黄山药总皂甙肠内菌代谢及代谢产物吸收的研究

目的：本离体和整体观察人和大鼠肠内菌对黄山药总皂苷（DX）的代谢作用及整体给予DX后吸收入血的有效成分，方法：用薄层色谱（TLC）及电喷雾质谱（ESI－MS）法检测粪中DX及其代谢产物。整体给予大鼠灌服DX900mg/kg，于给药后不同时间采集尿及血清样品，用ESI－MS检测吸收入血成分。结果：DX容易被人和大鼠消化道菌群代谢，随着代谢时间的延长，出现了各种甾体皂苷的降解产物及终产物薯蓣皂苷元（Dio)。整体实验表明，在大鼠血及尿中均发现分子量为415．3的代谢产物，经ESIMS二级质谱分析，上述分子量的化合物为Dio。结论：DX可被人和大鼠肠内菌代谢，DX经口服后Dio被吸收入血。     

人参皂苷Rg1的肠内菌代谢及其代谢产物吸收入血的研究

目的 :研究人参皂苷Rg1(Rg1)在人及大鼠体内经肠内菌代谢后的变化及吸收入血代谢物的确定。方法 :生物样品 (血、尿、粪便 )经处理后分别做TLC ,ESI MS及HPLC检测分析。结果 :在大鼠尿和血中有代谢物Rh1/F1存在 ;在人的尿中有Rh1存在。结论 :在大鼠和人的血内 ,Rg1主要以其代谢产物形式存在。     

人参皂苷Rg1 总被引：26，自引：1，他引：25

王毅  刘铁汉  王巍  王本祥 《药学学报》2000,35(4):284-288

黄山药总皂苷和薯蓣皂苷元抗高脂血症及体外抗血小板聚集的比较

目的 :比较黄山药总苷 (DX)和薯蓣皂苷元 (Dio)抗实验性高脂血症及体外抗血小板聚集作用强度。方法 :给小鼠和大鼠喂饲高胆固醇饲料造成高脂血症模型 ,之后灌胃或腹腔注射给予DX和Dio ,测定血清胆固醇含量。结果 :给小鼠灌胃DX( 4 0 0和 2 0 0mg·kg-1)和Dio( 160和 80mg·kg-1)时 ,Dio对小鼠高胆固醇血症有明显预防和治疗作用 ,而DX只有大剂量时才有一定预防作用。腹腔注射给药时 ,Dio( 4 0和 2 0mg·kg-1)仍然有效 ,但DX无效。给大鼠灌胃DX( 4 0 0和 2 0 0mg·kg-1)和Dio( 2 0 0和 10 0mg·kg-1) ,均能明显降低血中总胆固醇含量 ,但在上述剂量 ,Dio的预防效果明显优于DX。DX( 60～ 2 4 0 μg·ml-1)和Dio( 3 0～ 12 0 μg·ml-1)体外有明显的抗血小板聚集活性 ,但Dio的抑制率明显高于DX。结论 :Dio抗高脂血症及抗血小板聚集作用明显优于DX。     

人参皂苷Rb1在大鼠肠内菌代谢物吸收入血成分的研究

目的:研究口服人参皂苷Rb₁(G-Rb₁)被吸收入血的成分。方法:给大鼠igG-Rb₁500mg·kg^-1后,于不同时间采集粪、尿及血清样品,用电喷雾质谱(ESI-MS)检测吸收入血成分。结果:在血与尿中发现分子量为1108,946及784amu的代谢产物。经ESI-MS2级质谱分析,上述分子量的化合物分别为G-Rb₁,Rd和F₂。结论:G-Rb₁给大鼠ig后,原形及中间代谢产物Rd及F₂被吸收入血。     

地奥心血康肠道吸收作用的研究及其机制的初步探讨

目的　 本文通过给大鼠灌服地奥心血康 (DX)及薯蓣皂苷元 (Diosgenin ,Dio)后 ,观察两者在胃肠道内吸收的状况 ,借以进行药效学的比较及离体观察对胆固醇微胶粒形成的抑制作用。 方法 　给大鼠灌服DX及Dio后 ,收集粪样品 ,通过酸水解后 ,采用薄层扫描定量法 (TLCS)测定Dio的含量 ;将样品与胆固醇和胆汁充分混合后 ,测定对胆固醇微胶粒形成的抑制作用。 结果 　DX灌胃组经胃肠道排出的Dio占总体的 4 0 0 1% ,而Dio灌胃组经胃肠道排出的Dio占总体的 2 98% ;Dio明显抑制胆固醇与胆汁的结合 ,其抑制率为 98 8%。DX随浓度的提高 ,抑制胆固醇与胆汁结合的能力逐渐加强 ,且具明显的量效关系。 结论 　Dio在肠道中药物吸收利用度及抑制胆固醇与天然胆汁形成微胶粒的作用强度明显优于DX。     

地奥心血康肠道吸收作用的研究及其机制的初步探讨

目的 本文通过给大鼠灌服地奥心血康(DX)及薯蓣皂苷元(Diosgenin,Dio)后，观察两者在胃肠道内吸收的状况，借以进行药效学的比较及离体观察对胆固醇微胶粒形成的抑制作用。方法 给大鼠灌服DX及Dio后，收集粪样品，通过酸水解后，采用薄层扫描定量法(TLCS)测定Dio的含量；将样品与胆固醇和胆汁充分混合后，测定对胆固醇微胶粒形成的抑制作用。结果 DX灌胃组经胃肠道排出的Dio占总体的40．01％，而Dio灌胃组经胃肠道排出的Dio占总体的2．98％；Dio明显抑制胆固醇与胆汁的结合，其抑制率为98．8％。DX随浓度的提高，抑制胆固醇与胆汁结合的能力逐渐加强，且具明显的量效关系。结论 Dio在肠道中药物吸收利用度及抑制胆固醇与天然胆汁形成微胶粒的作用强度明显优于DX。     

参附汤体内代谢化学成分的初步研究

为了确定口服参附汤后体内吸收成分的化学结构 ,分离并鉴定了参附汤的组成成分之一———黑附片的主要成分 ;通过大鼠整体实验方法研究了参附汤体内代谢情况。结果显示 :口服参附汤后 ,乌头类生物碱卡米查林 (carmichaeline ,Ⅰ )、塔拉胺 (talatisamine ,Ⅱ )、附子灵 (fuziline ,Ⅲ )以原形形式被吸收 ,人参皂苷经肠内细菌代谢后以代谢产物CompoundK形式吸收进入体内     

人参皂甙Rb1的肠内菌代谢

目的:通过离体及整体实验观察了人和大鼠肠内菌对人参皂甙Rb1(G-Rb1)的代谢.方法:采用薄层色谱(TLC)和电喷雾质谱(ESI-MS)检测G-Rb1及其代谢产物.结果:离体实验表明,G-Rb1容易被大鼠和人消化道菌群代谢,随着代谢时间的延长,相继出现Rd, Rg3/F2, Rh2/C-K和Ppd 4种代谢产物.给大鼠ig G-Rb1 500 mg.kg-1后收集4 h和6 h粪,提取G-Rb1的代谢产物,证明粪中存在Rd和Rg3/F2两种代谢产物.结论:G-Rb1可被人和大鼠肠内菌代谢,其代谢模式为G-Rb1→Rd→F2→compound K(C-K)→20(S)protopanaxadiol(Ppd).     

人参皂苷Rg1在大鼠体内的代谢与排泄研究

目的 考察静注和口服给予大鼠人参皂苷Rg1溶液后的体内代谢与排泄情况.方法 以Wistar大鼠为模型动物,分别iv和ig给予一定量的人参皂苷Rg1溶液,然后按时收集其排泄物(尿液与粪便),预处理后用HPLC检测.结果 iv给予大鼠人参皂苷Rg1溶液后,有47.46%的原型药和代谢产物通过粪便排出体外;而51.31%的药物以原型或代谢产物的形式通过尿液排出体外;ig给予大鼠人参皂苷Rg1溶液后,绝大部分Rg1都被代谢,排泄物中仅有9.04%的原型药物,且仅有13.6%的人参皂苷Rg1被吸收进入人体再通过尿液排出,还有82.82%的原型药物和代谢产物直接通过粪便排出.结论 人参皂苷Rg1在胆汁中排泄明显,其口服吸收差,生物利用度低,且极易被代谢.     

人参皂甙Rb1的肠内菌代谢

通过离体及整体实验观察了人和大鼠肠内菌对人参皂甙Rb₁（G-Rb₁）的代谢。方法：采用薄层色谱（TLC）和电喷雾质谱（ESI-MS）检测G-Rb₁及其代谢产物。结果：离体实验表明,G-Rb₁容易被大鼠和人消化道菌群代谢,随着代谢时间的延长,相继出现Rd, Rg₃/F₂, Rh₂/C-K和Ppd 4种代谢产物。给大鼠ig G-Rb₁ 500 mg.kg^-1后收集4 h和6 h粪,提取G-Rb₁的代谢产物,证明粪中存在Rd和Rg₃/F₂两种代谢产物。结论：G-Rb₁可被人和大鼠肠内菌代谢,其代谢模式为G-Rb₁→Rd→F₂→compound K（C-K）→20（S）protopanaxadiol（Ppd）。     

Preliminary Studies on the Absorption,Distribution, Metabolism,and Excretion of THIP in Animal and Man using 14C-labelled Compound

Abstract: Distribution of radioactivity in rats, serum levels in human volunteers and rats and elimination of radioactivity in volunteers, rats, and mice following oral administration of ¹⁴C-labelled THIP have been investigated. Peak values of radioactivity in the organs and in serum were seen half an hour after administration, indicating a rapid absorption. Highest concentrations of radioactivity were found in the kidneys, but radioactivity was seen in all investigated tissues including the brain. The radioactivity was mainly excreted with urine (84–93%). Thin-layer chromatography of urine from volunteers, rats, and mice showed that most of the excreted radioactivity corresponds to unchanged THIP. Three metabolites were found in urine from rats each in amounts of 2–7% of the total dose given. Two of these metabolites were also found in urine from the volunteers in amounts of 30–35% and <2%, respectively, and in urine from mice in amounts of 21% and 6% of the total dose, respectively. No radioactivity corresponding to unchanged THIP was found in faeces indicating complete absorption of THIP following oral administration. One of the metabolites, the main one in man and mouse, seemed to be a glucuronic acid conjugate of THIP, but the chemical structure of the metabolites has not yet been established.     

Internal exposure of rats to benzidine derived from orally administered benzidine-based dyes after intestinal azo reduction

The role of the rat intestinal flora in the azo reduction of some benzidine-based dyes was studied in vitro and in vivo. The formation of benzidine was measured after anaerobic incubation of direct black 38, direct blue 6 and direct brown 95 in the presence of caecal bacteria in vitro. Benzidine was absorbed from the intestinal tract much better than the parent compounds. Oral administration of direct black 38 or direct brown 95 to Wistar rats results in the urinary excretion of mutagens. After oral administration of these dyes to germ-free Wistar rats no mutagenicity was observed in urine. The present results show that after oral administration, reduction by the intestinal flora should be considered as the first essential step in the biotoxification of benzidine-based dyes.     

Identification of in‐vivo and in‐vitro metabolites of palmatine by liquid chromatography–tandem mass spectrometry

Objectives Despite its important therapeutic value, the metabolism of palmatine is not yet clear. Our objective was to investigate its in‐vivo and in‐vitro metabolism. Methods Liquid chromatography–tandem electrospray ionization mass spectrometry (LC‐ESI/MSⁿ) was employed in this work. In‐vivo samples, including faeces, urine and plasma of rats, were collected after oral administration of palmatine (20 mg/kg) to rats. In‐vitro samples were prepared by incubating palmatine with intestinal flora and liver microsome of rats, respectively. All the samples were purified via a C₁₈ solid‐phase extraction procedure, then chromatographically separated by a reverse‐phase C₁₈ column with methanol–formic acid aqueous solution (pH 3.5, 70: 30 v/v) as mobile phase, and detected by an on‐line MSⁿ detector. The structure of each metabolite was elucidated by comparing its molecular weight, retention time and full‐scan MSⁿ spectra with those of the parent drug. Key findings The results revealed that 12 metabolites were present in rat faeces, 13 metabolites in rat urine, 7 metabolites in rat plasma, 10 metabolites in rat intestinal flora and 9 metabolites in rat liver microsomes. Except for six of the metabolites in rat urine, the other in‐vivo and in‐vitro metabolites were reported for the first time. Conclusions Seven new metabolites of palmatine (tri‐hydroxyl palmatine, di‐demethoxyl palmatine, tri‐demethyl palmatine, mono‐demethoxyl dehydrogen palmatine, di‐demethoxyl dehydrogen palmatine, mono‐demethyl dehydrogen palmatine, tri‐demethyl dehydrogen palmatine) were reported in this work.     

Identification of ginkgolic acid (15:1) metabolites in rats following oral administration by high-performance liquid chromatography coupled to tandem mass spectrometry

1.?In this article, metabolites of ginkgolic acid (GA) (15:1) in rats plasma, bile, urine and faeces after oral administration have been investigated for the first time by high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) with the aid of on-line hydrogen/deuterium (H/D) exchange technique and β-glucuronidase hydrolysis experiments.

2.?After oral administration of GA (15:1, M0) to rats at a dose of 10?mg/kg, it was found that metabolites M1-M5 together with parent compound (M0) existed in rat plasma; parent compound (M0) and metabolites M2–M5 were observed in rat bile, and parent compound (M0) with metabolites M1 and M2 were discovered in rat faeces, and there was no parent compound and metabolite detectable in rat urine.

3.?Two oxidative metabolites of GA (15:1, M0) were identified as 2-hydroxy-6-(pentadec-8-enyl-10-hydroxy) benzoic acid (M1) and 2-hydroxy-6-(pentadec-8-enyl-11-hydroxy-13-carbonyl) benzoic acid (M2), respectively. Metabolites M3, M4 and M5 were identified as the mono-glucuronic acid conjugates of parent compound (M0), M1 and M2, respectively.

4.?The results indicated that M1 and M2 with parent compound (M0) were mainly eliminated in faeces and three glucuronide metabolites (M3, M4 and M5) excreted in bile as the predominant forms after oral administration of GA (15:1) to rats.     

The metabolism of (+-)-methylephedrine in rat and man

1. Urinary metabolites of methylephedrine and their excretion after oral administration to rat and human volunteers have been studied. 2. The unchanged drug, ephedrine, norephedrine, their aromatic hydroxylated compounds and methylephedrine N-oxide were found in rat urine. The same metabolites, except the p-hydroxylated metabolites, were detected in human urine. The most abundant metabolite in rat urine was methylephedrine N-oxide, and in human urine was the unchanged drug. 3. Metabolites excreted in three days after administration of the drug to rat amounted to about 54% of the dose and those after administration to man, 70-72%.     

The metabolism of dimethylamphetamine in rat and man

1. Urinary metabolites of dimethylamphetamine after oral administration to rat and healthy human volunteers have been studied. 2. Six metabolites and unchanged drug were detected in rat urine and the same metabolites except p-hydroxyamphetamine were found in human urine. The major metabolite was dimethylamphetamine N-oxide in both cases, and methamphetamine and amphetamine were also excreted as minor metabolites. 3. Metabolites excreted in three days after administration of the drug to rat amounted to about 57% of the dose and those after administration to man, 53-56%.     

Metabolism of doxylamine succinate in Fischer 344 rats. Part II: Nonconjugated urinary and fecal metabolites

Elimination and metabolic profiles of doxylamine and its nonconjugated metabolites were determined after the oral administration of [14C]-doxylamine succinate (13.3 mg/kg and 133 mg/kg doses) to male and female Fischer 344 rats. Total urine and fecal recovery of the administered dose was greater than 90% regardless of sex or dose. The cumulative urinary and fecal elimination of these nonconjugated doxylamine metabolites at the 13.3 mg dose was 44.4 +/- 4.4% and 36.0 +/- 5.8% of the total recovered dose for male and female rats, respectively. The cumulative urinary and fecal elimination of the doxylamine nonconjugated metabolites at the 133 mg/kg dose was 38.7 +/- 2.7% and 41.4 +/- 1.0% of the total recovered dose for male and female rats, respectively. In order to determine the contribution of mammalian and bacterial enzymes in the overall metabolism and excretion patterns for doxylamine, two in vitro techniques were investigated. Incubation of [14C]-doxylamine succinate with human and rat intestinal microflora indicated that anaerobic bacteria were not capable of effecting the degradation of [14C]-doxylamine succinate. However, the incubation of [14C]-doxylamine succinate with isolated rat hepatocytes generated several metabolites similar to those observed in vivo. The nonconjugated doxylamine metabolites isolated and identified include: doxylamine N-oxide, desmethyldoxylamine, didesmethyldoxylamine and ring-hydroxylated products of doxylamine and desmethyldoxylamine. The studies demonstrate the role of hepatic metabolism in the elimination of doxylamine succinate in the rat.