Urinary metabolites of icariin, present in Epimedium, were investigated using rats. In the urine of rats administered icariin orally, two major metabolites were detected, which were identified as icariside II and icar...Urinary metabolites of icariin, present in Epimedium, were investigated using rats. In the urine of rats administered icariin orally, two major metabolites were detected, which were identified as icariside II and icaritin by means of spectral data.展开更多
仙灵骨葆口服制剂是我国治疗骨病的中药大品种,但近年来国家食品药品监督管理总局通报其易引起肝损伤。传统毒理学研究很难评价其肝损伤作用,我们前期发现仙灵骨葆肝损伤具有特异质属性,拆方研究发现补骨脂和淫羊藿是其导致特异质肝损...仙灵骨葆口服制剂是我国治疗骨病的中药大品种,但近年来国家食品药品监督管理总局通报其易引起肝损伤。传统毒理学研究很难评价其肝损伤作用,我们前期发现仙灵骨葆肝损伤具有特异质属性,拆方研究发现补骨脂和淫羊藿是其导致特异质肝损伤的主要药味,且配伍后其特异质肝损伤加重,呈现七情配伍中“相反”的特点。进一步研究发现,TNF-α介导的免疫应激是其重要诱因,免疫促进成分和肝损伤易感成分存在是其另一重要诱因。然而,具体机制尚不清楚。本研究通过建立动物模型,考察了免疫促进淫羊藿次苷Ⅱ联合肝损伤易感成分补骨脂甲素对小鼠肝损伤的影响;借助非靶向代谢组学技术评价了两个成分联合对肝损伤代谢标志物的影响;利用16S r RNA测序技术探讨了肠道菌群的物种组成和相对丰度的变化。结果表明在TNF-α诱导的免疫应激小鼠模型上发现,单独给药补骨脂甲素能够引起明显肝损伤,而淫羊藿次苷Ⅱ组却无明显变化,但是淫羊藿次苷Ⅱ能够协同补骨脂甲素导致特异质肝损伤;同时代谢组学结果揭示补骨脂甲素联合淫羊藿次苷Ⅱ能够引起小鼠肝脏中甲基氨基甲酰PAF、吲哚-3-醋酸甲酯等代谢物的水平升高,而甘氨酸-酪氨酸(Gly-Tyr)、L-亮氨酰-L-甘氨酸(Leu-Gly)和L-色氨酸-L-丝氨酸(Trp-Ser)等代谢物的水平则下降。这些与肝损伤相关的差异表达代谢物主要富集在鞘脂代谢、鞘脂信号通路和坏死等代谢途径。值得注意的是,补骨脂甲素联合淫羊藿次苷Ⅱ可以诱导肝损伤小鼠肠道中的乳酸杆菌和脱硫弧菌科丰度显著增加。相关性分析结果表明,类杆菌科和脱硫弧菌科与甲基氨基甲酰基PAF和吲哚-3-醋酸甲酯呈正相关,而与Gly-Tyr、Leu-Gly和Trp-Ser呈负相关。本研究初步阐明了补骨脂配伍淫羊藿引起特异质型药物性肝损伤的物质基础和机制,为中成药临床合理�展开更多
Further investigation of the metabolites of orally administered icariin in rats was made. Two minor metabolites, icariside I and icariside II, were identified in gastric content, and two metabolites, icariside II and ...Further investigation of the metabolites of orally administered icariin in rats was made. Two minor metabolites, icariside I and icariside II, were identified in gastric content, and two metabolites, icariside II and icaritin, in intestinal content. The major metabolic route of icariin was proposed.展开更多
The biliary metabolites of orally administered icariin in rats were investigated. Two metabolites B-l and B-2 were isolated and identified as icaritin 3-O-alpha-L-rhamnopyranosyl-7-O-beta-D-glucopyranuronoside and ica...The biliary metabolites of orally administered icariin in rats were investigated. Two metabolites B-l and B-2 were isolated and identified as icaritin 3-O-alpha-L-rhamnopyranosyl-7-O-beta-D-glucopyranuronoside and icariside II, respectively, on the basis of chemical and spectroscopic evidences.展开更多
Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
文摘Urinary metabolites of icariin, present in Epimedium, were investigated using rats. In the urine of rats administered icariin orally, two major metabolites were detected, which were identified as icariside II and icaritin by means of spectral data.
基金supported by the National Natural Science Foundation of China (82174071)。
文摘仙灵骨葆口服制剂是我国治疗骨病的中药大品种,但近年来国家食品药品监督管理总局通报其易引起肝损伤。传统毒理学研究很难评价其肝损伤作用,我们前期发现仙灵骨葆肝损伤具有特异质属性,拆方研究发现补骨脂和淫羊藿是其导致特异质肝损伤的主要药味,且配伍后其特异质肝损伤加重,呈现七情配伍中“相反”的特点。进一步研究发现,TNF-α介导的免疫应激是其重要诱因,免疫促进成分和肝损伤易感成分存在是其另一重要诱因。然而,具体机制尚不清楚。本研究通过建立动物模型,考察了免疫促进淫羊藿次苷Ⅱ联合肝损伤易感成分补骨脂甲素对小鼠肝损伤的影响;借助非靶向代谢组学技术评价了两个成分联合对肝损伤代谢标志物的影响;利用16S r RNA测序技术探讨了肠道菌群的物种组成和相对丰度的变化。结果表明在TNF-α诱导的免疫应激小鼠模型上发现,单独给药补骨脂甲素能够引起明显肝损伤,而淫羊藿次苷Ⅱ组却无明显变化,但是淫羊藿次苷Ⅱ能够协同补骨脂甲素导致特异质肝损伤;同时代谢组学结果揭示补骨脂甲素联合淫羊藿次苷Ⅱ能够引起小鼠肝脏中甲基氨基甲酰PAF、吲哚-3-醋酸甲酯等代谢物的水平升高,而甘氨酸-酪氨酸(Gly-Tyr)、L-亮氨酰-L-甘氨酸(Leu-Gly)和L-色氨酸-L-丝氨酸(Trp-Ser)等代谢物的水平则下降。这些与肝损伤相关的差异表达代谢物主要富集在鞘脂代谢、鞘脂信号通路和坏死等代谢途径。值得注意的是,补骨脂甲素联合淫羊藿次苷Ⅱ可以诱导肝损伤小鼠肠道中的乳酸杆菌和脱硫弧菌科丰度显著增加。相关性分析结果表明,类杆菌科和脱硫弧菌科与甲基氨基甲酰基PAF和吲哚-3-醋酸甲酯呈正相关,而与Gly-Tyr、Leu-Gly和Trp-Ser呈负相关。本研究初步阐明了补骨脂配伍淫羊藿引起特异质型药物性肝损伤的物质基础和机制,为中成药临床合理�
文摘Further investigation of the metabolites of orally administered icariin in rats was made. Two minor metabolites, icariside I and icariside II, were identified in gastric content, and two metabolites, icariside II and icaritin, in intestinal content. The major metabolic route of icariin was proposed.
文摘The biliary metabolites of orally administered icariin in rats were investigated. Two metabolites B-l and B-2 were isolated and identified as icaritin 3-O-alpha-L-rhamnopyranosyl-7-O-beta-D-glucopyranuronoside and icariside II, respectively, on the basis of chemical and spectroscopic evidences.
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
