetes disturbed the light microscopic structure of the hippocampus. In subgroup IIb and subgroup IIc the hippocampus retained an apparently normal appearance and the stratum pyramidale exhibited the pyramidal cells with rounded vesicular nuclei and acidophilic cytoplasm. Diabetic hippocampal sections revealed negative PCNA immunoreactivity inall layers of DG. In subgroup IIb and subgroup IIc, hippocampal sections showed positive immunoreactivity
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Objective To optimize a W/O microemulsion formulation of troxerutin and evaluate its physical properties such as morphology, droplet size, stability and content of troxerutin. Methods The W/O microemulsion was optimized using a pseudoternary phase diagram and the area of the microemulsion region was used to screen and determine microemulsion components.HPLC assay was used for determination of the loading content. Results The optimal formulation contained lecithin, ethanol, isopropyl myristate and water (23.30:11.67:52.45:12.59).The microemulsion was physicochemically stable with round shape and uniform size, and the mean droplet size was about 50. 20 nm. Conclusion Microemulsion was developed successfully.It will expect to be the new preparation for troxerutin.
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Aim To study the characteristics of the binding reaction of Troxetutin with bovine serum albumin (BSA) by fluorescence and ultra violet-visible absorption spectra.Methods The quenching mechanism of the fluorescence of BSA by troxerutin was studied with fluorescence.To determine the dynamic quenching constants and static binding constants,the Stern-Volmer equation and the double reciprocal Lineweaver-Burk equation were applied. The number of binding site was calculated with double logarithmic equation and the main binding force was discussed by thermodynamic equations. The binding distance and energy transfer efficiency between donor (BSA) and acceptor (troxerutin) were obtained effectively quenched fluorescence of BSA via static quenching processes. The binding constant Ka was calculated to be in the order of 106,indicating a strong interaction between Troxerutin and BSA. The number of binding site was approximately equal to 1,the binding distance was 1.97 nm,the energy transfer efficiency was 0.529,and the binding force was mainly hydrophobic force.Conclusion Troxerutin effectively quenchs the intrinsic fluorescence of BSA via static quenching mechanism,and the binding is mainly driven by the hydrophobic interaction.
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0.05).CONCLUSION:In the study,PVC infusion systems have no adsorption effect on troxerutin.
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152 patients with pseudobulbar paralysis resulting from ischemic cerebral infarction were treated with polysaccharide sulphate (PSS) or Troxerutin (TR) and their clinical curative effect and laboratory parameters were studied. 76 patients (M46,F30,mean ages 62+6 y),were treated with PSS:PSS 150 mg in 5% Glocose Solution 500 mL iv. drip. qd,for 14 days as a course. The other 76 patients (M46,F30,mean age 63 + 7 y) were treated with (TR);TR 600 mg in hydroxyethyi-starch 500 mL iv. drip ,qd .for 14 days as a course. The results showed that the total effective rates of the two groups were 94. 74% and 77. 63% .respectively. Moreover the plasma levels of cholesteral and triglyceride were decreased significantly ( P
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OBJECTIVE :To determine the content of Troxerutin in Troxerutin injection by HPLC METHODS :The separation was performed on a Hypersil BDS C18 column The mobile phase was composed of acetontrile-tetrahydrofuran-0.05 mol/Lsodium dihydrogen phosphate(15∶8∶77V/V ) ,adjusted to pH4 0 with phosphoric acid The flow rate was 0 8ml/ min The ultraviolet wavelength was 254nm RESULTS :The calibration curve showed good li nearityinrange of (20～200) ?g/ ml(r=0 9998) ;The mean recovery was 100 7 % The within -day RSD was 1 61 %,and inter-day RSD was 2 46 % CONC_ LUSION :The method was simple ,convenient and accurate and can be used for the quality control of Troxerutin injection