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INDUSTRIAL CROPS AND PRODUCTS · 2020 · IF 4.244

Morinda citrifolia L. leaves extracts obtained by traditional and eco-friendly extraction solvents: Relation between phenolic compositions and biological properties by multivariate analysis

Huilan Zhu,Jiachao Zhang,Congfa Li,Sixin Liu,Lu Wang

Morinda citrifolia L. leaves (MCLs) have attracted considerable interest in the agricultural, pharmaceutical, and food industries owing to its medicinal properties. This present work aims to investigate the influences of extraction solvents such as water, organic solvents (ethanol, methanol, acetone, and ethyl acetate) and eco-friendly deep eutectic solvents (DESs) on total phenolic content (TPC), total flavonoid content (TFC), biological properties, and antimicrobial activity of MCLs extracts. Results indicated that the MCLs extracts extracted by three types of DESs exhibited the highest TPC (25.17–30.93 mg GAE/g DW), while that extracted by ethyl acetate as extraction solvent had the lowest TPC and TFC. Phenolic compositions of the MCLs extracts were identified and quantified by HPLC-ESI-QTOF-MS/MS. Among them, gallic acid, orientin, rutin and ferulic acid were the dominant components in the MCLs extracts obtained by different solvents. In addition, the three DESs also showed more excellent performances on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azino-bis (3-ethylbenzo thiazoline-6-sulphonic acid) (ABTS), and hydroxyl free radical (OH − ) scavenging activities, ferric reducing antioxidant power (FRAP), and anti-microbial activity than traditional solvents. 50% ethanol/methanol were the most effective extraction solvent for inhibition of α -glucosidase. The results of multivariate analysis highlighted the influence of solvents on the TPC and biological activities of MCLs extracts. These findings clearly indicate that DESs can be used as the most effective solvents for extraction of phenolic compounds from MCLs extracts. The results suggest that the MCLs can be a promising source enriched with bio-active constituents for application in the pharmaceutical industries.

✓ 已验证 DOI 高影响因子
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BIORESOURCE TECHNOLOGY · 2015 · IF 4.494

Improved biosynthesis of ethyl (S)-4-chloro-3-hydroxybutanoate by adding l-glutamine plus glycine instead of NAD+ in β-cyclodextrin–water system

Yu-Cai He,Dan-Ping Zhang,Zhi-Cheng Tao,Yun Lu,Yun Ding,Feng Liu,Zheng-Zhong Zhu,Huan Rui,Gao-Wei Zheng,Xian Zhang

To reduce dependence on the expensive cofactor and effectively biotransform ethyl 4-chloro-3-oxobutanoate, l -glutamine and glycine were found to enhance the content of intracellular NADH and the reductase activity. Adding the mixture of 200   mM of l -glutamine and 500   mM of glycine to the reaction media, a 1.67-fold of reductase activity was increased over the control without the addition of the two compounds. Moreover, β-cyclodextrin (0.4   mol β-cyclodextrin/mol ethyl 4-chloro-3-oxobutanoate) was also added into this reaction media, and the biocatalytic activity of the whole-cell biocatalyst of Escherichia coli CCZU-K14 was increased by 1.34-fold than that without β-cyclodextrin. In this β-cyclodextrin–water media containing l -glutamine (200   mM) plus glycine (500   mM), ethyl ( S )-4-chloro-3-hydroxybutanoate (>99% ee ) could be obtained from 3000   mM ethyl 4-chloro-3-oxobutanoate in the yield of 98.0% after 8   h. All the positive features demonstrate the potential applicability of the bioprocess for the large-scale production of ethyl ( S )-4-chloro-3-hydroxybutanoate.

CAS / MDL: 56-85-9
✓ 已验证 产品关联 DOI PubMed 高影响因子
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BIOMACROMOLECULES · 2021 · IF 6.988

Poly(l-cysteine) Peptide Amphiphile Derivatives Containing Disulfide Bonds: Synthesis, Self-Assembly-Induced β-Sheet Nanostructures, pH/Reduction Dual Response, and Drug Release

Liang Dong,Hui Chen,Ting Liu,Junming Zhu,Min Yu,Qingmei Yuan

Three disulfide bond-containing peptide amphiphiles (PA1–3) with different lengths of alkyl tails (PA1 for C6, PA2 for C12, and PA3 for C18) were synthesized by ring-opening polymerization of α-amino acid N-carboxyanhydride followed by post-polymerization modification. The peptide segments were composed of 3-mercaptopropionic acid-modified poly(l-cysteine) [P(Cys-SS-CH2CH2COOH)]. We characterized the chemical structure and molecular parameters by 1H NMR, 13C NMR, gel permeation chromatography, Fourier transform infrared spectroscopy, and circular dichroism spectroscopy. It is found that alkyl-P(Cys-SS-CH2CH2COOH) mainly presents a β-sheet conformation at the solid state. However, the PAs present predominant random coils at pH 7.4 in aqueous solutions. The β-sheet conformation increased dramatically when the concentration of the PA exceeded its critical micelle concentration (ca. 0.3 mg/mL for PA3), indicating the formation of self-assembly-induced β-sheet nanostructures. Elongation of the alkyl chain length or a decrease of the pH of the PA solution can promote the formation of the β-sheet conformation. The three PAs can self-assemble into spherical micelles or nanofibrous hydrogels, which can be utilized as nanocarriers for systemic drug delivery or implants for localized drug delivery, respectively. Cisplatin (CDDP) was loaded as a model medicine to examine the drug delivery potential of PA3. We found that the CDDP-loaded PA3 micelles are stable at pH 7.4, have a spherical morphology with a hydrodynamic diameter of ca. 52 nm, and accomplish pH/reduction dual-responsive release of CDDP. In addition, alkyl-P(Cys-SS-CH2CH2COOH) can self-assemble into nanofibrous hydrogels at pH 5.0–6.0 or upon the addition of certain metal ions and show excellent dynamic reversibility. Moreover, the CDDP-loaded PA3 hydrogel exhibits a sustained release profile and a nearly linear release over 48 h. In vitro cytotoxicity of PA3 also indicates its nontoxicity. Thus, our findings suggest that alkyl-P(Cys-SS-CH2CH2COOH) has great potential for both systemic and localized delivery of therapeutics.

✓ 已验证 DOI PubMed 高影响因子
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Materials Today Chemistry · 2020 · IF 0

Programmable release of 2-O-d-glucopyranosyl-l-ascorbic acid and heparin from PCL-based nanofiber scaffold for reduction of inflammation and thrombosis

H. Wang,Y. Xia,J. Liu,Z. Ma,Q. Shi,J. Yin

Reduction of inflammation and thrombosis caused by implanted devices is critical for clinical success. To this end, the strategy based on programmable release of anti-inflammatory and anti-thrombotic agents from the widely-used polycaprolactone (PCL)/gelatin nanofiber scaffold is developed. The release of 2-O- d -Glucopyranosyl- l -ascorbic Acid (AA-2G) and heparin are controlled by reactive oxygen species (ROS)-responsive poly(ethylene glycol)-based β-thioether ester copolymer (PEGDA-EDT) and mesoporous silica nanoparticles (MSN) in the nanofiber, respectively. The in vitro assay demonstrate that the scaffolds are hemocompatible with the resistance of platelet adhesion; the control release of AA-2G prevents initial inflammation and oxidation of the blood cells, and the subsequent release of heparin entitles nanofibers with long-term anti-thrombotic capability. In addition, rapid endothelialization is obtained on the surface of nanofiber scaffolds for the further enhancement of the hemocompatibility. In vivo implant evaluation convinces that the nanofiber scaffolds possess high biocompatibility with the substantial resistance for inflammation and thrombosis. Hence, our work paves a new way to develop the anti-inflammatory and anti-thrombotic tissue-engineering substrates through programmable delivery of two or multiple drugs.

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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2021 ·Vol. 22 ·期 2 ·928 · IF 5.924

Enhancing the Physiochemical Properties of Puerarin via L-Proline Co-Crystallization: Synthesis, Characterization, and Dissolution Studies of Two Phases of Pharmaceutical Co-Crystals

Muhammad Inam,Lu Liu,Jian-Wei Wang,Ka-Xi Yu,Chi-Uyen Phan,Jie Shen,Wen-Hua Zhang,Guping Tang,Xiurong Hu

Puerarin (PUE) is a Chinese traditional medicine known to enhance glucose uptake into the insulin cells to downregulate the blood glucose levels in the treatment of type II diabetes. Nevertheless, the bioavailability of pristine PUE is limited due to its poor solubility and low intestinal permeability. In this work, we demonstrate that the solubility of PUE can be significantly enhanced via its co-crystallization with L-Proline (PRO). Two crystalline phases, namely, the solvate-free form [PUE][PRO] (I) and the solvated form [PUE]2[PRO]∙EtOH∙(H2O)2(II) are isolated. These two phases are characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), Fourier-transformed infrared (FT-IR) spectra, nuclear magnetic resonance (NMR), and thermogravimetric analysis in association with differential scanning calorimetry (TGA-DSC). The solubility and dissolution rate of bothIandIIin water, gastrointestinal tract at pH 1.2, and phosphate buffer at pH 6.8 indicates a nearly doubled increase as compared to the pristine PUE. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay of pristine PUE,IandIIagainst murine colon cancer cell lines CT-26 and human kidney cell lines HEK-293 indicated that neither compound exhibits obvious cytotoxicity after 24 h. This work showcases that the readily available and biocompatible PRO can be a promising adjuvant to enhance the physicochemical properties of PUE toward orally administered drug formulation with improved pharmacokinetics.Keywords:puerarin;L-proline;pharmaceutical co-crystal;crystal structure;solubility and dissolution rate;Chinese traditional medicine;Hirschfeld analysis;hydrogen-bonding

✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF BIOACTIVE AND COMPATIBLE POLYMERS · 2019 · IF 1.976

Supramolecular hydrogel containing multi-generation poly(L-lysine) dendrons for sustained co-delivery of docetaxel and matrix metallopeptidase-9 short hairpin RNA plasmid

Yumeng Yang,Shixin Liu,Xiang Cai,Dong Ma,Jun Xu

To obtain an efficient drug and gene co-delivery hydrogel, methoxy polyethylene glycol was reacted with the caprolactone units to form the MPEG-PCL block copolymer through the polymerization reaction, which is amphiphilic and can load the hydrophobic drugs. Then, MPEG-PCL conjugated with a multi-generation poly(L-lysine) dendron to form the guest molecule MPEG-PCL-PLLD. After interacted with α-cyclodextrin through host–guest inclusion, the drug and gene dual carrier of supramolecular hydrogel was obtained. The physical properties of the hydrogel, such as the gelation time, the hydrogel strength, or its shear viscosity, could be modulated by the hose molecule of α-cyclodextrin content. MPEG-PCL-PLLD could co-load the drug and gene effectively. After gelation, the loaded drug and gene could be released sustainedly, and the release rate of them was also modulated by the α-cyclodextrin content. The supramolecular hydrogel showed a sustained effect on tumor cells and could induce the cell apoptosis sustainedly. Moreover, the co-delivery strategy was superior to only drug or gene used in tumor cell inhibition. This supramolecular hydrogel as the high-efficiency and sustained co-delivery system showed a promising application in a long-term tumor therapy.

✓ 已验证 DOI 高影响因子
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Nutrition & Metabolism · 2020 ·Vol. 17 ·期 1 ·1-11 · IF 3.211

Beneficial effects of walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid prevents a prooxidant status and hyperlipidemia in pregnant rats with diabetes

Sun Bingmei,Yan Hua,Li Chao,Yin Linlin,Li Fei,Zhou Lianxiang,Han Xiuqing

Background Gestational diabetes mellitus has a long-term effect on pregnant women. Walnut (Juglans regia L.) oil-derived polyunsaturated fatty acid (PUFA) possesses multifarious pharmacological activities. This study investigated the beneficial effects of walnut oil-derived PUFA on glucose metabolism, pregnancy outcomes, oxidative stress, and lipid metabolism in gestational diabetes mellitus.Methods The GDM rat model was generated by intraperitoneal injection of streptozotocin (40 mg/kg) on gestational day (GD) 6, GD7 and GD8. The differences between groups were estimated using one-way ANOVA followed by the Tukey’s multiple comparison test for post-hoc analysis.Results The results indicated that PUFA could mitigate GDM in pregnant diabetic rats, as embodied by the decrease of fasting blood glucose and the increase of plasma insulin and hepatic glycogen levels. Also, PUFA could suppress oxidative stress in pregnant diabetic rats, as reflected by the decrease of malondialdehyde content, an increase of superoxide dismutase, catalase and gutathione peroxidase activities. PUFA could also mitigate the abnormal changes of lipid profiles in plasma and hepatic tissue. Moreover, the relative mRNA expression of sterol regulatory element-binding transcription factor-1, stearoyl-CoA desaturase-1, fatty acid synthase, and acetyl-coenzyme A carboxylase, was suppressed by PUFA in pregnant diabetic rats.Conclusion sThese results suggested that PUFA supplementation during pregnancy is beneficial in preventing diabetic complications in pregnant rats.

✓ 已验证 DOI PubMed 高影响因子
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Biomaterials Science · 2018 ·Vol. 6 ·期 10 ·2738-2749 · IF 5.831

Effects of large dimensional deformation of a porous structure on stem cell fate activated by poly(L-glutamic acid)-based shape memory scaffolds

Weijun Zhang,Kunxi Zhang,Guifei Li,Shifeng Yan,Lei Cui,Jingbo Yin

Shape memory scaffolds are minimally invasive cell carriers that are promising biomaterials for tissue regeneration. Since cell fate is critical for successful regeneration, the influence of mechanostructural stimuli induced by shape memory on cell fate is worthy of investigation. In this study, we developed a poly(L-glutamic acid)-based (PLGA-based) shape memory porous scaffold by cross-linking PLGA with poly(ε-caprolactone)-diols (PCL-diols) and by using the particle leaching method. After regulating the cross-linking density and molecular weight of the PCL-diols, the scaffolds exhibited excellent shape memory properties around physiological temperatures. The interconnected porous structure not only enabled the scaffold to be deformed to 20% of its original size but also supported tissue invasion. In vivo results demonstrated that the PLGA-based scaffold degraded within 6 months. Cell fate studies indicated that large dimensional deformation of the porous structure during the shape memory process induced significant death, detachment and reorganization of stem cells but had negligible effects on stemness and proliferation. These results indicate that the PLGA-based shape memory porous scaffold is a potential cell carrier for tissue regeneration, and they are also meaningful to investigate the effects of mechanostructural stimuli on stem cell fate in porous structures.

✓ 已验证 DOI PubMed 高影响因子
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JOURNAL OF MATERIALS SCIENCE · 2018 ·Vol. 53 ·期 20 ·14774-14788 · IF 2.993

Facile preparation of biocompatible poly(l-lactic acid)-modified halloysite nanotubes/poly(ε-caprolactone) porous scaffolds by solvent evaporation of Pickering emulsion templates

Hu Yang,Liu Shuifeng,Li Xin,Yuan Teng,Zou Xiuju,He Yinyan,Dong Xianming,Zhou Wuyi,Yang Zhuohong

Biocompatible porous scaffolds with tunable microstructures and drug delivery ability have aroused increasing attention in the application of the biomedical fields, especially in tissue engineering. In this study, we have facilely fabricated the poly( l -lactic acid)-modified halloysite nanotubes (m-HNTs)/poly(ε-caprolactone) (PCL) porous scaffolds by direct solvent evaporation of m-HNTs stabilized water in oil Pickering emulsion templates, which contain PCL in the oil phase. The obtained scaffolds have possessed the porous microstructures, which can be easily tailored by varying the preparation conditions of emulsion templates including m-HNTs concentrations and the volume ratios of water to oil. Furthermore, the antibacterial drug enrofloxacin (ENR) has been loaded into the scaffolds, and the in vitro release studies show the potential of m-HNTs/PCL porous scaffolds as drug carriers. And the antimicrobial test results have proved that the ENR-loaded porous scaffolds exhibit obvious and long-term antibacterial activity against Escherichia coli . In addition, mouse bone mesenchymal stem cells (mBMSCs) are cultured on the m-HNTs/PCL porous scaffolds, and the results of cell counting kit-8 assay and confocal laser scanning microscope observation show that the m-HNTs/PCL porous scaffolds are cytocompatible, because mBMSCs can attach, develop and proliferate well on the porous scaffolds. All the results indicate that the m-HNTs/PCL porous scaffolds hold great potential applications in tissue engineering as scaffolds and/or drug carriers.

✓ 已验证 DOI 高影响因子
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Small · 2021 ·Vol. 17 ·期 32 ·2101495 · IF 13.281

L-Arg-Rich Amphiphilic Dendritic Peptide as a Versatile NO Donor for NO/Photodynamic Synergistic Treatment of Bacterial Infections and Promoting Wound Healing

Jingwu Zhu,Jiang Tian,Chao Yang,Junpeng Chen,Lihuang Wu,Mengni Fan,Xiaojun Cai

The development of alternative strategies for the efficient treatment of subcutaneous abscesses that do not require the massive use of antibiotics and surgical intervention is urgently needed. Herein, a novel synergistic antibacterial strategy based on photodynamic (PDT) and NO gas therapy is reported, in which, a PDT-driven NO controllable generation system (Ce6@Arg-ADP) is developed with l -Arg-rich amphiphilic dendritic peptide (Arg-ADP) as a carrier. This carrier not only displays superior bacterial association and biofilm penetration performance, but also acts as a versatile NO donor. Following efficient penetration into the interior of the biofilms, Ce6@Arg-ADP can rapidly produce massive NO via utilizing the H 2 O 2 generated during PDT to oxidize Arg-ADP to NO and l -citrulline, without affecting singlet oxygen ( 1 O 2 ) production. The combination of 1 O 2 and the reactive by-products of NO offers notable synergistic antibacterial and biofilm eradication effects. Importantly, following efficient elimination of all bacteria from the abscess site, Arg-ADP can further generate trace quantities of NO to facilitate the angiogenesis and epithelialization of the wound tissues, thereby notably promotes wound healing. Together, this study clearly suggests that Arg-ADP is a versatile NO donor, and the combination of PDT and NO represents a promising strategy for the efficient treatment of subcutaneous abscesses.

✓ 已验证 DOI PubMed 高影响因子
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ACS Biomaterials Science & Engineering · 2025 · IF 5.5

Polydopamine-Coated Poly(l-lactide) Nanofibers with Controlled Release of IL-10 for Effective Management of Peripheral and Central Neuropathic Pain in Rats

Jie Zhao,Tao Xue,Zhiyuan Liu

Managing neuropathic pain is challenging due to the complex pathogenetic mechanisms and limited available drugs and therapeutic options. Innovative nanofiber systems offer a novel method to effectively administer therapeutic cytokines, drugs, or small molecule compounds to achieve better relief of neuropathic pain. Here, we report a novel nanofiber with controlled release of IL-10 for implantation into ligated nerve roots and hemisection-injured spinal cords to exert anti-inflammatory effects and attenuate neuropathic pain. An electrospun poly(l-lactide) (PLLA) nanofiber was modified by a polydopamine (PDA) coating, and this nanofiber demonstrated sustained release of IL-10 in vitro. We showed that L5 spinal nerve ligation and T13 spinal cord hemisection induced peripheral and below-level central neuropathic pain in rats, along with the development of neuroinflammation. Spinal IL-10 was also markedly changed after spinal nerve ligation (SNL) or spinal cord injury (SCI), especially in the spinal dorsal horn. Rats were treated postsurgically with IL-10 that was loaded on PDA@PLLA nanofibers as an implantable cytokine delivery system. IL-10 levels were significantly upregulated after the implantation of PDA@PLLA nanofibers in SNL and SCI rats. We further demonstrated that the implantation could inhibit glial activation and neuronal excitability in vivo, along with suppressing the expression levels of pro-inflammatory cytokines. Most importantly, IL-10-loaded PDA@PLLA nanofiber treatment attenuated the development and maintenance of peripheral and central neuropathic pain. Together, the combination of IL-10 and PDA@PLLA nanofibers provides a novel implantable delivery system for treating neuroinflammatory conditions and may emerge as a promising agent to prevent chronic neuropathic pain.

CAS / MDL: 68-12-2 75-09-2
✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF CONTROLLED RELEASE · 2014 · IF 7.261

Pharmacokinetics, biodistribution and in vivo efficacy of cisplatin loaded poly(l-glutamic acid)-g-methoxy poly(ethylene glycol) complex nanoparticles for tumor therapy

Haiyang Yu,Zhaohui Tang,Dawei Zhang,Wantong Song,Ying Zhang,Yan Yang,Zaheer Ahmad,Xuesi Chen

Platinum-based polymeric nano-drugs, especially cisplatin-loaded polymeric nanoparticles (CDDP-NPs), have been extensively exploited for the treatment of solid tumors . However, it is still unclear what role the processing procedure and the properties of the polymeric carrier materials may play in influencing the plasma pharmacokinetics , biodistribution and in vivo efficacy of CDDP-NPs. In this study, a series of poly( l -glutamic acid)- g -methoxy poly(ethylene glycol) (PLG- g -mPEG) copolymers were synthesized for the preparation of CDDP-loaded PLG- g -mPEG (CDDP/PLG- g -mPEG) nanoparticles . All of the parameters, including PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length, ultrafiltration purification and cisplatin loading content, were found to have a significant influence on the plasma pharmacokinetics of the CDDP/PLG- g -mPEG nanoparticles . The blood circulation time of the nanoparticles was prolonged with increases in PLG molecular weight, mPEG/PLG weight ratio, mPEG chain length and CDDP loading content. The use of ultrafiltration purification could prolong the blood circulation time of the nanoparticles as well. Experiments to measure the pharmacokinetics and biodistribution demonstrated that the selected CDDP/PLG- g -mPEG nanoparticles, NP10, had a long blood circulation time and could achieve selective and significant accumulation in Lewis lung carcinoma (LLC) tumors. The platinum plasma concentrations in the LLC tumor-bearing mice receiving NP10 remained up to 46-fold higher than that of mice receiving equivalent doses of free CDDP. In addition, the plasma area under the concentration time curve (AUC) of NP10 was 31-fold higher than that of free CDDP in 48   h. The platinum concentration ratio of NP10 to free CDDP in tumors reached as high as 9.4. The tumor AUC ratio of NP10 to CDDP was 6. Using a mouse C26 tumor model, here we demonstrate that NP10 improves the safety and tolerance in vivo when compared to CDDP and effectively inhibits the growth of C26 tumors. Furthermore, increasing the dosage of NP10 by 2 or 3-fold of free CCDP improved its anticancer efficacy to comparable or higher levels. These results indicate that CDDP/PLG- g -mPEG nanoparticles have greater potential for the treatment of solid tumors in clinical application.

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