MATERIALS & DESIGN
·
2025
·
IF 7.9
Lifang Xie,Tianxiang Yuan,Su Hu,Chenmin Zhao,WenLi Huang,Wei Ding,Ye Zhang,Xianwen Hu
Chronic diabetic wounds exhibit impaired healing due to a complex interplay of pathological mechanisms, including persistent hyperglycemia, excessive matrix metalloproteinase-9 (MMP9) activity, and chronic inflammation, which disrupt tissue repair and regeneration. A central driver of this dysregulated healing is macrophage polarization imbalance, with excessive pro-inflammatory M1 and insufficient reparative M2 macrophages, prolonging inflammation and delaying tissue remodeling. To address these challenges, we developed a dual-responsive hydrogel composed of phenylboronic acid-functionalized polyethyleneimine (PEI-PBA), polyvinyl alcohol (PVA), and Benzaldehyde-PEG-Benzaldehyde (DF-PEG-DF) for controlled co-delivery of interleukin-4 (IL-4) and salvianolic acid A (SalA). This dynamically crosslinked hydrogel responds to the diabetic wound microenvironment, enabling pH- and glucose-triggered release. IL-4 promotes M2 macrophage repolarization, resolving inflammation and enhancing tissue repair, while SalA scavenges reactive oxygen species (ROS) and inhibits MMP9 activity, preserving extracellular matrix (ECM) integrity and supporting regeneration. In vivo, the hydrogel significantly accelerated wound closure in diabetic mice by promoting M2 polarization and reducing MMP9-mediated matrix degradation. This coordinated modulation of the inflammatory and proteolytic microenvironment attenuated inflammation, enhanced angiogenesis, and increased collagen deposition, collectively facilitating tissue regeneration. These findings suggest this intelligent hydrogel is a promising therapeutic strategy for chronic diabetic wound healing with translational potential.
研究领域:
生物材料
·
药物递送
·
糖尿病创面修复
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免疫调控
·
再生医学
✓ 已验证
产品关联
DOI
高影响因子
Polymers
·
2025
·Vol. 17
·期 14
·1900
·
IF 4.9
Guoying Zhou,Yujia Yan,Linh Nguyen,Jiangkai Fan,Xiao Zhang,Li Gan,Tingzi Yan,Haitong Wan
Traumatic brain injury (TBI) leads to severe neurological dysfunction, disability, and even death. Surgical intervention and neurorehabilitation represent the current clinical management methods, yet there remains no effective treatment for recovery after TBI. Post-traumatic hyperinflammation and vascular injury are the key therapeutic challenges. Therefore, a novel-designed multifunctional HT/SAA/HSYA hydrogel based on hyaluronic acid (HA) co-loaded with salvianolic acid A (SAA) and hydroxysafflor yellow A (HSYA) was developed in order to simultaneously target inflammation and vascular injury, addressing key pathological processes in TBI. The HT hydrogel was formed through covalent cross-linking of tyramine-modified HA catalyzed by horseradish peroxidase (HRP). Results demonstrated that the HT hydrogel possesses a porous structure, sustained release capabilities of loaded drugs, suitable biodegradability, and excellent biocompatibility both in vitro and in vivo. WB, immunofluorescence staining, and PCR results revealed that SAA and HSYA significantly reduced the expression level of pro-inflammatory cytokines (IL-1β and TNF-α) and inhibited M1 macrophage polarization through the suppression of the TLR4/NF-κB inflammatory pathway. In vivo experiments confirmed that the HT/SAA/HSYA hydrogel exhibited remarkable pro-angiogenic effects, as evidenced by increased expression of CD31 and α-SMA. Finally, H&E staining showed that the HT/SAA/HSYA hydrogel effectively reduced the lesion volume in a mouse TBI model, and demonstrated more pronounced effects in promoting brain repair at the injury site, compared to the control and single-drug-loaded hydrogel groups. In conclusion, the HT hydrogel co-loaded with SAA and HSYA demonstrates excellent anti-inflammatory and pro-angiogenic effects, offering a promising therapeutic approach for brain repair following TBI.
研究领域:
神经外科学
·
生物材料学
·
免疫学
·
药理学
·
再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Chinese Medicine
·
2024
·Vol. 19
·期 1
·1-16
·
IF 5.3
Rao Chang,Hu Ruixue,Hu Yongxin,Jiang Yan,Zou Xu,Tang Huilan,Chen Xing,He Xiaoli,Hu Guang
Background Salvia miltiorrhiza (Danshen, DS) and Radix Paeoniae Rubra (Chishao, CS) herbal pair (DS-CS) is a famous traditional Chinese combination which has been used as antithrombotic formular for centuries. However, there is still lack of sufficient scientific evidence to illustrate its underlying mechanisms. The purpose of this study is to investigate the antithrombotic effects of DS-CS extract in zebrafish and explore its possible mechanism of action. Methods The quality of traditional Chinese medicines DS and CS granules was evaluated using High Performance Liquid Chromatography (HPLC). Subsequently, the therapeutic effect of the DS-CS combination and its components, Salvianolic Acid A (SAA) and Paeoniflorin (PF), in various concentrations on thrombosis was experimentally validated. Moreover, the interaction between DS-CS and the thrombosis disease targets was analyzed through network pharmacology, predicting the potential antithrombotic mechanism of DS-CS. Molecular docking and in vivo zebrafish experiments were conducted to validate the predicted targets, with qRT-PCR utilized for target validation. Results DS-CS exhibited anti-thrombotic effect in zebrafish with concentrations ranging from 25 to 300 μg/mL. The co-administration of PF and SAA at 25 μg/mL each revealed a synergistic antithrombotic effect exceeding that of individual components when contrasted with PHZ treatment. Protein–protein interaction (PPI) analysis identified key genes, including Albumin (ALB), Proto-oncogene tyro-sine-protein kinase Src (SRC), Matrix metalloproteinase-9 (MMP9), Caspase-3 (CASP3), Epidermal growth factor receptor (EGFR), Fibroblast growth factor 2 (FGF2), Vascular endothelial growth factor receptor 2 (KDR), Matrix metalloprotein-ase-2(MMP2), Thrombin (F2), and Coagulation factor Xa (F10), associated with the antithrombotic action of PF and SAA. Furthermore, KEGG pathway analysis indicated involvement of lipid metabolism and atherosclerosis pathways. Molecular docking revealed strong binding of PF and SAA to pivotal hub genes, such as SRC, EGFR, and F10. The experimental findings demonstrated that DS-CS could upregulate the mRNA expression levels of EGFR while inhibiting F10 and SRC mRNA levels, thereby ameliorating thrombotic conditions. Conclusion This research provided valuable insights into the potential mechanisms underlying the antithrombotic activity of DS-CS. Our findings suggested that PF and SAA could be the key active ingredients responsible for this activity. The antithrombotic effects of DS-CS appeared to be mediated through the regulation of mRNA expression of SRC, EGFR, and F10. These results enhanced our understanding of DS-CS's therapeutic potential and lay the groundwork for future studies to further elucidate its mechanisms of action.
研究领域:
药理学
·
分子生物学
·
中医药
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网络药理学
·
斑马鱼模型
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2025
·
IF 8.2
Yao Chen,Qingfa Tang,Qinglan Zhu,Meiting Lu,Errong Chang,Ziting Gao,Zidong Wang,Lu Zhang,Qiang Liu,Junju Zou,Zhong Zuo,Chunyan Shen,Cuiping Jiang
Atherosclerosis (AS) is a chronic cardiovascular disease characterized by the accumulation of excess lipids within arterial walls. Since oxidative stress is one of the key drivers in its pathogenesis, antioxidative therapy serves as a promising strategy for AS treatment. Despite the potent antioxidant properties of polyphenolic salvianic acid A (SAA) and salvianolic acid B (SAB), clinical application is limited by their short half-life, insufficient target selectivity, and poor chemical stability. To overcome these limitations, we developed a biomimetic platelet membrane-coated polyphenol–cerium dioxide nanozyme complex (SS-CeO2@PLTM) as a broad-spectrum antioxidative system for comprehensive AS treatment. The SS-CeO2@PLTM was constructed by conjugating SAA and SAB on the surface of cerium dioxide via a one-pot method, followed by surface coating with a biomimetic platelet membrane. Systematic characterization using UV–vis spectroscopy, Fourier transform infrared (FT-IR), X-ray photoelectron spectroscopy (XPS), transmission electron microscopy-energy dispersive X-ray spectroscopy (TEM-EDS) elemental mapping analysis, Forster resonance energy transfer (FRET), molecular simulations, and pH-responsive release assays validated the successful synthesis and pH-responsive drug release behavior of SS-CeO2@PLTM. It was also found that SS-CeO2@PLTM exhibited broad-spectrum antioxidant activities, effectively scavenging superoxide anions, DPPH, H2O2, and intracellular reactive oxygen species (ROS) while enhancing hepatic SOD and GSH activities. Further cellular uptake and in vivo targeting assays confirmed their specific targeting for atherosclerotic plaques. SS-CeO2@PLTM demonstrated great efficiency in attenuating oxidative stress, inhibiting lipid uptake and lipid accumulation, mediating cholesterol efflux, and inhibiting inflammatory factor (IL-1β, IL-6, and TNF-α) secretion in RAW264.7 cells. We also found that SS-CeO2@PLTM exhibited improved lipid metabolism and diminished plaque area in apoE–/– mice via attenuating oxidative stress and NF-κB-mediated inflammation. Furthermore, biosafety was verified via hemolysis and in vivo safety tests. This study is the first to reveal the superior efficacy of the PLTM-based nanozyme complex in targeted AS therapy, offering a paradigm shift for multifactorial cardiovascular disease management.
研究领域:
纳米医学
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心血管疾病
·
药物纳米技术
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抗氧化治疗
·
仿生学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2024
·
IF 3.3
Yanhong Niu,Zhili Wu,Qianfang Hu,Yuchen Wu,Qihua Jiang,Xiaolan Yang
Acetohydroxy acid synthase (AHAS) is a key enzyme that catalyzes the synthesis of branched-chain amino acids, which is indispensable for the survival and growth of Mycobacterium tuberculosis ( Mtb ). Aim to discover new AHAS inhibitors from natural products, here we performed computer assistant target-based screening for Mtb- AHAS inhibitors using Discovery Studio on TCMSP and SELLECK libraries. Mtb -AHAS structure was first simulated and verified for docking, and 80 compounds with top LIBDOCK and CDDOCK scores were obtained. By experimental verification, four compounds namely Salvianolic acid A, Embelin, Celastrol and Wushanicaritin showed inhibition potency against Mtb- AHAS with IC50 ranging from 805.5 nM–32.36 μM. The most potential inhibitor Celastrol exhibited bacteriostatic activity for both Mycobacterium smegmatis and Mycobacterium tuberculosis with MIC of 62.5 μM and 80 μM, respectively. This study revealed that Celastrol is the potential Mtb- AHAS inhibitor as an anti-tuberculosis lead compound.
研究领域:
药理学
·
微生物学
·
药物发现
·
计算生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Scientific Reports
·
2024
·Vol. 14
·期 1
·1-11
·
IF 3.8
Qiao Xilin,Cao Shuyu,Chen Shuaiyu,Guo Yan,Chen Nipi,Zheng Ying,Jin Bo
Oxidative stress induced endothelial dysfunction plays a particularly important role in promoting the development of cardiovascular diseases (CVDs). Salvianolic acid A (SalA) is a water-soluble component of traditional Chinese medicine Salvia miltiorrhiza Bunge with anti-oxidant potency. This study aims to explore the regulatory effect of SalA on oxidative injury using an in vitro model of H 2 O 2 -induced injury in human umbilical vein endothelial cells (HUVECs). In the study, we determined cell viability, the activities of Lactate dehydrogenase (LDH) and Superoxide dismutase (SOD), cell proliferation rate and intracellular reactive oxygen species (ROS). Flow cytometry was used to detect cell apoptosis. Western-blotting was used to evaluate the expression of cell senescence, apoptosis, autophagy and pyroptosis protein factors. The expression level of miRNA was determined by qRT-PCR. Compared with H 2 O 2 -induced HUVECs, SalA promoted cell viability and cell proliferation rate; decreased LDH and ROS levels; and increased SOD activity. SalA also significantly attenuated endothelial senescence, inhibited cell apoptosis, reversed the increase of LC3 II/I ratio and NLRP3 accumulation. Furthermore, miR-204-5p was regulated by SalA. Importantly, miR-204-5p inhibitor had similar effect to that of SalA on H 2 O 2 -induced HUVECs. Our results indicated that SalA could alleviate H 2 O 2 -induced oxidative injury by downregulating miR-204-5p in HUVECs.
研究领域:
药理学
·
心血管科学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHARMACOLOGICAL RESEARCH
·
2021
·
IF 7.658
Yujiao Yang,Junke Song,NanNan Liu,Guangyi Wei,Shan Liu,Sen Zhang,Nan Jiang,Haiguang Yang,Guanhua Du
Chronic cerebral ischemia (CCI) refers to long-term hypoperfusion of cerebral blood flow with the main clinical manifestations of progressive cognitive impairment . The pathological mechanism of CCI is complex, and there is a lack of effective treatments. Salvianolic acid A (SalA) is a neuroprotective extract of Salvia miltiorrhiza with the effects of anti-inflammation and anti-apoptosis. In this study, the effect of SalA on cognitive function and Drd2/Cryab/NF-κB signaling pathway in rats with CCI was investigated. Morris water maze and open field test were used to observe the effects of SalA on the cognitive function of CCI rats. The pathological changes in the brain were observed by HE, Nissl, and LFB staining. TUNEL staining, enzyme-linked immunosorbent assay, and western blot analysis were used to detect the inflammatory and apoptosis in the cortex and hippocampus. The expression of Drd2/Cryab/NF-κB pathway-related molecules and Drd2 localization were detected by western blotting and dual immunofluorescence, respectively. SH-SY5Y cells were exposed to chronic hypoglycemic and hypoxic injury in vitro, and Drd2 inhibitor haloperidol was used to verify the involved pathway. The results showed that SalA could improve the cognitive function of CCI rats, reduce pathological damage of cortex and hippocampus, inhibit neuroinflammation and apoptosis, and suppress the activation of NF-κB by regulating Drd2/Cryab pathway. And SalA inhibited NF-κB activation and nuclear translocation in SH-SY5Y cells by upregulating Drd2/Cryab pathway, which was reversed by haloperidol interference. In conclusion, SalA could relieve CCI-induced cognitive impairment in rats, at least partly through the Drd2/Cryab/NF-κB pathway.
研究领域:
神经科学
·
药理学
·
分子生物学
·
病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
·
2025
·Vol. 39
·期 2
·e6065
·
IF 1.7
Yong Jiang,Wenjun Ji,Ying Lu,Qin Wang,Linwei Chen
The high mortality rate of chronic heart failure (CHF) makes it a primary battlefield in the field of cardiovascular diseases. Qiangxin Lishui Prescription (QLP) is a traditional Chinese medicine (TCM) prescription used clinically for treating CHF, but its underlying mechanism remains unclear. This study integrated plasma metabolomics, network pharmacology, and experimental validation to reveal the pharmacological effects of QLP and its potential mechanism of anti-CHF. Using ultra-high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS/MS), 119 absorbed prototype compounds of QLP were identified from rat plasma. By applying network pharmacology and molecular docking techniques, a QLP absorption components–target–CHF network was constructed. The IL6/JAK/STAT3 signaling pathway is likely critical to QLP's therapeutic effect on CHF. A CHF mouse model was established using aortic ligation surgery to investigate the regulation of the IL6/JAK/STAT3 pathway by QLP in CHF mice. Network pharmacology analysis and in vivo experimental data indicate that QLP alleviates myocardial injury and inflammatory response in CHF mice by modulating the IL6/JAK/STAT3 pathway, significantly improving cardiac function. This presents a promising therapeutic strategy for CHF treatment.
研究领域:
中医药学
·
心血管疾病
·
药理学
·
代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2022
·
IF 3.571
Ming Meng,Haofang Wan,Yida Bao,Yu He,Chang Li,Haitong Wan
Guanxin Shutong capsule (GSC) is a traditional Chinese medicinal prescription used in the treatment of coronary heart disease (CHD) and angina pectoris in clinic. However, the chemical profile of GSC is still uncovered, which hindered the progress of pharmacological study and clinical application. Herein, high performance liquid chromatography (HPLC) together with high resolution mass spectrometry (HR-MS) techniques were employed to analyze the quality consistency and to identify chemical components in GSC. As a result, a total of 111 compounds were tentatively annotated. Quantitative analysis based on HPLC-ultraviolet detection (UV) was performed for 6 main components and fingerprints of 10 different batches of GSC were established. The developed method was validated for linearity, precision, repeatability, stability, and recovery. The quality evaluation and similarity analysis of the 10 batches were also performed. Furthermore, in vitro antioxidant activity assays demonstrated that GSC exhibited potential DPPH and hydroxyl radical scavenging capacities. Especially, salvianolic acids showed the strongest free radical scavenging capacities, which might be the main component for quality control of GSC.
研究领域:
药理学
·
分析化学
·
中药学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Chemistry
·
2022
·
IF 5.545
Shen Qing,Wang Haixing,Quan Bin,Sun Xiuhua,Wu Guohua,Huang Darong,Wang Qingcheng,Luo Pei
Salvia miltiorrhiza Bunge (SMB) has unambiguous biological functions in cardiovascular diseases, thus has been processed into different medicine forms. However, universal analytical method for fast quantification of bioactive compounds in SMB and SMB derived products is still missing. In this study, a polarity switching strategy was developed and optimized, which enabled the detection of the target compound in both positive and negative ion modes in a single run. The MS2 features of each compound were characterized to select the most prominent transitions for quantitative and qualitative analysis. Afterwards, the performance of this method was validated in terms of linearity (≥0.9916), limit of detection (LOD, 0.003–0.135 ngml−1), limit of quantification (LOQ, 0.010–0.450 ngml−1), precision (48.23 ± 2.58 ngml−1 to 53.72 ± 3.11 ngml−1), recovery (RSD 2.04%–5.79%), and stability (RSD ≤7.52%). Finally, the bioactive compounds in SMB and SMB derived products were determined, among which salvianate A, salvianolic acid A, and rosmarinic acid were the main components in all samples. In conclusion, the polarity switching UPLC-MS/MS method is efficient in accurate determining the bioactive compounds, which greatly shorten the time for analysis when compared with conventional methods. It has great potential quality control of SMB and SMB derived products.
研究领域:
药学
·
分析化学
✓ 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）