CURRENT DRUG METABOLISM
·
2024
·Vol. 25
·期 5
·317-329
·
IF 2.1
Xiaocui Li,Qi Liang,Caiyan Wang,Huawei Qiu,Tingting Lin,Wentao Li,Rong Zhang,Zhongqiu Liu,Lijun Zhu
BackgroundYunaconitine (YAC) is a hidden toxin that greatly threatens the life safety of patients who are prescribed herbal medicines containing Aconitum species; however, its underlying mechanism remains unclear.ObjectiveThe objective of this study is to elucidate the functions of P-glycoprotein (P-gp) in regulating the efficacy, toxicity, and pharmacokinetics of YAC.MethodsThe efflux function of P-gp on YAC was explored by using Caco-2 monolayers in combination with the P-gp inhibitor verapamil. The impact of P-gp on regulating the analgesic and anti-inflammatory effects, acute toxicity, tissue distribution, and pharmacokinetics of YAC was determined via male Mdr1a gene knocked-out mice and wild-type FVB mice.ResultsThe presence of verapamil significantly decreased the efflux ratio of YAC from 20.41 to 1.07 in Caco-2 monolayers (P < 0.05). Moreover, oral administration of 0.07 and 0.14 mg/kg YAC resulted in a notable decrease in writhing times in Mdr1a-/- mice by 23.53% and 49.27%, respectively, compared to wild-type FVB mice (P < 0.05). Additionally, the deficiency of P-gp remarkably decreased the half-lethal dose (LD50) of YAC from 2.13 to 0.24 mg/kg (P < 0.05). Moreover, the concentrations of YAC in the tissues of Mdr1a-/- mice were statistically higher than those in wild-type FVB mice (P < 0.05). Particularly, the brain accumulation of YAC in Mdr1a-/- mice significantly increased by 12- and 19-fold, respectively, after oral administration for 30 and 120 min, when compared to wild-type FVB mice (P < 0.05). There were no significant differences in the pharmacokinetic characteristics of YAC between Mdr1a-/- and wild-type FVB mice.ConclusionYAC is a sensitive substrate of P-gp. The absence of P-gp enhances the analgesic effect and toxicity of YAC by upregulating its brain accumulation. Co-administration with a P-gp inhibitor may lead to severe YAC poisoning.
研究领域:
药理学
·
毒理学
·
中药学
✓ 已验证
DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Lei Ding,Xuan Zhou,Xiaojie Liang,Yujin Dong,Cunbao Fang,Yueming Wu,Beixing Li,Wei Mu,Jin Lin,Yuekun Li
Pesticide residue has become the main technical barrier that restricts the export of Chinese wolfberry. Can we achieve high efficacy and low safety risk by balancing pesticide deposition on the leaves and fruits of Chinese wolfberry? In this research, the structural characteristics and wettability of leaves and fruits of Chinese wolfberry at different growth stages were studied. The adaxial and abaxial surfaces of leaves were hydrophobic, whereas the fruit surfaces were hydrophilic. Adding spray adjuvant could increase the retention of droplets on the leaf surfaces of Chinese wolfberry by 52.28–97.89% and reduce the retention on the fruit surfaces by 21.68–42.14%. A structural equation model analysis showed that the adhesion tension was the key factor affecting the retention of the solutions among various interface behaviors. When the concentrations of Silwet618, AEO-5, Gemini 31551, and 1227 were 2–5 times higher than their CMCs, the retention of pesticide solutions (pyraclostrobin and tylophorine) on Chinese wolfberry leaves significantly increased, and the control efficacies on aphids and powdery mildew also dramatically improved (65.90–105.15 and 41.18–133.06%, respectively). Meanwhile, the retention of pesticides on the fruit of Chinese wolfberry was reduced. This study provides new insights into increasing the utilization of pesticides in controlling pests and improving food safety.
研究领域:
植物保护
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food & Function
·
2018
·Vol. 9
·期 11
·5880-5890
·
IF 3.289
Xiuling Tang,Huanhuan Zhao,Wei Jiang,Song Zhang,Shun Guo,Xiaobo Gao,Peng Yang,Lei Shi,Linna Liu
Dry citrus peel (Chenpi) is not only consumed as a dietary supplement, but also used for the treatment of respiratory diseases. Pinelliae Rhizoma Praeparatum (Banxia) is always used with Chenpi for the treatment of respiratory diseases, but β-sitosterol, the main active component in Banxia, as a food additive, shows no respiratory system activity. In the present study, the pharmacokinetic characters showed that the absorption of the active components of Chenpi was accelerated under pathological conditions combined with Banxia. Although the bioavailability of active components did not significantly change, the distribution of active components in tissues increased, particularly in the target organ. These results are consistent with the combination of Chenpi with β-sitosterol. Furthermore, the pharmacodynamics result also indicated that Chenpi combined with Banxia or β-sitosterol was able to ameliorate histopathologic damage and decrease the levels of inflammatory factors. The results suggest that pharmacokinetic interactions improve the pharmacological activity of Chenpi in respiratory diseases.
研究领域:
药理学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PEST MANAGEMENT SCIENCE
·
2021
·Vol. 78
·期 2
·812-820
·
IF 4.845
Fengjiao Hao,Xiaohui Liu,Huizhu Yuan,Xiaojing Yan,Daibin Yang
BACKGROUND Seedling transplanting is widely used in rice cultivation. Systemic insecticides can be delivered to seedling roots by application through rice seedling boxes before transplanting. The most challenging aspect is to provide long-term control of rice pests and overcome transplanting shock. Precise control of the release rate of insecticide can meet these requirements. Pymetrozine is a promising insecticide used for the control of rice planthoppers resistant to neonicotinoid insecticides. RESULTS In this study, four controlled-release granular formulations of pymetrozine were prepared based on a mixture of cost-effective and biodegradable kaolin and xanthan gum or a mixture of calcined kaolin and xanthan gum. Fluorescence images showed that different 3D networks were formed in the four granular formulations. The four granular formulations showed different water uptake rates and release rates of pymetrozine in water. Pymetrozine release rate was positively correlated with the water uptake capacity, rather than the water uptake rate of granules. Diffusion was the dominant mechanism for the release of pymetrozine from granules. Pymetrozine was found to reduce the survival of transplanted rice seedlings suffering from transplanting shock. Incorporating pymetrozine in controlled-release granules alleviated this phytotoxicity. The survival rate of rice seedlings in granular pymetrozine treatments ranged 68.8–85.0%, whereas the survival rate was <50% for powdered pymetrozine treatments. Additionally, four prepared granule formulations had a significant control effect on rice planthopper with efficacies ranging from 76.7% to 98.0% 40 days after seedling box treatment. CONCLUSIONS The granule with an intermediate release rate of pymetrozine was shown to be more suitable for seedling box treatment than field application and traditional liquid spraying for the long-term control of paddy planthoppers. © 2021 Society of Chemical Industry.
研究领域:
农业科学
·
植物保护
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 5
·e0322835
·
IF 2.6
Fujie Xu,Xiaohang Shan,Jialin Li,Jing Li,Jiqiao Yuan,Daozeng Zou,Manyuan Wang
Artemisinin-based combination therapies (ACTs) constitute the principal strategy for combating malaria in contemporary times, and research into the multifaceted components of Artemisia annua L. ( A. annua ) has garnered widespread interest among scientists. The aim of this study was to prepare A. annua extracts (nACTs) and to explore whether nACTs have higher bioavailability and efficacy than artemisinin (ART) alone due to its multiple bioactive components. Initially, the in vivo antimalarial activity of nACTs was evaluated by two murine malaria models. The results revealed that the antimalarial effect of nACTs was about 10-fold higher than that of ART alone when administered at the same dosage of ART. Then, we analyzed the pharmacokinetic characteristics of nACTs in rat plasma. Remarkably, nACTs exhibited significantly enhanced oral bioavailability, longer half-life as well as extended mean retention time in rats. In addition, the impact of nACTs on P-glycoprotein (P-gp) was evaluated using the Caco-2 cell line. The results showed that both ART and nACTs reduced the efflux rate of the P-gp substrate rhodamine 123 (R123) and induced the expression of P-gp in Caco-2 cells over a range of concentrations. nACTs had certain components-deoxyartemisinin (DEART), artemisinic acid (AA), and dihydroartemisinic acid (DHAA)-that inhibited the efflux and translocation of P-gp and facilitated the reduction of ART efflux. In conclusion, A. annua extracts significantly improved the antimalarial efficacy and bioavailability compared with ART.
研究领域:
药理学
·
寄生虫学
·
植物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yafei Li,Mingfang Zhao,Rui Tang,Keer Fang,Yu Ye,Bing Zhu,Lei Chen,Yutian Chen,Weihong Ge,Weifeng Du
Ethnopharmacological relevance The quality control methods of different specifications of Corydalis Rhizoma in Zhejiang China (ZJ CR) are the same, so the quality of each specification couldnot be guaranteed. To clarify the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications could provide reference for the quality control of ZJ CR. Aim of the study The purpose of this study was to establish a quality control method for ZJ CR with different specifications and to screen out the pharmacodynamic material basis of ZJ CR with different specifications. Materials and methods Firstly, according to the existing grading standards, the medicinal materials were divided into specifications, and the character indexes of ZJ CR with different specifications were established. The quality indexes were established by HPLC, network pharmacology and literature retrieval. The correlation between the trait indexes and quality indexes of ZJ CR with different specifications was analyzed, and the best quality control method was established. Further combined with the pharmacodynamic indexes of ZJ CR with different specifications, the pharmacodynamic material basis of ZJ CR with different specifications was screened out by spectrum-effect analysis. The correlation between trait indexes and pharmacodynamic indexes was analyzed to verify the rationality of grade standard. Results The three specifications of ZJ CR were CR (Diameter ≥1.1 cm), CR (Diameter <1.1 cm), and CR (No size distinction). Diameter, width, thickness, grain weight, volume and 50 g grain number could be used as the trait indexes of ZJ CR. Protopine (CR1), palmatine hydrochloride (CR2), berberine hydrochloride (CR3), dehydrocorydaline (CR4), tetrahydropalmatine (CR5), tetrahydroberberine (CR6), corydaline (CR7), stylopine (CR8) and isoimperatorin (CR9) were identified. Total components, core components (CR5, CR6, CR7 and CR8), alcohol-soluble extracts (ASE) could be used as quality indexes. The best quality control methods of the three specifications respectively were: the larger the diameter and grain weight, the smaller the number of 50 g grains; The larger the diameter, the smaller the volume, thickness, width and number of 50 g particles; The larger the grain weight and volume, the smaller the number of 50 g grains. The main analgesic components of the three specifications respectively were: CR1, CR2 and core components; CR2, CR4; CR8, CR9. The larger the diameter and the less the number of 50 g grains, the better the analgesic effect of ZJ CR, and the grade standard was reasonable. Conclusions This study showed that the quality control methods and pharmacodynamic material basis of ZJ CR with different specifications were different, which may be caused by the differences in traits and the contribution of main active ingredients. This study constructed an evaluation model combining external traits, internal quality and overall efficacy, and provided theoretical support for the rationality of ZJ CR grade standard.
研究领域:
民族药理学
·
中药学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2022
·
IF 16.744
Tong-fang Jing,Da-xia Zhang,Yan Jin,Guo-dong Si,Bei-xing Li,Wei Mu,Feng Liu
Sorption is the key process that regulates the dispersion of pesticides in the environment once they are introduced into the soil. However, the relationship between the molecular structures of these compounds and the sorption mechanism needs to be further clarified. Our objectives were to uncover sorption drivers in distinct soil samples for the parent avermectin B1a (–OH:3) and pharmacophore-altered derivatives [derivative-1 (–OH:2) and derivative-2 (–OH:1) series]. Avermectin B1a sorption to soil was extensive and essentially irreversible, with avermectin B1a exhibiting significantly greater sorption than the derivatives. The sorption difference between avermectin B1a and derivatives in soil suggested that –OH pharmacophore was the main sorption site for avermectin B1a in soil. Further sorption tests on avermectin B1a and derivatives were carried out on humic acid fractions (HA1 and HA2) that we extracted from the soil. Avermectin B1a sorbed most extensively to humic acid fractions, followed by derivative-1 and derivative-2, thereby indicating the –OH pharmacophore remains the main site for the sorption of avermectin B1a and derivatives by the humic acid fractions. The HA1 fraction showed significantly greater sorption of the compound than the HA2 fraction. Elemental analysis and 13 C NMR analysis demonstrated that the HA1 fraction contains more polar functional groups than the HA2 fraction. This suggests that the sorption of avermectin B1a and derivatives by the soil is due to the interaction between the –OH pharmacophore and the polar functional groups in the humic acid, implying that hydrogen bonding may be the main sorption mechanism. This study highlighted the potential sorption mechanisms of pharmacophores in pesticide compounds with humic acid fractions.
研究领域:
环境科学
·
土壤学
·
农药化学
✓ 已验证
产品关联
DOI
高影响因子
Veterinary Sciences
·
2025
·Vol. 12
·期 4
·294
·
IF 2.3
Tiantian Gao,Xuesong Liu,Di Qiu,Yanan Li,Zongsheng Qiu,Jingjing Qi,Shuxin Li,Xiaoyan Guo,Yan Zhang,Ziqi Wang,Xiang Gao,Yuhui Ma,Tianwen Ma
Simple SummaryBacterial infection is a major cause of death in foals.Escherichia coli(E. coli) is a Gram-negative bacterium that causes sepsis, which can be life-threatening in horses. Cefquinome has broad-spectrum antimicrobial activity and is widely used in the treatment of animal diseases. At the same time, it is the fourth generation of cephalosporin antibiotics for veterinary use, and it has good antibacterial activity against both Gram-positive and Gram-negative bacteria. Cefquinome is utilized for the treatment of septicemia induced byE. coli, as well as respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, there is a lack of studies using cefquinome to targetE. colias a pathogen of sepsis. Pharmacokinetic/pharmacodynamic (PK/PD) modeling is a fundamental step in semi-mechanical methodology aimed at improving dose planning of systemically active antimicrobial agents. PK/PD models can determine the relationship between drug concentration, antibacterial action, and time, deriving the most effective dosing regimen. This study was based on this model to verify the optimal dosing regimen forE. coliinfection in foals and to provide a theoretical basis for the precision treatment of foals.Cefquinome is used to treat septicemia caused byEscherichia coli(E. coli) and respiratory infections caused byStreptococcus equisubsp.zooepidemicusin foals. However, studies reporting the use of cefquinome to targetE. colias pathogens of sepsis are lacking. Therefore, this study aimed to determine the optimal dosage regimen for cefquinome againstE. coliusing a PK/PD model. After the administration of 1 mg/kg cefquinome (intramuscularly or intravenously), blood samples were collected at different time points to determine the serum concentration of cefquinome via HPLC. The pharmacokinetic parameters were evaluated via NCA (WinNonlin 5.2.1 software). The main pharmacokinetic parameters of cefquinome in foals were as follows: after intravenous administration, the elimination half-life (T1/2β) was 2.35 h, the area under the curve (AUC0–last) was 12.33 μg·h/mL, the mean residence time (MRT0–last) was 2.67 h, and the clearance rate (CL) was 0.09 L/h/kg. After intramuscular administration, the peak concentration (Cmax) was 0.89 μg/mL, the time to reach the maximum serum concentration (Tmax) was 2.16 h, T1/2βwas 4.16 h, AUC0–lastwas 5.41 μg·h/mL, MRT0–lastwas 4.92 h, CL was 0.15 L/h/kg, and the absolute bioavailability (F) was 43.86%. An inhibitory sigmoid Emax model was used to integrate the PK/PD indices with ex vivo antimicrobial effects to identify pharmacodynamic targets (PDTs). According to the dose calculation formula, the doses of intramuscularly administered cefquinome required to achieve bacteriostatic effects, bactericidal effects, and bactericidal elimination were 1.10, 1.66, and 2.28 mg/kg, respectively. However, further studies are warranted to verify the therapeutic efficacy of cefquinome in clinical settings.
研究领域:
兽医学
·
微生物学
·
药物动力学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BMC Veterinary Research
·
2021
·Vol. 17
·期 1
·1-13
·
IF 2.741
Liu Xuesong,Yang Qingwen,Fan Yuying,Du Yuanyi,Lei Lei,Wang Dong,Liu Yun
Background Enrofloxacin is an antibacterial drug with broad-spectrum activity that is widely indicated for veterinary use. We aim to develop the clinical applications of Enrofloxacin against colibacillosis by using the neutropenic mice thigh infection model. Results The minimum inhibitory concentration (MIC) distribution of 67 isolated E. coli strains to ENR was calculated using CLSI guidelines. Whereas, the MIC 50 value calculation was considered as the population PD parameter for ENR against E. coli strains. The MIC values of 15 E. coli strains were found to be nearest to the MIC 50 i.e. , 0.25 μg/mL. Of all the tested strains, the PK-PD and E. coli disease model was established via selected E. coli strain i.e. , Heilong 15. We analyzed the PK characteristics of ENR and its metabolite ciprofloxacin (CIP) following a single subcutaneous (s.c.) injection of ENR (1.25, 2.5, 5, 10 mg/kg). The concentration-time profiling of ENR within the plasma specimens was determined by considering the non-compartmental analysis (NCA). The basic PK parameters of ENR for the peak drug concentration (C max ) and the area under the concentration-time curve (AUC) values were found to be in the range of 0.27–1.97 μg/mL and 0.62–3.14 μg.h/mL, respectively. Multiple s.c. injection over 24 h (1.25, 2.5, 5, 10 mg/kg at various time points i.e. , 6, 8, 12, and 24 h respectively) were administered to assess the targeted PD values. The Akaike Information Criterion (AIC) was used to choose PD models, and the model with the lowest AIC was chosen. The inhibitory E max model was employed to calculate the related PK-PD parameters. The results of our study indicated that there was a strong correlation between the AUC/MIC and various antibacterial activities (R 2 = 0.9928). The target values of dividing AUC/MIC by 24 h for bacteriostatic action were 1-log10 reduction, 2-log10 reduction, and 3-log10 reduction 0.325, 0.4375, 0.63, and 0.95 accordingly. Conclusion The identified pharmacodynamics targets for various antibacterial effects will be crucial in enhancing ENR clinical applications and serving as a key step in reducing bacterial resistance.
研究领域:
兽医学
·
微生物学
·
药理学
✓ 已验证
DOI
高影响因子
Nature Communications
·
2025
·Vol. 16
·期 1
·1-13
·
IF 15.7
Yang Jian,Gong Xia,Zheng Ying,Duan Hong,Chen Shuijin,Wu Tong,Yi Changqing,Jiang Lelun,Haick Hossam
Precision and personalized medicine for disease management necessitates real-time, continuous monitoring of biomarkers and therapeutic drugs to adjust treatment regimens based on individual patient responses. This study introduces a wearable Microneedle-based Continuous Biomarker/Drug Monitoring (MCBM) system, designed for the simultaneous, in vivo pharmacokinetic and pharmacodynamic evaluation for diabetes. Utilizing a dual-sensor microneedle and a layer-by-layer nanoenzyme immobilization strategy, the MCBM system achieves high sensitivity and specificity in measuring glucose and metformin concentrations in skin interstitial fluid (ISF). Seamless integration with a smartphone application enables real-time data analysis and feedback, fostering a pharmacologically informed approach to diabetes management. The MCBM system’s validation and in vivo trials demonstrate its precise monitoring of glucose and metformin, offering a tool for personalized treatment adjustments. Its proven biocompatibility and safety suit long-term usage. This system advances personalized diabetes care, highlighting the move towards wearables that adjust drug dosages in real-time, enhancing precision and personalized medicine.
研究领域:
生物医学工程
·
药理学
·
内分泌学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
XENOBIOTICA
·
2019
·
IF 1.902
Huanying Ye,Danjuan Sui,Wei Liu,Yuannan Yuan,Zhen Ouyang,Yuan Wei
1. CYP2C11 is the most abundant isoform of cytochrome P450s (CYPs) in male rats and is considered the main enzyme for warfarin metabolism.2. To further access the in vivo function of CYP2C11 in warfarin metabolism and efficacy, a CYP2C11-null rat model was used to study warfarin metabolism with both in vitro and in vivo approaches. Prothrombin time (PT) of warfarin was also determined.3. The maximum rate of metabolism (Vmax) and intrinsic clearance (CLint) of liver microsomes from CYP2C11-null males were reduced by 37 and 64%, respectively, compared to those in Sprague Dawley (S-D) rats. The Km of liver microsomes from CYP2C11-null males was increased by 73% compared to that of S-D rats. The time to reach the maximum plasma concentration (Tmax) of warfarin in CYP2C11-null males was significantly delayed compared to that in S-D males, and the CL rate was also reduced. The PT of CYP2C11-null rats was moderately longer than that of S-D rats.4. In conclusion, the clearance rate of warfarin was mildly decreased and its anticoagulant effect was moderately increased in male rats following CYP2C11 gene knockout. CYP2C11 played a certain role in the clearance and efficacy of warfarin, while it did not seem to be essential.
研究领域:
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 14
·4657
·
IF 4.927
Mengxin Cao,Jiawei Zuo,Jian-Guo Yang,Chenyao Wu,Yongan Yang,Wenjian Tang,Lili Zhu
To understand that 18β-Glycyrrhetic acid 3-O-mono-β-D-glucuronide (GAMG) showed better pharmacological activity and drug-like properties than 18β-Glycyrrhizin (GL); a rapid and sensitive HPLC-MS/MS method was established for the simultaneous determination of GAMG and its metabolite 18β-Glycyrrhetinic acid (GA) in rat plasma and tissues after oral administration of GAMG or GL. This analytical method was validated by linearity, LLOQ, specificity, recovery rate, matrix effect, etc. After oral administration, GAMG exhibited excellentCmax(2377.57 ng/mL),Tmax(5 min) and AUC0-T(6625.54 mg/L*h), which was much higher than theCmax(346.03 ng/mL),Tmax(2.00 h) and AUC0-T(459.32 mg/L*h) of GL. Moreover, GAMG had wider and higher tissue distribution in the kidney, spleen, live, lung, brain, etc. These results indicated that oral GAMG can be rapidly and efficiently absorbed and be widely distributed in tissues to exert stronger and multiple pharmacological activities. This provided a physiological basis for guiding the pharmacodynamic study and clinical applications of GAMG.Keywords:GAMG;glycyrrhetic acid;glycyrrhizin;pharmacokinetics;pharmacodynamics;tissue distribution
研究领域:
药理学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）