JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
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2020
·
IF 3.209
Baolin Wang,Yimeng Lu,Rong Wang,Shumeng Liu,Xiaolong Hu,Hao Wang
Amentoflavone, a kind of biflavonoid existing in several medicinal plants such as Selaginella moellendorfi and Gingko biloba , possesses anti-inflammatory, antioxidant, anti-virus, anti-tumor activities. In the present study, a new reliable and sensitive UHPLC-ESI-MS/MS method was developed to determine the permeability of amentoflavone under different conditions, and its metabolites in Caco-2 cells were identified by means of UHPLC-Q-TOF-MS/MS method. The results showed that amentoflavone could be considered as a compound with moderate intestinal absorption in Caco-2 cell model and its absorption characteristics might be involved in paracellular passive penetration and clathrin-mediated endocytosis with no participation of efflux transporters. Eight metabolites of amentoflavone were identified in Caco-2 cell model, indicating that the main metabolic pathways were oxidation, reduction, methylation and glucuronide conjugation. This study can provide valuable evidence for an in-depth understanding of absorption mechanism and transformation of amentoflavone in the intestine.
研究领域:
药理学
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分析化学
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生物化学
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2020
·
IF 4.192
Baolin Wang,Yimeng Lu,Xiaolong Hu,Jiahao Feng,Wei Shen,Rong Wang,Hao Wang
Amentoflavone, a biflavonoid occurring in many edible supplements, possesses some bioactivities, including antioxidant, anti-inflammation, antitumor, and neuroprotective activities. In the present study, an ultrahigh-performance liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS) method, combined with a three-step analytical strategy, was employed to identify metabolites in vivo (rat plasma, bile, urine, and feces) and in vitro (rat liver microsomes and rat intestine microsomes). A total of 39 metabolites in rats and nine metabolites in rat microsomes were elucidated by UHPLC-Q-TOF-MS/MS analysis, and the chemical structure of some isomers was further assigned by calculated Clog P values. Oxidation, internal hydrolysis, hydrogenation, methylation, sulfation, glucuronidation, glucosylation, O-aminomethylation, and degradation were the major metabolic pathways of amentoflavone. Noteworthy, O-aminomethylation and glucosylation could be considered as unique metabolic pathways of amentoflavone. This was the first report on metabolite identification of amentoflavone in vivo and in vitro, and the metabolic findings offer novel and valuable evidence for an in-depth understanding of the safety and efficacy of amentoflavone.
研究领域:
药理学
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分析化学
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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
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
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2023
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IF 5.6
Lin Fei,Lin Xinhua,Wang Xuewen,Mei Guanghui,Chen Bing,Yao Hong,Huang Lingyi
Introduction: Selaginella doederleinii Hieron is a traditional Chinese herbal medicine, the ethyl acetate extract from Selaginella doederleinii (SDEA) showed favorable anticancer potentials. However, the effect of SDEA on human cytochrome P450 enzymes (CYP450) remains unclear. To predict the herb-drug interaction (HDI) and lay the groundwork for further clinical trials, the inhibitory effect of SDEA and its four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) on seven CYP450 isoforms were investigated by using the established CYP450 cocktail assay based on LC-MS/MS.Methods: Appropriate substrates for seven tested CYP450 isoforms were selected to establish a reliable cocktail CYP450 assay based on LC-MS/MS. The contents of four constituents (Amentoflavone, Palmatine, Apigenin, Delicaflavone) in SDEA were determined as well. Then, the validated CYP450 cocktail assay was applied to test the inhibitory potential of SDEA and four constituents on CYP450 isoforms.Results: SDEA showed strong inhibitory effect on CYP2C9 and CYP2C8 (IC50 ≈ 1 μg/ml), moderate inhibitory effect against CYP2C19, CYP2E1 and CYP3A (IC50 < 10 μg/ml). Among the four constituents, Amentoflavone had the highest content in the extract (13.65%) and strongest inhibitory effect (IC50 < 5 μM), especially for CYP2C9, CYP2C8 and CYP3A. Amentoflavone also showed time-dependent inhibition on CYP2C19 and CYP2D6. Apigenin and Palmatine both showed concentration-dependent inhibition. Apigenin inhibited CYP1A2, CYP2C8, CYP2C9, CYP2E1 and CYP3A. Palmatine inhibited CYP3A and had a weak inhibitory effect on CYP2E1. As for Delicaflavone, which has the potential to develop as an anti-cancer agent, showed no obvious inhibitory effect on CYP450 enzymes.Conclusion: Amentoflavone may be one of the main reasons for the inhibition of SDEA on CYP450 enzymes, the potential HDI should be considered when SDEA or Amentoflavone were used with other clinical drugs. On the contrast, Delicaflavone is more suitable to develop as a drug for clinical use, considering the low level of CYP450 metabolic inhibition.
研究领域:
药理学
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中药学
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代谢组学
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产品关联
DOI
PubMed
高影响因子
Current Drug Delivery
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2022
·Vol. 19
·期 1
·41-48
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IF 3.758
Duan Shulei,Jia Jing fu,Hong Biao,Zhou Jie,Zhang Yi,Ge Fahuan,Li Ming
Introduction: The amentoflavone (AMF) loaded polymeric sub-micron particles were prepared using supercritical antisolvent (SAS) technology with the aim of improving the anticancer activity of AMF. Methods: Zein and phospholipid mixtures composed of Hydrogenated Phosphatidylcholine
(HPC) and egg lecithin (EPC) were used as carrier materials and, the effects of carrier composition on the product morphology and drug release behavior were investigated. When the mass ratio of Zein/HPC/ EPC was 7/2/1, the AMF loaded particles were spherical shape and sub-micron sized around
400 nm, with a drug load of 4.3±0.3 w% and entrapment efficacy of 87.8±1.8%. The in vitro drug release assay showed that adding EPC in the wall materials could improve the dispersion stability of the released AMF in an aqueous medium, and the introduction of
HPC could accelerate the drug release speed. Results: MTT assay demonstrated that AMF-loaded micron particles have an improved inhibitory effect on A375 cells, whose IC50 was 37.39μg/ml, compared with that of free AMF(130.2μg/ml). Conclusion: It proved that the AMF loaded sub-micron
particles prepared by SAS were a prospective strategy to improve the antitumor activity of AMF, and possibly promote the clinical use of AMF preparations.
研究领域:
药学
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纳米技术
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癌症研究
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药物递送系统
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DOI
PubMed
高影响因子
PLANTA MEDICA
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2018
·Vol. 84
·期 11
·759-767
·
IF 2.494
Zhen Zhang,Shuai Zhao,Xiaolei Li,Xiaoqi Zhuo,Wu Zhang,Qian Nie,Shuguang Wang,Lianqi Yan,Yu Sun
Wear debris-induced osteolysis is one of the major reasons for subsequent aseptic loosening after cementless hip arthroplasty. Increasing evidence suggests that receptor activator of nuclear factor kappa-B (NF-κB) ligand-mediated osteoclastogenesis and osteolysis are responsible for wear debris-induced aseptic loosening. In the present study, we explored the effect of amentoflavone (AMF) on inhibiting osteoclast generation and wear debris-induced osteolysis in vitro and in vivo. Twenty-four male C57BL/J6 mice were randomly divided into four groups: a sham group and groups with titanium wear debris treatment followed by intraperitoneal injection of various concentrations of AMF (0, 20, and 40 mg/kg/day). The micro computed tomography scanning and histological analysis were performed. Bone marrow-derived macrophages were cultured to investigate the effect of AMF on osteoclast generation and function. The results showed that AMF suppressed osteoclastogenesis, F-actin ring formation, and bone absorption without cytotoxicity. AMF prevented titanium wear debris-induced osteolysis in mice. AMF suppressed the relative proteins of NF-κB and mitogen-activated protein kinase (MAPKs) signaling pathways. Thus, the present study suggests that AMF derived from plants could inhibit osteoclastogenesis and titanium wear debris-induced osteolysis via suppressing NF-κB and MAPKs signaling pathways.
研究领域:
骨科
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药理学
·
分子生物学
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DOI
PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
·
2026
·
IF 2.6
Shilong Yang,Ying Tang,Mengyi Zhou,Wen Lu,Huayu Xue,Li Xu
Amentoflavone (Ame) is a kind of precious biflavonoids with various bioactivities. To further develop and use Ame, Ame was extracted and purified from ginkgo biloba leaves, and Ame complexes with metal ions (Mn 2+ /Fe 3+ /Co 2+ /Ni 2+ /Cu 2+ /Zn 2+ ) were first synthesized. The structures of Ame complexes were characterized by UV/Vis, FT-IR, HRMS and DFT calculation. The antioxidant capacity was evaluated by pyrogallol autoxidation and ABTS methods. DNA binding affinity were explored via fluorescence method and molecular docking. The structural analysis indicated the stoichiometric ratios of Ame and Mn 2+ /Co 2+ /Ni 2+ /Cu 2+ /Zn 2+ were 1:1, the chelation site was between 5''-hydroxyl and 4''-carbonyl. While the stoichiometric ratio of Ame and Fe 3+ was 2:2, and the chelation site was between 5''-hydroxyl and 4''-carbonyl, 5-hydroxyl and 4-carbonyl. The investigation of pyrogallol autoxidation and ABTS methods demonstrated Ame complexes had superior scavenging activities on O 2 -• and ABTS + • free radicals. What's more, scavenging free radical activity of some Ame complexes was stronger or similar comparing with VC. The results of fluorescence method indicated Ame complexes had stronger DNA binding affinity with intercalation mode. Molecular docking study confirmed Ame and its complexes interacted with DNA via Van der Waals, conventional hydrogen bond and π-π stacked effect. These results demonstrated bioactivities of Ame could be enhanced via forming complexes with metal ions and provided theoretical knowledge for biflavonoids acting as potential drug, dietary supplement and cosmetics.
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DOI
高影响因子
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