Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository
文献类型：期刊论文
| 作者 | Ye, Yaqing2,3,4; Xue, Mingzhen1,3; Tian, Xiaoting3; Gao, Hongwei5; Hu, Pei3; Wang, Linwei3,6; Leng, Jing2,4; Xue, Yaru3; Huang, Chenggang3
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| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
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| 出版日期 | 2023-10-28 |
| 卷号 | 315页码:11 |
| 关键词 | Anemoside B4 Pulsatilla chinensis metabolite identification Pharmacokinetics Rectal suppository |
| ISSN号 | 0378-8741 |
| DOI | 10.1016/j.jep.2023.116694 |
| 通讯作者 | Leng, Jing(lj986771558@163.com) ; Xue, Yaru(xueyaru3@simm.ac.cn) ; Huang, Chenggang(cghsimm@126.com) |
| 英文摘要 | Ethnopharmacological relevance: Pulsatilla chinensis (Bunge) Regel is a traditional Chinese herbal medicine used to treat intestinal amebiasis, malaria, vaginal trichomoniasis, and bacterial infections. Anemoside B4 (AB4), a pentacyclic triterpenoid saponin, is one of the primary bioactive substances in Pulsatilla chinensis (Bunge) Regel, and gavage administration of AB4 to animals has been demonstrated to exhibit anticancer, anti-inflammatory, and antiviral actions. However, AB4 exposure in plasma is very low after oral administration, and the biotransformation of AB4 in vivo after oral administration remains unknown. Aim of the study: The reason for conducting this research was to explore at the metabolite profile of AB4 in rats following oral administration. Additionally, we aimed to develop an appropriate extravascular formulation to increase the exposure and duration of AB4 in vivo.Materials and methods: A well-validated HPLC-QQQ-MS/MS method was used for the quantification of AB4 in plasma and was further applied to evaluate and compare the pharmacokinetic properties of AB4 dissolved in a saline solution and AB4 formulations in a rectal suppository or enteric capsule. Reliable UHPLC coupled to QExactive Plus high-resolution MS was used to identify the metabolites in rat plasma, bile, urine, and faeces. Results: AB4 was extensively metabolized, and a total of 29 metabolites were identified. The primary metabolic routes included deglycosylation, oxidation, dehydrogenation, reduction, sulfation, hydration, acetylation, and glucuronidation. The pharmacokinetic comparison showed that both the rectal suppository and enteric capsule increased the exposures of AB4 and one of its active metabolites, 23-hydroxybetulinic acid (23-HA). Notably, rectal suppositories increased systemic AB4 exposure (AUC0-infinity) by approximately 49 and 28 times higher than that of the AB4 saline solution and enteric capsules, respectively. The t1/2 of AB4 was extended to approximately 7 h after rectal administration compared to 2 h after oral administration. |
| WOS关键词 | LIQUID-CHROMATOGRAPHY ; ACID |
| 资助项目 | National Outstanding Youth Science Fund Project of the Natural Science Foundation of China[82204585] ; Chinese Academy of Sciences -Guangxi STS Program Project[KFJ-STS-QYZD-2021-03-001] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001010962500001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/306391]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Leng, Jing; Xue, Yaru; Huang, Chenggang |
| 作者单位 | 1.Nanjing Univ Chinese Med, Jiangsu Key Lab Funct Subst Chinese Med, Nanjing 210023, Peoples R China 2.Guangxi Univ Chinese Med, Guangxi Key Lab Translat Med Treating High Inciden, Nanning 530000, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 4.Guangxi Chinese Med Univ, Dept Microbiol & Immunol, Nanning 530000, Peoples R China 5.Guangxi Univ Chinese Med, Coll Pharm, Nanning 530000, Peoples R China 6.Shanghai Univ Engn Sci, Coll Chem & Chem Engn, Shanghai 201620, Peoples R China |
| 推荐引用方式 GB/T 7714 | Ye, Yaqing,Xue, Mingzhen,Tian, Xiaoting,et al. Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository[J]. JOURNAL OF ETHNOPHARMACOLOGY,2023,315:11. |
| APA | Ye, Yaqing.,Xue, Mingzhen.,Tian, Xiaoting.,Gao, Hongwei.,Hu, Pei.,...&Huang, Chenggang.(2023).Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository.JOURNAL OF ETHNOPHARMACOLOGY,315,11. |
| MLA | Ye, Yaqing,et al."Pharmacokinetic and metabolite profile of orally administered anemoside B4 in rats with an improved exposure in formulations of rectal suppository".JOURNAL OF ETHNOPHARMACOLOGY 315(2023):11. |
入库方式： OAI收割
来源：上海药物研究所
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