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Evodiae Fructus
JOURNAL OF ETHNOPHARMACOLOGY · 2020 · IF 3.69

CYP3A4 inducer aggravates big flower Evodiae Fructus-induced hepatotoxicity whereas limonin attenuates its hepatotoxicity

Wei Zhang,Mengjiao Wang,Huijie Song,Chengfeng Gao,Dongmei Wang,Huiming Hua,Yingni Pan,Xiaoqiu Liu

Ethnopharmacological relevance Evodiae Fructus (EF), the traditional Chinese medicine , has been typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It is a mild toxicity herb-medicine listed in Sheng Nong's Herbal Classic . Recently, EF was reported to have toxicity or no toxicity in some investigations. Toxicity and approaches to reducing toxicity of EF are of great interest. Limonin (LIM), a major triterpenoid component of EF, also had various pharmacological activities such as anti-inflammatory, anticancer, and antioxidant effects. However, little attention was paid to the role of LIM in EF-induced hepatotoxicity. Aim of study The study aimed to address the problem of controversial hepatotoxicity of EF, evaluate the role of CYP3A4 inducer/inhibitor in EF-induced hepatotoxicity and disclose the effect of LIM in EF-induced hepatotoxicity. Materials and methods The chemical compositions and hepatotoxicity of small flower EF (SEF), medium flower EF (MEF), big flower EF (BEF) and the “organ knock-out” samples (the shell and seed part of BEF) were investigated. Simultaneously, C57BL-6 mice were randomly divided into four groups, which were given orally administered BEF, BEF in combination with dexamethasone (DEX), BEF in combination with ketoconazole (KTC), and BEF in combination with LIM, respectively. Results In this study, more alkaloids and less LIM were detected in BEF compared with the compounds in SEF and MEF. Furthermore, we found that BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in SEF and MEF groups. In addition, no LIM was detected in the shell part of BEF and five alkaloids were not detected in the seed part of BEF. Correspondingly, the shell part of BEF group induced hepatotoxicity whereas no hepatotoxicity was observed in the seed part of BEF group. It was also found that the BEF-induced hepatotoxicity was remarkably exacerbated when the mice were pretreated with DEX whereas the BEF-induced hepatotoxicity could be reversed by pretreatment with KTC or LIM. Conclusions Based on the results in this study, the misuse of BEF but not SEF and MEF could produce hepatotoxicity. The hepatotoxicity difference of different categories of EF might be associated with the relative contents of alkaloids and LIM. In addition, the results demonstrated that CYP3A4 inducer aggravated BEF-induced hepatotoxicity and LIM attenuated its hepatotoxicity.

研究领域: 民族药理学 · 毒理学 · 药理学
✓ 已验证 DOI PubMed 高影响因子
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CHEMICO-BIOLOGICAL INTERACTIONS · 2020 · IF 3.723

Effect of CYP3A inducer/inhibitor on pharmacokinetics of five alkaloids in Evodiae Fructus

Wei Zhang,Jingyan Guo,Dongmei Wang,Shumeng Ren,Huiming Hua,Toshio Morikawa,Yingni Pan,Xiaoqiu Liu

Evodiae Fructus (EF), the dried nearly mature scented fruit of Tetradium ruticarpum (A.Juss.) T.G.Hartley, was typically used to treat headache, abdominal pain, hernias, and menorrhagia for thousands of years. It had been reported to be a mild toxic herb through metabolic activation mainly by CYP3A but was barely explained from pharmacokinetic interaction. The aim of the study was to investigate the role of CYP3A inducer/inhibitor in pharmacokinetics of five alkaloids (evodiamine (EVOD), rutaecarpine (RUTA), 1-methyl-2-undecyl-4(1 H )-quinolone (MUDQ), 1-methyl-2-nonyl-4(1 H )-quinolone (MNNQ) and evocarpine (EVOC)) associated with hepatotoxicity of EF in Sprague Dawley (SD) rats. The results demonstrated that the metabolism of the five alkaloids of EF were inhibited in presence of CYP3A inhibitor whereas the metabolism of the five alkaloids of EF were promoted in presence of CYP3A inducer . Therefore, the dose is required attention when EF is taken in conjunction with CYP3A inducer as there is an enhancement in drug metabolism, which might lead to toxicity.

CAS / MDL: 298-46-4 65277-42-1
研究领域: 中药学 · 药理学 · 毒理学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CHROMATOGRAPHY A · 2019 · IF 3.858

Analysis of Evodiae Fructus by capillary electrochromatography-mass spectrometry with methyl-vinylimidazole functionalized organic polymer monolilth as stationary phases

Yikun Liu,Wei Zhou,Zhenkun Mao,Zilin Chen

Evodiae Fructus is used as a traditional Chinese medicine for the treatment of several kinds of diseases with its bioactive constituents. In this study, a capillary electrochromatography-mass spectrometry (CEC-MS) method was developed to determine three bioactive compounds including evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit. Home-developed monolithic columns with methyl-vinylimidazole functionalized organic polymer monolilth as stationary phases were used in CEC-MS with excellent separation selectivity and high efficiency. The CEC-MS methods provided 4–16 folds improvement of LODs when compared with CEC-UV method. The conditions, which could affect separation efficiency and detection sensitivity, were optimized. Under optimum conditions, baseline separation with high detection sensitivity was obtained. The method showed good linearity (R 2 >0.99) of 0.8–160 μg mL −1 with low limits of detection of 0.15-0.31 μg mL −1 . Relative standard deviations of migration time and relative peak areas were <13.89%. Recoveries of evodiamine, rutaecarpine and limonin in Evodiae Fructus fruit were tested and calculated, which ranged from 102% to 113%. Finally, the three bioactive compounds in Evodiae Fructus herb samples from different regions were analyzed and studied. It has been demonstrated that the developed method has great potential for quality control of Evodiae Fructus herb.

研究领域: 中药分析 · 分析化学 · 药学
✓ 已验证 DOI 高影响因子
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JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES · 2025 · IF 2.8

Restricted access membrane roll with functionalized silica nanoparticles cross-linked by hydrophilic polymer chains on the surface for the direct extraction of Evodiae Fructus active components from rat plasma

Hongwu Zhang,Yuhao Zhong,Lidan Li,Xiaoyu Xin,Jiayi Zhuang,Yue Zhong,Mingfang Zhu

Evodiamine and other indole alkaloids are the main active constituents in Evodiae Fructus (EF), which is widely applied in traditional Chinese medicine. Recently, the toxic side effects of EF caused by the alkaloid evodiamine have gradually attracted the attention of researchers. In this regard, the rapid and accurate detection of these alkaloids in biological body fluids has become a challenging task. Therefore, it has become a priority that the rapid and efficient extraction of evodiamine etc. alkaloids from blood sample. In this research, a novel method was proposed to prepare the restricted access (RA) membrane with the hydrophobic functional silica nanoparticles cross-linked on the surface by hydrophilic poly-hydroxyethyl methacrylate ( p -HEMA). The poly-HEMA chains played the role of protein exclusion and the functional nanoparticles played the role of hydrophobic adsorbent. The RA membrane was wound into a roll shape and inserted into a 1 mL medical syringe to assemble a portable SPE device, named as SRAMR-SPE, for the direct and simultaneous extraction of evodiamine (EVO), rutecarpine (RUT) and dehydroevodiamine (DHE) in rat plasma after a simple dilution with PBS. The prepared functional nanoparticles and RA membrane were characterized by Fourier transform infrared (FT-IR) spectrometer, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM), respectively. HPLC-UV analysis was used to investigate the extraction performance of SRAMR. An associated SRAMR-SPE-HPLC method was constructed and applied to the detection of real rat plasma after the method validation for the verification of the reliability and applicability of the SRAMR-SPE. The experimental results showed that the RA membrane roll (RAMR) had a good ability to exclude plasma proteins and adsorb analytes with multiple reusability. For 3 consecutive cycles of SRAMR-SPE processes, the extraction recoveries of three components at three concentration levels were determined as follows: DHE 93.1–95.1 %, EVO 88.8–91.6 % and RUT 93.6–95.6 %, and the absolute recoveries of the entire SRAMR-SPE-HPLC-UV method were separately as follows: DHE 90.3–92.3 %, EVO 86.2–90.9 %, RUT 91.8–96.4 %. The linear ranges were detected as follows: 0.0600–6.00 μg mL −1 (DHE), 0.105–5.65 μg mL −1 (EVO) and 0.0632–6.32 μg mL −1 (RUT).

研究领域: 药理学 · 分析化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF APPLIED POLYMER SCIENCE · 2016 ·Vol. 134 ·期 7 · IF 1.866

A molecular imprinted polymer on the surface of superparamagnetic Fe3O4–graphene oxide (MIP@Fe3O4@GO) for simultaneous recognition and enrichment of evodiamine and rutaecarpine in Evodiae fructus

Jie-Ping Fan,Dan-Dan Liao,Yan-Long Xie,Bing Zheng,Jia-Xin Yu,Ya-Hui Cao,Xue-Hong Zhang,Hai-Long Peng

A composite material (MIP@Fe 3 O 4 @GO) based on molecular imprinted polymer (MIP), superparamagnetic Fe 3 O 4 particles and graphene oxide (GO) was prepared by the chemical coprecipitation method, and used to simultaneously separate and enrich two alkaloids (evodiamine and rutaecarpine) in the extract of Evodiae fructus . The as-prepared MIP@Fe 3 O 4 @GO was characterized by Fourier transform infrared spectroscopy (FT-IR), transmission electron microscopy (TEM), and vibrating sample magnetometer (VSM). The adsorption kinetics, isotherms, competitive adsorption, and reusability of MIP@Fe 3 O 4 @GO were also investigated. The results revealed that MIP@Fe 3 O 4 @GO was sensitive to the magnetic field and could be easily separated using an external magnet; MIP@Fe 3 O 4 @GO showed good recognition selectivity, as well as simultaneous enrichment and separation abilities for evodiamine and rutaecarpine in the extract of E. fructus with satisfactory recoveries. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017 , 134 , 44465.

CAS / MDL: 97-90-5 7782-42-5
研究领域: 材料科学 · 药物分析 · 中药学
✓ 已验证 产品关联 DOI 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2021 · IF 6.953

Physicochemical properties, antioxidant activities and α-glucosidase inhibitory effects of polysaccharides from Evodiae fructus extracted by different solvents

Gaoyin Xiong,Lisha Ma,Han Zhang,Yanping Li,Wanshuang Zou,Xiaofan Wang,Quansheng Xu,Jingteng Xiong,Yanping Hu,Xiaoyin Wang

In this study, polysaccharides from Evodiae fructus were extracted by water, 0.5 M HCl, 0.5 M NaOH, water + 0.5 M HCl and water + 0.5 M NaOH, which were named as ERP-W, ERP-AC, ERP-AK, ERP-W-AC and ERP-W-AK, respectively. Their physicochemical properties, antioxidant activities and α-glucosidase inhibitory effects were investigated and compared. Physico-chemical analysis showed that they were acidic heteropolysaccharides, which had α- and β-configurations. ERP-W, ERP-AK and ERP-W-AK were mainly composed of Rha, Ara, Gal, Glc and Gal-UA, while ERP-AC and ERP-W-AC were dominantly made up of Rha, Gal and Gal-UA. ERP-AK had the highest yield (24.5%) and the best thermal stability, ERP-AC and ERP-W-AC showed better homogeneity and lower molecular weight (83.6 and 41.6 kDa), and ERP-W possessed the highest neutral sugar content (50.7%) and molecular weight. Biological evaluation indicated that ERP-W, ERP-AK and ERP-W-AK had relatively stronger antioxidant activities, including ABTS, DPPH, OH and O 2 − radicals scavenging activities, Fe 2+ chelating ability and α-glucosidase inhibitory effects. Moreover, these actions were considerably related to their physicochemical properties especially monosaccharide composition and molecular weight. Therefore, polysaccharides extracted by water and alkaline solvents from Evodiae fructus could be developed as promising natural antioxidants and α-glucosidase inhibitors in the food and medicine industries.

研究领域: 药学 · 食品科学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES · 2023 · IF 8.2

Untargeted serum and liver metabolomics analyses reveal the gastroprotective effect of polysaccharide from Evodiae fructus on ethanol-induced gastric ulcer in mice

Jiang-Hong Luo,Wan-Shuang Zou,Jing Li,Wei Liu,Jing Huang,Hu-Wei Wu,Jian-Lin Shen,Fei Li,Jia-Shuang-Wei Yuan,An-Kang Tao,Liang Gong,Jun Zhang,Xiao-Yin Wang

This study aimed at investigating the gastroprotective effect of Evodiae fructus polysaccharide (EFP) against ethanol-induced gastric ulcer in mice. Biochemical indexes along with untargeted serum and liver metabolomics were determined. Results showed that pre-treatment of EFP alleviated ethanol-induced gastric ulcer in mice. EFP lessened oxidative stress and inflammation levels of stomachs, showing as increments of SOD and GSH-Px activities, GSH content and IL-10 level, and reductions of MDA and IL-6 levels. Meanwhile, EFP activated the Keap1/Nrf2/HO-1 signaling pathway through increasing Nrf2 and HO-1 protein expressions, and decreasing Keap1 protein expression. Serum and liver metabolomics analyses indicated that 10 metabolic potential biomarkers were identified among normal control, ulcer control and 200 mg/kg·bw of EFP groups, which were related to 5 enriched metabolic pathways including vitamin B6 metabolism, nicotinate and nicotinamide metabolism, pentose phosphate pathway, bile secretion and ascorbate and aldarate metabolism. Further pearson's correlation analysis indicated that there were some positive and negative correlations between the biomarkers and the biochemical indexes. It could be concluded that the gastroprotection of EFP might be related to anti-oxidative stress, anti-inflammation, activation of Keap1/Nrf2/HO-1 signaling pathway and alteration of metabolic pathways. This study supports the potential application of EFP in preventing ethanol-induced gastric ulcer.

CAS / MDL: 73590-58-6
研究领域: 药理学 · 胃肠病学 · 代谢组学 · 生物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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