JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Xiao-yu Zhang,Kai-rou Xia,Ya-ni Wang,Pei Liu,Er-xin Shang,Cong-yan Liu,Yu-Ping Liu,Ding Qu,Wei-wen Li,Jin-ao Duan,Yan Chen,Huang-qin Zhang
Ethnopharmacological relevance Coronary heart disease (CHD) is a chronic disease that seriously threatens people's health and even their lives. Currently, there is no ideal drug without side effects for the treatment of CHD. Trichosanthis Pericarpium (TP) has been used for several years in the treatment of diseases associated with CHD. However, there is still a need for systematic research to unravel the pharmacodynamic substances and possible mechanism of TP in the treatment of coronary heart. Aim of the study The purpose of current study was to explore the pharmacodynamic substances and potential mechanisms of TP in the treatment of CHD via integrating network pharmacology with plasma pharmacochemistry and experimental validation. Materials and methods The effect of TP intervention in CHD was firstly assessed on high-fat diet combined with isoprenaline-induced CHD rats and H 2 O 2 -induced H9c2 cells, respectively. Then, the LC-MS was utilized to identify the absorbed components of TP in the plasma of CHD rats, and this was used to develop a network pharmacology prediction to obtain the possible active components and mechanisms of action. Molecular docking and immunohistochemistry were used to explore the interaction between TP and key targets. Subsequently, the efficacy of the active ingredients was investigated by in vitro cellular experiments, and their metabolic pathways in CHD rats were further analyzed. Results The effects of TP on amelioration of CHD were verified by in vivo and in vitro experiments. Plasma pharmacochemistry and network pharmacology screened six active components in plasma including apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin. The interaction of these compounds with potential key targets AKT1, IL-1β, IL-6, TNF-α and VEGFA were preliminarily verified by molecular docking. And immunohistochemical results showed that TP reduced the expression of AKT1, IL-1β, IL-6, TNF-α and VEGFA in CHD rat hearts. Then cellular experiments confirmed that apigenin, phenylalanine, quercetin, linoleic acid, luteolin, and tangeretin were able to reduce the ROS level in H 2 O 2 -induced HUVEC cells and promote the migration and tubule formation of HUVEC cells, indicating the pharmacodynamic effects of the active components. Meanwhile, the metabolites of TP in CHD rats suggested that the pharmacological effects of TP might be the result of the combined effects of the active ingredients and their metabolites. Conclusion Our study found that TP intervention in CHD is characterized by multi-component and multi-target regulation. Apigenin, phenylalanine, linoleic acid, quercetin, luteolin, and tangeretin are the main active components of TP. TP could reduce inflammatory response and endothelial damage by regulating AKT1, IL-1β, IL-6, TNF-α and VEGFA, reduce ROS level to alleviate the oxidative stress situation and improve heart disease by promoting angiogenesis to regulate endothelial function. This study also provides an experimental and scientific basis for the clinical application and rational development of TP.
研究领域:
药理学
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心脏病学
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民族药理学
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分子生物学
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生物化学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Advances
·
2022
·
IF 0
Liwen Deng,Huidan Lu,Chenxi Tu,Tong Zhou,Wangbei Cao,Changyou Gao
Bacterial infection is a major obstacle to the wound healing process. The hydrogel dressings with a simpler structure and good antibacterial and wound healing performance are appealing for clinical application. Herein, a robust hydrogel was synthesized from acrylamide (AM), acrylic acid (AA) and N , N ′-methylene diacrylamide (MBA) via a redox initiating polymerization. The polymerization conditions were optimized to obtain the hydrogel with minimum unreacted monomers, which were 0.25% and 0.12% for AM and AA, respectively. The hydrogel had good mechanical strength, and could effectively resist damage by external forces and maintain a good macroscopic shape. It showed large water uptake capacity, and could post load a wide range of molecules via hydrogen bonding and electrostatic interaction. Loading of antibiotic doxycycline (DOX) enabled the hydrogel with good antibacterial activity against both Gram-positive bacteria and Gram-negative bacteria in vitro and in vivo . In a rat model of methicillin-resistant Staphylococcus aureus ( MRSA )-infected full-thickness skin defect wound, the DOX-loaded hydrogel showed good therapeutic effect. It could significantly promote the wound closure, increased the collagen coverage area, down-regulate the expressions of pro-inflammatory TNF-α and IL-1β factors, and up-regulate the expressions of anti-inflammatory IL-4 factor and CD31 neovascularization factor.
研究领域:
生物医学工程
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药剂学
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材料科学
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伤口愈合
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抗菌治疗
✓ 已验证
DOI
PubMed
ACS Biomaterials Science & Engineering
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2022
·
IF 5.395
Wenyi Xia,Tao Yan,Lianlei Wen,Shijie Zhu,Wang Yin,Miao Zhu,Meidong Lang,Chunsheng Wang,Changfa Guo
Despite the fact that heart transplantation (HTx) is a relatively mature procedure, heart ischemic and reperfusion (I/R) injury during HTx remains a challenge. Even after a successful operation, the heart will be at risk of primary graft failure and mortality during the first year. In this study, temperature-sensitive polymer poly(N-n-propylacrylamide-co-N-tert-butyl acrylamide) (PNNTBA) was coated on diallyl trisulfide (DATS)-loaded mesoporous silica nanoparticles (DATS-MSN) to synthesize hypothermia-triggered hydrogen sulfide (H2S) releasing particles (HT-MSN). Because the PNNTBA shell dissolves in phosphate-buffered saline at 4 °C, the loaded DATS could continuously release H2S within 6 h when activated by glutathione (GSH). Furthermore, after co-culturing biocompatible HT-MSN with cardiomyocytes, H2S released from HT-MSN at 4 °C was found to protect cardiomyocytes from ischemic and reperfusion (I/R) injury. In detail, the rate of cell apoptosis and lactate dehydrogenase activity was decreased, as manifested by increased BCL-2 expression and decreased BAX expression. More importantly, in an isolated heart preservation experiment, HT-MSN demonstrated potent protection against cardiac I/R injury and reduced expression of inflammatory factors TNF-α and IL-1β. This study provided a new method for the controlled release of H2S by the donor and myocardial protection from I/R injury.
研究领域:
药理学
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纳米技术
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心脏病学
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生物医学工程
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DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
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2024
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IF 5.7
Jiahui Wang,Wei Liu,Jia Lu,Mengyue Zhu,Yanni Wu,Wenhui Pan,Boyi Fan,Yan Song,Wenli Wang,Guangtong Chen
The prevalence of neurodegenerative diseases has increased in recent decades. Its exact pathogenesis is not yet fully understood, and only a few drugs can be used clinically to alleviate disease symptoms. Increasing evidence highlights plant-derived compounds are becoming a promising resource for mitigating the onset and progression of neurodegenerative diseases. Uvaol (1) is an ursane-type triterpenoid commonly found in olive leaves, fruits, and virgin olive oil. It is one of the rare compounds in olive oil that can penetrate the blood–brain barrier. Despite its potential neuroprotective activity, research on its structural variations and antineuroinflammatory properties remains sparse. This study explored the biotransformation of uvaol using three fungal species: Actinomucor elegans, Aspergillus flavus, and Circinella muscae. This process yielded 15 new compounds along with seven known ones. Their structures were determined through comprehensive spectroscopic analysis. Furthermore, the antineuroinflammatory activities of compounds were evaluated by using MTT and Griess assays. Notably, compound 9 was found to markedly suppress the transcriptional levels of inflammation-associated elements such as TNF-α, IL-1β, IL-6, iNOS, and COX-2 in BV-2 cells stimulated by lipopolysaccharides (LPS). Moreover, compound 9 also facilitated autophagy by upregulating ULK1 mRNA expression and downregulating the p62 protein. These results suggested that biotransformation was an effective approach for rapidly diversifying uvaol and providing a basal material for the discovery of candidates in treating neurodegenerative diseases.
研究领域:
药理学
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神经科学
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药物化学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Rong Wang,Bowen Yan,Yourui Yin,Xueyuan Wang,Mei Wu,Tiantian Wen,Yin Qian,Yong Wang,Caoxing Huang,Yongqiang Zhu
Pest management technology has been a promising bioconversion method for waste resource utilization. Unlike many pests that consume waste, the larvae of Lucilia sericata , also known as maggots, have many outstanding advantages as following: with their strong adaption to environment and not easily infected and exhibiting a medicinal nutritional value. Herein, the potential efficacies of maggot polysaccharides (MP), as well as their underlying mechanisms, were explored in Dextran sulfate sodium (DSS)-induced colitis mice and TNF-α-elicited Caco-2 cells. We extracted two bioactive polysaccharides from maggots, MP-80 and MP-L, whose molecular weights were 4.25 × 10 3 and 2.28 × 10 3 g/mol, respectively. MP-80 and MP-L contained nine sugar residues: 1,4-α-Arap, 1,3-β-Galp, 1,4,6-β-Galp, 1,6-α-Glcp, 1-α-Glcp, 1,4-β-Glcp, 1-β-Xylp, 1,2-α-Manp, and 1-β-Manp. We demonstrated that MP-80 and MP-L significantly ameliorated DSS-induced symptoms and histopathological damage. Immuno-analysis revealed that compared with MP-L, MP-80 could better restore intestinal barrier and reduced inflammation by suppressing NLRP3/NF-κB pathways, which might be attributed to its enriched galactose fraction. Moreover, 16S rRNA sequencing revealed that MP-80 and MP-L both improved the dysbiosis and diversity of gut microbiota and acted on multiple microbial functions. Our study sheds new light on the possibility of using maggot polysaccharides as an alternative therapy for colitis.
研究领域:
医学
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药理学
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微生物学
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营养学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2024
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IF 8.3
Xiong Zhao,Shuai Wu,Sheng Ni,Yuan Zhong,Xian Qin,Kun Zhang,Kai Qu,Li Zhu,Wei Wu
Rheumatoid arthritis (RA) is a chronic disease characterized by immune cell infiltration and cartilage damage. The local lesion of RA shows severe oxidative stress and proinflammatory cytokine secretion. For drug therapy, the efficacy of agents, such as methotrexate (MTX), may be greatly limited, resulting from the low bioavailability, immune clearance, and toxic side effects. A nanocarrier (TA-PBA NPs) was developed with anti-inflammatory and antioxidant activities, combined with MTX to prepare nanomedicine (MTX NPs) for synergistic treatment of RA. Moreover, inspired by the biological functions homing to inflammation lesion of macrophages, the biomimetic nanomedicine camouflaged with macrophage membrane (MM@MTX NPs) was constructed. TA-PBA NPs could timely promote MTX release in response to the overaccumulated ROS to exhibit high anti-inflammatory and antioxidant activities for alleviating RA progression. The experimental results confirmed that MM@MTX NPs could significantly reduce the secretion of proinflammatory cytokines (TNF-α) while significantly increasing the typical anti-inflammatory cytokines (IL-10), promote the phenotype transformation of macrophages from M1 to M2, and up-regulate the Nrf2-keap1 pathway-related proteins (HO-1 and NRF2) to positively regulate the local inflammation for effectively inhibiting RA development. Thus, MM@MTX NPs represent a possible candidate as a safe and efficient nanotherapy platform for RA management.
研究领域:
纳米技术
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药学
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免疫学
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风湿病学
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生物医学工程
✓ 已验证
产品关联
DOI
PubMed
高影响因子
IMMUNOBIOLOGY
·
2024
·
IF 2.5
Min Li,Wenjia Tong,Chao Dai,Guoping Lu,Danqun Jin,Fang Deng
Sepsis-associated acute kidney injury (S-AKI) is a prevalent and life-threatening complication in hospitalized and critically ill patients. Recent researches indicates that immunoproteasome, especially proteasome 20S subunit beta 8 (PSMB8), is highly associated with various kidney diseases. This study aims to investigate the potential involvement of PSMB8 in S-AKI and its impact on apoptosis and inflammation. The model of S-AKI induced by LPS (10 mg/kg) was assessed by histological examination. ELISA and Real-time PCR were used to detect the levels of inflammatory cytokines in the renal cortex. The role of shPSMB8 in LPS-induced apoptosis was detected by flow cytometry. Finally, western blot was performed to assess the NF-κB signaling pathway related proteins, and the nuclear translocation of NF-kB P65 was detected by immunofluorescence microscopy. PSMB8 knockdown substantially protected against renal injury by reducing blood urea nitrogen and creatinine levels and ameliorating inflammation. PSMB8 knockdown inhibited renal expression of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α) and COX-2 to improve inflammatory response. Mechanistic studies demonstrated that downregulation of PSMB8 blocked LPS-induced S-AKI phosphorylation and nuclear translocation of NF-κB P65. Collectively, our results suggest that inhibition of PSMB8 significantly contributes to S-AKI via regulation of NF-κB. These findings reveal the pathogenic role of PSMB8 in AKI and suggest a novel therapeutic target for the condition.
研究领域:
免疫学
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肾病学
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炎症研究
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2016
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IF 3.138
Ting Hu,Qilin Huang,Kahing Wong,Hong Yang
Four polysaccharide fractions, LRP-1, LRP-2, LRP-3 and LRP-4 were extracted stepwise from Lignosus rhinocerotis sclerotia with distilled water at 25, 95, 120 °C and 1.0 M NaOH solution at 4 °C. Their structure, molecular size and chain conformation were clarified using SEC-MALLS-RI, GC, FT-IR and UV–vis. Furthermore, their immunomodulatory activities were evaluated by the model of cyclophosphamide (Cy)-induced immunosuppression. The LRP-1 and LRP-2 were polysaccharide-protein complexes (46–68% β- d -glucan and 27–48% protein), while LRP-3 and LRP-4 were absolutely composed of β- d -glucose. The LRP-4 with low polydispersity had much higher molecular weight ( M w , 5.86 × 10 6 g/mol) and intrinsic viscosity ([ η ], 202.6 ml/g) than other LRP fractions. Based on M w , radius of gyration ( z 1/2 ) and [ η ] data with the exponent β of z 1/2 –M w and its U-shaped curve, all four LRP fractions were highly branched macromolecules and LRP-3 showed a more compact sphere-like conformation than LRP-2 in aqueous solution. Additionally, all four LRP fractions exhibited protective effects against Cy-induced immunosuppression in mice by improving immune organs as well as stimulating the release of major cytokines TNF-α and INF-γ. This work provides a theoretical basis for the application of polysaccharides and their protein complexes from Lignosus rhinocerotis sclerotia in food- or drug-based therapies.
研究领域:
药理学
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免疫学
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生物化学
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真菌学
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产品关联
DOI
PubMed
高影响因子
BIOSENSORS & BIOELECTRONICS
·
2019
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IF 9.518
Jingjing Sun,Jiumei Hu,Tong Gou,Xiong Ding,Qi Song,Wenshuai Wu,Guoping Wang,Juxin Yin,Ying Mu
A novel microfluidic chip employing power-free polydimethylsiloxane (PDMS) femtoliter-sized arrays was developed for the detection of low concentrations of protein biomakers by isolating individual paramagnetic beads in single wells. Arrays of femtoliter-sized wells were fabricated with PDMS using well-developed molding techniques. Paramagnetic beads were functionalized with specific antibodies to capture the antigens. These antigens were labeled with enzymes via conventional multistep immunosandwich approach. After suspending in aqueous solutions of enzyme substrate , the solutions were delivered to the arrays using a conventional micropipette . The aqueous solutions were introduced into the microwells by capillarity and the beads were loaded into microwells by gravity. A fluorocarbon oil was then flowed into the chip to remove excess beads from the surface of the array and meanwhile isolated the femtoliter-sized wells. All processes were achieved by conventional micropipette, without external pumping systems and valves. Finally, the arrays were imaged using standard fluorescence imaging after incubation 30 min for digital counting enzyme molecules. It was demonstrated that the chip platform possessed the performance of digital counting with a linear dynamic range from 1 aM to 1 fM for the detection of biotinylated β-galactosidase (BβG), achieving a limit of detection (LOD) of 930 zM. Using this chip, a digital immunoassay to detect Tumor Necrosis Factor α (TNF- α) was developed. Since the chip fabrication is low-cost and circumvents the surface modification, we expect it can become a new chip-based digital immunoassay platform for ultrasensitive diagnostic of biomarkers.
研究领域:
微流控技术
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生物工程
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分析化学
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免疫学
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诊断技术
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2017
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IF 4.581
Xiaoguang Gao,Ting Fu,Changyuan Wang,Chenqing Ning,Yulong Kong,Zhihao Liu,Huijun Sun,Xiaodong Ma,Kexin Liu,Qiang Meng
Recently obeticholic acid (OCA) which is a farnesoid X receptor (FXR) agonist was approved by FDA to treat cholestatic liver diseases, which provided us a novel therapeutic strategy against cholestasis . Herein, we used a novel computational strategy with two-dimensional virtual screening for FXR agonists. For the first time, we found that auraptene (AUR), a natural product, can activate FXR to exert hepatoprotective effect against cholestatic liver injury in vivo and in vitro . Importantly, AUR was found to significantly decrease the mortality of cholestatic mice. Dynamic change analysis of bile acids and gene analysis revealed that AUR promoted bile acid efflux from liver into intestine via an induction in FXR-target genes Bsep and Mrp2 expression, and reduced hepatic uptake through an inhibition in Ntcp . Furthermore, AUR reduced bile acid synthesis through repressing FXR-target genes Cyp7a1 and Cyp8b1, and increased bile acid metabolism through an induction in Sult2a1 . In addition, AUR promoted liver repair through an induction in liver regeneration-related gene, and suppressed liver inflammation through repressing inflammation-related gene NF-κB, TNF-α, IL-1β and IL-6. However, the changes in these genes and protein, as well as ameliorative liver histology induced by AUR were abrogated by FXR antagonist guggulsterone in vivo and FXR siRNA in vitro . These findings suggest that AUR may be an effective approach for the prevention against cholestatic liver diseases.
研究领域:
药理学
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肝病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BMC Complementary Medicine and Therapies
·
2022
·Vol. 22
·期 1
·1-13
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IF 2.838
Gong Linna,Miao Zhishuo,Zhang Li,Shi Birui,Xiao Zuoqi,Qiu Panzi,Liu Menghua,Zou Wei
Background Penyanqing (PYQ), a traditional Chinese medicine (TCM), has a good clinical efficacy for the treatment of pelvic inflammatory disease (PID). Previously, researches on its anti-inflammatory effect and mechanism in vitro, in silico, and in vivo have been reported by our team. However, the interrelationship between the anti-inflammatory activity and the active compounds in PYQ are not clear. Here, the pharmacokinetics-pharmacodynamics (PK-PD) study was carried out for more proper clinical use.Methods The plasma concentrations of salvianolic acid B (SAB), protocatechualdehyde (PRO), paeoniflorin (PE), astilbin (AST), ferulic acid (FE), and chlorogenic acid (CH) in SD rats after PYQ administration were determined by a selective and rapid HPLC–MS/MS method. In addition, the PK-PD on cell model was used to explore the relationship between the plasma concentration and inflammatory biomarkers (TNF-α, IL-1β).Results The results of this study showed that the six components could reach the peak blood concentration within 0.29 h, indicating the rapid absorption of it. The eliminations of AST, CH, FE, PE, and PRO were relatively fast due to their mean residence times (MRTs) within 3 h, while the elimination of SAB was slower (MRT 5.67 ± 0.66 h). Combined with a THP-1 cell model, there was a significant correlation between inflammatory factors and component plasma concentrations with correlation coefficients in the range of -0.9—-0.746. Correspondingly, the drug-containing plasma obtained at 0.25 h point exhibited the best inhibition effect on production of IL-1β and TNF-α in LPS-induced THP-1 cells.Conclusion The six main components in PYQ could be quickly absorbed, and there was a potential good correlation between their pharmacokinetics and the pharmacodynamics of PYQ.
研究领域:
药理学
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传统中药
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炎症研究
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
Cellular & Molecular Immunology
·
2024
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IF 21.8
Wu Xiaoxia,Zhao Xiaoming,Li Fang,Wang Yang,Ou Yangjing,Zhang Haiwei,Li Xiaoming,Wu Xuanhui,Wang Lingxia,Li Ming,Zhang Yue,Liu Jianling,Xing Mingyan,Liu Han,Tan Yongchang,Wang Yangyang,Xie Yangyang,Zhang Hanwen,Luo Yan,Li Hong,Wang Jing,Sun Liming,Li Yu,Zhang Haibing
The hypersecretion of cytokines triggers life-threatening systemic inflammatory response syndrome (SIRS), leading to multiple organ dysfunction syndrome (MODS) and mortality. Although both coagulopathy and necroptosis have been identified as important factors in the pathogenesis of SIRS, the specific cell types that undergo necroptosis and the interrelationships between coagulopathy and necroptosis remain unclear. In this study, we utilized visualization analysis via intravital microscopy to demonstrate that both anticoagulant heparin and nonanticoagulant heparin (NAH) pretreatment protect mice against TNF-α-induced mortality in SIRS. Moreover, the deletion of Mlkl or Ripk3 resulted in decreased coagulation and reduced mortality in TNF-α-induced SIRS. These findings suggest that necroptosis plays a key role upstream of coagulation in SIRS-related mortality. Furthermore, using a genetic lineage tracing mouse model (Tie2-Cre;Rosa26-tdT ), we tracked endothelial cells (ECs) and verified that EC necroptosis is responsible for the vascular damage observed in TNF-α-treated mice. Importantly, Mlkl deletion in vascular ECs in mice had a similar protective effect against lethal SIRS by blocking EC necroptosis to protect the integrity of the endothelium. Collectively, our findings demonstrated that RIPK3–MLKL-dependent necroptosis disrupted vascular integrity, resulting in coagulopathy and multiorgan failure, eventually leading to mortality in SIRS patients. These results highlight the importance of targeting vascular EC necroptosis for the development of effective treatments for SIRS patients.
研究领域:
免疫学
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病理生理学
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细胞生物学
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炎症
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血管生物学
✓ 已验证
DOI
PubMed
高影响因子
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