ACS Omega
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2022
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IF 4.132
Shan-Shan Wu,Li-Jun Hao,Yuan-Yuan Shi,Zhuo-Jian Lu,Jia-Lin Yu,Si-Qi Jiang,Qing-Ling Liu,Ting Wang,Shi-Ying Guo,Ping Li,Fei Li
Wang-Bi capsule (WB) is a traditional Chinese medicine (TCM)-based herbal formula, and it has been used in the treatment of rheumatoid arthritis (RA) in China for many years. Additionally, WB is also used as a supplement to the treatment of osteoarthritis (OA) in clinical practice. Our research aimed to reveal the therapeutic effects and underling mechanism of WB on RA and OA through computational system pharmacology analysis and experimental study. Based on network pharmacology analysis, a total of 173 bioactive compounds interacted with 417 common gene targets related to WB, RA, and OA, which mainly involved the PI3K-Akt signaling pathway. In addition, the serine–threonine protein kinase 1 (AKT1) might be a core gene protein for the action of WB, which was further emphasized by molecular docking. Moreover, the anti-inflammatory activity of WB in vitro was confirmed by reducing NO production in lipopolysaccharide (LPS)-induced RAW264.7 cells. The anti-RA and OA effects of WB in vivo were confirmed by ameliorating the disease symptoms of collagen II-induced RA (CIA) and monosodium iodoacetate-induced OA (MIA) in rats, respectively. Furthermore, the role of the PI3K-Akt pathway in the action of WB was preliminarily verified by western blot analysis. In conclusion, our study elucidated that WB is a potentially effective strategy for the treatment of RA and OA, which might be achieved by regulating the PI3K-Akt pathway. It provides us with systematic insights into the effects and mechanism of WB on RA and OA.
研究领域:
药理学
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中医
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风湿病学
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分子生物学
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系统生物学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Bioengineering and Biotechnology
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2022
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IF 6.064
Fu Zhihui,Wang Xiaohui,Lu Xuan,Yang Ying,Zhao Lingling,Zhou Lin,Wang Kaikai,Fu Hanlin
Ginsenoside Rb1 is a potential anti-inflammatory natural molecule, but its therapeutic efficacy was tremendously hampered by the low solubility and non-targeted delivery. In this study, we innovatively developed a mannose (Man)-modified albumin bovine serum albumin carrier (Man-BSA) to overcome the previously mentioned dilemmas of Rb1. The constructed Man-BSA@Rb1 NPs could improve the solubility and increase the cellular uptake of Rb1, finally leading to the enhanced anti-inflammatory effects. The robust therapeutics of Man-BSA@Rb1 NPs were measured in terms of nitrite, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, which might be achieved by potently inhibiting nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways in lipopolysaccharide (LPS)-induced Raw264.7 cells. Moreover, the therapeutic efficacy of Man-BSA@Rb1 NPs was further confirmed in the d-Gal/LPS-induced liver injury model. The results indicated that Man-BSA may offer a promising system to improve the anti-inflammatory therapy of Rb1.
研究领域:
药理学
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纳米技术
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炎症研究
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药物递送系统
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DOI
PubMed
高影响因子
Materials Today Bio
·
2023
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IF 8.2
Jiafeng Wang,Longhui Shao,Xiaoyu Wu,Chun Liu,Su Ni,Ting Dai,Hongwei Liu,Hongbin Zhao
Osteoblasts and osteoclasts play a crucial role in the dynamically coupled balance during bone regeneration and remodeling. They complement and restrict each other in the human body. Decreased osteoblasts lead to insufficient bone formation or excessive formation of osteoclasts, leading to increased bone resorption, which will destroy the structure of the bone tissue. This will greatly increase the risk of diseases such as osteoporosis and nonunions caused by bone defects. Herein, gelatin and polycaprolactone were used as substrates, and biomaterial membranes with mesh and sandwich structures were constructed using the electrospinning technology. Naringenin was loaded into the shell, and vitamin K 2 was loaded into the core layer of the nanofibrous membrane. The biocompatibility and osteogenic capacity of the membranes were assessed in vitro using mouse bone marrow mesenchymal stem cells (BMSCs). During osteoclast induction, the receptor activator of nuclear factor kappa-Β ligand (RANKL) was used to coculture RAW264.7 cells with various materials. The regulatory effect of various membranes on osteoclast growth was evaluated by detecting the expression levels of osteoclast-related genes and proteins in the cells. Subsequently, we constructed a model of a rat skull defect and implanted different membranes into the defect. Then, we evaluated the new bone formation in the defect using histological staining and micro-computed tomography after 4 and 8 weeks. The results of in vitro experiments confirmed that the incorporation of naringenin and vitamin K 2 stimulated the expression of osteogenesis-related genes and the secretion of osteogenesis-related proteins. Simultaneously, the results showed that naringenin and vitamin K 2 inhibited the formation and growth of osteoclasts. Therefore, naringenin and vitamin K 2 have a synergistic effect in promoting bone growth and regulating osteoclast growth.
研究领域:
生物材料
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组织工程
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骨再生
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细胞生物学
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材料科学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2024
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IF 10.7
Zian Mao,Liu Yang,Yishan Lv,Yuchi Chen,Mingyuan Zhou,Chengnan Fang,Bingqi Zhu,Fangmei Zhou,Zhishan Ding
A novel acidic glucuronogalactomannan (STHP-5) was isolated from the aboveground part of Tetrastigma hemsleyanum Diels et Gilg with a molecular weight of 3.225 × 10 5 kDa. Analysis of chain conformation showed STHP-5 was approximately a random coil chain. STHP-5 was composed mainly of galactose, mannose, and glucuronic acid. Linkages of glycosides were measured via methylation analysis and verified by NMR. Based on the structural characterization, the repeat unit of STHP-5 was proposed. In vitro, STHP-5 induced the production of nitric oxide (NO) and secretion of IL-6, MCP-1, and TNF-α in RAW264.7 cells, indicating STHP-5 had stimulatory activity on macrophages. STHP-5 was proven to function as a TLR4 agonist by inducing the secretion of secreted embryonic alkaline phosphatase (SEAP) in HEK-Blue™-hTLR4 cells. The TLR4 activation capacity was quantitatively measured via EC50, and it showed purified polysaccharides had stronger effects (lower EC50) on activating TLR4 compared with crude polysaccharides. In conclusion, our findings suggest STHP-5 may be a novel immunomodulator.
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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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2024
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IF 4.8
Anyi Zhao,Jiangmin Su,Qingxia Xu,Jun Zhang,Jinzhu Jiang,Sha Chen,Jintang Cheng,Chang Chen,Lianmei Wang,Jipeng Di,Xianju Liu,Liang Jiang,Li Liu,Yan Liu,An Liu,Cong Guo
Ethnopharmacological relevance Xiebai San (XBS), a classic Chinese prescription, has been used for the clinical treatment of pneumonia-related diseases for thousands of years. However, the anti-pneumonia pharmacodynamic material basis of XBS and its underlying mechanisms remain unclear. Aim of the study This study aimed to comprehensively investigate and verify the anti-pneumonia pharmacodynamic material basis and mechanisms of XBS. Materials and methods This study explored the anti-pneumonia activity and key pneumonia targets of XBS in lipopolysaccharide (LPS)-induced zebrafish and RAW264.7 cells in vivo and in vitro through transcriptomics, western blotting, and reverse transcription–quantitative polymerase chain reaction (RT–qPCR). The chemical fingerprint of XBS was established using high-performance liquid chromatography, and the similarities and areas of characteristic peaks of 15 batches of XBS were analyzed. Based on the spectrum–efficacy relationship, the potential anti-inflammatory components were screened according to their peak areas and efficacy using principal component analysis (PCA), bivariate correlation, and partial least squares regression analysis. Active components that bind to core targets were further screened based on surface plasmon resonance (SPR). The binding mode of proteins and components was simulated via molecular docking, which enabled the identification of the primary active components of XBS, thereby elucidating its anti-pneumonia properties. Finally, the anti-inflammatory activities of these components were verified in vitro . Results XBS decreased neutrophil aggregation in zebrafish and nitric oxide (NO) secretion in RAW264.7 cells as well as suppressed the release of downstream inflammatory cytokines such as iNOS, TNF-α, IL-1β, IL-18, and CXCL10 related to TNF and JAK–STAT signaling pathways. The phosphorylation of IκBα, Akt, and Stat3 was alleviated after XBS in cells. The fingerprint similarities of 15 batches of XBS ranged from 0.381 to 0.994, with a large difference. A total of 15 characteristic peaks were identified, and the relative standard deviation of their peak areas ranged from 24.1% to 70.7%. The results of in vitro anti-inflammatory activities of 15 batches of XBS showed that all samples inhibited the expression levels of NO and nine inflammatory markers. The anti-inflammatory index of 15 batches of XBS was determined to be 0.69–0.96 based on transformation of the anti-inflammatory rate and composite index method via PCA. The spectrum–efficacy relationship model of 15 characteristic peak areas and the anti-inflammatory index showed that 7 main potential active components were related to the anti-inflammatory activity of XBS. Moreover, four components (mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid) screened based on SPR had different affinities toward TNFR1, Akt1, and Stat3 proteins, and the binding modes were elucidated via molecular docking. Finally, in LPS-induced RAW264.7 cells, all four active components (at a concentration of 60 μM) significantly inhibited the expression levels of NO and inflammatory markers. Conclusions Based on the comprehensive strategy of spectrum–efficacy relationship and SPR, mulberroside A, isoquercitrin, liquiritigenin, and glycyrrhizic acid were identified as the primary pharmacodynamic active components involved in the anti-pneumonia activity of XBS and were found to intervene in TNF and JAK–STAT signaling pathways.
研究领域:
药理学
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民族药理学
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转录组学
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生物化学
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分子生物学
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分析化学
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产品关联
DOI
PubMed
高影响因子
CHEMISTRY & BIODIVERSITY
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2024
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IF 2.3
Qiaoying Song,Lingbiao Gu,Lingqi Kong
In this manuscript, the polysaccharide (VPP-I) from Veronica persica Poir., was characterized in detail by high performance gel permeation chromatography (HPGPC), high performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance spectroscopy (NMR). In addition, lipopolysaccharide (LPS) induced inflammation model of RAW264.7 cells was used to evaluate the in vitro anti-inflammatory activity of VPP-I. The results showed that the relative molecular weight of VPP-I was 2.355 KDa, which was mainly composed of mannose (Man), glucose (Glc) and galactose (Gal) in a ratio of 1 : 32.46 : 28.76. Moreover, the VPP-I contained sugar alcohol derivatives of T-DGlcp(1→, →4)-D-Galp(1→, →3,6)-D-Manp(1→, →4)-D-Glcp(1→, →6)-D-Galp(1→ and →6)-D-Glcp(1→. In vitro anti-inflammatory results showed that VPP-I could inhibit the secretion of IL-β, IL-6 and TNF-α in RAW264.7 cells induced by LPS. Moreover, compared to the LPS group, the mRNA expression levels of iNOS, COX-2, IL-β, IL-6 and TNF-α produced by RAW264.7 were significantly decreased after treatment with VPP-I (P<0.05). In addition, VPP-I could increase the SOD and GSH−Px enzymes activity and decrease the content of MDA in LPS-induced RAW264.7 cells (P<0.05). In summary, this paper laid theoretical foundation for the application of Veronica persica Poir. in the field of medicine. Graphical
研究领域:
药理学
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生物化学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
eLife
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2021
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IF 8.146
Fan Xue,Zhenlei Zhao,Yanpei Gu,Jianxin Han,Keqiang Ye,Ying Zhang
Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.
研究领域:
药理学
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骨生物学
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神经科学
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC CHEMISTRY
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2020
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IF 4.831
Qi-Ji Li,Peng-Fei Tang,Xin Zhou,Wei-Jia Lu,Wen-Jun Xu,Jun Luo,Ling-Yi Kong
Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum , the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(−)-elodeoidols A-F ( 1 – 6 )), along with three biogenetical homologues ( 7 – 9 ) were isolated from the herbaceous plant of Hypericum elodeoides . Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1 – 6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5 , 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)- 5 was 6.25 μg/ml; Compounds 3 , 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC 50 : 10.39 ± 0.49 ~ 34.25 ± 2.32 μM).
研究领域:
药用植物学
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天然产物化学
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药物化学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
PHYTOCHEMISTRY
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2023
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IF 3.8
Quan-Hao Wei,Xin-Xin Cao,De-Feng Xu,Shu-Ting Wang,Jun-Sheng Zhang,Hua Zhang
Twenty-two labdane-type diterpenoids , including ten pairs of 15-epimers and a pair of 13,15-epimers, were obtained from the aerial parts of a well-known medicinal plant Leonurus japonicus Houtt. While these epimers were separated by chiral HPLC , their structures were established mainly via spectroscopic methods especially NMR , X-ray crystallography and ECD techniques. Among them, seventeen compounds, encompassing three pairs of solvolysis artefacts likely due to the use of ethanol as extracting solvent, were reported for the first time in the current work. Our preliminary anti-inflammatory screening demonstrated that seven diterpenoids displayed noteworthy inhibitory effect on the NO production in LPS-induced RAW264.7 cells. In addition, the release of pro-inflammatory factors TNF-α, IL-1β and IL-6, as well as the expression of iNOS and COX-2 proteins, was also suppressed by the unreported 15,16-epoxy-6β-hydroxy-15α-methoxy-7,16-dioxolabd-8,13-diene. Further investigation into the preliminary anti-inflammatory mechanism of this compound indicated that it could block the activation of NF-κB signaling pathway .
研究领域:
药理学
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有机化学
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植物科学
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生物化学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2020
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IF 7.182
Xuewei Jia,Yanchao Yao,Guofeng Yu,Lili Qu,Tianxiao Li,Zhenjie Li,Chunping Xu
Polysaccharides are ideal green synthetic raw materials to improve the biocompatibility of metal nanoparticles. However, polysaccharides generally have weak reducibilities, being challenging supports for the direct preparation of Ag nanoparticles. In this work, gold nanoclusters were prepared using a triple helix glucan (Lentinan) via microwave-assisted synthesis and subsequently employed as seeds for the synthesis of a series of Ag-Au alloy nanoparticles (Ag-AuNPs). The results showed that gold nanoclusters can remarkably speed up the preparation of Ag-AuNPs without the addition of any other chemicals. The particle size of Ag-AuNPs increased at increasing Ag contents in the alloy. Results of UV–vis, transmission electron microscope (TEM) and inductively coupled plasma mass spectrometry (ICP-MS) suggested that Ag + was quickly reduced to irregular silver nanoparticles (with gold nanoparticles as seeds), then gradually form more regular nano-alloys. Additionally, X-ray diffraction (XRD) and zeta potential results suggested that Ag-AuNPs could entrap the hydrophobic cavity of triple helix polysaccharides during the renaturation process. The nanocomposites exhibited good antifungal activity and low cytotoxicity to RAW264.7, Hela and LO2 cell lines in vitro .
研究领域:
纳米技术
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材料科学
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生物技术
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药学
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2022
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IF 10.723
Wangting Zhou,Tingting Yang,Weiqi Xu,Yujie Huang,Linwu Ran,Yamei Yan,Jia Mi,Lu Lu,Yi Sun,Xiaoxiong Zeng,Youlong Cao
The antidiabetic effect and potential mechanisms of the polysaccharides from the fruits of Lycium barbarum L. (LBPs) by the mouse model of high-fat diet/streptozotocin-induced diabetes were investigated. Six-week oral administration of LBPs (200 mg/kg/day) resulted in improvement in the levels of fasting blood glucose (13.51% decrease) and glycated hemoglobin and β-cell function in diabetic mice, and simultaneously induced a 3.3-fold increment in one taxon belonging to genus Allobaculum in gut bacterial community. The experiments of fecal microbiota transplantation and antibiotics treatment confirmed that the LBPs-mediated gut microbiota participated in the glycemic control of the diabetes management. Moreover, LBPs intervention guarded the intestinal barrier function via upregulating the expression of zonula occludens 1 both in vivo (analyzing the gut permeability in diabetic mice) and in vitro (using intestinal-like Caco-2/RAW264.7 cells co-culture inflammation model). Collectively, our study showed that LBPs could confer anti-diabetic effect through modifying gut microbiota and intestinal barrier.
研究领域:
药理学
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微生物学
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糖尿病研究
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营养科学
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胃肠病学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Kunmei Xie,Feibiao Wang,Yue Yang,Shoujie Pan,Junyao Wang,Nan Xiao,Xinyan Wang,Zhihao Ma,Xiaolong Xu,Zibo Dong
Sepsis-associated acute liver injury (ALI) is a deadly condition resulting from a systemic inflammatory response to liver cell damage and malfunction. Monotropein (MON) belongs to the iris group of compounds extracted from the natural product Mollen dae officinalis radix, which has strong anti-inflammatory and antioxidant pharmacological effects. The purpose of this study was to elucidate the underlying mechanism of MON in the treatment of sepsis ALI. In this study, an in vivo caecal ligation puncture (CLP)-induced ALI model and in vitro LPS-stimulated AML12 cells and RAW264.7 cells model were established. Additionally, a variety of experimental techniques, including CCK8, H&E staining, DHE probe labelling, biochemical, QPCR, and Western blotting and blocking tests, were used to explore the role of MON in ALI. The results showed that MON improved liver morphological abnormalities, oedema, histopathological injury, and elevated ALT and AST, providing a protective effect against ALI. MON reduced CYP2E1 expression, alleviated oxidative stress (downregulation of MDA levels and upregulation of GSH, CAT, and T-AOC levels) and ROS accumulation with the involvement of the NRF2-Keap-1 pathway. MON inhibited inflammation via the TLR4/NF-κB/NLRP3 inflammasome pathway. In addition, it activated the Akt (Ser473)/GSK3β (Ser9)/Fyn pathway and accelerated NRF2 nuclear accumulation; MK-2206 blockade reversed the NRF2 nuclear accumulation and anti-inflammatory function of MON. MON also restricted the mitochondrial apoptosis pathway, a process specifically blocked by MK-2206. In summary, we concluded that MON alleviated septic ALI by restricting oxidative stress, inflammation, and apoptosis via the AKT (Ser473)/GSK3β (Ser9)/Fyn/NRF2 pathway.
研究领域:
药理学
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免疫学
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分子生物学
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细胞生物学
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病理学
✓ 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）