Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs

BackgroundAnemoside B4 (AB4), a pentacyclic triterpenoid saponin extracted from the traditional Chinese medicinal herb Pulsatilla chinensis, has shown anti-inflammatory and immunomodulatory effects in both preclinical and clinical studies. However, pharmacokinetic and safety data in dogs remain limi...

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Main Authors: Jinzhao Ji, Yuqiao Ma, Shaobing Wan, Xiaoqing Ding, Jingyu Wang, Yongcheng Zhong, Yangyang Song, Junqing Zhao, Zhetong Su, Kun Jia, Shoujun Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Veterinary Science
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Online Access:https://www.frontiersin.org/articles/10.3389/fvets.2025.1645372/full
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author Jinzhao Ji
Jinzhao Ji
Yuqiao Ma
Yuqiao Ma
Shaobing Wan
Shaobing Wan
Xiaoqing Ding
Xiaoqing Ding
Jingyu Wang
Jingyu Wang
Yongcheng Zhong
Yongcheng Zhong
Yangyang Song
Junqing Zhao
Zhetong Su
Kun Jia
Kun Jia
Shoujun Li
Shoujun Li
author_facet Jinzhao Ji
Jinzhao Ji
Yuqiao Ma
Yuqiao Ma
Shaobing Wan
Shaobing Wan
Xiaoqing Ding
Xiaoqing Ding
Jingyu Wang
Jingyu Wang
Yongcheng Zhong
Yongcheng Zhong
Yangyang Song
Junqing Zhao
Zhetong Su
Kun Jia
Kun Jia
Shoujun Li
Shoujun Li
author_sort Jinzhao Ji
collection DOAJ
description BackgroundAnemoside B4 (AB4), a pentacyclic triterpenoid saponin extracted from the traditional Chinese medicinal herb Pulsatilla chinensis, has shown anti-inflammatory and immunomodulatory effects in both preclinical and clinical studies. However, pharmacokinetic and safety data in dogs remain limited. This study aimed to evaluate the pharmacokinetics, bioavailability, and safety of AB4 in healthy Beagle dogs.MethodsIn the single-dose pharmacokinetic study, 40 dogs received subcutaneous AB4 at 10, 20, or 40 mg/kg, or an intravenous bolus at 20 mg/kg. Plasma concentrations were measured using a validated HPLC–MS/MS method to determine pharmacokinetic parameters, bioavailability, dose proportionality, and sex-related differences. In the repeated-dose study, 10 dogs received 20 mg/kg subcutaneously once daily for 7 consecutive days to evaluate drug accumulation and fluctuation. In the target animal safety study, 32 dogs were randomly assigned to receive 1× (20 mg/kg), 3× (60 mg/kg), or 5× (100 mg/kg) doses of AB4, and saline as a control, via daily subcutaneous injection for 7 days. Routine clinical examinations, hematology, serum biochemistry, gross necropsy, and histopathology were assessed.ResultAB4 exhibited rapid elimination, high absolute bioavailability, and dose-proportional pharmacokinetics in the 10–40 mg/kg range. No evidence of accumulation after repeated dosing. Within the dose range of 20–100 mg/kg, AB4 demonstrated good safety, with no observable toxicity or adverse effects. No significant effects were observed on physiological parameters. Histopathological analysis revealed no consistent or target-organ specific lesions.DiscussionThese findings provide fundamental pharmacokinetic and safety data to support the rational clinical use of AB4 in veterinary medicine and lay the groundwork for future clinical applications.
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spelling doaj-art-bc82c7257ff548c4b65d8ef90ea6494a2025-08-20T02:50:08ZengFrontiers Media S.A.Frontiers in Veterinary Science2297-17692025-07-011210.3389/fvets.2025.16453721645372Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogsJinzhao Ji0Jinzhao Ji1Yuqiao Ma2Yuqiao Ma3Shaobing Wan4Shaobing Wan5Xiaoqing Ding6Xiaoqing Ding7Jingyu Wang8Jingyu Wang9Yongcheng Zhong10Yongcheng Zhong11Yangyang Song12Junqing Zhao13Zhetong Su14Kun Jia15Kun Jia16Shoujun Li17Shoujun Li18College of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaGuangxi Innovate Pharmaceutical Co., Ltd., Liuzhou, Guangxi, ChinaGuangxi Innovate Pharmaceutical Co., Ltd., Liuzhou, Guangxi, ChinaGuangxi Innovate Pharmaceutical Co., Ltd., Liuzhou, Guangxi, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou, ChinaGuangdong Technological Engineering Research Center for Pet, Guangzhou, ChinaBackgroundAnemoside B4 (AB4), a pentacyclic triterpenoid saponin extracted from the traditional Chinese medicinal herb Pulsatilla chinensis, has shown anti-inflammatory and immunomodulatory effects in both preclinical and clinical studies. However, pharmacokinetic and safety data in dogs remain limited. This study aimed to evaluate the pharmacokinetics, bioavailability, and safety of AB4 in healthy Beagle dogs.MethodsIn the single-dose pharmacokinetic study, 40 dogs received subcutaneous AB4 at 10, 20, or 40 mg/kg, or an intravenous bolus at 20 mg/kg. Plasma concentrations were measured using a validated HPLC–MS/MS method to determine pharmacokinetic parameters, bioavailability, dose proportionality, and sex-related differences. In the repeated-dose study, 10 dogs received 20 mg/kg subcutaneously once daily for 7 consecutive days to evaluate drug accumulation and fluctuation. In the target animal safety study, 32 dogs were randomly assigned to receive 1× (20 mg/kg), 3× (60 mg/kg), or 5× (100 mg/kg) doses of AB4, and saline as a control, via daily subcutaneous injection for 7 days. Routine clinical examinations, hematology, serum biochemistry, gross necropsy, and histopathology were assessed.ResultAB4 exhibited rapid elimination, high absolute bioavailability, and dose-proportional pharmacokinetics in the 10–40 mg/kg range. No evidence of accumulation after repeated dosing. Within the dose range of 20–100 mg/kg, AB4 demonstrated good safety, with no observable toxicity or adverse effects. No significant effects were observed on physiological parameters. Histopathological analysis revealed no consistent or target-organ specific lesions.DiscussionThese findings provide fundamental pharmacokinetic and safety data to support the rational clinical use of AB4 in veterinary medicine and lay the groundwork for future clinical applications.https://www.frontiersin.org/articles/10.3389/fvets.2025.1645372/fullanemoside B4pharmacokineticssafetydogveterinary medicine
spellingShingle Jinzhao Ji
Jinzhao Ji
Yuqiao Ma
Yuqiao Ma
Shaobing Wan
Shaobing Wan
Xiaoqing Ding
Xiaoqing Ding
Jingyu Wang
Jingyu Wang
Yongcheng Zhong
Yongcheng Zhong
Yangyang Song
Junqing Zhao
Zhetong Su
Kun Jia
Kun Jia
Shoujun Li
Shoujun Li
Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
Frontiers in Veterinary Science
anemoside B4
pharmacokinetics
safety
dog
veterinary medicine
title Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
title_full Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
title_fullStr Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
title_full_unstemmed Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
title_short Pharmacokinetics and safety evaluation of anemoside B4 in healthy Beagle dogs
title_sort pharmacokinetics and safety evaluation of anemoside b4 in healthy beagle dogs
topic anemoside B4
pharmacokinetics
safety
dog
veterinary medicine
url https://www.frontiersin.org/articles/10.3389/fvets.2025.1645372/full
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