ORAL DISEASES
·
2023
·
IF 3.8
Shiqun Sun,Tongtong Yan,Nan Yang,Jian Wu,Zhihui Liu
Objectives The aim of this study was to explore the potential role of zinc-finger homeodomain transcription factor (TCF8) in osteoclastogenesis and inflammation during periodontitis. Materials and Methods Rats with periodontitis were induced via Porphyromonas gingivalis -lipopolysaccharide (Pg-LPS) injection. The recombinant lentivirus delivering short hairpin RNA (shRNA) against TCF8 was used to downregulate TCF8 in vivo. Alveolar bone loss in rats was determined by micro-computed tomography (Micro-CT). Typical pathological changes, periodontal tissue inflammation, and osteoclastogenesis were evaluated via histological analyses. The RAW264.7-derived osteoclasts were induced by RANKL stimulation. TCF8 downregulation in vitro was achieved by lentivirus infection. The osteoclast differentiation and inflammatory signaling in RANKL-induced cells were measured via immunofluorescence methods and molecular biology approaches. Results Porphyromonas gingivalis -lipopolysaccharide induced rats exhibited overexpressed TCF8 in their periodontal tissues, while TCF8 knockdown attenuated the bone loss, tissue inflammation, and osteoclastogenesis in LPS-induced rats. Besides, TCF8 silencing inhibited RANKL-induced osteoclast differentiation in RAW264.7 cells, as evidenced by the reduced numbers of TRAP-positive osteoclasts, less formation of F-actin rings, and downregulated expressions of osteoclast-specific markers. It also exerted an inhibitory effect on the NF-κB signaling in RANKL-induced cells via blocking NF-κB p65 phosphorylation and nuclear translocation. Conclusions TCF8 silencing inhibited alveolar bone loss, osteoclast differentiation, and inflammation in periodontitis.
研究领域:
牙科学
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分子生物学
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炎症
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转录因子
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骨骼生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF AUTOIMMUNITY
·
2024
·
IF 7.9
Qishun Geng,Jiahe Xu,Xiaoxue Cao,Zhaoran Wang,Yi Jiao,Wenya Diao,Xing Wang,Zihan Wang,Mengxiao Zhang,Lu Zhao,Lei Yang,Tingting Deng,Bifa Fan,Yuan Xu,Lansi Jia,Cheng Xiao
Introduction Rheumatoid arthritis (RA) is a systemic inflammatory autoimmune disease characterized by joint inflammation and bone damage, that not only restricts patient activity but also tends to be accompanied by a series of complications, seriously affecting patient prognosis. Peroxisome proliferator-activated receptor gamma (PPARG), a receptor that controls cellular metabolism, regulates the function of immune cells and stromal cells. Previous studies have shown that PPARG is closely related to the regulation of inflammation. However, the role of PPARG in regulating the pathological processes of RA is poorly understood. Materials and methods PPARG expression was examined in the synovial tissues and peripheral blood mononuclear cells (PBMCs) from RA patients and the paw of collagen-induced arthritis (CIA) model rats. Molecular biology experiments were designed to examine the effect of PPARG and cannabidiol (CBD) on RAW264.7 cells and CIA rats. Results The results reveal that PPARG accelerates reactive oxygen species (ROS) clearance by promoting autophagy, thereby inhibiting ROS-mediated macrophage polarization and NLRP3 inflammasome activation. Notably, CBD may be a promising candidate for understanding the mechanism by which PPARG regulates autophagy-mediated inflammation. Conclusions Taken together, these findings indicate that PPARG may have a role for distinguishing between RA patients and healthy control, and for distinguishing RA activity; moreover, PPARG could be a novel pharmacological target for alleviating RA through the mediation of autophagy. CBD can act as a PPARG agonist that alleviates the inflammatory progression of RA.
研究领域:
免疫学
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风湿病学
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药理学
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细胞生物学
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DOI
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2021
·
IF 5.279
Yanfang Li,Ming Li,Jiaping Liu,Wenhao Zheng,Yaqiong Zhang,Tongcheng Xu,Boyan Gao,Liangli Yu
The profiles of soluble and insoluble phenolic compounds in 11 commercial red sorghums (B11, B12, B13, B14, J124, J127, J138, J140, J142, J152, and J158) were investigated using ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) analysis. A total of 48 phenolic compounds including 35 phenolic acids and their derivatives, 12 flavonoids, and 1 proanthocyanidin were identified, and 8 phenolic compounds were reported for the first time in sorghums. Four major 3-deoxyanthocyanidins were also quantified, with their soluble forms accounting for 99.75–99.87% of the total contents. Pearson’s correlation analyses indicated that 3-deoxyanthocyanidins significantly contributed to the antioxidant capacities of the red sorghums and that 5-methoxy-luteolinidin showed the strongest correlation. Besides, the soluble phenolic fraction of B13 dose-dependently inhibited the proliferation of Caco-2 cells and the secretion of IL-1β and NO in RAW264.7 macrophages, which might be attributed to its relatively high total phenolic (TPC), flavonoid (TFC), and proanthocyanidin content (TPAC) values and radical scavenging capacities.
研究领域:
食品科学
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营养学
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药理学
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分析化学
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产品关联
DOI
PubMed
高影响因子
Brain Sciences
·
2022
·Vol. 12
·期 5
·571
·
IF 3.333
Chao Song,Chao Gao,Zhenxin Wang
(1) Background: Chemotherapy-induced cognitive impairment (CICI) is often observed in cancer patients and impairs their life quality. Grape-seed-orientated procyanidin has been shown to have anti-inflammatory and neuroprotective effects, yet its effects in preventing CICI have not been investigated. (2) Method: Adult male mice received 2.3 mg/kg cisplatin or saline injections for three cycles consisting of five daily injections followed by 5 days of rest. Procyanidin or saline was administered 1 h prior to cisplatin treatment. Cognitive testing, gelatin zymography, and blood–brain-barrier (BBB) penetration tests were performed after treatment cessation. RAW264.7 cells were treated by stimulated supernatant of SHSY5Y cells. In addition, high-mobility group protein B1 (HMGB1) expression and MMP-9 activity were tested. (3) Results: Repeated cisplatin treatment increased BBB penetration, MMP-9 activity, impaired performance in contextual fear conditioning, and novel object recognition tasks. The knockout of MMP-9 rescues cognitive impairment and cisplatin-induced upregulation of HMGB1 in SHSY5Y cells. HMGB1/TLR4/IP3K/AKT signaling contributes to the increased MMP-9 activity in RAW264.7 cells. Procyanidin treatment attenuates MMP-9 activity, BBB damage, and CICI. (4) Conclusions: The results indicated that MMP-9 activation and BBB disruption is involved in CICI. Procyanidin may effectively alleviate the harmful effects of cisplatin.Keywords:cisplatin;chemotherapy;MMP-9;RAW264.7 cells;procyanidin;blood–brain barrier (BBB);chemotherapy-induced cognitive impairment (CICI)
研究领域:
肿瘤学
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神经科学
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药理学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN POLYMER JOURNAL
·
2022
·
IF 5.546
Zhi Li,Lifen Zhang,Changning Xue,Yuman Zhang,Yao Yu,Xinhong Guo,Zhenzhong Zhang
Hydroxypropyl-β-Cyclodextrin (HP-β-CD) was used to form the HP-β-CD/Oridonin inclusion complex. Then, the novel Multi-loaded nanovesicles systems (NVs) were established to encapsulate both hydrophilic (Trehalose) and hydrophobic drugs (Oridonin inclusion complex) with peptides. NVs had an average size of 224.4 ± 10.84 nm and a zeta potential of 17.83 ± 1.05 mV. Furthermore, these NVs significantly decreased lipid over-accumulation, and reverse the formation of foam cells in RAW264.7 cells. Oridonin and Trehalose in NVs provided significant synergistic effects to inhibit lipid over-accumulation (CI < 1). In addition, NVs could modulate the release of IL-1β, IL-6 and TNF-α, promote the formation of autophagosomes. Taken together, the Multi-loaded NVs may be used as an effective drug delivery system, providing new insights into decrease the formation of foam cells and regulate the inflammation.
研究领域:
药学
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生物技术
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细胞生物学
·
药物递送系统
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产品关联
DOI
高影响因子
Natural Products and Bioprospecting
·
2024
·Vol. 14
·期 1
·1-12
·
IF 4.8
Shi Yuru,Zhang Xiaoqian,Pei Shengji,Wang Yuhua
Adenosma buchneroides Bonati, also known as fleagrass, is an important medicinal plant used by the Akha (Hani) people of China for treating inflammation-related skin swelling, acne, and diarrhoea, among other conditions. In this study, we aimed to evaluate the anti-inflammatory activities and explore the molecular mechanisms of fleagrass on treating skin swelling and acne. The results demonstrated that fleagrass inhibited the enzymatic activities of 5-LOX and COX-2 in vitro, and decreased the release of NO, IL-6, TNF-α, and IL-10 in the LPS-induced RAW264.7 macrophages. The levels of proteins associated with the nuclear factor-kappa B (NF-κB) pathway were examined by western blotting and immunofluorescence, demonstrating that fleagrass downregulated the expression of TLR4, MyD88, NF-κB/p65, and iNOS and blocked the nuclear translocation of NF-κB/p65. Furthermore, fleagrass exhibited acute anti-inflammatory activity in paw oedema models. The results confirm that fleagrass exhibits remarkable anti-inflammatory activity and can be used in alleviating inflammation, suggesting that fleagrass has the potential to be a novel anti-inflammatory agent. Graphical Abstract
研究领域:
民族药理学
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药理学
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炎症
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药用植物
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产品关联
DOI
PubMed
高影响因子
Journal of Biomedical Nanotechnology
·
2015
·Vol. 11
·期 3
·403-415
·
IF 5.338
Wang Jiao,Zhu Rongrong,Sun Dongmei,Sun Xiaoyu,Geng Zhengsong,Liu Hui,Wang Shi-Long
Curcumin (Cur) is a naturally derived, novel anti-inflammatory agent, but its poor solubility limits its clinical use. The aim of the present study was to encapsulate Cur into solid lipid nanoparticles (SLNs) to improve its anti-inflammatory activity. The Cur-loaded SLNs (Cur-SLNs)
were prepared using emulsification and low-temperature solidification methods. In contrast to free Cur, the particles were well dispersed in aqueous medium, showing a narrow size distribution with a range of 55 ± 1.2 nm, a zeta potential value of –26.2 ± 1.3 mV, and a high
drug loading efficiency of 37% ± 2.5%. The sustained release of Cur was observed for up to 6 days. The particles displayed enhanced stability in phosphate-buffered saline by protecting the encapsulated Cur against hydrolysis and biotransformation, as well as increasing biocompatibility.
Cur-SLNs were more effective than free Cur at reducing the expression levels of several proinflammatory mediators, including inflammatory cytokines (IL-6, TNF-α, and IL-1β) and nitric oxide (NO), under in vitro conditions. By Western blotting, we found that
Cur-SLNs were more active than free Cur in inhibiting the LPS-induced activation of the inflammatory transcription factor NF-κB through the suppression of IκB kinase activation. Compared to free Cur, Cur-SLNs had an increased intracellular uptake over time (observed
after 24 h) in RAW264.7 cells. Moreover, the Cur-SLNs (≥20 μM) significantly improved RAW264.7 cell viability by inhibiting apoptosis. Thus, these results demonstrated that SLNs could be used as potential anti-inflammatory drug carriers for the treatment of various chronic diseases.
研究领域:
药理学
·
纳米技术
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免疫学
·
药物开发
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DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Xin Qiao,Xiaojuan Cao,Shuang Xu,Cunlin Wang,Rui Guo,Xiaojuan Yao,Qiong Zhang
Background: Dysregulated and excessive inflammatory reactions can lead to tissue damage, which is the underlying cause of most human diseases. Menisoxoisoaporphine A (MA), a novel oxoisoaporphine alkaloid, was obtained from Menispermi Rhizoma, a traditional Chinese medicinal herb used in the treatment of inflammatory conditions in clinical practice. This suggests that MA has very promising potential for the development of anti-inflammatory therapeutics. Hence, this study aims to investigate the anti-inflammatory effects and underlying mechanisms of MA.Method: The anti-inflammatory effects of MA were evaluated in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. Its underlying mechanisms were explored through RNA sequencing and Western blotting. The binding modes and interactions sites between MA and phosphodiesterase 4B (PDE4B) were predicted using molecular docking and validated by molecular dynamics simulation.Results: MA treatment significantly reduced LPS-induced morphological changes, inflammatory cytokine relesae, and proinflammatory genes expression in RAW264.7 cells compared to the LPS-induced controls. Transcriptome sequencing analysis suggested that PDE4B might be a key target for MA to exert its therapeutic effect. Mechanismly, MA directly acted on Tyr405 site of PDE4B, thus leading to a sustained elevation of the cyclic adenosine monophosphate (cAMP) levels, which subsequently inactivated NF-κB signaling pathway by phosphorylating protein kinase A (PKA). MA inhibited the NF-κB-mediated inflammatory response depending on PDE4B.Conclusion: MA, a natural and novel compound, exerted anti-inflammatory effects in LPS-induced RAW264.7 macrophage cells. It demonstrated a strong binding ability to the Tyr405 sites of PDE4B, thereby inhibiting NF-κB signaling pathway by regulating the cAMP-PKA axis. Elucidating the interaction between MA and PDE4B holds significant potential for the advancement of innovative therapeutic strategies aimed at inflammatory diseases. By strategically modulating this interaction, it may be feasible to achieve more precise regulation of inflammatory responses, thereby offering promising therapeutic benefits for conditions such as rheumatoid arthritis, asthma, and inflammatory bowel disease.
研究领域:
药理学
·
免疫学
·
分子生物学
·
炎症性疾病
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产品关联
DOI
PubMed
高影响因子
RSC Medicinal Chemistry
·
2024
·
IF 4.1
Die Zhang,Wenping Wang,Huiping Ou,Jinhua Ning,Yingxun Zhou,Jin Ke,Anguo Hou,Lingyun Chen,Peng Li,Yunshu Ma,Wenbin Jin
To develop new anti-inflammatory agents with improved pharmaceutical profiles, a series of novel chalcone analogues were designed and synthesized. In vitro anti-inflammatory activity of these compounds has been evaluated by screening inhibitory effects of the NO production in RAW264.7 cell lines. The most promising compounds 3h and 3l were selected to further investigated by assessment of their dose-dependent inhibitory activity against cytokines such as TNF-α, IL-1β, IL-6, and PGE2 release. The further study also indicated that 3h and 3l could significantly suppress expressions of iNOS and COX-2 through NF-κB/JNK signaling pathway. Furthermore, compounds 3h and 3l could also remarkably inhibit the mRNAs expressions of inflammation-related genes. Docking simulation was conducted to position compounds 3h and 3l into the iNOS binding site to predict the probable binding mode. In conclusion, a series of chalcone analogues with reasonable drug-likeness obtained by in silico rapid prediction could be used as promising lead candidates.
研究领域:
药理学
·
炎症研究
·
药物发现
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DOI
PubMed
高影响因子
Journal of Functional Foods
·
2016
·
IF 3.973
Tong Di,Guijie Chen,Yi Sun,Shiyi Ou,Xiaoxiong Zeng,Hong Ye
In this work, crude polysaccharides from Gracilaria rubra (GRPS) and its three purified fractions, GRPS-1-1, GRPS-2-1 and GRPS-3-2, were obtained through hot water extraction and chromatographic purification with DEAE-52 cellulose column and Sephadex G-50 column. The three purified fractions, being homogeneous heteropolysaccharides with average molecular weights of 1310, 691, 923 kD and sulfuric radical contents of 5.96, 8.46 and 12.03%, respectively, were all composed of galactose and fucose. GRPS-2-1 and GRPS-3-2 had little toxicity to L-02 cells. Crude GRPS and its purified fractions exhibited strong scavenging activities against ABTS and superoxide radicals and lipid peroxidation inhibition. At a cellular level, GRPS-3-2 showed the strongest protective effect on H 2 O 2 -induced oxidative injury in PC12 cells. Moreover, GRPS-3-2 exhibited a much stronger immunostimulating activity on RAW264.7 cells than GRPS-1-1 and GRPS-2-1. The results suggested that GRPS, especially GRPS-3-2, could be developed as a promising functional food supplement.
研究领域:
海洋生物学
·
药理学
·
生物化学
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产品关联
DOI
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Jing Ye,Linjing Zheng,Weipeng Pan,Yayan Huang,Na Zhang,Dongda Yang,Yucheng Yang,Bingde Zheng,Xueqin Zhang,Meitian Xiao
Polysaccharides from sea cucumbers are known for their biological activities, but little is known about those from sea cucumber viscera. The present study isolated a sulfated polysaccharide (SCVP-2) from the viscera of Apostichopus japonicas , which had a molecular weight of 209.1 kDa. SCVP-2 comprised 66.3 % total sugars, 2.1 % uronic acid, 4.5 % proteins, and 25.5 % sulfate groups, containing glucosamine, galactosamine, glucose, galactose, and fucose. FT-IR and NMR analyses identified SCVP-2 as a fucoidan sulfate with sulfation patterns of the fucose branches as Fuc2S, Fuc4S, and Fuc0S. SEM and AFM analyses showed irregular clusters and linear conformations. SCVP-2 demonstrated strong anti-inflammatory properties both in vitro and in vivo . In lipopolysaccharide (LPS)-induced inflammation in macrophage RAW264.7 cells, SCVP-2 significantly reduced nitric oxide (NO) and cytokine secretion (IL-1β, IL-6, TNF-α). Additionally, it downregulated the expression of these cytokine genes. Furthermore, the anti-inflammatory mechanism of SCVP-2 was related to the inhibition of the MAPKs and NF-κB pathways. SCVP-2's anti-inflammatory capacity was confirmed in acute inflammation models, including xylene-induced ear swelling and acetic acid-induced peritoneal capillary permeability, and in high-fat diet-induced systemic low-grade chronic inflammation. In conclusion, SCVP-2 exhibits significant anti-inflammatory activity, suggesting its potential for development as a functional food ingredient or therapeutic agent for inflammation-related diseases.
研究领域:
海洋生物学
·
药理学
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免疫学
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产品关联
DOI
PubMed
高影响因子
MOLECULAR IMMUNOLOGY
·
2025
·
IF 3
Aiping Li,Mengjiao Wang,Min Guo,Yuetao Liu,Ke Li,Lichao Zhang,Xuemei Qin,Guangzhen Liu
Astragali Radix (AR), a homologous of medicine and food, has been extensively recorded to possess a nephroprotective impact on individuals suffering from chronic kidney disease (CKD). Astragaloside IV (ASIV) is one of the prominent bioactive constituents derived from AR. This study aimed to investigate how ASIV promotes M2 polarization of macrophages and whether this contributes to the protection of podocytes from injury, using a combination of lipidomics and molecular biology techniques.The effect of ASIV on adriamycin (ADR)-induced renal injury in rats was evaluated in vivo, with a particular emphasis on elucidating the potential involvement of macrophages. The M1 polarization model of RAW264.7 cells induced by ADR was established in vitro . The impact of ASIV on ADR-induced macrophage polarization was comprehensively assessed by measuring the expression levels of M1 and M2 macrophage marker proteins, along with their associated mRNA profiles. Flow cytometry was employed to analyze surface marker expression, while Western blot (WB) was used to quantify protein levels, and real-time quantitative PCR (qPCR) allowed for the measurement of gene expression. Notably, we found that the macrophage supernatant intervened by ASIV was found to have a protective effect against podocyte injury, which was evaluated through cell adhesion and apoptosis assays. Innovatively, we explored the mechanism by which ASIV affects macrophage polarization from the perspective of lipid metabolism, using lipidomics methods. During this process, the role of peroxisome proliferator-activated receptor gamma (PPARγ) in macrophage polarization caught our attention. This receptor is closely associated with lipid metabolites, as confirmed by molecular docking. ASIV has been shown to effectively ameliorate kidney injury, with macrophages playing a pivotal role in renal podocyte repair process. The protein and mRNA expressions of ARG-1, CD206 and IL-10, M2 macrophage markers, was increased by ASIV and M2 macrophages polarization was promoted by ASIV (P < 0.05). In addition, it was observed that the supernatant of macrophages intervened by ASIV exerts a protective effect on podocyte injury, which was confirmed through podocyte adhesion assays and cell apoptosis experiments. This study suggests that ASIV enhances the M2 polarization of macrophages, and the supernatant from these polarized macrophages has a protective effect on podocytes. From the perspective of lipid metabolism, the underlying mechanism of this effect may involve the modulation of sphingolipids, arachidonic acid, glycerophospholipids, and other lipid metabolites, which activate the receptor PPARγ, thereby exerting protective effects on podocytes.
研究领域:
药理学
·
免疫学
·
肾脏病学
·
生物化学
·
分子生物学
·
细胞生物学
·
脂质组学
·
药物化学
✓ 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）