JOURNAL OF DRUG TARGETING
·
2024
·
IF 4.3
Can Wang,Yihang Yang,Ruming Liang,Shikui Wu,Chengrui Xuan,Wei Lv,Jian Li
We successfully prepared mercury sulphide nanoparticle hydrogels by physical encapsulation method. The successfully prepared mercuric sulphide nanoparticle hydrogel was a zinc folate hydrogel, which showed an obvious porous structure with interconnected and uniformly distributed pores and a pore size range of about 20 μm. The maximum drug loading of the hydrogels was 3%, and the in vitro cumulative release degree was in accordance with the first-order kinetic equation Mt = 149.529 (1 − e−0.026t). The particles in mercuric sulphide nanoparticle hydrogels significantly down-regulated the expression of the cell surface co-stimulatory molecule CD86 (p < .0001). Meanwhile, the inflammatory response was regulated through the NF-κB pathway in LPS-induced inflammatory cells. Later, it was observed that mercuric sulphide nanoparticle hydrogels could significantly counteract the inflammatory and immune models through a mouse ear swelling model, a rat foot-plantar swelling model and a rheumatoid arthritis model. This design targets the immunomodulatory, and anti-inflammatory effects through nanocomposite hydrogel technology. It reduces the drawbacks of low mercury utilisation and susceptibility to accumulation of toxicity. It aims to provide an experimental basis for the development of mercuric sulphide and the treatment of inflammatory and immune-related diseases.
HighlightsMercury sulphide nanoparticle hydrogel has an optimal mercury sulphide nanoparticle content of 2%, is structurally homogeneous and stable, and does not exhibit significant liver or kidney toxicity.Mercuric sulphide nanoparticle hydrogel exerts anti-inflammatory effects in cells and rats, and regulates the expression of macrophage surface molecules and factors related to the NF-κB pathway.Mercuric sulphide nanoparticle hydrogel improves the condition of ankle synovial joints in a rat model of rheumatoid arthritis.
研究领域:
纳米技术
·
药学
·
免疫学
·
炎症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Zhi-guo Wu,Nan Jin,Yu-feng Deng,Xin-fang Shen,Cui-yun Liu,Bao-yue Ding,Long-hua Guo,Yun-xiao Liu,Zhen-rong Huang,Lei Li,Shui-lin Sun,Bao-gang Xie
The contents of selenomethionine (SeMet) and selenomethylcysteine (SeMC) in Selenium-Enriched black garlic extract (Se-BGE), a popular functional food in Asian countries, were 2.9 ± 0.6 μg/g and 12.2 ± 2.3 μg/g by PITC pre-column derivatization UPLC-MS method. Improved histological injury, significant extension of the median survival time, and attenuated serum levels of alanine aminotransferase, total bilirubin and SOD activity were observed in the acute liver failure (ALF) rats treated with Se-BGE (1.0 g/mL). 1 HNMR-based metabonomics revealed that serum levels of lactate, pyruvate, betaine, choline, taurine, and glycine were restored, and 16S rDNA sequencing analysis showed that the composition and number of the intestinal flora were regressed to healthy levels in ALF rats treated by Se-BGE. Serum choline and betaine showed significant correlations with g_Lactobacillus and g_Escherichia. Our findings demonstrated that Se-BGE protects against LPS/D-GalN-induced ALF in rats, possibly due to antioxidation, metabolism, and intestinal flora regulations of Se-BGE.
研究领域:
药理学
·
肝病学
·
营养保健品
·
代谢组学
·
微生物组
✓ 已验证
产品关联
DOI
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 7
·1534
·
IF 4.2
Zhizhi Chen,Lei Wang,Dongxia He,Qi Liu,Qinqin Han,Jinyang Zhang,A-Mei Zhang,Yuzhu Song
Antibiotic resistance has emerged as a grave threat to global public health, leading to an increasing number of treatment failures. Antimicrobial peptides (AMPs) are widely regarded as potential substitutes for traditional antibiotics since they are less likely to induce resistance when used. A novel AMP named Brevinin-1BW (FLPLLAGLAASFLPTIFCKISRKC) was obtained by the Research Center of Molecular Medicine of Yunnan Province from the skin of thePelophylax nigromaculatus. Brevinia-1BW had effective inhibitory effects on Gram-positive bacteria, with a minimum inhibitory concentration (MIC) of 3.125 μg/mL againstEnterococcus faecalis(ATCC 29212) and 6.25 μg/mL against bothStaphylococcus aureus(ATCC 25923) and multidrug-resistantStaphylococcus aureus(ATCC 29213) but had weaker inhibitory effects on Gram-negative bacteria, with a MIC of ≥100 μg/mL. Studies using scanning electron microscopy (SEM) and flow cytometry have revealed that it exerts its antibacterial activity by disrupting bacterial membranes. Additionally, it possesses strong biofilm inhibitory and eradication activities as well as significant lipopolysaccharide (LPS)-binding activity. Furthermore, Brevinin-1BW has shown a significant anti-inflammatory effect in LPS-treated RAW264.7 cells. In conclusion, Brevinin-1BW is anticipated to be a promising clinical agent with potent anti-Gram-positive bacterial and anti-inflammatory properties.
研究领域:
微生物学
·
药理学
·
传染病学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2025
·
IF 9.6
Shuangfeng Ge,Xing-Huo Wang,Juntao Fan,Haofei Liu,Youtao Xin,Xiaohui Li,Yunjian Yu,Ying-Wei Yang,Hui Gao
Sepsis is an underappreciated yet severe threat to human life, marked by organ dysfunction and high mortality resulting from disordered inflammatory responses to blood infection. Unfortunately, no specific drugs are available for effective sepsis treatment. As a pivotal biomarker for sepsis, lactate levels are closely related to vascular permeability and sepsis-associated mortality. Herein, a dual-pipeline lactate removal strategy is reported from circulating blood to ameliorate vascular permeability and lipopolysaccharide (LPS)-induced sepsis. This is achieved by formulating lactate oxidase (LOX)-encapsulated hollow manganese dioxide (HMnO 2 ) nanohybrids (LOX@HMnO 2 -P[5]A) bearing pillar[5]arene (P[5]A) macrocycle with excellent host-guest properties. The highly biocompatible nanohybrids enable direct lactate consumption through LOX catalytic degradation and block lactate production by P[5]A-mediated LPS trapping, allowing for dual-pipeline lactate removal to maximize the reversal of lactate-mediated vascular hyperpermeability. Besides, HMnO 2 cores decompose hydrogen peroxide produced from lactate oxidation into oxygen, further contributing to lactate consumption and mitigating the hypoxic inflammatory environment. In vivo investigations demonstrate that intravenous administration of LOX@HMnO 2 -P[5]A nanohybrids with extended blood circulation can effectively ameliorate endothelial barrier dysfunction, inflammatory responses, and multiple organ injury, ultimately improving survival outcomes in LPS-induced sepsis. Taken together, this dual-pipeline lactate removal strategy offers a promising approach for efficient sepsis treatment.
研究领域:
医学
·
药理学
·
纳米技术
·
免疫学
·
重症监护
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FITOTERAPIA
·
2018
·
IF 2.642
Hong-Bo Xu,Tong-Hua Yang,Pei Xie,Zhi-Shu Tang,Xiao Song,Huai-Li Xu,Yan-Hong Li,Dong-Bo Zhang,Yan-Ru Liu,Yan-Ni Liang,Yu Zhang,Shi-Jun Liu,Si-Min Wei,Chen Sun,Hong-Bo Liu,Chong Deng,Wei Wang
Gracilistones A ( 1 ) and B ( 2 ), two new eudesmane-type sesquiterpenoids with an unusual tetrahydrofuran-fused 6/6/5 tricyclic ring system, were obtained from Acanthopanax gracilistylus under the guidance of LC-MS investigation. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and quantum calculation methods. Compounds 1 and 2 showed potent inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages, compared with the positive control L-NMMA. In addition, compounds 1 and 2 were also evaluated for their antioxidant (DPPH • and ABTS •+ ) and xanthine oxidase (XO) inhibitory activities, and they exhibited weak inhibitory effects at 100 μM.
研究领域:
药用植物学
·
药物化学
·
炎症研究
·
天然产物化学
✓ 已验证
DOI
PubMed
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Qingfeng Guo,Shenyu Shen,Xinyang Wang,Lei Shi,Yuwei Ren,Dandan Li,Zhenhua Yin,Juanjuan Zhang,Baocheng Yang,Xuewei Wang,Gang Ding,Lin Chen
The chemical engineering of natural extracts has emerged as an effective strategy for the production of diverse libraries of chemicals, making it integral to drug discovery. A chemical engineering strategy based on the epoxidation and ring-opening reactions was used to prepare diversity-enhanced extracts of Chaetomium madrasense 375. Eleven unnatural cytochalasan derivatives ( 1–11 ) with unique functional groups, such as amine and isoxazole, were isolated and characterized from these chemically engineered extracts of C. madrasense 375. The identification of these new structures was accomplished through comprehensive spectroscopic analysis, supplemented by synthetic considerations. Notably, compounds 5 and 13 – 16 displayed potent phytotoxic effects on Arabidopsis thaliana , while compounds 1 , 2 , 5 , 10 , and 12 demonstrated inhibitory activities on LPS-induced NO production in RAW264.7 cells. Among them, compound 1 was found to be able to inhibit the upregulated expression of the inducible nitric oxide synthase (iNOS) protein induced by LPS, while also decreasing the production of pro-inflammatory cytokines (IL-6) and influencing the phosphorylation of p38, ERK1/2, and JNK at 100 μM. Our findings demonstrate that the chemical engineering of natural product extracts can be an efficient technique for the generation of novel bioactive molecules.
研究领域:
药理学
·
化学工程
·
天然产物化学
·
免疫学
·
植物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOMEDICINE
·
2024
·
IF 6.7
Jia-Yi Dou,Mei-Jie Zhou,Mei-Yan Xuan,Jia Guo,Sai-Hu Liu,Li-Hua Lian,Zhen-Yu Cui,Ji-Xing Nan,Yan-Ling Wu
Background Astilbin (ATB), a natural dihydroflavonol compound, exists in many plants, processed and functional foods. ATB has multiple pharmacological effects, such as antioxidant, lipid-lowering, and hepatoprotective. However, its anti-hepatic fibrosis and mechanisms remain unclearly elucidated. Purpose This study explored the effect of ATB against the hepatic fibrosis and its regulation of hepatic microenvironment by regulating hepatic stellate cells-macrophage crosstalk. Method Thioacetamide (TAA) was intraperitoneal injected to establish hepatic fibrosis mice, and treated with ATB or curcumin by gavage, respectively. Hepatic stellate cells (HSCs) were stimulated with TGF-β or conditioned medium (CM) from LPS-induced THP-1, then cultured with ATB, PXR agonist or antagonist. Results In TAA-induced mice, ATB improved histopathological changes, serum transaminases increase; alleviated extracellular matrix (ECM) deposition, epithelial-mesenchymal transformation (EMT), inflammatory infiltration, PTEN induced kinase 1 (PINK1)/Parkin-mediated mitophagy and activated pregnane X receptor (PXR) expression. In vitro , ATB significantly reduced ECM, inflammatory cytokines release, mitophagy, EMT, and activated PXR expression. ATB could increase PXR and decrease PINK1/Parkin, functioning as a PXR agonist. PXR deficiency in LX-2 could degrade the regulation of ATB on ECM, inflammation, EMT, and mitophagy. CM from LPS-induced THP-1 activated LX-2 and resulted in PXR decreasing, while ATB could regulate the crosstalk between HSCs and macrophages. Deficiency of PXR, whether in LX-2 or in macrophages, all weakened the inhibitory effect of ATB on α-SMA, EMT, inflammatory cytokines, and PINK1/Parkin signaling. Conclusion ATB ameliorated hepatic fibrosis by inhibiting HSCs activation, inflammation and EMT through PXR-mediated PINK1/Parkin signaling. Especially, ATB targeted the hepatic microenvironment between hepatic stellate cells and macrophages, which might be a promising strategy for the treatment of hepatic fibrosis.
研究领域:
药理学
·
肝病学
·
细胞生物学
·
免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Changfeng Zhong,Changmei Wang,Wei Li,Wenyuan Li,Xuemei Chen,Jieqing Guo,Yifan Feng,Xia Wu
Parkinson's disease (PD) is the fastest growing neurodegenerative disease in the world at present. Neuroinflammation plays an important role in Parkinson's disease. In our study, we initially screened magnolol/honokiol derivatives synthesized by our group for their potential anti-neuroinflammatory properties. This was done using LPS-activated BV-2 microglial cell and MPP + -induced PC-12 cell models. Most of derivatives had increased anti-inflammatory activities and decreased toxicities compared to raw materials. Then, compounds were scored with inflammatory factors IL-1β, TNF-α and IL-6 by molecular docking in silico . Our studies revealed the strongest binding compound HM568 which binds with honokiol and metformin. Furthermore, HM568 showed no acute toxicity in mice through acute toxicity. And it is stable under high temperature, high humidity and strong light irradiation. Combining cell experiments and computer results, HM568 was considered for further in vivo pharmacological validations. Intraperitoneal injection administration of MPTP into C57BL/6 mice was utilized as Parkinson's animal model. Results showed that administration of HM568 for 14 days in MPTP-PD mice led to a significant alleviation in weight loss and movement disorders. Further HM568 could significantly down-regulate the expression levels of inflammatory factors IL-1β, IL-6 and TNF-α in brain tissue of the mouse model, reduce the level of caspase-3 and the ratio of Bcl-2/Bax, and up-regulate the level of transforming factor TGF-β, thus producing anti-apoptosis and anti-neuroinflammatory effects on neuronal cells. In terms of pathological features, HM568 could reduce the infiltration of neuronal cells and alleviate the development of lesions, promote the transformation of microglia from M1 negative phenotype to M2 type, and reverse the reduction of TH-positive immune cells in mouse neurons induced by MPTP. The administration of HM568 could reduce the abnormal accumulation of α-syn, and thus produce neuroprotective effect on MPTP-PD mice. Cell experiments, molecular docking and animal experiments thus depict HM568 as a promising agent to delay neuronal degeneration in PD, and its mechanism is related to anti-neuroinflammation.
研究领域:
神经科学
·
药理学
·
神经退行性疾病
·
炎症
·
药物发现
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 19
·10406
·
IF 4.9
Yan Zhang,Yaping Yang,Huicong Liang,Yuerun Liang,Guixin Xiong,Fang Lu,Kan Yang,Qi Zou,Xiaomin Zhang,Guanhua Du,Ximing Xu,Jiejie Hao
Asthma is a chronic airway inflammation that is considered a serious public health concern worldwide. Nobiletin (5,6,7,8,3′,4′-hexamethyl flavonoid), an important compound isolated from several traditional Chinese medicines, especially Citri Reticulatae Pericarpium, is widely used for a number of indications, including cancer, allergic diseases, and chronic inflammation. However, the mechanism by which nobiletin exerts its anti-asthmatic effect remains unclear. In this research, we comprehensively demonstrated the anti-asthmatic effects of nobiletin in an animal model of asthma. It was found that nobiletin significantly reduced the levels of inflammatory cells and cytokines in mice and alleviated airway hyperresponsiveness. To explore the target of nobiletin, we identified PDE4B as the target of nobiletin through pharmacophore modeling, molecular docking, molecular dynamics simulation, SPR, and enzyme activity assays. Subsequently, it was found that nobiletin could activate the cAMP-PKA-CREB signaling pathway downstream of PDE4B in mouse lung tissues. Additionally, we studied the anti-inflammatory and anti-airway remodeling effects of nobiletin in LPS-induced RAW264.7 cells and TGF-β1-induced ASM cells, confirming the activation of the cAMP-PKA-CREB signaling pathway by nobiletin. Further validation in PDE4B-deficient RAW264.7 cells confirmed that the increase in cAMP levels induced by nobiletin depended on the inhibition of PDE4B. In conclusion, nobiletin exerts anti-asthmatic activity by targeting PDE4B and activating the cAMP-PKA-CREB signaling pathway.
研究领域:
药理学
·
免疫学
·
分子生物学
·
呼吸医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
International Journal of Biological Sciences
·
2024
·
IF 8.2
Jianzhi Wu,Liping Gong,Yijie Li,Tiegang Liu,Rong Sun,Kexin Jia,Runping Liu,Fei Dong,Xiaohong Gu,Xiaojiaoyang Li
Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic matrix deposition and irreversible aberrant tissue remodeling. Their mechanisms of action are associated with the activation of macrophages and a disturbed immune environment. We aim to determine how these activated macrophages influenced the pathogenesis of pulmonary fibrosis. We found the fibrotic areas of IPF patients contained more serum and glucocorticoid-induced kinase 1 (SGK1)-positive and M2-type macrophages. Similarly, bleomycin (BLM)+LPS significantly triggered high expression of SGK1 in the IPF mice, accompanied by destroyed lung structure and function, increased fibrosis markers and disturbed immune microenvironment. Mechanistically, SGK1 markedly promoted the reprogramming of M2-type macrophages in fibrotic lungs by triggering glycogen synthase kinase 3beta (GSK3β)-tat-interacting protein 60 (TIP60)- histone-3 lysine-27 acetylation (H3K27ac) signalings, which further released chemokine (C-C motif) ligand 9 (CCL9) to attract Th17 cells and delivered TGF-β to fibroblasts for synergistically destroying immune microenvironment, which was largely reversed by macrophage depletion in mice. We took macrophages as the entry point to deeply analyze IPF pathogenesis and further provided insights for the development of novel drugs represented by SGK1.
研究领域:
肺科学
·
免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2024
·
IF 14.3
Haochen Yao,Sheng Ma,Juanjuan Huang,Xinghui Si,Ming Yang,Wantong Song,Guoyue Lv,Guoqing Wang
Reversing the hepatic inflammatory and immunosuppressive microenvironment caused by gut microbiota-derived lipopolysaccharides (LPS), accumulating to the liver through the gut-liver axis, is crucial for suppressing hepatocellular carcinoma (HCC) and metastasis. However, synergistically manipulating LPS-induced inflammation and gut microbiota remains a daunting task. Herein, a Trojan-horse strategy is proposed using an oral dextran-carbenoxolone (DEX-CBX) conjugate, which combines prebiotic and glycyrrhetinic acid (GA) homologs, to targeted delivery GA to HCC through the gut-liver axis for simultaneous modulation of hepatic inflammation and gut microbiota. In the orthotopic HCC model, a 95–45% reduction in the relative abundances of LPS-associated microbiota is observed, especially Helicobacter , caused by DEX-CBX treatment over phosphate-buffered saline (PBS) treatment. Notably, a dramatic increase (37-fold over PBS) in the abundance of Akkermansia , which is known to strengthen systemic immune response, is detected. Furthermore, DEX-CBX significantly increased natural killer T cells (5.7-fold) and CD8 + T cells (3.9-fold) as well as decreased M2 macrophages (59% reduction) over PBS treatment, resulting in a tumor suppression rate of 85.4%. DEX-CBX is anticipated to offer a novel strategy to precisely modulate hepatic inflammation and the gut microbiota to address both the symptoms and root causes of LPS-induced immunosuppression in HCC.
研究领域:
癌症生物学
·
免疫学
·
微生物学
·
药理学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2024
·Vol. 22
·期 1
·1-18
·
IF 10.6
Yin Mingjing,Lei Doudou,Liu Yalan,Qin Tao,Gao Huyang,Lv Wenquan,Liu Qianyue,Qin Lian,Jin Weiqian,Chen Yin,Liang Hao,Wang Bailei,Gao Ming,Zhang Jianfeng,Lu Junyu
Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO 2 ) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.
研究领域:
纳米技术
·
药学
·
生物医学工程
·
炎症
·
呼吸医学
✓ 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）