Acta Pharmaceutica Sinica B
·
2019
·
IF 5.808
Yahui Huang,Shuqiang Chen,Shanchao Wu,Guoqiang Dong,Chunquan Sheng
A great challenge in multi-targeting drug discovery is to identify drug-like lead compounds with therapeutic advantages over single target inhibitors and drug combinations. Inspired by our previous efforts in designing antitumor evodiamine derivatives, herein selective histone deacetylase 1 (HDAC1) and topoisomerase 2 (TOP2) dual inhibitors were successfully identified, which showed potent in vitro and in vivo antitumor potency. Particularly, compound 30a was orally active and possessed excellent in vivo antitumor activity in the HCT116 xenograft model (TGI = 75.2%, 150 mg/kg, p.o .) without significant toxicity, which was more potent than HDAC inhibitor vorinostat, TOP inhibitor evodiamine and their combination. Taken together, this study highlights the therapeutic advantages of evodiamine-based HDAC1/TOP2 dual inhibitors and provides valuable leads for the development of novel multi-targeting antitumor agents.
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Advanced Healthcare Materials
·
2025
·
IF 9.6
Qiang Zhou,Kui Wang,Dahong Yang,Yue Huang,Mengjun Yu,Dandan Xie,Jia Wang,Shiwen Chen,Jing Gong,Min Yang,Yu Zhao,Jingbin Huang
Immunotherapy is a promising treatment for triple-negative breast cancer (TNBC), but the immunosuppressive tumor microenvironment (TME) compromises its efficacy. Therefore, the nano-drug TPGS@EVO/Ppa (TEP) is designed and prepared to achieve chemotherapy and enhance immunotherapy. Evodiamine (EVO) demonstrates chemotherapeutic efficacy and enhanced CD8 + T cell infiltration within the TME. Additionally, laser irradiation of Pyropheophorbide-a (Ppa) generates singlet oxygen, promoting tumor cell apoptosis and inducing immunogenic cell death (ICD). In vitro and in vivo experiments demonstrate that TEP exhibits significant cytotoxicity against 4T1 tumor cells and markedly inhibits tumor growth. Furthermore, TEP promotes the release of damage-associated molecular patterns (DAMPs) such as calreticulin (CRT), high mobility group box 1 protein (HMGB1), and adenosine triphosphate (ATP), which stimulates dendritic cells (DCs) maturation and activate adaptive immunity. Bilateral tumor experiments reveal that the combination therapy significantly increases the proportions of CD4 + and CD8 + T cells in tumors and central memory T cells (TCMs) in the spleen, demonstrating potent immunotherapy efficacy. In summary, TEP emerges as an innovative nano-drug with exceptional anti-tumor properties, offering a novel strategy for the treatment of TNBC.
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PHARMACEUTICAL BIOLOGY
·
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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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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JOURNAL OF MEDICINAL CHEMISTRY
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2023
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IF 7.3
Xiao-Meng Liu,Zhe Li,Xin-Ru Xie,Jia-Qian Wang,Xin Qiao,Xin Qiao,Cheng-Zhi Xie,Jing-Yuan Xu
Exploring multi-targeting chemotherapeutants with advantages over single-targeting agents and drug combinations is of great significance in drug discovery. Herein, we employed phytogenic evodiamine (EVO) and conventional Pt(II) drugs to design and synthesize multi-target EVO–Pt(IV) anticancer prodrugs (4–14). Among them, compound 10 exhibited a 118-fold enhancement in the IC50 value compared to cisplatin and low toxicity to normal cells. Further studies proved that 10 significantly enhanced intracellular Pt accumulation and DNA damage, perturbed mitochondrial membrane potential, inhibited cell migration and invasion, upregulated reactive oxygen species levels, and induced apoptosis and autophagic cell death. Molecular docking assay revealed that 10 fits perfectly into the extracellular signal-regulated protein kinase (ERK)-1 pocket, which was verified to produce profound ERK suppression. Most strikingly, compound 10 exhibited superior in vivo antitumor efficiency and effectively attenuated systemic toxicity. Our results emphasize that functionalizing platinum drugs with the multi-target EVO could generate synergistically excellent anticancer activity with low toxicity and decreased resistance, which may represent a brand-new cancer therapy modality.
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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.
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