PHARMACEUTICAL BIOLOGY
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2022
·
IF 3.889
Ruifeng Liang,Wenjing Ge,Bingjie Li,Weifeng Cui,Xiaofan Ma,Yuying Pan,Gengsheng Li
Context Patients with non-alcoholic steatohepatitis (NASH) may have a simultaneous intake of pravastatin and evodiamine-containing herbs.Objective The effect of evodiamine on the pharmacokinetics of pravastatin and its potential mechanisms were investigated in NASH rats.Materials and methods The NASH model was conducted with feeding a methionine choline-deficient (MCD) diet for 8 weeks. Sprague-Dawley rats were randomised equally (n = 6) into NASH group, evodiamine group (10 mg/kg), pravastatin group (10 mg/kg), and evodiamine (10 mg/kg) + pravastatin (10 mg/kg) group. Normal control rats were fed a standard diet. Effects of evodiamine on the pharmacokinetics, distribution, and uptake of pravastatin were investigated.Results Evodiamine decreased Cmax (159.43 ± 26.63 vs. 125.61 ± 22.17 μg/L), AUC0-t (18.17 ± 2.52 vs. 14.91 ± 2.03 mg/min/L) and AUC0-∞ (22.99 ± 2.62 vs. 19.50 ± 2.31 mg/min/L) of orally administered pravastatin in NASH rats, but had no significant effect in normal rats. Evodiamine enhanced the uptake (from 154.85 ± 23.17 to 198.48 ± 26.31 pmol/mg protein) and distribution (from 736.61 ± 108.07 to 911.89 ± 124.64 ng/g tissue) of pravastatin in NASH rat liver. The expression of Oatp1a1, Oatp1a4, and Oatp1b2 was up-regulated 1.48-, 1.38-, and 1.51-fold by evodiamine. Evodiamine decreased the levels of IL-1β, IL-6, and TNF-α by 27.82%, 24.76%, and 29.72% in NASH rats, respectively.Discussion and conclusions Evodiamine decreased the systemic exposure of pravastatin by up-regulating the expression of OATPs. These results provide a reference for further validation of this interaction in humans.
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CHEMICO-BIOLOGICAL INTERACTIONS
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2023
·
IF 5.1
Yun Yang,Yuan Xiong,Guanghao Zhu,Mengru Sun,Kun Zou,Yitian Zhao,Yong Zhang,Zhijian Xu,Yiming Li,Weiliang Zhu,Qi Jia,Bo Li,Guangbo Ge
Human carboxylesterase 2A (hCES2A) is a key serine hydrolase responsible for the metabolic clearance of large number of compounds bearing the ester- or amide-bond(s). Inhibition of hCES2A can relieve the chemotherapy-induced toxicity and alter the pharmacokinetic bahaviors of some orally administrate esters-containing agents. However, most of the hCES2A inhibitors show poor cell-membrane permeability and poor specificity. Herein, guided by the structure activity relationships (SAR) of fifteen natural alkaloids against hCES2A, fifteen new seven-membered ring berberine analogues were designed and synthesized, and their anti-hCES2A activities were evaluated. Among all tested compounds, compound 28 showed potent anti-hCES2A effect (IC 50 = 1.66 μM) and excellent selectivity over hCES1A (IC 50 > 100 μM). The SAR analysis revealed that the seven-membered ring of these berberine analogues was a crucial moiety for hCES2A inhibition, while the secondary amine group of the ring-C is important for improving their specificity over other serine hydrolases. Inhibition kinetic analyses and molecular dynamic simulation demonstrated that 28 strongly inhibited hCES2A in a mixed-inhibition manner, with an estimated K i value of 1.035 μM. Moreover, 28 could inhibit intracellular hCES2A in living HepG2 cells and exhibited suitable metabolic stability. Collectively, the SAR of seven-membered ring berberine analogues as hCES2A inhibitors were studied, while compound 28 acted as a promising candidate for developing highly selective hCES2A inhibitors.
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Frontiers in Pharmacology
·
2019
·
IF 3.845
Li Chen-Guang,Zeng Qiong-Zhen,Chen Ming-Ye,Xu Li-Hui,Zhang Cheng-Cheng,Mai Feng-Yi,Zeng Chen-Ying,He Xian-Hui,Ouyang Dong-Yun
Evodiamine is a major ingredient of the plant Evodia rutaecarpa, which has long been used for treating infection-related diseases including diarrhea, beriberi and oral ulcer, but the underlying mechanism is unclear. Here we aimed to explore whether evodiamine influenced NLRP3 (NLR family, pyrin containing domain 3) inflammasome activation in macrophages, which is a critical mechanism for defending the host against pathogenic infections. We uncovered that evodiamine dose-dependently enhanced NLRP3 inflammasome activation in lipopolysaccharide-primed macrophages, as indicated by increased interleukin (IL)-1β production and caspase-1 cleavage, accompanied by increased ASC speck formation and pyroptosis. Mechanistically, evodiamine induced acetylation of α-tubulin around the microtubule organization center (indicated by γ-tubulin) in lipopolysaccharide-primed macrophages. Such evodiamine-mediated increases in NLRP3 activation and pyroptosis were attenuated by activators of α-tubulin deacetylase, resveratrol and NAD+, or dynein-specific inhibitor ciliobrevin A. Small interfering RNA knockdown of αTAT1 (the gene encoding α-tubulin N-acetyltransferase) expression, which reduced α-tubulin acetylation, also diminished evodiamine-mediated augmentation of NLRP3 activation and pyroptosis. Evodiamine also enhanced NLRP3-mediated production of IL-1β and neutrophil recruitment in vivo. Moreover, evodiamine administration evidently improved survival of mice with lethal bacterial infection, accompanied by increased production of IL-1β and interferon-γ, decreased bacterial load, and dampened liver inflammation. Resveratrol treatment reversed evodiamine-induced increases of IL-1β and interferon-γ, and decreased bacterial clearance in mice. Collectively, our results indicated that evodiamine augmented the NLRP3 inflammasome activation through inducing α-tubulin acetylation, thereby conferring intensified innate immunity against bacterial infection.
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CHROMATOGRAPHIA
·
2012
·Vol. 75
·期 9
·499-511
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IF 1.195
Zhang Chunhua,Wu Huiqin,Huang Xiaolan,Zhu Zhixin,Luo Huitai,Huang Fang,Lin Xiaoshan
A sensitive and selective method for simultaneous determination of 29 toxic alkaloids in human blood and 31 in urine using high-performance liquid chromatography–electrospray ionization-tandem mass spectrometry was developed and validated. The samples were diluted with 0.1 mol L −1 HCl, and the target alkaloids were purified by solid phase extraction. The separation of 31 alkaloids was carried out on a C18 column using a gradient mobile phase with 10 mmol L −1 ammonium formate in water with 0.1% formic acid and methanol at the rate of 0.25 mL min −1 . The triple-quadrupole mass spectrometer equipped with an electrospray source in the positive mode was set up in the dynamic multiple reactions monitoring mode (dynamic MRM) to detect the ion transitions of 31 alkaloids. The calibration curves were linear over a range of 0.5–400, 1–400, or 4–400 μg L −1 for target alkaloids in human blood and urine, and the correlation coefficients ( r
2 ) was higher than 0.9943. The limit of determination and limit of quantification were 0.2–1 and 0.5–4 μg L −1 for blood and urine, respectively. The only exceptions were sanguinarine and chelerythrine in human blood. All the target alkaloids were stable under the test condition. In addition, the solvent effect and reconstituted solution were investigated. The method was validated and proved to be accurate and precise over the studied concentrations and suitable for poisoning diagnosis and forensic toxicology.
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MEDICAL ONCOLOGY
·
2016
·Vol. 33
·期 2
·1-9
·
IF 2.486
Li Yang-ling,Pan Yi-ni,Wu Wen-jue,Mao Shi-ying,Sun Jiao,Zhao Yi-ming,Dong Jing-yin,Zhang Da-yong,Pan Jian-ping,Zhang Chong,Lin Neng-ming
Erlotinib is effective in NSCLC patients with known drug-sensitizing EGFR mutations, but its clinical efficacy in patients with wild-type EGFR or acquired resistance to erlotinib remains modest. Evodiamine is a chemical extracted from the Evodia rutaecarpa (Juss.) Benth, we showed that evodiamine could induce anti-proliferation and apoptosis in four wild-type EGFR NSCLC cell lines, and combining evodiamine with erlotinib might successfully inhibit cell proliferation and survival in wild-type EGFR NSCLC cells, characterized as erlotinib-resistant. In addition, evodiamine plus erlotinib significantly increased the apoptotic rate of NSCLC cells, as compared to single agent treatment alone. Further investigation of the mechanism underlying these effects revealed that evodiamine plus erlotinib might downregulate Mcl-1 expression through the mTOR/S6K1 control of its translation. Thus, our study has revealed evodiamine as a pertinent sensitizer to erlotinib and the strategy of combining erlotinib with evodiamine appears to be an attractive option for reversing resistance to erlotinib.
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Biochimica et Biophysica Acta-Gene Regulatory Mechanisms
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2015
·
IF 6.332
Lushan Yu,Zhangting Wang,Minmin Huang,Yingying Li,Kui Zeng,Jinxiu Lei,Haihong Hu,Baian Chen,Jing Lu,Wen Xie,Su Zeng
The constitutive androstane receptor (CAR) is a key sensor in xenobiotic detoxification and endobiotic metabolism. Increasing evidence suggests that CAR also plays a role in energy metabolism by suppressing the hepatic gluconeogenesis and lipogenesis . In this study, we investigated the effects of two evodia alkaloids, rutaecarpine ( Rut ) and evodiamine ( Evo ), on gluconeogenesis and lipogenesis through their activation of the human CAR (hCAR). We found that both Rut and Evo exhibited anti-lipogenic and anti-gluconeogenic effects in the hyperlipidemic HepG2 cells. Both compounds can potently activate hCAR, and treatment of cells with hCAR antagonists reversed the anti-lipogenic and anti-gluconeogenic effects of Rut and Evo . The anti-gluconeogenic effect of Rut and Evo was due to the CAR-mediated inhibition of the recruitment of forkhead box O1 (FoxO1) and hepatocyte nuclear factor 4α (HNF4α) onto the phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) gene promoters. In vivo, we showed that treatment of mice with Rut improved glucose tolerance in a CAR-dependent manner. Our results suggest that the evodia alkaloids Rut and Evo may have a therapeutic potential for the treatment of hyperglycemia and type 2 diabetes. This article is part of a Special Issue entitled: Xenobiotic nuclear receptors : New Tricks for An Old Dog, edited by Dr. Wen Xie.
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FOOD CHEMISTRY
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2014
·
IF 3.259
Junyan Wang,Minmin Huang,Haihong Hu,Lushan Yu,Su Zeng
The induction of drug-metabolising enzymes is being increasingly recognised for its clinical importance in drug research and development. In the present study, we used a pregnane X receptor (PXR)-mediated reporter gene assay to evaluate the activating effects of various food, herb, and horticultural plant constituents on the PXR and a UGT1A1 reporter gene DNA construct. The results showed that of 102 naturally occurring constituents tested, 50 activated the PXR signaling pathway and induced expression of the UGT1A1 -reporter gene DNA construct. Eleven constituents strongly induced gene expression (a response of >70% compared to that associated with rifampicin), and were further evaluated in in vitro experiments to confirm the induction of UGT1A1 mRNA and protein expression. The results suggest that foods and herbs containing these constituents should be consumed with caution to avoid undesirable drug–drug interactions with co-administered drugs that are substrates for UGT1A1.
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JOURNAL OF MOLECULAR HISTOLOGY
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2025
·Vol. 56
·期 6
·1-14
·
IF 2.2
Wang Pu,Sun Congcong,Shi Chao,Gao Yong,Luan Chunyu,Yan Chao
Osteoarthritis (OA) is a degenerative joint disease characterized by pathological changes such as articular cartilage degeneration and bone hyperplasia. Mitochondrial dysfunction in chondrocytes has been identified as a critical factor contributing to the progression of OA. Although Evodiamine (Evo) has been demonstrated effeicacy in inhibiting inflammatory responses and matrix degradation in OA chondrocytes, its effects and underlying mechanisms regarding mitochondrial dysfunction in these cells remain to be elucidated. IL-1β was utilized to stimulate chondrocytes in order to establish an in vitro OA model. Subsequently, the proliferation, lactate dehydrogenase (LDH) release, and apoptosis of chondrocytes were systematically evaluated. Mitochondrial function in chondrocytes was evaluated by quantifying of ATP content, ROS level, mitochondrial DNA (mtDNA) copy number, activities of mitochondrial respiratory chain Complexes I and III, as well as mitochondrial membrane potential change. Furthermore, the protein expression levels of the SIRT1/PGC-1α signaling pathway were examined, and an intervention involving the SIRT1 inhibitor EX527 was conducted to elucidate the potential mechanisms underlying the effects of Evo on chondrocytes. Evo treatment significantly elevated the proliferation activity of IL-1β-stimulated chondrocytes, inhibited LDH release and apoptosis, increased mtDNA copy number and ATP content, enhanced the enzymatic activities of Complexes I and III, and suppressed ROS production as well as mitochondrial membrane potential loss. Furthermore, Evo treatment activated the SIRT1/PGC-1α signaling pathway. However, the addition of the SIRT1 inhibitor EX-527 partially attenuated the protective effects of Evo against IL-1β-induced chondrocyte injury by exacerbating mitochondrial dysfunction. Evo promotes mitochondrial biosynthesis, reduces ROS production and improves mitochondrial function by activating SIRT1/PGC-1α pathway, thereby inhibiting IL-1β-induced chondrocyte injury.
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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
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2025
·Vol. 66
·期 3
·44-44
·
IF 4.7
Boda Li,Junpeng Liu,Di Zhang,Yiran Chu,Zeying Chen,Jiaruei Tsao,Taige Chen,Jiaxuan Jiang,Kai Hu
Purpose:This study aims to explore the therapeutic efficacy of evodiamine (EVO) in the treatment of dry eye disease (DED).Methods:Mouse models of DED was developed using benzalkonium chloride eye drops and subcutaneous atropine injections. Corneal epithelial defects were assessed by fluorescein sodium staining, and tear secretion was measured with the phenol red thread test. For the in vitro model, human corneal epithelial cells were cultured in a sodium chloride–enriched medium. Phenotypic and mechanistic analyses were conducted using real-time quantitative PCR, Western blotting, flow cytometry, and immunofluorescence staining.Results:The administration of EVO eye drops significantly enhanced tear secretion in mice, ameliorated ocular surface damage, decreased the expression of corneal inflammatory factors, and increased the density of conjunctival goblet cells. Furthermore, EVO reduced oxidative stress by promoting autophagy. Mechanistically, EVO-induced autophagy was mediated via the p53/mammalian target of rapamycin pathway.Conclusions:These findings suggest that EVO is a potential therapeutic agent for the treatment of DED, with its beneficial effects attributed to the activation of autophagy through the p53/mammalian target of rapamycin pathway.
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MICROCHEMICAL JOURNAL
·
2025
·
IF 5.1
Huiying Wu,Lei Zeng,Mengling Wei,Liwei Chen,Jiajia Guo,Yun Huang,Fuhou Lei,Hao Li
Biomass materials, such as rosin obtained from pine trees, are increasingly employed in developing high-performance liquid chromatography (HPLC) stationary phase due to their environmental sustainability, abundant resources, cost-effectiveness and renewability. In this study, we synthesized a novel mixed-mode chromatographic stationary phase (Sil-HRE-DPM) with reversed-phase, hydrophilic, and weak anion-exchange functionalities via thiol-ene click chemistry by copolymerizing hydrogenated rosin acrylic glycol ester (HRE) and N-(3-dimethylaminopropyl)methacrylamide (DPM). The successful synthesis of Sil-HRE-DPM was confirmed through comprehensive characterizations. Sil-HRE-DPM demonstrated excellent chromatographic stability, repeatability and excellent efficiency (71,796 plate/m). The retention mechanism of Sil-HRE-DPM was examined utilizing the linear solvation energy relationship (LSER) model and thermodynamic analysis. Various probes, including Tanaka test mixtures, hydrophobic and hydrophilic analytes, and anionic chemicals were employed to evaluate retention mechanisms and separation performance. It was found that Sil-HRE-DPM provides various interactions, such as hydrophobic, π-π, hydrophilic and weak anionic exchange. Finally, the column was effectively applied to separate the active components of the natural medicines, specifically Erigeron breviscapus, herb Evodia rutaecarpa and Panax notoginseng . This study provides a theoretical foundation for the quality control of traditional Chinese medicine and the efficient utilization of rosin, thereby facilitating advancements in both pharmaceutical and industrial applications.
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