Natural Product Communications
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2022
·
IF 1.496
Ruolan Yang,Jingjing Ma,Hui Guo,Qinghua Meng,Yuwei Wang,Hao Yan,Ruyi Jin,Zhi Li,Lingjie Meng
MS, and IR, 1H NMR and 13C NMR spectroscopy were employed to elucidate 4 novel evodiamine (EVO) derivatives with nitro, amino, and methoxy groups, namely 2-NO2-EVO (7a), 10-OCH3-2-NO2-EVO (7b), 2-NH2-EVO (8a), and 10-OCH3-2-NH2-EVO (8b). The amino compounds (8a, 8b) were obtained by the reduction of nitro derivatives (7a, 7b) with SnCl2/HCl. The antiproliferative activities of these compounds were tested by Cell Counting Kit-8 assay for 48 h against the MDA-MB-231 and sw620 cancer cell lines, as well as the normal LO2 cells. The in vitro experiment showed that 8a possesses the most potent inhibitory activities against MDA-MB-231 and SW620 cells, with IC50 values of 0.79 and 1.28 μM, respectively. The cytotoxicity of 8a against the 2 cancer cell lines was higher than that of EVO.
研究领域:
药物化学
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肿瘤学
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有机合成
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产品关联
DOI
高影响因子
JOURNAL OF APPLIED POLYMER SCIENCE
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2016
·Vol. 134
·期 7
·
IF 1.866
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.
研究领域:
材料科学
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药物分析
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中药学
✓ 已验证
产品关联
DOI
高影响因子
PHYTOMEDICINE
·
2025
·
IF 8.3
Xiaoyu Tao,Yifei Gao,Zhengsen Jin,Shan Lu,Zhiqi Li,Siyu Guo,Qiqi Fan,Jiaqi Li,Chuanqi Qiao,Huiling Lei,Zhiqiang Zhang,Chongjun Zhao,Jiarui Wu
Background The combined therapeutic mechanisms of evodiamine (EVO) and berberine (BBR), which are the primary bioactive components contributing to the pharmacological effects of Euodiae Fructus and Rhizoma Coptidis , a classic herb pair used for colitis, have not yet been fully elucidated Purpose This study aimed to investigate the critical mechanisms by which co-administration EVO and BBR mitigated EVO-induced hepatotoxicity while exerting therapeutic effects against colitis. Methods Safety and therapeutic outcomes of EVO alone and combined BBR were validated in normal and colitis models. RNA-seq sequencing was performed on liver and colon tissues from different groups, while metagenomic sequencing was utilized to analysis fecal samples. An integrated bioinformatics analysis of transcriptomic and metagenomic data was conducted to reveal the mechanisms underlying EVO-induced hepatotoxicity and the protective and synergistic effects of BBR against colitis. Molecular biology experiments were employed to validate the regulatory mechanism, with a particular emphasis on the interactions within the gut- liver axis, including those related to lipid metabolism and inflammatory pathways. Results BBR attenuated EVO-induced hepatotoxicity in C57 mice by ameliorating pathological injuries and hepatic steatosis as well as inhibiting abnormal AST/ALT elevation, thereby revealing its hepatoprotective effects. In colitis mice, the combination therapy exhibited enhanced efficacy in reducing mucosal damage, restoring goblet cells populations, and suppressing pro-inflammatory cytokines production compared to monotherapy. Integrated analysis of RNA-seq combined with experimental validation revealed that EVO-induced hepatotoxicity was associated with the disrupted fatty acid β-oxidation and cholesterol synthesis homeostasis. Notably, co-administration of BBR effectively rescued metabolic disturbance through modulating core regulatory targets such as ACSL1, CPT1B, SQLE, DHCR7. Additionally, the combination treatment synergistically inhibited IL-17/NF-κB signaling, upregulated tight junction proteins, and rectified gut microbiota dysbiosis, thereby alleviating intestinal injury in colitis mice. Furthermore, ACSL3, a central regulator of fatty acid β-oxidation, was identified as a pivotal target through which the combination of EVO combined BBR suppressed lipid peroxidation-mediated activation of IL-17/NF-κB, leading to alleviate inflammation in LPS-induced NCM460 cell. Conclusion ACSL3 was identified as the critical therapeutic target through underlying the amelioration of fatty acid metabolism-mediated inflammatory injury in colitis by the combined administration of EVO and BBR, thereby offering a scientific foundation for precise and safe clinical drug administration.
研究领域:
药理学
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毒理学
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胃肠病学
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系统生物学
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生物信息学
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分子生物学
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民族药理学
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代谢
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Gastroenterology Research and Practice
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2020
·
IF 1.806
Guo-xiang Wang,Yan-li Xiang,Hong-gang Wang,Yang-de Miu,Guang Yu
Evodiamine (Evo) is an indole alkaloid extracted from the traditional Chinese medicinal herb Evodia rutaecarpa. Evo may regulate gastrointestinal motility, but the evidence is insufficient, and the mechanisms remain unknown. The aim of this study was to investigate the effect of Evo on colonic motility of rats and the underlying mechanisms in vitro. Rat colonic muscle was exposed to Evo (10 and 100 μM) followed by immunohistochemistry of cholecystokinin receptor 1 (CCK1R). Muscle contractions were studied in an organ bath system to determine whether CCK1R, nitric oxide (NO), and enteric neurons are involved in the relaxant effect of Evo. Whole-cell patch-clamp was used to detect L-type calcium currents () in isolated colonic smooth muscle cells (SMCs). CCK1R was observed in SMCs, intermuscular neurons, and mucosa of rat colon. Evo could inhibit spontaneous muscle contractions; NO synthase, inhibitor L-NAME CCK1R antagonist, could partly block this effect, while the enteric neurons may not play a major role. Evo inhibited the peak in colonic SMCs at a membrane potential of 0 mV. The current-voltage (I–V) relationship of L-type calcium channels was modified by Evo, while the peak of the I–V curve remained at 0 mV. Furthermore, Evo inhibited the activation of L-type calcium channels and decreased the peak . The relaxant effect of Evo on colonic muscle is associated with the inhibition of L-type calcium channels. The enteric neurons, NO, and CCK1R may be partly related to the inhibitory effect of Evo on colonic motility. This study provides the first evidence that evodiamine can regulate colonic motility in rats by mediating calcium homeostasis in smooth muscle cells. These data form a theoretical basis for the clinical application of evodiamine for treatment of gastrointestinal motility diseases.
研究领域:
药理学
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生理学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY A
·
2019
·
IF 3.858
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
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分析化学
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药学
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DOI
高影响因子
PEST MANAGEMENT SCIENCE
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2025
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IF 3.8
Wenhao Liang,Xiaoxiao Xu,Tong Shi,Shengyang Xu,Qizhi Wang,Bi Wang
BACKGROUND Phytophthora capsici is a devastating oomycete pathogen with major economic concern. However, the use of traditional chemical fungicides is associated with environmental pollution, and fungicide resistance is increasingly prevalent. Consequently, developing safe, effective, and environmentally friendly alternatives is critically required. Evodiamine (EVO), a bioactive alkaloid from plants, has been extensively investigated for its anti-cancer properties. However, its inhibitory effects against phytopathogens have not yet been fully elucidated. This study evaluated EVO's antimicrobial activity toward P. capsici and its potential mode of action. RESULTS EVO significantly inhibited P. capsici mycelial growth and spore germination, with median effective concentration (EC 50 ) values of 6.48 μg mL −1 and 7.13 μg mL −1 respectively, across 108 P. capsici isolates. EVO exerted its antimicrobial effects by disrupting the cellular integrity of P. capsici , specifically targeting both the cell membrane and wall. Furthermore, EVO exhibited strong protective and curative efficacies in pepper leaves and seedlings. Genome-wide transcriptional analysis revealed that EVO treatment significantly altered the gene expression profile of P. capsici , especially affecting genes relevant to cell membrane integrity and transporter activity. CONCLUSION Overall, this study revealed that EVO showed great control efficacy against P. capsici and held promise as a novel botanical fungicide. © 2025 Society of Chemical Industry.
研究领域:
植物病理学
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农业微生物学
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分子植物-病原互作
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天然产物药理学
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农药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
OncoTargets and Therapy
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2022
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IF 4.345
Rong Wang,Danni Deng,Naiyuan Shao,Yuan Xu,Lian Xue,Ya Peng,Yatian Liu,Feng Zhi
Background Glioblastoma multiforme (GBM) is the most malignant primary tumor of the central nervous system and is associated with a very poor prognosis. No further improvements in outcomes have been reported since radiotherapy-temozolomide therapy was introduced. Therefore, developing new agents to treat GBM is important.Aim This study aimed to evaluate the anti-tumor effect of evodiamine (Evo) on GBM cells, and to determine the underlying mechanisms involved.Results According to MTT assay results, Evo significantly inhibited the cell proliferation in a time- and dose-dependent manner. Fluorescence microscopy and flow cytometry analyses revealed that Evo induced cell apoptosis in a concentration-dependent manner. Moreover, Evo induced reactive oxygen species (ROS) production and mitochondrial membrane potential (MMP) disruption. Finally, Evo induced apoptosis in cancer cells by suppressing PI3K/AKT signaling and inducing MAPK phosphorylation (p38 and JNK, but not ERK) to regulate apoptotic proteins (Bax, Bcl-2, Cytochrome c, Caspase-3, and PARP).Conclusion In summary, Evo inhibits cell proliferation by inducing cellular apoptosis via suppressing PI3K/AKT and activating MAPK in GBM; these results indicate that Evo may be regarded as a new approach for GBM treatment.
研究领域:
肿瘤学
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药理学
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细胞生物学
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DOI
PubMed
高影响因子
MOLECULES
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2013
·Vol. 18
·期 12
·15750-15768
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IF 2.428
Senchuan Song,Zhiyong Chen,Shaoxue Li,Yanmin Huang,Yiqian Wan,Huacan Song
Attempting to improve the anticancer activity and solubility of evodiamine in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) solutions, thirty-eight N13-substituted evodiamine derivatives were designed, synthesized and tested for antitumor activities against six kinds of human cancer cell lines, namely prostate cancer (DU-145 and PC-3), lung cancer (H460), breast cancer (MCF-7), colon cancer (HCT-5) and glioblastoma (SF-268). The solubility of these compounds in SGF and SIF solutions was evaluated, and apoptosis induced by2-2,2-3,2-16and3-2was determined. The results showed: (1) among all compounds examined,2-16showed the highest antitumor activity and a broader spectrum of activity, with IC50values ranging from 1–2 µM; (2) their solubility was obviously improved; (3)2-3,2-16and3-2had a significant impact inducing apoptosis in some cancer cell lines. The preliminary structure-activity relationships of these derivatives were discussed.Keywords:N13-substituted evodiamine derivatives;antitumor activity;apoptosis;solubility
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DOI
PubMed
高影响因子
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.
研究领域:
免疫学
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药理学
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微生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Qiuyue Huang,Ruoxuan Xu,Yanchen Liu,Na Li,Yuanyuan Sun,Rongxia Liu
Evo and Cur directly co-assembled into carrier-free nanoparticles • COS@EC NPs prolonged intestinal retention and increased systemic exposure • COS@EC NPs reduced ROS and VSMC proliferation with Nrf2/HO-1 upregulation • CETSA and DARTS supported HO-1 involvement in the cellular response • Oral COS@EC NPs reduced plaque burden in high-fat diet-fed ApoE −/− mice Oxidative stress and dysregulated vascular smooth muscle cell (VSMC) proliferation drive atherosclerotic (AS) progression and plaque development. Natural phytochemicals, including evodiamine (Evo) and curcumin (Cur), show anti-atherosclerotic potential, but poor aqueous solubility and insufficient intestinal absorption limit their oral use. Here, Evo and Cur were co-assembled into carrier-free Evo–Cur nanoparticles (EC NPs) and coated with chitosan oligosaccharide (COS) to obtain COS-coated EC nanoparticles (COS@EC NPs). Spectroscopic analyses and molecular dynamics simulations indicated that hydrophobic interactions, hydrogen bonding, and π–π stacking mediated Evo–Cur nanoassembly. Under simulated gastrointestinal conditions, COS@EC NPs reduced gastric Cur release and increased intestinal Cur release. After oral administration, COS@EC NPs prolonged intestinal residence and increased systemic exposure. In platelet-derived growth factor-BB (PDGF-BB)-stimulated VSMCs, COS@EC NPs suppressed excessive proliferation, reduced intracellular reactive oxygen species (ROS), elevated nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression, and restrained cell-cycle progression. This antiproliferative effect was partially reversed by the HO-1 inhibitor zinc protoporphyrin IX, suggesting HO-1 involvement. Cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS) analyses showed treatment-associated increases in the apparent thermal and proteolytic stability of HO-1, further supporting its involvement. In high-fat diet-fed ApoE −/− mice, oral administration of COS@EC NPs reduced plaque burden, improved lipid profiles, and alleviated oxidative stress without detectable systemic toxicity. Overall, these findings support COS@EC NPs as a potential carrier-free oral nanomedicine strategy for AS therapy and suggest that HO-1-associated redox regulation contributes to their vascular protective effects.
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DOI
高影响因子
JOURNAL OF MEDICINAL CHEMISTRY
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2022
·
IF 8.039
Shanchao Wu,Yahui Huang,Ting Wang,Keliang Li,Junjie Lu,Min Huang,Guoqiang Dong,Chunquan Sheng
On the basis of the synergism of topoisomerase (Top) and histone deacetylase (HDAC) inhibitors in antitumor therapy, a series of novel Top/HDAC dual inhibitors were designed and synthesized by the pharmacophore fusion strategy. After systematic structure–activity relationship studies, lead compound 16j was identified to simultaneously inhibit both Top and HDAC with good potency, which showed potent antiproliferative activities with a broad spectrum. Mechanistic studies indicated that compound 16j efficiently induced apoptosis with S cell-cycle arrest in HEL cancer cells. It was orally active in HEL xenograft models and exhibited excellent in vivo antitumor efficacy (TGI = 68.5%; 10 mg/kg). Altogether, this work highlights the therapeutic potential of evodiamine-inspired Top/HDAC dual inhibitors and provides a valuable lead compound for the development of novel antitumor agents for leukemia therapy.
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DOI
PubMed
高影响因子
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
·
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.
研究领域:
眼科
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药理学
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细胞生物学
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分子生物学
✓ 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）