PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Risheng Zhao,Min Zhang,Gege Yang,Wei Liu,Hui Yu,Shuang Yan,Ting Ren,Linxin Zhang,Mengyang Wang,Haiming Sun
Hypertensive heart failure pathogenesis involves angiotensin II (Ang II)-mediated mechanisms through both hemodynamic overload and direct cellular signaling pathways. This study investigates the therapeutic potential of Portulaca oleracea L. (POL) extract and its active constituent Oleracein E (OE) in attenuating Ang II-induced pathological cardiac remodeling and subsequent heart failure progression. An experimental model of hypertensive heart failure was established in C57BL/6 mice through continuous subcutaneous infusion of Ang II for 4 weeks, with Oleracein E (OE) intervention administered during the final 2 weeks of the protocol. To elucidate the molecular mechanisms underlying OE's cardioprotective effects, we employed an integrated approach combining RNA sequencing analysis, molecular docking simulations, and target validation through drug affinity response target stability (DARTS) and cellular thermal shift assay (CETSA) techniques. The experimental results demonstrated that both POL extract and its active component OE exerted significant cardioprotective effects against Ang II-induced cardiac dysfunction in murine models, primarily through attenuation of pathological cardiac hypertrophy and suppression of inflammatory responses. Transcriptomic profiling via RNA sequencing identified the MAPK signaling pathway as a critical mediator of these protective effects. Subsequent transcription factor analysis revealed STAT2 as a key regulatory component in this pathway. Importantly, OE treatment effectively mitigated inflammatory responses in both in vivo cardiac tissues and in vitro cultured cardiomyocytes by specifically inhibiting the Ang II-activated MAPKs/STAT2 signaling cascade. Genetic ablation experiments further confirmed the essential role of this pathway, as the anti-inflammatory efficacy of OE was completely abolished in cardiomyocytes with MAPKs or STAT2 deficiency. Molecular interaction studies employing in silico docking simulations combined with experimental validation through DARTS and CETSA techniques provided direct evidence of physical binding between OE and the STAT2 protein. Our findings demonstrate that Oleracein E (OE) confers cardioprotection against Ang II-induced myocardial injury through a novel mechanism involving STAT2 targeting and subsequent suppression of MAPK signaling-mediated inflammatory cascades. These results not only elucidate a previously unrecognized pharmacological pathway but also suggest that OE and its derivatives hold significant therapeutic promise for the clinical management of hypertensive heart failure, potentially offering a targeted approach to modulate pathological cardiac remodeling.
研究领域:
药理学
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心血管病学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2017
·
IF 3.887
He-Lin Xu,Zi-Liang Fan,De-Li ZhuGe,Bi-Xin Shen,Bing-Hui Jin,Jian Xiao,Cui-Tao Lu,Ying-Zheng Zhao
Severe toxicity and poor tumour penetration are two intrinsic limited factors to hinder the broad clinical application for most of first-line chemotherapeutics. In this study, a novel vitamin E succinate-grafted ε-polylysine (VES-g-PLL) polymer was synthesized by using ε-polylysine as backbone. By adjusting VES graft ratio, VES-g-PLL (50) with a theoretic VES graft ratio of 50% could self-assemble into a supermolecular micelle with a hydrodynamic diameter (D h ) of ca.20 nm, and Zeta potential of 19.6 mV. VES-g-PLL micelles themselves displayed a strong anti-tumour effect on glioma. The poorly water-soluble curcumin was effectively encapsulated in VES-g-PLL micelles with the drug loading amount and entrapment efficiency reaching 4.32% and 82.27%, respectively. In a physiologic medium, curcumin-loaded VES-g-PLL micelles (Cur-Micelles) not only remained stable without obvious drug leakage but also sustained the release of its encapsulated curcumin for a long time. Because of the ultra-small size and positively-charged surface, Cur-Micelles penetrated the deeper tumour zone than free curcumin, resulting in a significant inhibition of tumour spheroids growth. Moreover, in vivo strong antitumor effect of Cur-Micelles was also exhibited at assistance of ultrasound-targeted microbubble destruction and the real-time MRI imaging demonstrated a nearly complete suppression of glioma after 28 days of treatment. TUNEL staining showed that the therapeutic mechanism of Cur-Micelles was relevant to the apoptosis of tumour cells. Finally, in vivo nontoxicity of Cur-Micelles against normal organs including heart, liver, spleen, lung and kidney tissues was also demonstrated by the HE staining. In conclusion, VES-g-PLL micelles may serve as a potential carrier for curcumin to enhance tumour penetration and improve therapeutic effect on glioma.
研究领域:
药学
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肿瘤学
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生物材料学
✓ 已验证
DOI
高影响因子
JOURNAL OF PHARMACEUTICAL SCIENCES
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2020
·
IF 2.997
Zipeng Huang,Xinru Chen,Ying Li,Junqiu Zhai,Yan Ma
Curcumin (CUR) has attracted wide research interests due to its abundant bioactivities and potential advantages in cancer treatment. But the poor water solubility, instability, and quick metabolization and elimination after oral administration severely restrict the efficacy and further clinical application of CUR. Derivation is an approach often used to improve the druggability of active ingredients, so the study aim to prepare a CUR derivate with better stability, satisfactory pharmacokinetics , and inherent self-assembled ability in contrast with CUR. The derivate was designed and evaluated in vitro and in vivo . Vitamin E (VE) was used to perform the esterification reaction with CUR, and the cytotoxicity of derivative CUR-VE ester on MCF-7 tumor cells was similar to CUR. Besides the better stability in simulated gastric and intestinal fluid, plasma and liver homogenate, the self-assembly CUR-VE nanoparticles were fabricated by feasible and controllable nanoprecipitation method. The Transmission Electron Microscope (TEM) showed CUR-VE NPs were spherical with an average particle size of 172.9 nm , and drug loading was up to 93%. CUR-VE NPs exhibited a sustained-release behavior and fitted to Fick's diffusion mechanism. Differential Scanning Calorimeter (DSC), X-ray Powder Diffractometer (XRPD) and Fourier Transform Infrared Spectrometer (FTIR) declared no crystalline substances were formed, and the self-assembly process of CUR-VE relied on driving forces including van der Waals forces , hydrogen bonding forces, intermolecular forces . In pharmacokinetics, C max and AUC 0-∞ of CUR-VE NPs by the route of oral administration were (104.69 ± 40.72) ng/mL and (3496.92 ± 1088.93) ng/mL∗h, which were about three times and 18 times more compared with CUR. The eliminated half-time of CUR-VE extended to 28 h ascribed to the outstanding stability and surface PEGylation of NPs. It prompted that appropriately PEGylated NPs via oral administration was beneficial to prolong systemic circulation similar to intravenous PEGylated NPs. In summary, the study provides a convenient way to fabricate the self-assembled CUR-VE NPs qualified with high drug loading, satisfactory stability and desired pharmacokinetics. CUR-VE has the potent advantage to be an ideal substitute for CUR in the future of healthcare and clinical application.
研究领域:
药学
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纳米技术
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药物递送系统
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
DYES AND PIGMENTS
·
2016
·
IF 4.055
Yahui Zhang,Huiling Mao,Lingwei Kong,Yong Tian,Zhonglin Tian,Xiangkai Zeng,Junge Zhi,Jianbing Shi,Bin Tong,Yuping Dong
E/Z isomers of hexaphenyl-1,3-butadiene (HPB) derivative containing dialdehyde groups, 4,4’-((1E,3E)-1,2,3,4-tetraphenylbuta-1,3-diene-1,4-diyl)dibenzaldehyde (EE-HPB-CHO), 4,4’-((1Z,3E)-1,2,3,4-tetraphenylbuta-1,3-diene-1,4-diyl)-dibenzaldehyde (EZ-HPB-CHO) and 4,4’-((1Z,3Z)-1,2,3,4-tetra-phenylbuta-1,3-diene-1,4-diyl)dibenzaldehyde (ZZ-HPB-CHO), were firstly synthesized in one-pot and readily separated by silica gel column chromatography . The E/Z isomers containing conjugated diene exhibited remarkable differences in the fields of aggregation-induced emission (AIE) or aggregation-enhancement emission (AEE) behavior, thermostability, and mechanochromic performance. Among them, EE-HPB-CHO with dense molecular packing and strong intermolecular interaction was a better AIEgen while the EZ- and ZZ-isomers exhibited AEE behavior. Moreover, EE-HPB-CHO hardly displayed the mechanochromic performance. EZ-HPB-CHO irreversibly exhibited a blue-shift of 23 nm by grinding treatment, which could not be restored by fuming with organic solvents or heating. In contrast, owing to its twisting conformation and relative loose packing, ZZ-HPB-CHO reversibly displayed a red-shift of 20 nm during multiple repeating cycles of grinding and fuming treatments, showing superior mechanochromic performance.
研究领域:
有机化学
·
材料科学
✓ 已验证
DOI
高影响因子
PHARMACEUTICAL RESEARCH
·
2019
·Vol. 36
·期 12
·1-16
·
IF 3.896
Qiao Xiaoyin,Yang Yikun,Huang Ruiying,Shi Xuelei,Chen Haoxiang,Wang Jian,Chen Yanxiang,Tan Yongjun,Tan Zhikai
Purpose Combination chemotherapy is gradually receiving more attention because of its potential synergistic effect and reduced drug doses in clinical application. However, how to precisely control drug release dose and time using vehicles remains a challenge. This work developed an efficient drug delivery system to combat breast cancer, which can enhance drug effects despite reducing its concentration. Methods Controlled-release poly-lactic-co-glycolic acid (PLGA) scaffolds were fabricated by E-jet 3D printing to deliver doxorubicin (DOX) and cisplatin (CDDP) simultaneously. Results This drug delivery system allowed the use of a reduced drug dosage resulting in a better effect on the human breast cancer cell apoptosis and inhibiting tumor growth, compared with the effect of each drug and the two drugs administrated without PLGA scaffolds. Our study suggested that DOX-CDDP-PLGA scaffolds could efficiently destroy MDA-MB-231 cells and restrain tumor growth. Conclusions The 3D printed PLGA scaffolds with their time-programmed drug release might be useful as a new multi-drug delivery vehicle in cancer therapy, which has a potential advantage in a long term tumor cure and prevention of tumor recurrence.
研究领域:
药学
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生物医学工程
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Animals
·
2025
·Vol. 15
·期 23
·3491
·
IF 2.7
Yongjie Zhang,Liyang Guo,Shun Wang,Jie Zhang,Xinlei Ren,Rui Li,Jichang Li,Chunli Chen
Simple SummaryPolymyxin E is widely considered the last resort for treating multidrug-resistant Gram-negative bacteria. However, due to the emergence of the plasmid-mediated MCR-1 resistance gene, an increasing number of strains have developed resistance to polymyxin E. Additionally, the prevalence ofEscherichia coliin chickens has imposed a heavy burden on the global food and poultry farming industries. This study aimed to investigate the in vitro and in vivo synergistic effects and mechanisms of quercetin (QUE) combined with polymyxin E against MCR-1-positiveE. coliJD37 from chickens. The in vitro and in vivo synergistic effects of QUE and polymyxin E were confirmed through in vitro drug sensitivity tests, growth curves, time-kill curves, agar diffusion tests, and in vivo chick infection experiments. The results showed that QUE restored the sensitivity of polymyxin E toE. coliJD37 and restored the sensitivity of polymyxin E toE. coliJD37 mainly by increasing the permeability of the cell membrane, elevating the fluidity of the cell membrane, increasing the membrane potential, and reducing the expression of the AcrAB-TolC efflux pump and Lipopolysaccharide (LPS) regulatory-related genes. Molecular docking results revealed the key binding sites of QUE to MCR-1.In animal husbandry and livestock farming, with the spread of the plasmid-mediated MCR-1 gene, polymyxin E, as the last line of defense against drug-resistant Gram-negative bacteria, is facing severe challenges. This study investigated the in vitro and in vivo synergistic effects and mechanisms of QUE combined with polymyxin E against MCR-1-positive chickenE. coliJD37. In vitro experiments showed that QUE could restore the sensitivity ofE. coliJD37 to polymyxin E (FIC = 0.34375) and enhance the bactericidal effect of polymyxin E by increasing cell membrane permeability, fluidity, and membrane potential, downregulating the expression of the AcrAB-TolC efflux pump and LPS-related genes. Molecular docking further identified the key residues for QUE binding to the MCR-1 protein. The in vivo chick infection model confirmed that combination therapy increased survival rates, reduced bacterial load in tissues, alleviated pathological damage, and decreased levels of intestinal inflammatory factors. Our results demonstrate the synergistic bactericidal effect of the QUE-polymyxin E combination against MCR-1-positiveE. coliand elucidate its underlying mechanism.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2021
·
IF 8.947
Ri-Tong Lan,Yue Ren,Xin Wei,Li-Zhi Tang,Nouman Ali Shah,Lu Xu,Shi-Shu Huang,Rizwan M. Gul,Jia-Zhuang Xu,Zhong-Ming Li
Oxidative stability of radiation crosslinked ultrahigh molecular weight polyethylene (UHMWPE) artificial joints is significantly improved by vitamin E (VE), but there is a dilemma that VE hinders crosslinking and thus jeopardizes the wear of UHMWPE. In this effort, we proposed an efficient strategy to stabilize UHMWPE under limited antioxidant contents, where VE and D-sorbitol (DS) were used as the primary antioxidant and the secondary antioxidant respectively. For non-irradiated blends with fixed antioxidant contents, oxidative stability accessed by oxidation induction time (OIT) of VE/DS/UHMWPE blends was superior to that of VE/UHMWPE blends, while DS/UHMWPE blends showed no increase in OIT. The cooperation between DS and VE exhibited a synergistic effect on enhancing the oxidative stability of UHMWPE. Interestingly, the irradiated VE/DS/UHMWPE blends showed comparable OIT but a significantly higher crosslink density than the irradiated VE/UHMWPE blends. The crystallinity, melting point, and in vitro biocompatibility of the blends were not affected by VE and DS. The quantitative relationships of mechanical properties , oxidation stability, crystallinity and crosslink density were established to unveil the correlation of these key factors. The overall properties of VE/UHMWPE and VE/DS/UHMWPE blends were compared to elucidate the superiority of the antioxidant compounding strategy. These findings provide a paradigm to break the trade-off between oxidative stability, crosslink density and mechanical properties, which is constructive to develop UHMWPE bearings with upgraded performance for total joint replacements. Statement of significance VE-stabilized UHMWPE is the most commonly used material in total joint replacements at present. However, oxidation and wear resistance of VE/UHMWPE implants cannot be unified since VE reduces the efficiency of radiation crosslinking. It limits the use of VE. Herein, we proposed a compounding stabilization by the synergy between VE and DS. The antioxidation capability of VE was revived by DS, thus enhancing the oxidation stability of unirradiated UHMWPE. The irradiated VE/DS/UHMWPE exhibited similar oxidation stability but higher crosslink density than irradiated VE/UHMWPE, which is beneficial to combat wear of UHMWPE and to inhibit the occurrence of osteolysis . This synergistic antioxidation strategy endows the UHMWPE joint material with good overall performance, which is of clinical significance.
研究领域:
材料科学
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生物医学工程
·
骨科手术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHINESE JOURNAL OF CHEMICAL ENGINEERING
·
2023
·
IF 3.8
Xiaoyun Hou,Qinghong Shi
We described a novel polymer-lipase conjugate for high-efficient esterification of vitamin E using vitamin E and succinic anhydride as the substrates in nonaqueous media. In this work, the monomer, N -isopropylacrylamide (NIPAM), was grafted onto Candida rugosa lipase (CRL) to synthesize poly(NIPAM) ( p NIPAM)-CRL conjugate by atom transfer radical polymerization via the initiator coupled on the surface of CRL. The result showed that the catalytic efficiencies of p NIPAM-CRL conjugates (19.5 – 30.3 L·s -1 ·mmol -1 ) were at least 7-times higher than that of free CRL (2.36 L·s -1 ·mmol -1 ) in DMSO. It was attributed to a significant increase in K cat of the conjugates in nonaqueous media. The synthesis catalyzed by p NIPAM-CRL conjugates was influenced by the length and density of the grafted polymer, water content, solvent polarity and molar ratio of the substrates. In the optimal synthesis, the reaction time was shortened at least 7-times, and yields of vitamin E succinate by p NIPAM- g -CRL and free CRL were obtained to be 75.4% and 10.1 % at 55°C after the reaction for 1.5 h. The result argued that conjugation with p NIPAM induced conformational change of the lid on CRL based on hydrophobic interaction, thus providing a higher possibility of catalysis-favorable conformation on CRL in nonaqueous media. Moreover, p NIPAM conjugation improved the thermal stability of CRL greatly, and the stability improved further with an increase of chain length of p NIPAM. At the optimal reaction conditions (55°C and 1.5 h), p NIPAM- g -CRL also exhibited good reusability in the enzymatic synthesis of vitamin E succinate and kept ∼ 70% of its catalytic activity after ten consecutive cycles. The research demonstrated that p NIPAM- g -CRL was a more competitive biocatalyst in the enzymatic synthesis of vitamin E succinate and exhibited good application potential under harsh industrial conditions.
研究领域:
生物技术
·
酶工程
·
有机化学
·
药学
✓ 已验证
产品关联
DOI
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Wang Huan,Fan Yanmiao,Yang Qiaoli,Sun Xiaoyu,Liu Hao,Chen Wei,Aziz Ayesha,Wang Shenqi
Redox activity is an important indicator for evaluating electrochemical biosensors. In this work, we have successfully polymerized indole-5-carboxylic acid into poly-5-carboxyindole nanomaterials (PI-5-CA), using its superior redox activity, and introduced carboxylated single-walled carbon nanotubes (C-SWCNTs) to synthesize a composite material. Finally, a synthesized composite material was used for the modification of the glass carbon electrode to fabricate the PI-5-CA/C-SWCNTs/GCE-based immunosensor and was successfully applied for the sensitive detection of E. coli O157:H7. The fabricated immunosensor exhibited an outstanding electrocatalytic activity toward the detection of E. coli O157:H7 with a remarkably lowest limit of detection (2.5 CFU/ml, LOD = 3 SD/k, n = 3) and has a wide linear range from 2.98×101 to 2.98×107 CFU/ml. Inspired from the excellent results, the fabricated electrode was applied for the detection of bacteria from real samples (water samples) with a good recovery rate (98.13–107.69%) as well as an excellent stability and specificity. Owing to its simple preparation, excellent performance, and detection time within 30 min, our proposed immunosensor will open a new horizon in different fields for the sensitive detection of bacteria from real samples.
研究领域:
生物传感
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材料科学
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微生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2023
·Vol. 28
·期 24
·8061
·
IF 4.6
Jiaying Lv,Ruimao Hua
A two-step, one-pot synthesis of 3-substituted 1H-dibenzo[e,g]indazoles in good to high yields via a LiOtBu-promoted intramolecular 1,3-dipolar cyclization of 2′-alkynyl-biaryl-2-aldehydeN-tosylhydrazones was developed. TheN-Ts-hydrazones used were prepared in situ via the reactions of 2′-alkynyl-biaryl-2-aldehydes and TsNHNH2(p-methylbenzenesulfonohydrazide). Two types of signals related to the hydrogen bonds, forming in several products, were observed in the1H NMR spectra recorded in DMSO-d6, assigned to N-H bonds in their dimeric species of product and tautomer.Keywords:N-tosylhydrazones;1H-dibenzo[e,g]indazoles;intramolecular cycloaddition;lithiumtert-butoxide;hydrogen bonds
研究领域:
有机化学
·
药物化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2016
·
IF 3.994
Jinli Li,Xudong Cheng,Yan Chen,Weiming He,Li Ni,Peihua Xiong,Minggang Wei
Luteolin (LUT) is an active agent in cancer prevention and a potential candidate for clinical chemotherapy. However, poor water solubility and extensive excretion have limited the clinical use of luteolin. Herein, we attempted to develop vitamin E d-α-tocopherol acid polyethylene glycol 1000 succinate (TPGS) coated liposomes to improve the accumulation of luteolin in lung cancer. Luteolin or coumarin-6 loaded liposomes were prepared using film-dispersion methods and characterized according to their particle size, polydispersity, zeta potential , and drug encapsulation efficiency. Cellular uptake properties and cytotoxicities of luteolin or coumarin-6 loaded liposomes were determined in A549 cells. Optical in vivo imaging was employed as a method of assessing tumor targeting. The antitumor effect was evaluated in mice xenotransplanted with A549 cancer cells. The results showed that TPGS coated liposomes are spherical, and are ∼176.2 nm in size. TPGS coated liposomes enhanced cellular uptake and apoptosis by upregulating the Bax/Bcl-2 ratio, resulting in improved cytotoxicity in A549 cells. TPGS coated liposomes significantly accumulated in tumor tissue and enhanced tumor inhibition without altering the structures of other organs. Thereby, TPGS coated liposomes provide an effective strategy in cancer chemotherapy for model drugs with poor water solubility such as luteolin.
研究领域:
药剂学
·
肿瘤学
·
药物递送系统
·
纳米技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2018
·Vol. 6
·期 12
·3397-3409
·
IF 5.831
Jing-Bo Hu,Di Liu,Jing Qi,Kong-jun Lu,Fei-yang Jin,Xiao-Ying Ying,Jian You,Yong-Zhong Du
Based on the overproduction of matrix metalloproteinase-2 (MMP-2) in renal tissue during acute kidney injury (AKI) occurrence, we developed a MMP-2 enzyme-triggered polymeric prodrug with sialic acid (SA) as the targeting group to the inflamed vascular endothelial cells for enhanced therapeutic outcomes. An MMP-2-responsive peptide, PVGLIG, was used to endow the polymeric prodrug with the ability to rapidly release the anti-inflammatory drug, curcumin (CUR), after the targeted site is reached and to improve the drug concentration in the target tissue. The sialic acid–dextran–PVGLIG–curcumin (SA-DEX-PVGLIG-CUR) polymeric prodrug was successfully synthesized via multi-step chemical reactions and characterized by 1H NMR. The water solubility of CUR was significantly increased in the polymeric prodrug and was approximately 23-fold higher than that of free CUR. The in vitro drug release results showed that the release rate of SA-DEX-PVGLIG-CUR was significantly enhanced compared to that of SA-DEX-CUR in a dissolving medium containing the MMP-2 enzyme, suggesting that SA-DEX-PVGLIG-CUR had rapid drug release characteristics in an inflammatory environment. A cellular uptake test confirmed that SA-DEX-PVGLIG-CUR was effectively internalized by inflamed vascular endothelial cells in comparison with that by normal cells, and the mechanism was associated with the specific interaction between SA and E-selectin receptors specifically expressed on inflamed vascular endothelial cells. Bio-distribution results further demonstrated the rapid and increased renal accumulation of SA-DEX-PVGLIG-CUR in AKI mice. Benefiting from the rapid drug release in renal tissue, SA-DEX-PVGLIG-CUR effectively ameliorated the pathological progression of AKI compared with free CUR and SA-DEX-CUR, as reflected by the improved renal functions, histopathological changes, pro-inflammatory cytokine production, oxidative stress and expression of apoptosis related proteins. Altogether, this study provided a new therapeutic strategy for the treatment of AKI.
研究领域:
药学
·
肾病学
·
药物递送系统
·
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）