FITOTERAPIA
·
2025
·
IF 2.6
Wenjing Ren,Yue Zhou,Jiahui Zhao,Xiutong Ge,Shiru Jiang,Yang Chen,Gui Xu,Shuo Zhang,Li Li,Ji Shi,Fan Zhang
Songaria Cynomorium Herb (SCH), a traditional Chinese medicinal herb, is recognized for its dual role as both a dietary supplement and a therapeutic agent. It is traditionally reputed to have kidney-tonifying and Yang-strengthening effects, which have made it a common ingredient in nutritious food supplements and health products. This study investigates the underlying mechanisms by which wine-steamed SCH, enhances kidney aphrodisiac qualities, focusing on the tyrosine kinase/signal transduction and transcriptional activation factor (JAK/STAT) signaling pathway. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to qualitatively analyze the chemical constituents of SCH both before and after the wine-steaming process, and the significant differential components were screened out. A kidney-Yang deficiency model was induced by intragastric administration of hydrocortisone. Subsequently, the rats were treated with either raw SCH (RSCH) or wine-steamed SCH (WSCH) medicinal solutions. Urine output, organ indices, target gland axis-related indices, and renal tissue lesions were recorded and statistically compared between the treatment and control groups. RT-qPCR and Western blot analysis were utilized to assess the mRNA and protein expression levels of the JAK/STAT pathway and HIF-1α in the renal tissues of the animals. The results indicated that the chemical composition of the SCH underwent changes before and after the steaming process. The tonifying effects observed were more pronounced with WSCH than with RSCH, suggesting that the mechanism involves the inhibition of the JAK/STAT pathway and the downregulation of HIF-1α expression.
研究领域:
中药学
·
分子生物学
·
药理学
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产品关联
DOI
PubMed
高影响因子
CHEMICAL RESEARCH IN TOXICOLOGY
·
2019
·
IF 3.274
Xiucai Guo,Wei Li,Qingmei Li,Yan Chen,Guode Zhao,Ying Peng,Jiang Zheng
Tofacitinib (TFT) is an oral JAK inhibitor which has been approved for the treatment of moderately and severely active rheumatoid arthritis. TFT was found to show concentration-, time-, and NADPH-dependent inhibition of CYP3A4, and irreversibility of the inactivation was also observed. Incubation (40 min, 37 °C) of recombinant CYP3A4 with TFT at 200 μM resulted in >70% loss of CYP3A4 activity. Estimated kinact and KI were 0.037 min–1 and 93.2 μM, respectively. GSH and superoxide dismutase/catalase revealed minor or little protection against the CYP3A4 inactivation. Furthermore, ketoconazole attenuated TFT-mediated CYP3A4 inactivation. Epoxide and α-keto-aldehyde intermediates of TFT were trapped and characterized in microsomal incubations, respectively. The aldehyde intermediate is believed to be the key for the enzyme inactivation. Multiple P450 enzymes, including CYPs2C19, 3A4, 2D6, and 1A2, participated in the metabolism of TFT to the epoxide, while the formation of the aldehyde was mainly catalyzed by CYP3A4. In conclusion, TFT was proven to be a mechanism-based inactivator of CYP3A4.
研究领域:
药理学
·
药物代谢
·
酶学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CONTROLLED RELEASE
·
2024
·
IF 10.5
Qibin Li,Yameng Wang,Qing Guo,Jie Cao,Yangjun Feng,Xue Ke
Alopecia areata affects over 140 million people worldwide and causes severe psychological distress. The Janus kinase (JAK) inhibitor, tofacitinib, shows significant potential in therapeutic applications for treating alopecia areata; however, the systemic adverse effects of oral administration and low absorption rate at the target site limit its application. Hence, to address this issue, we designed topical formulations of tofacitinib-loaded cationic lipid nanoparticles (TFB-cNLPs) with particle sizes of approximately 200 nm. TFB-cNLPs promoted percutaneous absorption and hair follicle targeting in an ex vivo pig ear model. TFB-cNLP decreased IFN-γ-induced alopecia areata symptoms in an in vitro follicle model by blocking the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. It also reduced the number of CD8 + NKG2D + T cells in a C3H mouse model of alopecia areata in vivo, thereby inhibiting the progression of alopecia areata and reversing hair loss. These findings suggest that TFB-cNLP enhanced hair follicle targeting and has the potential for topical treatment or prevention of alopecia areata.
研究领域:
药剂学
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皮肤科
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纳米技术
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免疫学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL & ENGINEERING CHEMISTRY RESEARCH
·
2024
·
IF 3.8
Yali Zhang,Xiaoxue Wang,Jianjun Zhang
Rheumatoid arthritis (RA), an autoimmune disease, is related to environmental factors, sex hormones, genetics, and other factors, affecting 0.5–1% of the global population. The JAK-STAT pathway plays an important role in the signal transduction of inflammatory cytokines and chemokines in the pathogenesis of RA. Tofacitinib (TF), the first approved JAK inhibitor for treating RA, can reduce inflammatory reactions, improve RA conditions, prevent irreversible joint injury, and improve the quality of life of patients. However, the traditional oral administration of TF causes poor compliance and severe side effects owing to the long-term and high-frequency treatment. Therefore, highly efficient pharmaceutical formulations for TF are necessitated. Here, a novel TF-loaded poly(lactic-co-glycolic acid) (PLGA) sustained release nanoparticle (NanoTF-PLGA) was prepared using a high-gravity nanoprecipitation technique (HGNPT), and its therapeutic effect on RA was verified in vitro and in vivo. The influence of the different operation parameters of HGNPT on the particle size of PLGA, including the rotating speed of the rotating bed, the volume ratio of solvent to antisolvent, and the concentration of the surfactant, was investigated using an orthogonal design. The optimum reaction conditions for preparing PLGA nanoparticles were selected by optimizing the formula, and TF was then added to the reaction mixture to prepare NanoTF-PLGA. The results demonstrated that NanoTF-PLGA had a smaller size (603.8 nm), a more uniform shape, a higher drug loading efficiency, and long-term sustained release properties (over 14 days). Furthermore, in vitro experiments proved that NanoTF-PLGA could enter RAW264.7 cells by cell uptake, demonstrated good biocompatibility, inhibited the migration of RAW264.7 cells, and simultaneously inhibited the expression of IL-6, IL-1β, and TNF-α in a dose-dependent manner. In vivo experiments showed that subcutaneous administration of NanoTF-PLGA significantly alleviated articular cartilage injury and reduced the level of inflammatory cell infiltration into the joint cavity. This study presents a promising technique for preparing sustained drug formulations that can be extended to numerous therapeutic drugs.
研究领域:
药学
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纳米技术
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风湿病学
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药物递送系统
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生物医学工程
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Lei Han,Jimin Huang,Zhiyong Zhang,Guijuan Feng,Yi Zheng,Yufang Zhu,Huang Li
Periodontal bone regeneration is hindered by the inflammatory microenvironment with high reactive oxygen species levels. Current barrier membranes lack sufficient antioxidative and bioactive properties, leading to poor bone regeneration. To overcome this, a novel guided bone regeneration membrane was developed by combining manganese-incorporated bioactive glass (MnBG) with biodegradable poly(lactic- co -glycolic acid (PLGA) and polycaprolactone (PCL). This PLGA/PCL/MnBG (PPMnBG) membrane could protect bone marrow mesenchymal stem cells (BMMSCs) and RAW264.7 cells from oxidative damage, promote cell proliferation, adhesion, and osteogenic differentiation, and inhibited M1 macrophage polarization. It enhanced macrophage oxidative stress resistance and suppressed glycolysis in M1 macrophages via the JAK-STAT1/NLRP3 pathway, reducing inflammation. In vivo studies using SD rat alveolar bone defect confirmed the membrane's efficacy in alleviating oxidative stress, reprogramming macrophage metabolism, and promoting bone regeneration. These findings highlighted the PPMnBG membrane's potential in treating inflammatory alveolar bone defects by mitigating oxidative stress, enhancing osteogenesis, and modulating macrophage metabolism.
研究领域:
牙医学
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生物材料
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组织工程
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免疫调节
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再生医学
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细胞生物学
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炎症研究
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产品关联
DOI
高影响因子
CARBOHYDRATE POLYMERS
·
2020
·
IF 7.182
Wei Xu,Sijia Fang,Yong Wang,Xiaoqing Chi,Xiaodan Ma,Tao Zhang,Songhua Hu
The present study was to investigate the molecular mechanism underlying lymphocyte activation by total polysaccharides from Atractylodis macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted the secretions of cytokines (IFN-γ, IL-1α, IL-21, IFN-α, CCL4, CXCL9 and CXCL10), increased the proportions of CD4 + and CD8 + subpopulations, and enhanced the expressions of c-JUN, NFAT4, STAT1 and STAT3. microRNA sequencing identified 67 differentially expressed miRNAs (DEMs) in RAMPtp-stimulated SMLN lymphocytes, including 55 up-regulated and 12 down-regulated. GO and KEGG enrichment analyses of the predicted DEMs-targeted genes indicated that they were associated with immune system pathways, including PI3K-Akt, MAPKs, Jak-STAT and Calcium signaling pathways, which were confirmed by western blot and pathway inhibition assays. RAMPtp was further observed to favor immunostimulatory effect on both T and B lymphocytes via binding to TCR and membrane Ig individually. These findings might explain the immunomodulatory mechanism of RAMPtp in ameliorating the bovine intramammary infection.
研究领域:
免疫学
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分子生物学
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兽医学
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药理学
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DOI
PubMed
高影响因子
ACS Omega
·
2023
·
IF 4.1
Siwen Feng,Gonghao Xu,Yuchen Fu,Qi Ding,Yuanyuan Shi
Asthma is a chronic respiratory disease. Bergamot essential oil (BEO) is extracted from the bergamot peel, which is widely used as a medicinal and food plant in China. Modern pharmacological studies have confirmed that BEO has anti-inflammatory properties, suggesting potential in treating asthma. First, the main active ingredients of BEO were detected and analyzed by gas chromatography–mass spectrometry (GC-MS). Network pharmacology methods were used to explore the possible core targets and main pathways of BEO in asthma treatment. Then ovalbumin (OVA)-induced in vivo and lipopolysaccharide (LPS)-induced in vitro models were established to investigate the antiasthmatic effects of BEO. BEO showed a good antiasthmatic effect by improving lung inflammation and inhibiting collagen deposition. Then, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR) were used to explore the possible mechanism of BEO in asthma treatment. Furthermore, experimental verification showed that BEO could suppress the release of inflammatory factors in vitro and inhibit the activation of MAPK and JAK-STAT signaling pathways. This study demonstrated the anti-inflammatory effects of BEO against asthma. Moreover, it supplies a theoretical basis for the clinical application of BEO.
研究领域:
药理学
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呼吸医学
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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
Advanced Science
·
2024
·
IF 14.3
Junjie Mao,Zhenqian Sun,Shidong Wang,Jianqiang Bi,Lu Xue,Lu Wang,Hongliang Wang,Guangjun Jiao,Yunzhen Chen
In this study, a novel bionic periosteum (BP)-bioactive glass fiber membrane (BGFM) is designed. The introduction of magnesium ion (Mg 2+ ) and zinc ion (Zn 2+ ) change the phase separation during the electrospinning (ES) jet stretching process. The fiber's pore structure transitions from connected to closed pores, resulting in a decrease in the rapid release of metal ions while also improving degradation via reducing filling quality. Additionally, the introduction of magnesium (Mg) and zinc (Zn) lead to the formation of negative charged tetrahedral units (MgO 4 2− and ZnO 4 2− ) in the glass network. These units effectively trap positive charged metal ions, further inhibiting ion release. In vitro experiments reveal that the deigned bionic periosteum regulates the polarization of macrophages toward M2 type, thereby establishing a conducive immune environment for osteogenic differentiation. Bioinformatics analysis indicate that BP enhanced bone repair via the JAK-STAT signaling pathway. The slow release of metal ions from the bionic periosteum can directly enhance osteogenic differentiation and vascularization, thereby accelerating bone regeneration. Finally, the bionic periosteum exhibits remarkable capabilities in angiogenesis and osteogenesis, demonstrating its potential for bone repair in a rat calvarial defect model.
研究领域:
生物材料
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组织工程
·
骨再生
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免疫学
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
VETERINARNI MEDICINA
·
2023
·
IF 0.7
Weifeng Zhang,Hualong Deng,Yanfen Liu,Shaohong Chen,You Liu,Yuntao Zhao
Peste des petits ruminants virus (PPRV), a member of the family Paramyxoviridae, belongs to the genus Morbillivirus. It causes devastating viral diseases in small ruminants and has been rapidly spreading over various regions in Africa, the Middle East, and Asia. Although vaccination is thought to be an effective management strategy against PPR infections, the heat sensitivity of PPRV vaccines severely restricts their use in regions with hot climates. In this research, we studied the antiviral activities of ribavirin and aimed to understand the potential mechanisms of action of ribavirin in the African green monkey kidney cells (Vero cells). In brief, the adsorption, intrusion, replication, and release of PPRV, as well as the mRNA expression level of RNA-dependent RNA polymerase ( RdRp ), were significantly inhibited in the ribavirin-treated Vero cells compared to those in the PPRV-infected cells that were not treated with ribavirin. Additionally, ribavirin has potential as an antiviral drug against PPRV, and its antiviral activity is mediated by the Janus kinase signal transducer and activator of transcription (JAK/STAT) and PI3K/AKT pathways.
研究领域:
兽医学
·
病毒学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ADVANCED FUNCTIONAL MATERIALS
·
2022
·Vol. 32
·期 16
·2109173
·
IF 19.924
Jie Deng,Deqing Lin,Xiangyu Ding,Yuan Wang,YuHan Hu,Hui Shi,Lin Chen,Bingyang Chu,Lei Lei,Chunmei Wen,Jiaqing Wang,Zhiyong Qian,Xingyi Li
Peptide-drug conjugates (PDCs) are an important class of therapeutic agents that combine one or more active molecules with a short peptide via a biodegradable spacer to generate prodrugs. Here an antioxidant (i.e., 3,5-dihydroxybenzoic acid), a non-steroidal anti-inflammatory drug (i.e., ibuprofen, IPF), and a self-assembled peptide motif (i.e., Gly-Phe-Phe-Tyr-Asp, GFFYD) are integrated to produce a peptide-drug amphiphile, which self-assembles to form hydrogel and further exerts the synergistic effects, and consequently emerges high therapeutic efficacy. In the in vitro study toward lipopolysaccharide-activated RAW264.7 macrophages, the resulting hydrogel significantly reduces the production of cytokines (e.g., IL-1β, IL-6 and tumor necrosis factor-α (i.e., TNF-α)) compared with that of native IPF via the inhibition of nuclear factor-κB (i.e., NF-κB), janus kinase-signal transducer and activator of transcription (i.e., JAK-STAT) signals and NLR family pyrin domain containing 3 (i.e., NLRP3) inflammasome activation. Moreover, a rabbit model of endotoxin induced uveitis evidences the superior therapeutic efficacy of the resulting hydrogel over that of clinically used 0.1 wt% diclofenac sodium eyedrop. Overall, this work offers new insights into the anti-inflammatory mechanism of PDCs hydrogel and presents the therapeutic values in the treatment of ocular disorders, and ultimately fulfils the potential clinical benefits of PDCs.
研究领域:
药学
·
材料科学
·
免疫学
·
眼科学
✓ 已验证
DOI
高影响因子
Journal of Functional Foods
·
2021
·
IF 4.451
Xiaoyan Su,Ming Zhao,Xinyu Fu,Xiaodan Ma,Wei Xu,Songhua Hu
Polysaccharides from Rubus chingii Hu fruits (RFPs) were extracted, purified, characterized and investigated for immunomodulatory activity. Results indicated that RFPs were heteropolysaccharides with molecular weight of 51.7 kDa and contained carbohydrate contents of 96.83%. RFPs with characteristic absorptive peaks of polysaccharide structure and α-configuration were composed of mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose, arabinose and fucose with a molecular ratio of 0.08:0.17:0.16:0.48:5.73:1.00:1.79:0.03. RFPs promoted splenocyte proliferation, NO release, cytokine production and intracellular Ca 2+ concentration. The mechanism underlying splenocyte activation by RFPs was elucidated by RNA-Seq, in which 2214 differentially expressed genes (DEGs), 2030 GO terms and 92 KEGG pathways were identified. RFPs were further proved to induce a balanced Th1/Th2/Th17 response pattern through MAPK, NF-κB, Jak-STAT and Calcium signaling pathways in splenocytes. These findings provided a fundamental basis for the further application of RFPs as immunomodulators in food and medicine.
研究领域:
免疫学
·
药理学
·
分子生物学
·
生物化学
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DOI
高影响因子
CURRENT MICROBIOLOGY
·
2025
·Vol. 82
·期 10
·1-12
·
IF 2.6
Bi Jinli,Huang Xin,Meng Liqin,Li Jinghan,He Yu,Jin Jing,Li Taijie
Hypervirulent Klebsiella pneumoniae (hvKP) possesses multiple virulence factors and causes severe infections with elevated mortality rates. It induces a strong inflammatory response in the host, with macrophages playing a key role in defense and inflammation. However, the signaling pathways of macrophages involved in response to hvKP infection remain unclear. In this study, we developed a stable hvKP infection model in differentiated THP-1 macrophages, confirmed by CFU assay and LDH cytotoxicity assay, and subsequently performed transcriptomic profiling analysis of hvKP-infected cells to characterize infection-induced gene expression changes. Pathway and differential gene correlation network analyses identified 14 potential regulatory genes primarily involved in inflammation. These changes in gene expression were further validated by Reverse transcription quantitative PCR (RT-qPCR). KEGG and GO analyses revealed several key signaling pathways involved in inflammation and immune response, particularly the TNF, IL-17, NF-κB, and JAK-STAT pathways. Further analysis indicated that the NF-κB signaling pathway plays a central role in the inflammatory response to hvKP infection, whereas the TNF and IL-17 pathways act synergistically to upregulate pro-inflammatory cytokines and chemokines. Western blot analysis confirmed the expression of TRAF6 and NF-κB p65 protein during hvKP infection. This study provides valuable insights into the molecular mechanisms of macrophage responses to hvKP, offering potential targets for therapeutic intervention.
研究领域:
微生物学
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免疫学
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分子生物学
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传染病学
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基因组学
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细胞生物学
·
生物信息学
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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）