INDUSTRIAL CROPS AND PRODUCTS
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2025
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IF 6.2
Tengteng Yang,Wenquan Wang,Xiaoli Wang,Qiaowei Miao,Junhai Liu,Hansheng Wang,Lun Liu,Xiaohui Ji,Chenyang Wei
Camptothecin (CPT) has significant biological activity and has been extensively studied. This study established an efficient and green ultrasonic-assisted deep eutectic solvent (UAE-DES) and combined it with macroporous resin purification technology to extract and purify CPT and 10-hydroxycamptothecin (HCPT) from Camptotheca acuminata fruit. In total, 33 natural DES were prepared, among which choline chloride-1,4-butanediol was the most effective. The single-factor and response surface optimization extraction experiments were carried out to determine optimal conditions as follows: ultrasonic time = 27 min, solid-liquid ratio = 1:35 g/mL, ultrasonic temperature = 70 °C, DES moisture content, = 29 %, and total extraction rate = 0.1318 %. Furthermore, the scanning electron microscopy revealed that the UAE-DES treatment significantly disrupted the cell-wall structure of C. acuminata fruits, promoting the release of the target constituents. Moreover, AB-8-type macroporous resin was employed to optimize adsorption and desorption, which optimized 63.4 % and 77.3 % adsorption and desorption of CPT and HCPT, respectively. Density functional theory (DFT) was employed for assessing electrostatic potential (ESP), complexation energy, and reduced density gradient (RDG), to identify the non-covalent interactions between DES, conventional solvent ethanol, and CPT-like compounds during the extraction process. This study comprehensively explained the extraction mechanism and confirmed that DES had better extraction potential and good biocompatibility. These findings provide a theoretical basis and technical support for the green and efficient extraction and purification of CPT-like compounds.
研究领域:
天然产物化学
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药物分析
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植物药学
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绿色化学
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分子互作机制
✓ 已验证
产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2019
·Vol. 20
·期 8
·1961
·
IF 4.183
Bing Yu,Qingye Meng,Hao Hu,Tao Xu,Youqing Shen,Hailin Cong
Polymeric micelles (PMs) have been applied widely to transport hydrophobic drugs to tumor sites for cancer treatment. However, the low load efficiency of the drug in the PMs significantly reduces the therapeutic efficiency. We report here that disulfide-linked camptothecin (CPT) as a kind of dimeric drug can be effectively embedded in the core of poly(ε-caprolactone)–poly(ethylene glycol)–poly(ε-caprolactone) (PCL–PEG–PCL) PMs for improving drug-loading efficiency, and PEG can be used as a hydrophilic shell. Moreover, the dimeric CPT-loaded PCL–PEG–PCL PMs exhibited excellent solubility in phosphate-buffered saline (PBS) media and significant cytotoxicity to cancer cells.Keywords:dimeric drug;camptothecin;micelles;cancer therapy
研究领域:
药学
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肿瘤学
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产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2017
·Vol. 7
·期 20
·12185-12193
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IF 3.108
Yuhua Zhang,Keming Jiang,Degang Qing,Bing Huang,Jiayi Jiang,Shumei Wang,Chunyan Yan
Camptotheca acuminata Decne (Nyssaceae) is a major natural source of the anticancer drug camptothecin (CPT) and its derivatives. The leaves and stems are two of the main regions that accumulate CPT in C. acuminata. In this study, we successfully isolated cambial meristematic cells (CMCs) and dedifferentiated cells (DDCs) from C. acuminata stems and leaves, identified their characteristic features using micrograph analysis, and assessed their hypersensitivity to γ-irradiation and zeocin. The growth and kinetics curves of CMCs and DDCs were also studied. Furthermore, the accumulation of CPT and 10-hydroxycamptothecin (HCPT)—a more potent and less toxic CPT derivative—was assessed by liquid chromatography, and the transcriptional levels of nine genes encoding key enzymes involved in CPT and HCPT biosynthesis was assessed using quantitative real-time polymerase chain reaction (PCR) in CMCs and DDCs. The results showed that CMCs induced were particularly hypersensitive to γ-irradiation and zeocin and presented with abundant and small vacuoles, whereas DDCs were not. The above morphological and physiological characteristics of CMCs were consistent with previous reports. B5 medium was determined as the best growth medium for CMCs and DDCs. The accumulation of CPT and HCPT was higher in CMCs than DDCs, and the expression of IPI, G10H, ASA1, TSB, TDC1, TDC2, and STR was significantly upregulated in CMCs compared with DDCs; HMGR2 and HMGR3 were downregulated in CMCs. We speculate that the high accumulation of CPT and HCPT in CMCs was due to the upregulation of these seven genes.
研究领域:
药理学
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植物生物学
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分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Wenyan Guo,Yi Yang,Guangyuan Liu,Jiaojiao Zhao,Yuyu Zhang,Yahui Li,Bingkun Yang,Xiaoque Zhu,Dandan Li,Xia Qin,Panpan Zhang,Zuxiao Yang,Wei Guo,Dezhi Kong,Wei Zhang
Ethnopharmacological relevance Cepharanthine (CEP) is an alkaloid extracted from Stephania cephalantha Hayata, a traditional Chinese medicine (TCM) renowned for its heatclearing and dehumidifying properties. For centuries, Stephania cephalantha Hayata has been employed in the treatment of a wide range of diseases, including pain, edema, inflammation, and fever. Aim of the study Our research aims to investigate the role and mechanism of Cepharanthine in ameliorating uric acid (UA) induced neuroinflammatory responses. Materials and methods The Connectivity Map (CMap) was utilized to identify the therapeutic drug Cepharanthine, based on the proteomic disturbances associated with uric acid (UA). Limited proteolysis small molecule mapping (LiP-SMap) and thermal proteome profiling (TPP) technologies were used to identify the direct target proteins for UA and Cepharanthine. Additionally, we used the induced-fit docking algorithm integrated within the Schrodinger suite to explore the interactions between Cepharanthine and uric acid targets. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology was employed to determine the concentration of Cepharanthine in the mice cerebral cortex. The pro-inflammatory cytokine genes were also quantified by qPCR in U251 cells and in hyperuricemic mice. Results The findings indicated that uric acid increased the transcription of pro-inflammatory cytokines and the expression levels of proteins linked to inflammation in U251 cells. PPP2R1A was identified as a potential candidate for direct interaction with uric acid, potentially initiating inflammation. Based on the CMap prediction, Cepharanthine was identified as a candidate drug for interaction with PPP2R1A. TPP analysis indicated that Cepharanthine could reduce the thermal stability of PPP2R1A. Molecular docking confirmed that Cepharanthine could directly bind to PPP2R1A. Furthermore, the detection of Cepharanthine in the cerebral cortex suggested its ability to cross the blood-brain barrier. Proteomic analysis of Cepharanthine-treated mice revealed significant enrichments of differentially expressed proteins (DEPs) in inflammation-related pathways and biological processes. Additionally, Cepharanthine was effective in decreasing the expression of pro-inflammatory cytokine genes induced by uric acid in U251 cells and in hyperuricemic mice. Conclusion Cepharanthine could effectively alleviate hyperuricemia-induced neuroinflammation via binding to PPP2R1A. This study offers a novel approach for prevention and treatment of neurological diseases caused by hyperuricemia.
研究领域:
药理学
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神经科学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Materials Chemistry B
·
2024
·
IF 6.1
Ran Hao,Meng Jiao,Xingguo Xu,Di Wu,Haiying Wei,Leyong Zeng
Delivery nanosystems were popularly developed to improve chemotherapy efficacy, but the non-specific leakage of drugs was still not satisfactory. Here, using gold nanocages (AuNCs) as carrier and thermo-sensitive liposome (TSL) as protection shell, a camptothecin (CPT) loaded delivery nanosystem (AuNCs/CPT@TSL) was designed for photothermal-modulated drug release, by which the non-specific leakage of CPT was avoided, and the combination of photothermal therapy (PTT) and chemotherapy was achieved. In the simulated tumor microenvironment (pH=5.5), the TSL shell protected CPT from leakage at 37℃, and the release rate of CPT was only 11.4%. However, the release rate of CPT greatly increased to 85.4% by elevating temperature to 45℃. The photothermal conversion efficiency of AuNCs/CPT@TSL reached up to 46.1%. When the incubation temperature was 37℃, the cell survival rate was reduced to 43.6% in AuNCs/CPT, but was still above 90% in AuNCs/CPT@TSL, demonstrating the good protection of TSL shell. Under the combination of PTT/chemotherapy, the cell viability greatly decreased to 10.9%, and the tumors completely disappeared, confirming the safe and reliable antitumor effect of AuNCs/CPT@TSL.
研究领域:
纳米医学
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肿瘤学
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药物递送
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产品关联
DOI
PubMed
高影响因子
SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY
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2014
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IF 2.129
Linlin Wang,Yizhong Shen,Shaopu Liu,Jidong Yang,Wanjun Liang,Dan Li,Youqiu He
The interactions of topotecan hydrochloride (THC), neutral red (NR) and thioglycolic acid (TGA) capped CdTe/CdS quantum dots (QDs) built a solid base for the controlling of the fluorescent reversible regulation of the system. This study was developed by means of ultraviolet–visible (UV–vis) absorption, fluorescence (FL), resonance Rayleigh scattering (RRS) spectroscopy and transmission electron microscopy (TEM). Corresponding experimental results revealed that the fluorescence of TGA-CdTe/CdS QDs could be effectively quenched by NR, while the RRS of the QDs enhanced gradually with the each increment of NR concentration. After the addition of THC, the strong covalent conjugation between NR and THC which was in carboxylate state enabled NR to be dissociated from the surface of TGA-CdTe/CdS QDs to form more stable complex with THC, thereby enhancing the fluorescence of the TGA-CdTe/CdS QDs-NR system. What is more, through analyzing the optical properties and experimental data of the reaction between TGA-CdTe/CdS QDs and NR, the possible reaction mechanism of the whole system was discussed. This combination of multiple spectroscopic techniques could contribute to the investigation for the fluorescent reversible regulation of QDs and a method could also be established to research the interactions between camptothecin drugs and dyes.
研究领域:
药理学
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纳米生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Horticulture Research
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2021
·
IF 6.793
Hao Xiaolong,Xie Chenhong,Ruan Qingyan,Zhang Xichen,Wu Chao,Han Bing,Qian Jun,Zhou Wei,Nützmann Hans-Wilhelm,Kai Guoyin
The limited bioavailability of plant-derived natural products with anticancer activity poses major challenges to the pharmaceutical industry. An example of this is camptothecin, a monoterpene indole alkaloid with potent anticancer activity that is extracted at very low concentrations from woody plants. Recently, camptothecin biosynthesis has been shown to become biotechnologically amenable in hairy-root systems of the natural producer Ophiorrhiza pumila. Here, time-course expression and metabolite analyses were performed to identify novel transcriptional regulators of camptothecin biosynthesis in O. pumila. It is shown here that camptothecin production increased over cultivation time and that the expression pattern of the WRKY transcription factor encoding gene OpWRKY2 is closely correlated with camptothecin accumulation. Overexpression of OpWRKY2 led to a more than three-fold increase in camptothecin levels. Accordingly, silencing of OpWRKY2 correlated with decreased camptothecin levels in the plant. Further detailed molecular characterization by electrophoretic mobility shift, yeast one-hybrid and dual-luciferase assays showed that OpWRKY2 directly binds and activates the central camptothecin pathway gene OpTDC. Taken together, the results of this study demonstrate that OpWRKY2 acts as a direct positive regulator of camptothecin biosynthesis. As such, a feasible strategy for the over-accumulation of camptothecin in a biotechnologically amenable system is presented.
研究领域:
植物生物技术
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分子生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Materials Today Nano
·
2021
·
IF 8.109
R. Sun,Q. Luo,X. Li,X. Huang,L. Teng,Z. Shen,W. Zhu
PEGylated drugs and their self-assembled nanoparticles have been used as a first-line technology in nanomedicines . However, premature disassembly before reaching the lesions under dilute conditions limits their bioavailability. This challenge can be overcome by covalent crosslinking. However, undefined molecular structures of the prodrugs are introduced, which hinder large-scale production and clinical translation. Herein, a supramolecular PEGylated camptothecin nanodrug with a crosslinked architecture and defined molecular drug structure was developed. PEGylated mono-tetraethylenepentamine β-cyclodextrin (mPEG-TEPA-CD) and adamantane modified camptothecin (AD-SS-CPT) were first synthesized. The host-guest coupling of β-cyclodextrin (β-CD) and adamantine (AD) moieties between mPEG-TEPA-CD and AD-SS-CPT induced the formation of supramolecular PEGylated camptothecin, which could self-assemble into micelles in the aqueous medium. They were further stabilized by the addition of a diacrylate crosslinker for reaction with the amine groups on mPEG-TEPA-CD, maintaining the unaltered AD-SS-CPT. The nanodrugs can internalize into tumor cells quickly and release free camptothecin in response to glutathione . They also have prolonged blood circulation time and can accumulate efficiently at tumor sites, thus showing effective antitumor activity . This supramolecular drug delivery system provides a new strategy for the design of nanodrugs.
研究领域:
药学
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纳米医学
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肿瘤学
✓ 已验证
DOI
高影响因子
Journal of Materials Chemistry B
·
2015
·Vol. 3
·期 10
·2127-2136
·
IF 4.726
Wei Zhang,Xiaoyan Zhou,Tao Liu,Dong Ma,Wei Xue
The co-delivery of multiple drugs has become the primary strategy in cancer therapy in recent years, because this technique could promote synergistic actions, reduce side effects and deter the development of drug resistance. To achieve a controlled and sustained release of the loaded drugs, a supramolecular hydrogel based on the host–guest interactions between a hyperbranched polyglycerol derivative and α-cyclodextrin was prepared and used to co-load camptothecin and doxorubicin for sustainedly synergistic tumor therapy. The gelation kinetics, hydrogel strength and supramolecular structure of the obtained hydrogel were studied by dynamic and steady rheometry under various concentrations of α-CD. The sustained dual drug release from the supramolecular hydrogel in vitro, and their synergistic effect in vitro and in vivo were also explored. Moreover, the supramolecular hydrogel showed receivable blood compatibility and non-cytotoxicity by in vitro and in vivo assays. Therefore, this supramolecular hydrogel could potentially be applied in sustainedly synergistic tumor therapy.
研究领域:
药剂学
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肿瘤学
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材料科学
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产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
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2013
·Vol. 97
·期 21
·9365-9375
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IF 3.689
Pu Xiang,Qu Xixing,Chen Fei,Bao Jinku,Zhang Guolin,Luo Yinggang
Camptothecin (CPT), the third largest anticancer drug, is produced mainly by Camptotheca acuminata and Nothapodytes foetida . CPT itself is the starting material for clinical CPT-type drugs, but the plant-derived CPT cannot support the heavy demand from the global market. Research efforts have been made to identify novel sources for CPT. In this study, three CPT-producing endophytic fungi, Aspergillus sp. LY341, Aspergillus sp. LY355, and Trichoderma atroviride LY357, were isolated and identified from C. acuminata . Most CPT produced by these fungi was found in the fermentation broth, and their corresponding CPT yields were 7.93, 42.92, and 197.82 μg l −1 , respectively. The CPT-producing capability of LY341 and LY355 was completely lost after repeat subculturing. A substantial decrease of CPT production was also observed in the second generation of LY357. However, a stable and sustainable production of CPT was found from the second generation through the eighth generation of LY357. The fermentation medium, time, pH, temperature, and agitation rate were optimized for CPT production. Methyl jasmonate and XAD16 were proven to be an optimum elicitor and adsorbent resin, respectively, in view of that CPT yield was increased 3.4- and 11-fold through their use. A 50- to 75-fold increase of CPT yield was obtained when the optimized fermentation conditions, elicitor, and adsorbent resin were combined and applied to the culture of the seventh and eighth generations of LY357, and the highest CPT yield was 142.15 μg l −1 . The CPT-producing T. atroviride LY357 paves a potential to uncover the mysteries of CPT biosynthesis.
研究领域:
药用植物学
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微生物学
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药物开发
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2014
·
IF 3.785
Zhichao Wang,Qingyong Li,Xiuhua Zhao,Baihe Sun,Qiaochu Zhu,Wenqing Gao,Changlong Hua
The purpose of this work is to prepare a formulation using mannitol coupling Camptothecin (CPT) nanoparticles (CPT-NPs) to circumvent the difficult solubilization practice based on central composite experimental statistical design. CPT-NPs were prepared with a high-pressure homogenization technique method. The independent variables considered for the optimization of CPT-NPs were percentage of CPT in raw material (CPT and mannitol), concentration of CPT in working liquid, cycles numbers and homogenizer pressure for drug loading efficiency, particle size and polydispersity index. Analysis of variance (ANOVA) statistical test was used to assess the optimization. The optimized CPT-NPs showed an appropriate drug loading efficiency (18.09 ± 2.13%), a homogeneous particle size (165.33 ± 37.23 nm) and a low polydispersity index (0.29 ± 0.01). The CPT-NPs group show higher inhibition ratio (79.95%) of H22 tumor growth in vivo compared with TPT and CPT at the same dose. Changes in mice body weight demonstrate CPT-NPs have the lower toxicity. The results of biodistribution studies indicated the obviously superiority of CPT-NPs in increasing the accumulation of CPT within tumor. Overall, CPT-NPs under optimum conditions are considered to be potentially feasible to overcome formulation challenges for drug delivery.
研究领域:
药剂学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
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2021
·
IF 6.244
Heng Yongqing,Liang Yupei,Zhang Junqian,Li Lihui,Zhang Wenjuan,Jiang Yanyu,Wang Shiwen,Jia Lijun
The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）