Journal of Pharmaceutical Analysis
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2020
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IF 2.673
Siqi Ren,Jingjing Liu,Yunwen Xue,Mei Zhang,Qiwei Liu,Jie Xu,Zunjian Zhang,Rui Song
Saikosaponins (SSs) are the main active components extracted from Bupleuri Radix (BR) which has been used as an important herbal drug in Asian countries for thousands of years. It has been reported that the intestinal bacteria plays an important role in the in vivo disposal of oral SSs. Although the deglycosylated derivatives (saikogenins, SGs) of SSs metabolized by the intestinal bacteria are speculated to be the main components absorbed into the blood after oral administration of SSs, no studies have been reported on the characteristics of SGs for their intestinal absorption, and those for SSs are also limited. Therefore, a rapid UHPLC-MS/MS method was developed to investigate and compare the apparent permeability of three common SSs (SSa, SSd, SSb 2 ) and their corresponding SGs (SGF, SGG, SGD) through a bidirectional transport experiment on Caco-2 cell monolayer model. The method was validated according to the latest FDA guidelines and applied to quantify the six analytes in transport medium samples extracted via liquid-liquid extraction (LLE). The apparent permeability coefficient ( P app ) determined in this study indicated that the permeability of SGs improved to the moderate class compared to the corresponding parent compounds, predicting a higher in vivo absorption. Moreover, the efflux ratio (ER) value demonstrated an active uptake of SSd and the three SGs, while a passive diffusion of SSa and SSb 2 .
研究领域:
药理学
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药剂学
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分析化学
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中药学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2023
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IF 6.1
Bowen Qin,Yijun Yao,Jing Zhang,Lifeng Wang
At present, most of the research on coix seed polyphenols (CSPs) focuses on the separation, purification, structure analysis, and biological functions of specific components, and few studies have considered the overall bioavailability and the metabolites that play a role after digestion and absorption and their biological functional activities. In this study, we constructed a MKN28 and Caco-2 cell monolayer continuous transport model (MCTM) to study the bioavailability of CSPs in the digestion and absorption stages of the stomach and small intestine. Using this model, we innovatively divided CSPs into easy-to-digest and hard-to-digest polyphenols and studied their intracellular lipid-lowering function and their influence on human intestinal flora. Transwell experiments showed that ferulic acid, rutin, naringin, arbutin, and syringetin had high transmembrane transport efficiency, especially syringetin. The methylation reaction in the monolayer membrane of Caco-2 cells may be the reason for the higher transport rate of syringetin. Further experiments showed that CPL reduced TG accumulation by more than 50% during 3T3-L1 differentiation and promoted the transformation of adipocytes into brown cells (p < 0.05). Finally, in vitro fermentation experiments showed that CSP_AP can increase the abundance of Lactobacillus and Bifidobacterium of human gut microbiota at the genus level (p < 0.05).
研究领域:
药理学
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营养学
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细胞生物学
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胃肠生理学
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微生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 26
·期 1
·72
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IF 4.9
Chaoji Li,Min Zhang,Yanni Zhao,Dan Yang,Mei Zhao,Leyuan Shang,Xiaodong Sun,Shuo Zhang,Pengjiao Wang,Xiuli Gao
Mycophenolic acid (MPA) is a commonly used immunosuppressant. In the human body, MPA is metabolized into mycophenolic acid 7-O-glucuronide (MPAG) and mycophenolic acid acyl-glucuronide (AcMPAG) mainly through liver glucuronidation, which involves UDP-glucuronosyltransferase (UGTs) and transfer proteins. Research has indicated that the pharmaceutical excipient PEG400 can impact drug processes in the body, potentially affecting the pharmacokinetics of MPA. Due to the narrow therapeutic window of MPA, combination therapy is often used, and PEG400 is widely used in pharmaceutical preparations. Therefore, investigating the pharmacokinetic influence of PEG400 on MPA could offer valuable insights for optimizing MPA’s clinical use. In this study, we examined the impact of a single oral dose of PEG400 on the blood levels of MPA in rats through pharmacokinetic analysis. We also investigated the distribution of MPA in various tissues using mass spectrometry imaging. We explored the potential mechanism by which PEG400 affects the metabolism of MPA using hepatic and intestinal microsomes and the Caco-2 cellular transporter model. Our findings reveal that the overall plasma concentrations of MPA were elevated in rats following the co-administration of PEG400, with the AUC0-tof MPA and its metabolite MPAG increasing by 45.53% and 29.44%, respectively. Mass spectrometry imaging showed increased MPA content in tissues after PEG400 administration, with significant differences in the metabolites observed across different tissues. Microsomal and transport experiments showed that PEG400 accelerated the metabolism of MPA, promoted the uptake of MPA, and inhibited efflux. In conclusion, PEG400 alters the in vivo metabolism of MPA, potentially through the modulation of metabolic enzymes and transport.
研究领域:
药理学
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免疫抑制剂
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药物代谢
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药用辅料
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体内和体外研究
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2019
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IF 4.213
Ruoning Wang,Jiawei Han,Ai Jiang,Rong Huang,Tingming Fu,Lingchong Wang,Qin Zheng,Wen Li,Junsong Li
Curcumin (CUR) has gained increasing interest worldwide due to multiple biological activities . However, the therapeutic application remains limited because of its low aqueous solubility, intestinal metabolism and poor membrane permeability. In present study, an excipient-free CUR solid dispersion co-formed with piperine (PIP), the absorption enhancer involving metabolism-permeability, was successfully prepared by melting and quench cooling (co-amorphous CUR-PIP). The co-amorphous CUR-PIP exhibited superior performance in non-sink dissolution compared with crystalline and amorphous CUR, and showed physically stable at least 3 months, attributing to the strong molecular interactions between CUR and PIP as evaluated by FTIR spectra. Furthermore, the combination of PIP with CUR in the co-amorphous formulation could inhibit the glucuronidation of CUR, as exhibited in the in vitro assay of rat intestinal microsomes. The co-amorphous CUR-PIP would also exhibit higher gastrointestinal membrane permeability of CUR, as confirmed by P app of CUR in Caco-2 model. After administration of co-amorphous CUR-PIP, the AUC of CUR significantly increased by 2.16- and 1.92-fold those in crystalline and amorphous CUR, respectively. This study demonstrates that the developed co-amorphous CUR-PIP can enhance the bioavailability of CUR by increasing its dissolution, inhibiting metabolic processes, and facilitating membrane permeability.
研究领域:
药剂学
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药理学
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
Pharmaceuticals
·
2022
·Vol. 15
·期 4
·418
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IF 5.215
Qiong Yang,Maochen Xing,Ke Wang,Qiang Wei,Jiarui Zhao,Yuan Wang,Kai Ji,Shuliang Song
The Caco-2 model is a common cell model for material intestinal absorption in vitro, which usually takes 21 days to establish. Although some studies have shown that adding puromycin (PM) can shorten the model establishment period to 7 days, this still requires a long modeling time. Therefore, exploring a shorter modeling method can reduce the experimental costs and promote the development and application of the model. Fucoidan is an acidic polysaccharide with various biological activities. Our study showed that the transepithelial electrical resistance (TEER) value could reach 600 Ω·cm2on the fourth day after the addition of fucoidan and puromycin, which met the applicable standards of the model (>500 Ω). Moreover, the alkaline phosphatase (AKP) activity, fluorescein sodium transmittance, and cell morphology of this model all met the requirements of model establishment. Fucoidan did not affect the absorption of macromolecular proteins and drugs. The results indicate that fucoidan can be applied to establish the Caco-2 model and can shorten the model establishment period to 5 days.Keywords:fucoidan;Caco-2 model;absorption of macromolecules
研究领域:
药理学
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细胞生物学
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生物技术
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产品关联
DOI
PubMed
高影响因子
BIOPHARMACEUTICS & DRUG DISPOSITION
·
2021
·Vol. 42
·期 9
·435-443
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IF 1.627
Hui Qiu,Zhengbing Guo,Qian Xu,Shengfang Mao,Wenming Wu
The present study was aimed to systemically assess the absorption risks of amentoflavone (AMF). Physicochemical properties of AMF were evaluated using in vitro assays including water solubility and stability in both simulated gastric and intestinal fluids, as well as logD, pka and permeability studies in a monolayer Caco-2 model. The results together suggested that AMF was a compound with moderate intestinal absorption and the poor solubility was the key rate-limiting step for the oral absorption of AMF, and PVP-K30 were thus used as a solubilizer to improve its solubility and oral bioavailability. Furthermore, studies on pharmacokinetics and biliary excretion of AMF with tween 80 or PVP-K30 were performed after oral administration, and the results showed that the percentage of AMF conjugates in bile was determined up to be 96.73% and no AMF conjugates were detected in rat plasma. The above results revealed that the poor oral absorption of AMF may probably be attributed to the low solubility, high level of metabolism and hepatic first-pass effects. The relative bioavailability of AMF solubilized by PVP-K30 was about 2-fold than that of AMF suspended in 1% tween 80. The present study may help provide scientific insights to guide the rational design of AMF into more efficient formulation systems.
研究领域:
药理学
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药物递送系统
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药剂学
✓ 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）