BIOORGANIC CHEMISTRY
·
2025
·
IF 4.7
Xiuyan Han,Changming Chen,Renxiang Zhao,Jing Wu,Shujing Zhang,Yuzhuo Wu,Yufang Ma,Chao Wang,Xiaochi Ma
Euphorbia fischeriana has been traditionally used in Chinese medicine for tuberculosis (TB) treatment since ancient times. In this study, we first report the identification of an abietane-type diterpenoid, 17-hydroxy-jolkinolide B (HJKB), from E. fischeriana , which exhibits potent antimycobacterial activity against both Mycobacterium tuberculosis H37Ra strain and clinical isolates. The minimum inhibitory concentrations (MICs) of HJKB against diverse M. tuberculosis strains range from 1 to 12 μg/mL. Notably, HJKB demonstrates significant bactericidal activity against intracellular M. tuberculosis H37Ra in macrophage models, accompanied by anti-inflammatory effects at concentrations of 2–5 μg/mL. Using a combination of chemoproteomic analysis and pull-down assays, we explored the preliminary antimycobacterial mechanism of HJKB. Results indicate that HJKB interacts with the target proteins RpoB and RpoC in M. tuberculosis H37Ra, a finding further corroborated by molecular docking studies. RpoB and RpoC are essential subunits of the DNA-directed RNA polymerase holoenzyme, which is critical for bacterial ribosomal transcription regulation. In summary, HJKB represents a bioactive constituent of E. fischeriana with anti-TB efficacy, acting as a transcription inhibitor against M. tuberculosis . This study not only elucidates its antimycobacterial mechanism but also provides a preclinical foundation for the development of natural product-based TB therapeutics.
研究领域:
药理学
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微生物学
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天然产物研究
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药物化学
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生物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2020
·
IF 3.209
Shi-Kang Zhou,Yi Zhang,Yong-Hui Ju,Qiao Zhang,Da Luo,Yu-Dan Cao,Wei-Feng Yao,Yu-Ping Tang,Li Zhang
The dried roots of Euphorbia kansui (EK) are especially beneficial for the treatment of edema, but the severe toxicity limits their clinical applications. Euphorbia kansui stir-fried with vinegar (VEK) is traditionally employed to reduce the toxicity of EK. However, the material basis for the toxicity reduction with effectivity conservation is still unclear. Therefore, in this study, a rapid, sensitive, and reliable ultra-fast liquid chromatography tandem mass spectrometry (UFLC-MS/MS) method was firstly established to simultaneously determine six ingenane-type diterpenoids, i.e. kansuiphorin C (1) , 5- O -benzoyl-20-deoxyingenol (2) , 20-deoxyingenol (3) , 3- O -(2’ E ,4’ E -decadienoyl)-20- O -acetylingenol (4) , 20- O -(2’ E ,4’ Z -decadienoyl)ingenol (5) , and ingenol (6) , in EK and VEK based on the processing conversion. Then, the toxicity evaluation on zebrafish embryos and modulation of the expression of aquaporin-3 (AQP3) proteins in HT-29 cells were employed to investigate the toxicity-activity of six compounds. Chromatographic separation was obtained on Waters BEH RP18 column (2.1 mm × 100 mm, 2.5 μm) with the mobile phase composed of 0.1 % formic acid in acetonitrile and water, respectively. The column temperature was 35 ℃ at a flow rate of 0.4 mL min −1 . Multiple reaction monitoring was conducted in both positive and negative modes for quantitative analysis. The method was then successfully used for the determination of six compounds in EK and VEK. In addition, 1 , 2 , 4 , and 5 had evident cardiotoxicity, intestinal irritation and nutrient absorption disorders on zebrafish larvae, while no in-vivo toxicity was seen for groups given 3 and 6 (LC 50 > 200 μM). Meanwhile, 1 , 2 , 4 , 5 , and 6 significantly increased the expression of AQP3 protein ( p < 0.05) to promote the excretion of water in the colon. This study demonstrated that toxic ingenane-type diterpenoids converted into the less toxic compounds with the same core structure through the breakage of multiple ester bonds in the side chain. At the same time, the laxative effect was retained, providing useful information for the optimization of the process of EK and quality evaluation of other similar toxic Chinese herbal medicines.
研究领域:
药理学
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毒理学
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分析化学
·
药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
·
2018
·Vol. 15
·期 11
·e1800386
·
IF 1.617
Qian Wang,Yong-Qi Zhen,Feng Gao,Shuai Huang,Xian-Li Zhou
A new premyrsinane-type diterpenoid, premylanin ( 1 ), and four new lathyrane-type diterpenoids named Euphorbia Factors L 30 –L 33 ( 2 – 5 ) were isolated from the seeds of Euphorbia lathyris , together with thirteen known ones ( 6 – 18 ). Their structures were elucidated through spectroscopic analyses, including IR, UV, HR-ESI-MS, 1D- and 2D-NMR. The cytotoxicities of compounds 1 – 4 and 6 – 18 against HCT116, MCF-7, 786–0, HepG2 cell lines were evaluated, and compound 13 exhibited considerable cytotoxic activities with an IC 50 values of 6.44, 8.43, 15.3, 9.32 μ m , respectively. Graphical
研究领域:
植物化学
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药理学
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肿瘤学
✓ 已验证
DOI
高影响因子
Journal of the Taiwan Institute of Chemical Engineers
·
2015
·
IF 3
Jiming Wu,Jinghan Li,Jin Zhang,Xinyue Hu,Dahong Yao,Liang Ma,Liang Ouyang,Xinhui Pan,Jian Huang,Ruichao Lin,Jinhui Wang
Euphorbia lathyris ( E. lathyris ), a traditional Chinese medicine, rich in diterpenoids, has been widely used for the treatment of hydropsy, especially the ascites in China, with its mechanism is still unclear. For exploring possible diuresis mechanism of E. lathyris , in this study, a potential diuresis related target, urea transporter B (UT-B), and its potential ligands were discovered by using bioinformatics method of “Inverse Docking”. Then, homology modeling, molecular docking and ligand-based pharmacophore methods were applied to research the possible mechanism of diuresis. Bioinformatics analysis showed that most of diterpenoids in E. lathyris were optimal ligands for the UT-B protein and these predicted compounds also exhibited stable affinity to UT-B binding site, a hydrophobic region in urea passage. The HPLC-TOF-MS method was used to characterize the main diterpenoids content of E. lathyris extracts and three out of eight proposed diterpenoids were detected and assigned. In vitro UT-B inhibition experiment of erythrocyte lysis assay was then applied to confirm the diuretic effects of the diterpenoids concentrated extracts of E. lathyris . The half erythrocyte lysis rate of 23.89 µg/ml of diterpenoids concentrated extracts showed moderate UT-B inhibition efficacy. All these performances might also raise an alternative approach for the design of new diuretic drugs.
研究领域:
药理学
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生物信息学
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中药学
✓ 已验证
产品关联
DOI
高影响因子
CHEMICAL & PHARMACEUTICAL BULLETIN
·
2018
·Vol. 66
·期 6
·674-677
·
IF 1.258
Jia-Xi Wang,Qian Wang,Yong-Qi Zhen,Shuang-Mei Zhao,Feng Gao,Xian-Li Zhou
We isolated two new lathyrane-type diterpenes L27 (1) and L28 (2) along with seven known compounds (3–9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with 1H-NMR, 13C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by comprehensive interpretation of their nuclear Overhauser effect (NOE) relationship and showed they were first natural lathyrane-type diterpenes possessing α-configuration substitutes at C-3. Cytotoxicity assay of isolated compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231, 786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L28 (2) showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC50 value of 9.43 and 13.22 µM, respectively, which preliminarily suggested that the configuration of lathyrane-type diterpene at C-3 has a significant effect on its bioactivity.
研究领域:
药用植物研究
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天然产物化学
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肿瘤生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 7
·2958
·
IF 4.6
Bi Wang,Guodong Zhang,Jingjing Yang,Linwei Li,Pirui Li,Shu Xu,Xu Feng,Yu Chen
Phytophthora capsiciis a highly destructive phytopathogenic oomycete with a broad host range and is responsible for tremendous losses. Euphorbia factor L3(EFL3) is a natural plant-derived compound that has been widely studied in medicine and cosmetic applications. In this study, the sensitivity of 105P. capsiciisolates to EFL3was determined, and the biological activity and physiological effects of EFL3againstP. capsiciwere investigated. The median effective concentration (EC50) values for EFL3inhibition mycelial growth and spore germination ranged from 0.66 to 8.94 μg/mL (mean, 2.96 ± 0.91 μg/mL) and 1.63 to 13.16 μg/mL (mean, 5.30 ± 1.64 μg/mL), respectively. EFL3treatment resulted in cell wall and cell membrane damage ofP. capsici, which was revealed by morphological and ultrastructural observations, propidium iodide (PI) and calcofluor white (CFW) staining, and measurements of relative conductivity as well as malondialdehyde (MDA) and glycerol contents. In addition, the contents of phospholipid and cellulose, which are the major components of cell membrane and cell wall, were significantly reduced following EFL3treatment. Furthermore, EFL3provided protective as well as curative efficacies againstP. capsicion detached tomato leaves and pepper seedlings in vivo. These data show that EFL3exhibits strong inhibitory activity againstP. capsici, thereby suggesting that it could be an effective alternative for controllingP. capsici-induced diseases.Keywords:baseline sensitivity;botanical fungicide;Euphorbia factor L3;action mechanism;Phytophthora capsici
研究领域:
植物病理学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2025
·
IF 2.6
Ren-Fen Ma,Xin-Cheng Zhuang,Qian Wu,Hua Zhang
An intensive phytochemical study on the aerial parts of Euphorbia wallichii afforded ten lathyrane-type diterpenoids, including six formerly unreported ones ( 1 – 4 , 6 and 8 ). Their structures were determined via comprehensive spectroscopic analyses, and the absolute stereochemistries were assigned on the basis of electronic circular dichroism technique. Among these diterpenoids, compound 2 exhibited the best inhibitory activity on NO production and its potential anti-inflammatory mechanism was then explored by network pharmacology analysis. Further experimental validation demonstrated that diterpenoid 2 could exert its anti-inflammatory effect by suppressing pro-inflammatory factors and modulating PI3K/Akt/mTOR signaling pathway. In short, the present work confirms the promising potential of E. wallichii as a source of natural anti-inflammatory agents.
研究领域:
植物化学
·
药理学
·
药物化学
·
天然产物研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 6
·2830
·
IF 4.6
Xiaoyi Feng,Jianchun Li,Hongmei Li,Xuanqin Chen,Dan Liu,Rongtao Li
Euphorbia kansuiis clinically used for the treatment of esophageal cancer, lung cancer, cancerous melanoma, asthma, pleural disorders, ascites, and pertussis, among other conditions. In this study, 12 steroids were obtained and identified fromE. kansui, and cynsaccatol L (5), which showed the best effects in terms of inhibiting the proliferation of HepG2 cells and the immune regulation of macrophages. Furthermore,5induced typical apoptotic characteristics in HepG2 cells, such as morphological changes and the caspase cascade, as well as inducing autophagy-dependent apoptosis via mitochondrial dysfunction and reactive oxygen species (ROS) accumulation. The antitumor mechanism of5might be related to promoting the endocytosis and degradation of ATP1A1 protein and then down-regulating the downstream AKT and ERK signaling pathways. Furthermore, the antiproliferation effect of5in co-cultivation with macrophages was investigated, which showed that5promoted the apoptosis of HepG2 cells by modulating the release of inflammatory cytokines, such as TNF-α and IFN-γ; regulating the M2-subtype polarization of macrophages; promoting the phagocytosis of macrophages. In conclusion,5exerted anti-proliferative effects by promoting the degradation of ATP1A1 and inhibiting the ATP1A1-AKT/ERK signaling pathway in HepG2. Furthermore, it regulated macrophage function in co-cultivation, thereby further exerting adjuvant anti-HepG2 activity.Keywords:Euphorbia kansui;antitumor;immunomodulatory;Na+, K+-ATPase;α1 subunit of NAK;dual antitumor activity
研究领域:
药理学
·
肿瘤学
·
免疫学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2024
·
IF 2.5
Ren-Fen Ma,Qian Wu,Yin-Po Pan,Hu Liu,Xin-Cheng Zhuang,Hua Zhang
The Euphorbia plants are famous for their diterpenoid constituents with diverse structures and broad biological activities. Herein, the discovery of 15 ingenane diterpenoids including 10 previously unreported ones ( 1 − 10 ) from Euphorbia antiquorum was presented. Structures of the undescribed compounds were established via detailed spectroscopic analyses. Meanwhile, a preliminary anti-inflammatory screening revealed that compound 6 showed significant inhibitory activity against the production of nitric oxide, as well as downregulated the expression of COX-2 and IL-6, in lipopolysaccharide-stimulated RAW264.7 macrophages. Further mechanistical exploration revealed that compound 6 could exert its anti-inflammatory effect by inhibiting NF-κB and activating Nrf2 signaling pathways.
研究领域:
药理学
·
化学
·
免疫学
·
植物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Wei-ni Qin,Kai-cheng Zhang,Ting Geng,Fang-fang Cheng,Pei-dong Chen,Wei-feng Yao,Li Zhang,Yu-dan Cao
Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it’s toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it’s toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.
研究领域:
药理学
·
毒理学
·
发育生物学
·
生物化学
✓ 已验证
DOI
PubMed
高影响因子
NATURAL PRODUCT RESEARCH
·
2022
·
IF 2.488
Xin Liu,Zhihong Cheng
Euphorbia factor L1 (EFL1, 1) is a natural tri-ester of 6,17-epoxylathyrol with cancer multidrug resistance (MDR) reversal activity. Several EFL1 derivatives (2–9) were prepared by chemical and microbial transformations and their ability to inhibit P-glycoprotein (P-gp) activity was estimated. Six de-acylated derivatives (2–7) were obtained through base-hydrolysis of 1, and the base-catalysed hydrolysis via KOH and NaOH yielded different hydrolysed products of 1. Two biotransformed products (8–9) were directly obtained via microbial transformation of 1, and 8 was also formed by microbial conversion of the hydrolysed product 3. The P-gp modulation of 1–9 was assessed by a zebrafish model. The substrate 1 and its biotransformed product 9 as the tri-esters of lathyranes possessed the highest P-gp inhibitory activity with IC50 values of 34.97 and 15.50 µM, respectively, through down-regulating P-gp expression at the protein level rather than at MDR1 mRNA level.
研究领域:
药理学
·
生物化学
·
毒理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 18
·10123
·
IF 4.9
Xiaoyi Feng,Lizhong Wang,Li Pu,Jianchun Li,Hongmei Li,Dan Liu,Rongtao Li
Euphorbia kansui, a toxic Chinese medicine used for more than 2000 years, has the effect of “purging water to promote drinking” and “reducing swelling and dispersing modules”. Diterpenes and triterpenes are the main bioactive components ofE. kansui. Among them, ingenane-type diterpenes have multiple biological activities as a protein kinase C δ (PKC-δ) activator, which have previously been shown to promote anti-proliferative and pro-apoptotic effects in several human cancer cell lines. However, the activation of PKC subsequently promoted the survival of macrophages. Recently, we found that 13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate (compound A) fromE. kansuishowed dual bioactivity, including the inhibition of tumor-cell-line proliferation and regulation of macrophage polarization. This study identifies the possible mechanism of compound A in regulating the polarization state of macrophages, by regulating PKC-δ-extracellular signal regulated kinases (ERK) signaling pathways to exert anti-tumor immunity effects in vitro, which might provide a new treatment method from the perspective of immune cell regulation.
研究领域:
药理学
·
免疫学
·
肿瘤学
·
分子生物学
✓ 已验证
DOI
高影响因子
危险品化学品经营许可证（带存储）