Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry （LC-MS/MS） method ...Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry （LC-MS/MS） method has been developed and validated for the determination of the active component--bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil C18 column （150mim×4.6mm, 5μm） with isocratic elution using a mobile phase consisting of water- methanol （30：70, v/v） at a flow rate of 0.6 mL/min. The detection was accomplished by a triple- quadrupole tandem mass spectrometer in multiple-reaction monitoring （MRM） scanning via an electrospray ionization （ESI） source operating in the negative mode. The optimized mass transition ion-pairs （m/z） for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5 min between injections. The calibration curve exhibited good linearity （r2〉 0.99） over a range of 1.00-2000 ng/mL for bergenin. The lower limit of quantitation （LLOQ） was 1.00ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors （RE） were within the range of 0.0-4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats.展开更多
[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg)...[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg),medium(50 mg/kg)and low(25 mg/kg)dose bergenin groups with 10 mice in each group.Except for the blank group,the other mice were sensitized by basic ways combined with attack to replicate the AR model.From the 15th d of modeling(from the second d after the end of the basic modeling),the drug group was given bergenin orally for 15 d,and the blank group and model group were given the same volume of normal saline once a day.24 h after the last establishment of the model,the content of interleukin 4(IL-4),IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of mice in each group was detected by ELISA.The expression of TLR-4,NF-κB and p-NF-κB in nasal mucosa of mice was detected by Western blot.[Results]Compared with the blank group,the content of inflammatory factors IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of model group was significantly increased,and the protein expression of TLR-4 and p-NF-κB was significantly increased.After the intervention of bergenin,the content of IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum and TLR-4 and p-NF-κB protein in tissue was significantly inhibited in bergenin group.[Conclusions]Bergenin can effectively reduce allergic inflammation in AR model mice,and its mechanism may be related to inhibition of inflammation and down-regulation of TLR-4/NF-κB signal pathway.展开更多
A RP-HPLC analytical method was developed for determining bergenin in rat urine, feces and tissues. The separation was performed on a C18 analytical column with methanol-water as the mobile phase at a flow rate of 0.8...A RP-HPLC analytical method was developed for determining bergenin in rat urine, feces and tissues. The separation was performed on a C18 analytical column with methanol-water as the mobile phase at a flow rate of 0.8 mL/min. The column temperature was 40℃ and the eluate was monitored at 220 nm. The calibration curve for urine analysis showed a good linearity （r = 0.9989） over the range of 0.5-100 μg/mL, and the absolute recoveries were in the range of 90.0%-92.6%. A good linearity （r≥0.9996） for all tested tissues was obtained over the range of 0.3-150 μg/g except for lung, which had a linearity range of 0.5-150 μg/g. The absolute recoveries from tissues were higher than 63.9%. The method was successfully applied to determine the bergenin levels in several biological samples after rats were given bergenin formulation through tail vein injection. The results demonstrated that the amount of bergenin recovered from urine was about 35.36% of the total dose, and that from feces was less than 10%. Bergenin can be quickly and widely distributed in the rat, accumulating high levels in the kidney in comparison to all other tissues investigated. It was not distributed into the brain at any significant level owing to its hydrophilic property.展开更多
Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, ...Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl_4-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C_(18) analytical column with acetonitrile and water(11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100^(–1)0 000 ng·m L^(–1). The lower limit of quantification was 50 ng·m L~(^(–1)). The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin(100 mg·kg^(–1)) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC_((0–∞)) of bergenin in hepatic injury rats was elevated to 2.11-fold and C_(max) was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.展开更多
To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzy...To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted(3a, 4a, 5a, 6a, 7a) and doublysubstituted(8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.展开更多
基金supported by the Natural Science Foundation of Guangdong Province (Nos. 9151008018000003)
文摘Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry （LC-MS/MS） method has been developed and validated for the determination of the active component--bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil C18 column （150mim×4.6mm, 5μm） with isocratic elution using a mobile phase consisting of water- methanol （30：70, v/v） at a flow rate of 0.6 mL/min. The detection was accomplished by a triple- quadrupole tandem mass spectrometer in multiple-reaction monitoring （MRM） scanning via an electrospray ionization （ESI） source operating in the negative mode. The optimized mass transition ion-pairs （m/z） for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5 min between injections. The calibration curve exhibited good linearity （r2〉 0.99） over a range of 1.00-2000 ng/mL for bergenin. The lower limit of quantitation （LLOQ） was 1.00ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors （RE） were within the range of 0.0-4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats.
文摘[Objectives]To explore the effect and possible mechanism of bergenin in relieving allergic rhinitis(AR)in mice.[Methods]50 C57/BL6 mice were randomly divided into blank group(n=10),model group(n=10)and high(100 mg/kg),medium(50 mg/kg)and low(25 mg/kg)dose bergenin groups with 10 mice in each group.Except for the blank group,the other mice were sensitized by basic ways combined with attack to replicate the AR model.From the 15th d of modeling(from the second d after the end of the basic modeling),the drug group was given bergenin orally for 15 d,and the blank group and model group were given the same volume of normal saline once a day.24 h after the last establishment of the model,the content of interleukin 4(IL-4),IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of mice in each group was detected by ELISA.The expression of TLR-4,NF-κB and p-NF-κB in nasal mucosa of mice was detected by Western blot.[Results]Compared with the blank group,the content of inflammatory factors IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum of model group was significantly increased,and the protein expression of TLR-4 and p-NF-κB was significantly increased.After the intervention of bergenin,the content of IL-4,IL-6,TNF-αand IL-1βin nasal lavage fluid and serum and TLR-4 and p-NF-κB protein in tissue was significantly inhibited in bergenin group.[Conclusions]Bergenin can effectively reduce allergic inflammation in AR model mice,and its mechanism may be related to inhibition of inflammation and down-regulation of TLR-4/NF-κB signal pathway.
基金Natural Science Foundation of Gansu Province (Grant No. ZS021-A25-051-N)Scientific & Technological Tackle Key Projects of Gansu Province,China.(Grant No. 2GS035-A43-048-01).
文摘A RP-HPLC analytical method was developed for determining bergenin in rat urine, feces and tissues. The separation was performed on a C18 analytical column with methanol-water as the mobile phase at a flow rate of 0.8 mL/min. The column temperature was 40℃ and the eluate was monitored at 220 nm. The calibration curve for urine analysis showed a good linearity （r = 0.9989） over the range of 0.5-100 μg/mL, and the absolute recoveries were in the range of 90.0%-92.6%. A good linearity （r≥0.9996） for all tested tissues was obtained over the range of 0.3-150 μg/g except for lung, which had a linearity range of 0.5-150 μg/g. The absolute recoveries from tissues were higher than 63.9%. The method was successfully applied to determine the bergenin levels in several biological samples after rats were given bergenin formulation through tail vein injection. The results demonstrated that the amount of bergenin recovered from urine was about 35.36% of the total dose, and that from feces was less than 10%. Bergenin can be quickly and widely distributed in the rat, accumulating high levels in the kidney in comparison to all other tissues investigated. It was not distributed into the brain at any significant level owing to its hydrophilic property.
基金supported by Health Innovation Personnel Training Project of Changzhou City(No.CWKJ 2010-368)Changzhou High Level Health Personnel Training Project
文摘Bergenin, isolated from the herb of Saxifrage stolonifera Curt.(Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl_4-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C_(18) analytical column with acetonitrile and water(11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100^(–1)0 000 ng·m L^(–1). The lower limit of quantification was 50 ng·m L~(^(–1)). The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin(100 mg·kg^(–1)) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC_((0–∞)) of bergenin in hepatic injury rats was elevated to 2.11-fold and C_(max) was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.
基金supported by the Natural Science Foundation of China(Nos.81274064 and 81373956)the National Fund for Fostering Talents of Basic Science(NFFTBS)(No.J1030830)the Science and Technology Supporting Project of Xinjiang(No.201291160)
文摘To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and 1H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted(3a, 4a, 5a, 6a, 7a) and doublysubstituted(8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.
