PHARMAZIE
·
2021
·Vol. 76
·期 10
·499-502
·
IF 1.267
Tao Lijun,Chen Lina,Pei Yanmin,Ma Ping,Xu Qingbin,Wang Jialing,Yu Yang,Cheng Jiang,Zhou Ru
The aim of this study was to investigate the vasodilatory effects of betaine, an alkaloid isolated from Lycium barbarum, on isolated pulmonary artery rings in rats and its possible mechanisms. Pulmonary vessels of normal Sprague–Dawley rats were isolated and pre-contracted
using norepinephrine. Then, betaine was cumulatively added in differing concentrations (0.02-0.14 mg/mL), and the tension curve was observed and recorded. Changes in the tension of the pulmonary artery rings with an intact endothelium and a dissected endothelium were recorded. The interactions
among betaine and NG-nitro-L-arginine methyl ester, indomethacin, 4-aminopyridine, barium chloride, and glibenclamide were evaluated. The experimental results show that betaine can relax the pulmonary artery rings pre-contracted by norepinephrine. Furthermore, pre-incubation with NG-nitro-L-arginine
methyl ester and indomethacin did not inhibit betaine vasodilation, demonstrating that vasodilation by betaine is endothelium-dependent. Additionally, pretreatment of pulmonary artery rings with 4-aminopyridine and glibenclamide had no effect on betaine. However, pretreatment of pulmonary
artery rings with barium chloride attenuated the effects of betaine. In conclusion, the vasodilatory effects of betaine on pulmonary artery rings is associated with inward rectifier potassium channels.
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BMC Complementary Medicine and Therapies
·
2021
·Vol. 21
·期 1
·1-11
·
IF 0
Lou Hai-xia,Fu Wen-cheng,Chen Jia-xiang,Li Tian-tian,Jiang Ying-ying,Liu Chun-hui,Zhang Wen
Background Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. Methods We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. Results AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. Conclusions Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.
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Journal of Materials Chemistry B
·
2021
·Vol. 9
·期 26
·5272-5283
·
IF 6.331
Min He,Bo Yang,Fangjun Huo,Li Xie,Mo Yang,Weidong Tian
The immune response elicited by the bone endoprosthesis is currently considered an important factor that affects its interfacial osteointegration. In this work, a metal-phenolic-based drug-loaded coating with universal adhesion properties and intelligent drug delivery feature was created to promote osteointegration by manipulating a beneficial osteoimmune microenvironment. A novel pro-drug with inflammation-responsive release function was firstly synthesized via the esterification reaction between tannic acid (TA) and indometacin (IND), and then the coating was developed by chelating it with Fe3+. In the normal biological environment, the coating was stable, while, in the inflammatory environment, the release of TA and IND motifs could be triggered by the overexpressed esterase. The released TA and IND displayed synergistic effects on macrophage polarization, leading to a downregulation expression of pro-inflammatory cytokines, and an upregulation expression of anti-inflammatory cytokines and osteogenic-related factors. When stimulated by a conditioned medium generated by macrophages seeded onto the coating, the osteogenic differentiation potential of BMSCs was significantly enhanced. Finally, the designed coating significantly promoted the osteointegration of the implant, demonstrated by the increase of the bone-implant contact by two times. Additionally, the coating was substrate-independent and can be formed within seconds without special equipment, thus, it showed great potential applications to endow advanced hard tissue implants with favorable osteoimmunomodulation.
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Frontiers in Pharmacology
·
2020
·
IF 4.225
Liu Tengwen,Guo Yuhong,Zhao Jingxia,He Shasha,Bai Yunjing,Wang Ning,Lin Yan,Liu Qingquan,Xu Xiaolong
The outbreak of coronavirus disease 2019 (COVID-19) has affected millions of people worldwide. Critically ill COVID-19 patients develop viral septic syndrome, including inflammatory damage, immune dysfunction, and coagulation disorder. In this study, we investigated ShenFuHuang formula (SFH), a traditional Chinese medicine, which has been widely used as complementary therapy for clinical treatment of COVID-19 in Wuhan, to understand its pharmacological properties. Results of systems pharmacology identified 49 active compounds of SFH and their 69 potential targets, including GSK3β, ESR1, PPARG, PTGS2, AKR1B10, and MAPK14. Network analysis illustrated that the targets of SFH may be involved in viral disease, bacterial infection/mycosis, and metabolic disease. Moreover, signaling pathway analysis showed that Toll-like receptors, MAPK, PPAR, VEGF, NOD-like receptor, and NF-kappa B signaling pathways are highly connected with the potential targets of SFH. We further employed multiple zebrafish models to confirm the pharmacological effects of SFH. Results showed that SFH treatment significantly inhibited the inflammatory damage by reducing the generation of neutrophils in Poly (I:C)-induced viral infection model. Moreover, SFH treatment could improve the phagocytosis of macrophages and enhance the expression of immune genes in an immune deficiency model. Furthermore, SFH treatment exhibited promising anti-thrombosis effect in a thrombus model. This study provided additional evidence of SFH formula for treating COVID-19 patients with septic syndrome using multiple-scale estimation.
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ACS Applied Materials & Interfaces
·
2020
·
IF 8.758
Kun Fang,Rong Wang,Hua Zhang,Linjie Zhou,Ting Xu,Ying Xiao,Yang Zhou,Guorong Gao,Jing Chen,Donglei Liu,Fanrong Ai,Jun Fu
Acute wounds subject to frequent deformations are difficult to be treated because the healing process was easily interfered by external mechanical forces. Traditional wound dressings have limited efficacy because of their poor mechanical properties and skin adhesiveness and difficulty in the delivery of therapeutic drugs effectively. As such, tough and skin-adhesive wound dressings with sustainable and stimuli-responsive drug release properties for treatment of those wounds are highly desirable. For this purpose, we have developed a mechano-responsive poly(sulfobetaine methacrylate) hydrogel which aims to control the delivery of antibiotic drug upon application of mechanical forces. Diacrylated Pluronic F127 micelles were used as a macro-cross-linker of the hydrogel and loaded with hydrophobic antimicrobial drugs. The micelle-cross-linked hydrogel has excellent mechanical properties, with the ultimate tensile strength and tensile strain of up to 112 kPa and 1420%, respectively, and compressive stress of up to 1.41 MPa. Adhesiveness of the hydrogel to the skin tissue was ∼6 kPa, and it did not decrease significantly after repetitive adhesion cycles. Protein adsorption on the hydrogel was significantly inhibited compared to that on commercial wound dressings. Because of the mechano-responsive deformation of micelles, the release of drug from the hydrogel could be precisely controlled by the extent and cycles of mechanical loading and unloading, endowing the hydrogel with superior antibacterial property against both Gram-positive and Gram-negative bacteria. In addition, drug penetration into the skin tissue was enhanced by mechanical stress applied to the hydrogel. The micelle-cross-linked zwitterionic hydrogel also showed good cell biocompatibility, negligible skin irritation, and healing capacity to acute skin wounds in mice. Such a tough mechano-responsive hydrogel holds great promise as wound dressings for acute wounds subjected to frequent movements.
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Acta Biomaterialia
·
2020
·
IF 7.242
Chuanfeng An,Weijian Liu,Yang Zhang,Bo Pang,Hui Liu,Yujie Zhang,Haoyue Zhang,Liyuan Zhang,Hongbing Liao,Changle Ren,Huanan Wang
The encapsulation of cells in microscale hydrogels can provide a mimic of a three-dimensional (3D) microenvironment to support cell viability and functions and to protect cells from the environmental stress, which have been widely used in tissue regeneration and cell therapies. Here, a microfluidics-based approach is developed for continuous encapsulation of mesenchymal stem cells (MSCs) at the single-cell level using alginate microgels. This microfluidic technique integrated on-chip encapsulation, gelation , and de-emulsification into a one-step fabrication process, which enables scalable cell encapsulation while retaining the viability and functionality of loaded cells. Remarkably, we observed MSCs encapsulated in Ca-alginate microgels at the single-cell level showed significantly enhanced osteogenesis and accelerated mineralization of the microgels which occurred only after 7 days of induction. Furthermore, MSCs laden in alginate microgels displayed significantly enhanced bone formation compared to MSCs mixed with microgels and acellular microgels in a rat tibial ablation model. To conclude, the current microfluidic technique represents a significant step toward continuous single cell encapsulation, fabrication, and purification . These microgels can boost bone regeneration by providing a controlled osteogenic microenvironment for encapsulated MSCs and facilitate stem cell therapy in the treatment of bone defects in a minimally invasive delivery way. Statement of Significance The biological functions and therapeutic activities of single cells laden in microgels for tissue engineering remains less investigated. Here, we reported a microfluidic-based method for continuous encapsulation of single MSCs with high viability and functionality by integrating on-chip encapsulation, gelation, and de-emulsification into a one-step fabrication process. More importantly, MSCs encapsulated in alginate microgels at the single-cell level showed significantly enhanced osteogenesis, remarkably accelerated mineralization in vitro and bone formation capacity in vivo . Therefore, this single-cell encapsulation technique can facilitate stem cell therapy for bone regeneration and be potentially used in a variety of tissue engineering applications.
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PLoS One
·
2020
·Vol. 15
·期 5
·e0227844
·
IF 2.74
Renjie Xu,Hongdan Zhu,Lingmin Hu,Beimeng Yu,Xiaohua Zhan,Yichu Yuan,Ping Zhou
Morroniside is a biologically active polyphenol found in Cornus officinalis Sieb . et Zucc (CO) that exhibits a broad spectrum of pharmacological activities, such as protecting nerves, and preventing diabetic liver damage and renal damage. However, little data are available regarding the mechanism of its intestinal absorption. Here, an in vitro human intestinal epithelial cell model of cultured Caco-2 cells was applied to study the absorption and transport of morroniside. The effects of donor concentration, pH and inhibitors were investigated. The bidirectional permeability of morroniside from the apical (AP) to the basolateral (BL) side and in the reverse direction was studied. When administered at three tested concentrations (5, 25 and 100 μM), the apparent permeability coefficient (P app ) values in the AP-to-BL direction ranged from 1.59 × 10 −6 to 2.66 × 10 −6 cm/s. In the reverse direction, BL-to-AP, the value was ranged from 2.67 × 10 −6 to 4.10 × 10 −6 cm/s. The data indicated that morroniside transport was pH-dependent. The permeability of morroniside was affected by treatment with various inhibitors, such as multidrug resistance protein inhibitors MK571 and indomethacin, as well as the breast cancer resistance protein inhibitor apigenin. The mechanisms of the intestinal absorption of morroniside may involve multiple transport pathways, such as the passive diffusion and efflux protein-mediated active transport especially involving multidrug resistance protein 2 and breast cancer resistance protein. After the addition of CO, the P app values in the AP-to-BL direction increased significantly, therefore, it can be assumed that some ingredients in the CO promote morroniside absorption in the small intestine.
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JOURNAL OF HAZARDOUS MATERIALS
·
2021
·
IF 10.588
Yue Wang,Wenchang Zhao,Ruixia Gao,Sameer Hussain,Yi Hao,Jiahao Tian,Shihui Chen,Yunhao Feng,Yubo Zhao,Yuyao Qu
17β-estradiol (E2), as one of the pharmaceutical and personal care product , frequently contaminates environmental water as estrogen pollutant and possesses great risk to human survival as well as the sustainable development of the ecosystem. Herein, to achieve an effective adsorbent system for the selective removal of E2 from the environmental water, Fe 3 O 4 nanoparticles are subjected to chemical etching to reduce the overall mass and then employed as carriers to prepare a novel type of lightweight daisy-like magnetic molecularly imprinted polymers (LD-MMIPs) adopting template immobilization strategy. The LD-MMIPs based etched magnetic nanoparticles not only exhibit light mass but also have plentiful imprinted sites in the etched channels, which significantly increases the adsorption capacity for E2. The daisy-like LD-MMIPs own strong magnetic responsiveness, well crystallinity , fast binding kinetics, high adsorption amount, and excellent selectivity . Moreover, combining with HPLC, the LD-MMIPs as adsorbents have been successfully used to specifically recognize and detect trace E2 in environmental water. Thus, the proposed LD-MMIPs with high adsorption capacity hold great potential in monitoring water pollution . Additionally, this work also provides an alternative strategy for improving the adsorption capacity of magnetic molecularly imprinted polymers through a convenient chemical etching technology .
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POLYMER BULLETIN
·
2021
·Vol. 79
·期 10
·8617-8631
·
IF 2.87
Wang Shihai,Zhou Yu,Tao Wangwang,Liu Jingyi,Chen Hongxiang,Zhao Zuyi
In order to obtain polyurethane micelles with targeting property and excellent stability, Fe 3 O 4 -modified magnetic amphiphilic polyurethane (MAPU) was successfully synthesized by grafting amphiphilic polyurethane to the surface of Fe 3 O 4 nanoparticles. The structure of MAPU was confirmed by Fourier-transform infrared spectroscopy, proton nuclear magnetic resonance spectroscopy ( 1 H NMR), gel permeation chromatography and thermogravimetric analyzer. MAPU could form micelles with the particle size of less than 45 nm, and the micelles showed excellent stability of anti-dilution and storage, determined by dynamic light scattering. MAPU micelles had superparamagnetic property, and magnetically targeted property in HeLa cells measured by vibrating sample magnetometer (VSM) and Prussian blue staining method, respectively. Methyltetrazolium (MTT) assay experiment indicated that MAPU micelles were almost non-cytotoxic. In addition, MAPU micelles could encapsulate hydrophobic model drugs such as Indometacin (IMC) and had a release-sustained effect for IMC.
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Frontiers in Pharmacology
·
2021
·
IF 5.811
Feng Huixia,Chen Guilin,Zhang Yongli,Guo Mingquan
Podophyllum sinense (P. sinense) has been used as a traditional herbal medicine for ages due to its extensive pharmaceutical activities, including antiproliferative, anti-inflammatory, antiviral, insecticidal effects, etc. Nevertheless, the specific bioactive constituents responsible for its antiproliferative, anti-inflammatory, and antiviral activities remain elusive, owing to its complicated and diversified chemical components. In order to explore these specific bioactive components and their potential interaction targets, affinity ultrafiltration with multiple drug targets coupled with high performance liquid chromatography/mass spectrometry (UF–HPLC/MS) strategy was developed to rapidly screen out and identify bioactive compounds against four well-known drug targets that are correlated to the application of P. sinense as a traditional medicine, namely, Topo I, Topo II, COX-2, and ACE2. As a result, 7, 10, 6, and 7 phytochemicals were screened out as the potential Topo I, Topo II, COX-2, and ACE2 ligands, respectively. Further confirmation of these potential bioactive components with antiproliferative and COX-2 inhibitory assays in vitro was also implemented. Herein, diphyllin and podophyllotoxin with higher EF values demonstrated higher inhibitory rates against A549 and HT-29 cells as compared with those of 5-FU and etoposide. The IC50 values of diphyllin were calculated at 6.46 ± 1.79 and 30.73 ± 0.56 μM on A549 and HT-29 cells, respectively. Moreover, diphyllin exhibited good COX-2 inhibitory activity with the IC50 value at 1.29 ± 0.14 μM, whereas indomethacin was 1.22 ± 0.08 μM. In addition, those representative constituents with good affinity on Topo I, Topo II, COX-2, or ACE2, such as diphyllin, podophyllotoxin, and diphyllin O-glucoside, were further validated with molecular docking analysis. Above all, the integrated method of UF–HPLC/MS with multiple drug targets rapidly singled out multi-target bioactive components and partly elucidated their action mechanisms regarding its multiple pharmacological effects from P. sinense, which could provide valuable information about its further development for the new multi-target drug discovery from natural medicines.
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Journal of Functional Foods
·
2019
·
IF 3.197
Yanbei Tu,Kai Wang,Jian-Bo Wan,Chengwei He
Glycine tabacina (Labill.) Benth, a renowned Chinese medicinal herb, has been used for treatment of rheumatoid arthritis (RA) and joint infection. This study aimed to investigate inhibitory effect of its ethanol extract (GTE) on RA-associated inflammation. Nine isoflavonoids of twelve ones which were found in G. tabacina roots were identified by UHPLC-DAD-MS/MS. GTE treatment suppressed lipopolysaccharide-stimulated overproduction of nitric oxide, TNF-α and IL-6, and iNOS expression in macrophages. GTE blocked the activation of NF-κB and MAPK pathways, as indicated by reduced levels of phosphorylation of IKKα/β, IκBα, p38, ERK and JNK, and the suppressed nuclear translocation of NF-κB p65. Additionally, GTE administration decreased swelling of arthritic paw and serum TNF-α and IL-1β levels in collagen-induced arthritis (CIA) mice. These results demonstrated that GTE exhibited strong anti-inflammatory and anti-arthritic activities through suppressing NF-κB and MAPK pathways activation in activated macrophages and CIA mice, suggesting the potential applications of this species in RA prevention and treatment as functional food or therapeutic agent.
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Phytochemistry Letters
·
2019
·
IF 1.338
Hua-Xuan Li,Chao-Jiang Xiao,Min Wang,Shu-Jun Cui,Hai-Feng Li,Kai-Ling Wang,Xiang Dong,Bei Jiang
Four new phenylethanoid glycosides, terngymnosides A–D ( 1 – 4 ), together with sixteen known compounds ( 5 – 20 ) were isolated from the aerial parts of Ternstroemia gymnanthera . Structures of the isolated compounds were determined by the comprehensive analyses of the physicochemical properties and spectral data (1D NMR, 2D NMR, and MS). Compounds 1 – 3 , 8 and 10 showed significant analgesic effect with the inhibition rates ranging from 56.2% to 65.3% at a dose of 50 mg/kg, that was superior to the standard drug aspirin and was equivalent to indomethacin.
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