IMMUNOPHARMACOLOGY AND IMMUNOTOXICOLOGY
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2019
·
IF 2.086
Rui-Li Zhu,Ying-Kun Zhi,Lang Yi,Jin-Fang Luo,Jing Li,Sha-Sha Bai,Liang Liu,Pei-Xun Wang,Hua Zhou,Yan Dong
Objective: To investigate the cellular mechanism that sinomenine (SIN) inhibits inflammation in macrophages induced by LPS through α7 nicotinic acetylcholine receptor (α7nAChR).Materials and methods: RAW264.7 cells were stimulated with LPS and treated by SIN or nicotine (Nic). A selective antagonist of α7nAChR, α-bungarotoxin (BTX) was used to block α7nAChR. AG490 was used to inhibit JAK2 activation. ELISA was performed to detect the levels of TNF-α and MCP-1. Western blotting was used to analyze the expression of MIF, MMP-9, CD14, TLR4, STAT3 and p-STAT3. Intracellular-free calcium level was measured by Fluorescent probe fluo-3/AMResults: SIN inhibited the production of TNF-α, MCP-1, MIF, and MMP-9, decreased the expression of CD14 and TLR4, and inhibited the release of intracellular-free calcium from intracellular stores in RAW 264.7 cells stimulated by LPS. JAK-specific inhibitor AG490 attenuated the inhibitory effect of SIN on TNF-α. SIN increased the phosphorylation of STAT3. And the above effects of SIN were attenuated by antagonist of α7nAChR.Conclusions: SIN can decrease the expression of CD14/TLR4 and intracellular free calcium level, activate JAK2/STAT3 pathway to inhibit inflammatory response through α7nAChR in macrophages.
研究领域:
免疫学
·
药理学
·
细胞生物学
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炎症研究
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DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2026
·
IF 12.6
Li Cai,Jian Gao,Kai Zhang,Bing Xiao,SiJia Xu,Wei Zhao,Juan Li,Yanli Zhou,WenYing Zhu,ShuYuan Liu,TingTing Pei,JunHua Li,Yang Chen,ShiXian Chen,Ji Li,Juan Li
Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic synovial inflammation, cartilage destruction, and bone loss. Current therapeutic approaches are often limited by short drug half-life, insufficient local drug release, and substantial systemic side effects.In this study, we developed a composite thermosensitive hydrogel system that integrates in situ gelation, sustained drug release, and multitarget therapeutic effects for localized precision treatment of RA.The system consists of a thermosensitive hydrogel matrix composed of hydroxypropyl methylcellulose (HPMC), hyaluronic acid (HA), and glycerol, in which gelatin methacryloyl (GelMA) hydrogel microspheres are embedded. The microspheres efficiently encapsulate Drynaria rhizome-derived extracellular vesicles (DR-EVs), while sinomenine is incorporated into the thermosensitive hydrogel to enhance anti-inflammatory activity. Characterization by transmission electron microscopy (TEM), scanning electron microscopy (SEM), nanoparticle tracking analysis (NTA), rheological measurements, and Fourier-transform infrared spectroscopy (FTIR) confirmed the intact morphology of DR-EVs, the uniform porous structure of the microspheres, and the favorable thermoresponsive gelation behavior and controllable degradation properties of the composite system. Functional assays revealed that, in vitro, the system effectively suppressed TH17 cell proliferation, promoted Treg cell differentiation, and inhibited M1 macrophage polarization.Meanwhile, it upregulated osteogenesis-related genes (Runx2, BMP2) and inhibited osteoclast formation. In a collagen-induced arthritis (CIA) rat model, the system significantly alleviated joint swelling, restored cartilage and bone architecture, and suppressed the progression of synovial inflammation. In summary, this composite thermosensitive hydrogel system possesses injectability, thermoresponsive behavior, prolonged release capability, and multiple biological activities, offering a safe, efficient, and controllable novel strategy for localized precision therapy of RA.
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高影响因子
PHARMACOLOGICAL RESEARCH
·
2026
·
IF 12.2
Muqiu Liu,Huaizhi Du,Junhui Zheng,Min Liu,Zhihao Jiang,Jieying Huang,Sihe Jiang,Lang Yi,Lingyu Zhang,Yanwu Li,Qun Du,Liang Liu,Haojie Ni,Xiaojun Zhang,Hua Zhou,Yan Dong
Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is a severe extra-articular manifestation with limited treatment options. Identifying anti-arthritic agents that concurrently protect against ILD is clinically significant. Sinomenine (SIN), a natural alkaloid used clinically to treat RA, shows potential anti-fibrotic activity, but its efficacy and mechanism in RA-ILD remain unclear. Here, integrative bioinformatic analyses identified ILD-associated signature characterized by upregulated CHRNA7 (encoding α7nAChR) and downregulated GLUL , specifically in pulmonary fibroblasts and myofibroblasts, and GLUL was a crucial mediator between RA and ILD. In the adjuvant-induced arthritis (AIA) model with pulmonary inflammatory and fibrotic remodeling, the phenotype that recapitulates early-stage RA-ILD, pulmonary ACh and α7nAChR expression were observed upregulated. SIN ameliorated arthritis and pulmonary lesions, suppressed pulmonary α7nAChR signaling, inhibited AKT/FOXO3 activation, restored GLUL expression and improved autophagy-related changes in this model. Microscale thermophoresis (MST), molecular docking and molecular dynamics simulation supported a direct binding between SIN and α7nAChR. In vitro , α7nAChR activation with PNU-282987 promoted fibroblast-to-myofibroblast transition (FMT), whereas its genetic knockdown inhibited FMT, suppressed AKT/FOXO3 activation, and restored GLUL expression in TGF-β-stimulated MRC-5 cells. We confirmed direct FOXO3 binding to the GLUL promoter by ChIP-qPCR. SIN inhibited FMT and regulated the AKT/FOXO3/GLUL axis in an α7nAChR-dependent manner. Pharmacological inhibition and siRNA-mediated knockdown of GLUL abolished SIN-mediated regulation of mTOR-autophagy signaling and FMT. Our findings identify the α7nAChR/AKT/FOXO3/GLUL axis as a novel fibrotic driver and highlight SIN as a potential therapeutic candidate to inhibit RA-ILD by targeting this axis.
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高影响因子
NEUROCHEMICAL RESEARCH
·
2026
·Vol. 51
·期 4
·237
·
IF 4.5
Han Zhipeng,Li Xing,Yang Li,Li Jinglin,Zhao Kaiyang,Xie Junxiong,Zhou Siyuan,Shi Wenli,Zhang Xiaolina
Neuropathic pain (NP) is chronic pain caused by injury or disease affecting the nervous system. SIN@Lip-HA was prepared and characterised for particle size, zeta potential, encapsulation efficiency and morphology. Sprague-Dawley rats with spared nerve injury (SNI) were randomly divided into the six groups. Analgesic effects were assessed via behavioural tests. Histopathological changes were examined using H&E staining. Astrocyte polarisation was detected using immunofluorescence, and Western blotting was used to assess related protein expression. qRT-PCR measured mRNA level of genes, while ELISA evaluated inflammatory cytokines and oxidative stress markers. The study showed that the particle size of SIN@Lip-HA was 111 ± 5.13 nm, with an encapsulation efficiency of 85.47% and a zeta potential of -24.86 ± 1.20 mV. The in vitro release profile showed sustained drug release, and the formulation remained stable for 3 months. Compared with the model group, SIN@Lip-HA significantly increased PWT and PWL, alleviated spinal cord pathology and was associated with a shift in astrocyte reactivity, as indicated by a reduction in A1-related markers and an increase in A2-related markers. SIN@Lip-HA downregulated CGRP/SP and GFAP. It was also found to inhibit JAK2/STAT3 pathway activation by reducing p-JAK2/p-STAT3 expression and decrease TNF-α, IL-1β and IL-6 whilst increasing IL-10. It also mitigated oxidative stress. Concomitant use with gabapentin markedly enhanced therapeutic efficacy. These findings suggest that sinomenine liposomes alleviate NP in SNI rats in a manner associated with inhibition of JAK2/STAT3 signaling and correlated with astrocyte reactivity, and reduced pain mediators.
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高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 5
·1-10
·
IF 2.447
Yan Zhou,Shuai Chen,Wenxian Gu,Xiao Sun,Linxiao Wang,Liming Tang
Sinomenine is a pure alkaloid that can be isolated from the root of Sinomenium acutum and has been found to exert anti‑inflammatory and immunosuppressive effects. The present study investigated the effects of sinomenine hydrochloride (SIN) on inflammation and the gut microbiota composition in the colon of mouse models of dextran sulfate sodium (DSS)‑induced colitis. DSS‑induced mice colitis was established by treating the mice with drinking water containing 3% (w/v) DSS for 7 days. The disease activity index of each mouse was calculated on a daily basis. All mice were sacrificed on day 11, then the weight of their spleen and length of their colons were measured. The histological analysis was measured by hematoxylin‑eosin staining. Oral administration of SIN (100 mg/kg/day) attenuated the DSS‑induced increases in the disease activity indices and spleen indices, DSS‑induced shortening of the colon length and histological damage. In addition, reverse transcription‑quantitative PCR data showed that SIN treatment effectively regulated the expression of inflammatory mediators, specifically by suppressing the expression of proinflammatory gene (TNF‑α, IL‑6 and inducible nitric oxide synthase) whilst increasing those associated with inhibiting inflammation (IL‑10 and arginine 1). Gut microbiota analysis was conducted using 16S ribosomal DNA sequencing. The results revealed that SIN improved bacterial community homeostasis and diversity, which were damaged by DSS. Furthermore, western blotting showed that the activation of the NOD‑, LRR‑ and pyrin domain‑containing protein 3 (NLRP3) inflammasome was markedly suppressed by SIN treatment. In conclusion, these results indicated that SIN may ameliorate experimental colitis by modulating the gut microbiota composition and suppressing the activation of the NLRP3 inflammasome in mice. Overall, these findings suggested a broad protective effect of SIN in treating inflammatory gut diseases, including ulcerative colitis.
研究领域:
药理学
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免疫学
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胃肠病学
·
微生物学
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PubMed
高影响因子
Journal of Diabetes Investigation
·
2023
·Vol. 14
·期 3
·364-375
·
IF 3.2
Ji Chen,Peng Guo,Xinxin Liu,Huizhi Liao,Kemin Chen,Yuxia Wang,Jie Qin,Fengrui Yang
Introduction We tried to show the effect of sinomenine (SIN) in diabetic peripheral neuropathic pain (DPNP) and the related underlying mechanism. Methods Network pharmacological analysis and bioinformatics analysis were carried out for identification of the active ingredients of Sinomenium acutum and the related genes. The DPNP rat model was constructed and primary rat spinal cord microglial cells were isolated for in vitro cell experiments. The therapeutic role of SIN in DPNP was determined in vivo and in vitro through analysis of microglial cell activation and inflammatory response. Results Therapeutic role of S. acutum in DPNP was mainly achieved by regulating 14 key genes, among which the target gene prostaglandin-endoperoxide synthase 2 ( PTGS2 ) of SIN might be the key gene . An in vivo experiment showed that SIN inactivated the inositol-requiring enzyme 1 alpha–X-box binding protein 1 pathway by downregulating PTGS2 , which relieved pain symptoms in DPNP rats. It was confirmed in vivo that SIN inhibited the pathway through PTGS2 to alleviate the activation of spinal cord microglial cells and inflammatory response . Conclusion SIN decreases the expression of PTGS2 to inactivate the inositol-requiring enzyme 1 alpha–X-box binding protein 1 signaling pathway, which inhibits microglial activation, as well as the release of inflammatory factors, thus alleviating DPNP.
研究领域:
药理学
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神经科学
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糖尿病
·
疼痛管理
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）