INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
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2023
·Vol. 24
·期 7
·6844
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IF 5.6
Guoying Zhou,Jiayan Zhu,Liang Jin,Jing Chen,Ruojiao Xu,Yali Zhao,Tingzi Yan,Haitong Wan
Inflammatory dysfunction and angiogenesis inhibition are two main factors leading to the delayed healing of diabetic wounds. Hydrogels with anti-inflammatory and angiogenesis-promoting effects have been considered as promising wound care materials. Herein, a salvianolic acid B (SAB)-loaded hyaluronic acid (HA) self-healing hydrogel (HA/SAB) with anti-inflammatory and pro-angiogenesis capacities for diabetic wound healing is reported. The HA hydrogel was prepared via the covalent cross-linking of aldehyde groups in oxidized HA (OHA) and hydrazide groups in adipic dihydrazide (ADH)-modified HA (HA-ADH) with the formation of reversible acylhydrazone bonds. The obtained HA hydrogel exhibited multiple favorable properties such as porous structures, excellent self-healing properties, a sustainable release capacity of SAB, as well as excellent cytocompatibility. In addition, the effects of the SAB-loaded HA self-healing hydrogel were investigated via a full-thickness skin defect model using diabetic rats. The HA/SAB hydrogel showed enhanced skin regeneration effects with accelerated wound closure, shorter remaining dermal space length, thicker granulation tissue formation, and more collagen deposition. Furthermore, reduced inflammatory response and enhanced vascularization were found with HA/SAB2.5 hydrogel-treated wounds, indicating that the hydrogel promotes diabetic wound healing through the promotion of anti-inflammation and angiogenesis. Our results suggest that the fabricated SAB-loaded HA self-healing hydrogel is promising as a wound dressing for the treatment of diabetic wounds.Keywords:diabetic wound healing;self-healing hydrogel;salvianolic acid B;anti-inflammation;angiogenesis
研究领域:
药学
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材料科学
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生物医学工程
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DOI
PubMed
高影响因子
PLoS One
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2015
·Vol. 10
·期 4
·e0118274
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IF 3.234
Xin Peng,Wei Qi,Renliang Huang,Rongxin Su,Zhimin He
Salvianolic acid B and rosmarinic acid are two main water-soluble active ingredients from Salvia miltiorrhiza with important pharmacological activities and clinical applications. The interactions between salvianolic acid B (or rosmarinic acid) and bovine serum albumin (BSA) in the presence and absence of gold nanoparticles (Au NPs) with three different sizes were investigated by using biophysical methods for the first time. Experimental results proved that two components quenched the fluorescence of BSA mainly through a static mechanism irrespective of the absence or presence of Au NPs. The presence of Au NPs decreased the binding constants of salvianolic acid B with BSA from 27.82% to 10.08%, while Au NPs increased the affinities of rosmarinic acid for BSA from 0.4% to 14.32%. The conformational change of BSA in the presence of Au NPs (caused by a noncompetitive binding between Au NPs and drugs at different albumin sites) induced changeable affinity and binding distance between drugs and BSA compared with no Au NPs. The competitive experiments revealed that the site I (subdomain IIA) of BSA was the primary binding site for salvianolic acid B and rosmarinic acid. Additionally, two compounds may induce conformational and micro-environmental changes of BSA. The results would provide valuable binding information between salvianolic acid B (or rosmarinic acid) and BSA, and also indicated that the Au NPs could alter the interaction mechanism and binding capability of drugs to BSA, which might be beneficial to understanding the pharmacokinetics and biological activities of the two drugs.
研究领域:
药理学
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生物物理学
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DOI
PubMed
高影响因子
Annals of Hepatology
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2020
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IF 2.125
Shuxia Tian,Min Chen,Bing Wang,Yonglong Han,Haonan Shang,Junming Chen
Introduction and objectives The activation of hepatic stellate cells (HSCs) is the main cause of liver fibrosis. The beneficial effects of fibroblast growth factor (FGF) 19 on liver fibrosis were recently reported. The S. miltiorrhiza as well as S. miltiorrhiza derived bioactive chemical components has shown prominent antifibrotic effects in liver fibrosis but the mechanism is still not fully understood. We aimed to investigate the bioactive compounds derived from S. miltiorrhiza which exerts antifibrotic effects in HSCs via regulating FGF19. Materials and methods FGF19 level in culture media was determined by enzyme-linked immunosorbent assay. Cell proliferation was measured by Cell Counting Kit-8 assay. Further, mRNA and protein expressions were assessed by quantitative polymerase chain reaction and western blotting, respectively. Knocking down of FGF receptor 4 (FGFR4) by transfection with siRNA was used to confirm the role of FGF19/FGFR4 signaling. Results Using the human HSC cell line LX-2, we screened several natural products and found that bioactive compounds isolated from Salvia miltiorrhiza , particularly salvianolic acid B, strongly upregulated FGF19 secretion by LX-2 cells. We further showed that salvianolic acid B inhibited lipopolysaccharide (LPS)-induced HSC proliferation and activation. LPS treatment may also reduce the mRNA and protein levels of FGF19 and its receptor FGFR4. Salvianolic acid B treatment restored the impaired expressions of FGF19 and FGFR4. Finally, FGFR4 knockdown abolished the antifibrotic effects of salvianolic acid B in the LPS-induced HSC activation model. Conclusions Salvianolic acid B prevented LPS-induced HSC proliferation and activation by enhancing antifibrotic FGF19/FGFR4 signaling.
研究领域:
药理学
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分子生物学
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细胞生物学
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肝病学
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DOI
PubMed
高影响因子
Evidence-based Complementary and Alternative Medicine
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2022
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IF 2.65
Qianqian Wang,Xiaogang Li,Lijun Cao,Yan Li,Yonghui Liu,Lianqing Sun
Background. Salvianolic acid B (Sal B) is a bioactive component of Radix Salviae, which has antiinflammation and antiapoptotic activity in diabetic complications. However, the molecular mechanism of action of Sal B on diabetic peripheral neuropathy (DPN) is unknown. This study was designed to identify a mechanism for Sal B in the treatment of DPN by using a pharmacology network, molecular docking, and in vitro experiments. Methods. Sal B and DPN-related targets from Gene Cards and OMIM platforms were retrieved and screened. Then, an analysis of possible targets with STRING and Cytoscape software was conducted. KEGG signaling pathways were determined using the R software. Subsequently, the binding capacity of Sal B to target proteins was analyzed by molecular docking and in vitro experiments. Results. A total of 501 targets related to Sal B and 4662 targets related to DPN were identified. Among these targets, 108 intersection targets were shared by Sal B and DPN. After topological and cluster analysis, 11 critical targets were identified, including p38MAPK. KEGG analysis revealed that the AGE-RAGE signaling pathway likely plays an important role in Sal B action on DPN. The p38MAPK protein is a key target in the AGE-RAGE signaling pathway. Molecular docking results suggested that Sal B and p38MAPK have excellent binding affinity (<−5 kcal/mol). The in vitro experiments revealed that Sal B downregulates the expressions of p-P38MAPK, inflammatory cytokines, and apoptosis targets, which are upregulated by hyperglycemia. Conclusion. Sal B may alter DPN by inhibiting inflammation and apoptosis activated by p38MAPK.
研究领域:
药理学
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分子生物学
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生物信息学
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糖尿病研究
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DOI
PubMed
高影响因子
PHYTOMEDICINE
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2019
·
IF 4.18
Ziru Zhang,Jianbo Ji,Dawei Zhang,Maoqiang Ma,Longru Sun
Background The root of Salvia miltiorrhiza f. alba (RSMA) (Lamiaceae) is used for the treatment of patients with thromboangiitis obliterans (TAO) in traditional Chinese medicine . Previously, a mixture of phenolic acids extracted from RSMA has shown significant protective effects on TAO rats. Purpose This study investigates the inhibitory effects of salvianolic acid B on TAO induced by sodium laurate injection in rats to explore the effective constituents of RSMA in TAO treatment. Methods TAO rats were developed using injected sodium laurate. After treatment with ligustrazine hydrochloride (15 mg/kg) and various doses of salvianolic acid B (10, 20, 40 mg/kg) by tail intravenous injection , levels of thromboxane B 2 (TXB 2 ), 6-keto-prostaglandin F 1α (6-keto-PGF 1α ) and endothelin-1 (ET-1) in plasma were determined using enzyme-linked immunosorbent assay. The right femoral arteries were studied by hematoxylin and eosin staining and immunohistochemical analysis to determine pathological changes and overexpression of tumor necrosis factor (TNF)–α and inducible nitric oxide synthase (iNOS) in the femoral artery walls of TAO rats. Results Salvianolic acid B significantly decreased the expressions of TXB 2 and ET-1 and increased the expression of 6-keto-PGF 1α in plasma, and significantly inhibited the overexpression of TNF-α and iNOS in the femoral artery walls of TAO rats at medium and high doses. Conclusion Salvianolic acid B has a protective effect on TAO rats. The mechanism may involve inhibition of thrombosis and TAO-associated inflammatory responses, which may explain the success of RSMA treatment of TAO in humans in traditional Chinese medical practice. Hence, it may be a potential drug for TAO treatment in conventional medicine.
研究领域:
药理学
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免疫学
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病理学
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传统中药
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心血管疾病
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
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IF 13.2
Liang Song,Weiwei Zheng,Shuqin Wang,Zihe Zhai,Shifen Li,Jie Ding,Liyin Shen,Jinyue Zhang,Yang Zhu,Changyou Gao
Pathology of myocardial infarction (MI) undergoes continuous spatiotemporal transformation, during which immediate elevated reactive oxygen species (ROS) and subsequent upregulated connective tissue growth factor (CTGF) exacerbate the impairment of cardiac functions. The major challenge lies in designing biomaterials that can adaptively respond to the temporal changes in the MI microenvironment. Herein, we prepared ROS-responsive dual drug-loaded core–shell microgels (SaB/Cand@C-S MGs) using microfluidic chip technology. The hydrogel shell was made from ROS-eliminating hyperbranched poly(acrylate-capped thioketone-containing ethylene glycol) (HBPAK) and methacrylated hyaluronic acid (HAMA), which was further encapsulated with hydrophilic salvianolic acid B (SaB). The oleogel core was loaded with hydrophobic candesartan (Cand). This structure enabled programmed drug release by utilizing ROS-responsive shell. The release of Cand from the SaB/Cand@C-S MGs in vitro was significantly accelerated in the presence of H 2 O 2 , reaching to 68% over 21 d, compared to 24% in PBS. In a rat MI model, minimally invasive injection of the SaB/Cand@C-S MGs into the infarcted area demonstrated both short-term anti-inflammatory effect and long-term benefit in fibrosis suppression. This phase-targeted approach ultimately resulted in improved cardiac functions, reduced fibrosis, and decreased ventricular dilation. The core–shell microgels as a drug reservoir offer a programmed drug delivery strategy adaptive to the specific phases of MI, showing great potential for applications.
研究领域:
药理学
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生物医学工程
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心脏病学
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产品关联
DOI
高影响因子
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