JOURNAL OF ETHNOPHARMACOLOGY
·
2026
·
IF 6.8
Yu Yang,Hongda Liu,Junling Ren,Lin Liu,Hui Sun,Li Wang,Guangli Yan,Ying Han,Xijun Wang
Ethnopharmacological relevance Danggui Buxue Decoction (DBD) is a classic traditional Chinese medicine formula that has shown significant efficacy in treating blood deficiency syndrome (BDS), though its mechanisms of action remain unclear. Aim of the study To identify the absorbed bioactive components of DBD and elucidate its molecular mechanisms in BDS by integrating metabolomics and bioinformatics. Materials and methods Using a benzene induced BDS mouse model, we analyzed serum-absorbed components of DBD via UPLC-Q/TOF-MS. A multi-omics approach combining metabolomics, molecular docking, and dynamics simulations was utilized to identify therapeutic targets and bioactive components, followed by experimental validation using pharmacological assays, Western blot, and cellular thermal shift assay (CETSA). Results In the BDS mouse model, DBD primarily corrected nicotinate and nicotinamide metabolism and improved hematopoietic function. Furthermore, it significantly decreased the levels of inflammatory cytokines that activate the STAT3 signaling pathway, including interleukin-6 (IL-6), interleukin-17 (IL-17), and transforming growth factor-β (TGF-β). It also suppressed the expression of p-JAK2/JAK2 and p-STAT3/STAT3. Under the effective status of DBD, we identified eleven prototype components and three metabolites derived from DBD, among which astragaloside IV was a high-affinity binder to STAT3, with molecular dynamics simulations and CETSA confirming its binding stability. Conclusion Our integrated approach suggests that DBD may alleviate BDS by normalizing metabolic imbalance and suppressing the IL-6/JAK2/STAT3 signaling pathway. A role for astragaloside IV as a potent bioactive compound of DBD with high-affinity binder to STAT3 is supported by molecular dynamics simulations and CETSA experiments. These findings provide a mechanistic foundation for DBD's therapeutic effects in treating BDS.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
HYPERTENSION
·
2018
·
IF 6.823
Jibo Han,Shiju Ye,Chunpeng Zou,Taiwei Chen,Jingying Wang,Jieli Li,Liqin Jiang,Jianjiang Xu,Weijian Huang,Yi Wang,Guang Liang
Evidence indicates that Ang II (angiotensin II) activates STAT3 (signal transducer and activator of transcription 3) in cardiomyocytes. However, the mechanisms underlying STAT3 activation and downstream responses are not fully known. In this study, we show that Ang II caused biphasic STAT3 activation in cardiomyocytes. A rapid and early activation was mediated by direct association between TLR4 (toll-like receptor-4) and STAT3. This early activation increased IL-6 (interleukin-6) production, which in turn, induced the second STAT3 activation through the IL-6/gp130 (glycoprotein 130)/JAK2 (Janus-family tyrosine kinases 2) pathway, resulting in unregulated expression of genes for cardiac remodeling. Moreover, STAT3 inhibition or TLR4 knockout in mice protected against Ang II–induced hypertrophy, fibrosis, and cardiac functional deficits. Thus, Ang II–induced STAT3 activation in cardiomyocytes was biphasic, providing a sequential induction of IL-6 and myocardial remodeling genes, respectively. This work supports a novel mechanism on STAT3 activation in Ang II–induced cardiac dysfunction and remodeling.
研究领域:
心脏病学
·
分子生物学
·
免疫学
✓ 已验证
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2021
·Vol. 9
·期 7
·3722-3731
·
IF 2.863
Lin Zhu,Yingjuan Liu,Xiaolin Wu,Yuqian Ren,Qinghua Zhang,Leiming Ren,Yunliang Guo
Cerebroprotein hydrolysate-I (CH-I)，a mixture of peptides extracted from porcine brain tissue，has shown a neuroprotective effect, but its role in brain senescence is unclear. In the present study, we established a senescence model of PC12 cells and mice to investigate the effect of CH-I on brain senescence via JAK2/STAT3 pathway. The results showed that CH-I could improve cell viability, inhibit the apoptosis of cells, and reduce the senescence-positive cells induced by D-galactose. In vivo , CH-I improved the learning ability and memory of aging mice, reduced neuronal damage in mice hippocampus. Mechanism studies showed that CH-I could adjust BDNF protein expressions, activate JAK2/STAT3 pathway, and finally enhance telomerase activity. All these findings indicated that CH-I showed a neuroprotective effect against brain senescence. These results might provide further reference and support for the application of CH-I in delaying aging.
研究领域:
神经科学
·
衰老研究
·
药理学
✓ 已验证
产品关联
DOI
PubMed
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.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Yu Wang,Meihao Peng,Xin Yang,Liming Tu,Jiamin Liu,Yixi Yang,Rui Li,Xue Tang,Yuqing Hu,Guowu Zhang,Qi Zhao,Qiuxia Lu
ABSTRACT Ethnopharmacological relevance Fritillaria cirrhosa D. Don (FCD) is a traditional Chinese medicine used to treat respiratory disorders, known for its effects in clearing heat, moistening the lungs, resolving phlegm, and relieving cough. Additionally, the total alkaloids extracted from FCD can alleviate asthma symptoms and reduce airway inflammation. However, no studies have investigated the effects of total alkaloids on lung macrophages. Aim of the study This study explored whether the total alkaloids of FCD (TAs-FCD) reduce M2 macrophage polarization and, consequently, attenuate airway remodeling in asthmatic mice. This study further elucidated its mechanism of action in treating allergic asthma. Materials and methods The extracted TAs-FCD was analyzed for its composition using UPLC-Q-TOF/MS. Network pharmacology was employed to identify the active ingredients and potential mechanisms of TAs-FCD in the treatment of allergic asthma. A mouse model of ovalbumin-induced allergic asthma was established, adopted, and validated through in vivo experiments. Hematoxylin-eosin staining (H&E), immunohistochemistry (IHC), immunofluorescence staining (IF), enzyme-linked immunosorbent assay (ELISA), Western blotting (WB), and real-time fluorescence quantitative polymerase chain reaction (q-PCR) were used to investigate the role of TAs-FCD in inhibiting M2 macrophage polarization in the context of allergic asthma. Results A total of 66 active ingredients were screened from 116 compounds using SWISSADME. The targets of these 66 compounds were predicted by SwissTargetPrediction, resulting in 808 unique drug targets after excluding duplicates. Additionally, 1,756 targets related to allergic asthma were identified from the DisGeNET, Genecard, and OMIM databases. This led to 267 cross-targets between the active ingredient targets and allergic asthma targets, including interleukin (IL)-1β, tumor necrosis factor (TNF), and STAT3. Animal experiments demonstrated that TAs-FCD improved histopathological injury in mouse lungs, reduced peri-airway collagen fiber accumulation, airway mucus secretion, and airway smooth muscle proliferation. TAs-FCD also lowered IL-1β, TNF-α and IL-4 levels in lung tissues and alleviated airway inflammation. Furthermore, TAs-FCD significantly reduced levels of Arg1 and CD206, which are closely associated with M2 macrophages, and downregulated the expression of p-STAT3 and p-JAK2. Conclusion TAs-FCD may inhibit M2 macrophage polarization by regulating the JAK2/STAT3 pathway, thereby alleviating airway remodeling and inflammation in allergic asthmatic mice.
研究领域:
药理学
·
免疫学
·
呼吸医学
·
中医药
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Xingfan Li,Rong Ji,Linyan Duan,Zhizhong Hao,Yujing Su,Hao Wang,Fangxia Guan,Shanshan Ma
The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.
研究领域:
神经科学
·
生物材料
·
再生医学
·
炎症
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jing Guo,Qi-Yun Zhang,Lin Xu,Min Li,Qian-Yun Sun
Acute lung injury (ALI) is an acute respiratory-related progressive disorder, which lacks specific pharmacotherapy. Icariin (ICA) has been shown to be effective in treating ALI. However, the targets and pharmacological mechanisms underlying the effects of ICA in the treatment of ALI are relatively lacking. Based on network pharmacology and molecular docking analyses, the gene functions and potential target pathways of ICA in the treatment of ALI were determined. In addition, the underlying mechanisms of ICA were verified by immunohistochemistry, immunofluorescence, quantitative Real-time PCR, and Western blot in LPS-induced ALI mice. The biological processes targeted by ICA in the treatment of ALI included the pathological changes, inflammatory response, and cell signal transduction. Network pharmacology, molecular docking, and in vivo experimental results revealed that ICA inhibited the complement C5a-C5aR1 axis, TLR4 mediated NF-κB, MAPK, and JAK2-STAT3 signaling pathways related gene and protein expressions, and decreased inflammatory cytokine, chemokine, adhesion molecule expressions, and mitochondrial apoptosis in LPS-induced ALI.
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
Journal of Advanced Research
·
2023
·
IF 10.7
Yujun Wu,Xiangyu Zhang,Xiaoyi Liu,Yi Li,Dandan Han,Yu Pi,Melanie A. Whitmore,Xingmiao Lu,Guolong Zhang,Jinkai Zheng,Junjun Wang
Introduction Galactooligosaccharides (GOS) are lactogenic prebiotics that exert health benefits by stimulating the growth of different Lactobacillus strains in the gastrointestinal (GI) tract. Objectives This study aimed to investigate the mechanism of action of different GOS-enriched lactobacilli in intestinal health. Methods Piglets and mice were supplemented with GOS to identify specific enrichment of Lactobacillus . The protective effects of individual GOS-enriched lactobacilli were investigated in Salmonella -infected mice. Macrophage depletion and transcriptome analysis were further performed to assess the involvement of macrophages and the underlying mechanisms of individual lactobacilli. An in vitro cell co-culture system was also used to evaluate the anti-adhesive and anti-invasive activities of lactobacilli against Salmonella in epithelial cells. Results GOS markedly increased the relative abundance of three lactobacilli including L. delbrueckii , L. johnsonii , and L. reuteri in both piglets and mice. Supplementation with GOS further alleviated Salmonella infection in mice. L. delbrueckii (ATCC®BAA 365™), but not L. johnsonii or L. reuteri , enhanced propionate production in the intestinal tract and ameliorated Salmonella -induced intestinal inflammation and barrier dysfunction by suppressing the JAK2-STAT3 signaling and M1 macrophage polarization. L. johnsonii (BNCC 186110), on the other hand, inhibited Salmonella adhesion and invasion of epithelial cells through competitive exclusion. However, L. reuteri (BNCC 186135) failed to protect mice against Salmonella infection. Conclusion GOS-enriched lactobacilli show a differential role in protecting against Salmonella -induced intestinal barrier dysfunction and inflammation. Our results provide novel insights into the mechanism of action of GOS and individual Lactobacillus strains in the control and prevention of intestinal inflammatory disorders.
研究领域:
微生物学
·
免疫学
·
营养科学
·
胃肠病学
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
·
2025
·
IF 4.9
Yang Liu,Quanwei Sun,Xuefei Xu,Mengmeng Li,Wenheng Gao,Yunlong Li,Ye Yang,Dengke Yin
Ulcerative colitis (UC) is a chronic inflammatory disorder with a complex etiology, characterized by intestinal inflammation and barrier dysfunction. Platycodon grandiflorus polysaccharides (PGP), the primary component of Platycodon grandiflorus , and hesperidin (Hesp), a prominent active component in Citrus aurantium L. (CAL), have both demonstrated anti-inflammatory properties. This study aims to elucidate the underlying mechanism of the synergistic effect of PGP combined with Hesp on UC, focusing on the coordinated interaction between the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathways. A mouse model of UC induced by dextran sulfate sodium (DSS) and a cell model using lipopolysaccharide (LPS)-induced RAW264.7/IEC6 cells were employed to investigate the in vitro and in vivo anti-inflammatory effects of PGP combined with Hesp on UC and its potential mechanism of action. The results indicated that compared to the effects of either drug alone, the combination of PGP and Hesp significantly modulated inflammatory factor levels, inhibited oxidative stress, regulated colonic mucosal immunity, suppressed apoptosis, and restored intestinal barrier function in vitro and in vivo . Further in vitro studies revealed that PGP significantly inhibited the PI3K/AKT signaling pathway, while Hesp significantly inhibited the JAK2/STAT3 signaling pathway. The use of inhibitors and activators targeting both pathways validated the synergistic effects of PGP combined with Hesp on the PI3K/AKT and JAK2/STAT3 signaling pathways. These findings suggest that PGP combined with Hesp exhibits a synergistic effect on DSS-induced colitis, potentially mediated through the phosphatase and tensin homolog (PTEN)/PI3K/AKT and interleukin-6 (IL-6)/JAK2/STAT3 signaling pathways.
研究领域:
免疫学
·
分子生物学
·
药理学
·
炎症性肠病研究
·
信号转导
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Molecular Medicine Reports
·
2024
·Vol. 30
·期 2
·1-15
·
IF 3.4
Jingxia Du,Yibo Dong,Jingjing Song,Hanqi Shui,Chengyao Xiao,Yue Hu,Shiyao Zhou,Shanshan Wang
Myocardial ischemia/reperfusion injury (MIRI) is a significant challenge in the management of myocardial ischemic disease. Extensive evidence suggests that the macrophage‑mediated inflammatory response may play a vital role in MIRI. Mesenchymal stem cells and, in particular, exosomes derived from these cells, may be key mediators of myocardial injury and repair. However, whether exosomes protect the heart by regulating the polarization of macrophages and the exact mechanisms involved are poorly understood. The present study aimed to determine whether exosomes secreted by bone marrow mesenchymal stem cells (BMSC‑Exo) harboring miR‑25‑3p can alter the phenotype of macrophages by affecting the JAK2/STAT3 signaling pathway, which reduces the inflammatory response and protects against MIRI. An in vivo MIRI model was established in rats by ligating the anterior descending region of the left coronary artery for 30 min followed by reperfusion for 120 min, and BMSC‑Exo carrying miR‑25‑3p (BMSC‑Exo‑25‑3p) were administered through tail vein injection. A hypoxia‑reoxygenation model of H9C2 cells was established, and the cells were cocultured with BMSC‑Exo‑25‑3p in vitro. The results of the present study demonstrated that BMSC‑Exo or BMSC‑Exo‑25‑3p could be taken up by cardiomyocytes in vivo and H9C2 cells in vitro. BMSC‑Exo‑25‑3p demonstrated powerful cardioprotective effects by decreasing the cardiac infarct size, reducing the incidence of malignant arrhythmias and attenuating myocardial enzyme activity, as indicated by lactate dehydrogenase and creatine kinase levels. It induced M1‑like macrophage polarization after myocardial ischemia/reperfusion (I/R), as evidenced by the increase in iNOS expression through immunofluorescence staining and upregulation of proinflammatory cytokines through RT‑qPCR, such as interleukin‑1β (IL‑1β) and interleukin‑6 (IL‑6). As hypothesized, BMSC‑Exo‑25‑3p inhibited M1‑like macrophage polarization and proinflammatory cytokine expression while promoting M2‑like macrophage polarization. Mechanistically, the JAK2/STAT3 signaling pathway was activated after I/R in vivo and in LPS‑stimulated macrophages in vitro, and BMSC‑Exo‑25‑3p pretreatment inhibited this activation. The results of the present study indicate that the attenuation of MIRI by BMSC‑Exo‑25‑3p may be related to JAK2/STAT3 signaling pathway inactivation and subsequent inhibition of M1‑like macrophage polarization.
研究领域:
心脏病学
·
分子生物学
·
干细胞研究
·
炎症
·
外泌体治疗
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Cell Host & Microbe
·
2024
·
IF 20.6
Zhen He,Jing Yu,Junli Gong,Jinjie Wu,Xuan Zong,Zhanhao Luo,Xiaowen He,Wai Ming Cheng,Yugeng Liu,Chen Liu,Qiang Zhang,Lei Dai,Tao Ding,Beile Gao,Raad Z. Gharaibeh,Jinlin Huang,Christian Jobin,Ping Lan
Various forms of solid tumors harbor intracellular bacteria, but the physiological consequences of these microorganisms are poorly understood. We show that Campylobacter is significantly enriched in primary colorectal cancer (CRC) lesions from patients with metastasis. Campylobacter jejuni -derived cytolethal distending toxin (CDT) promotes CRC metastasis through JAK2-STAT3-MMP9 signaling in liver or pulmonary metastatic mice models, as confirmed in C. jejuni -infected human colonic tissue and CDT-treated colonic tumoroids from patients. Genetic deletion of cdtB ( ΔcdtB ) or purified CdtB protein demonstrates that the genotoxin is essential for C. jejuni’s pro-metastatic property. In C.-jejuni -colonized mice, increased translocation of CDT-producing C. jejuni to extraintestinal implanted tumors potentially leads to accelerated metastasis of these tumors. Overall, these findings demonstrate that an intratumor-bacteria-derived genotoxin accelerates tumor metastasis, potentially opening a new diagnostic and therapeutic avenue for cancer management.
研究领域:
肿瘤学
·
微生物学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ANNALS OF MEDICINE
·
2025
·
IF 4.3
Yun Yang,Lengqiu Guo,Jinghua Yu,Wei Peng,Qi Wang,Lan Wei,Xihua Chen,Chunyan Min,Xiaogang Jiang,Song Zhu,Haixin Zhao,Zhenyu Xuan,Jianzhong Yu,Jian Zhang
Background Da-Yuan-Yin Decoction (DYY), used since the early Qing Dynasty in China for damp-heat syndrome, was evaluated for its comprehensive protective effects.Materials and methods Rats received a high-fat/high-sugar diet for 14 days, then daily exposure to high temperature/humidity (31.0 ± 0.5°C, 85%-95%) for 10 hours over 14 days. Damp-heat syndrome was induced on day 29 via intraperitoneal lipopolysaccharide (LPS) injections (1 mg/kg and 0.5 mg/kg after 4 hours). Two hours post-modeling, rats received DYY (400 or 800 mg/kg/day) orally for 5 days. Symptoms were scored. On day 33, kidney, spleen, tongue, lung, liver, stomach, and colon tissues underwent histopathological and immunochemical/immunofluorescence analysis. Serum levels of inflammation factors, C-reactive protein (CRP), cell-free DNA (cfDNA), myeloperoxidase (MPO), and superoxide dismutase (SOD) were quantified. Complete blood count (CBC), blood biochemistry, short-chain fatty acids (SCFAs), gut microbiota composition in the colon, and metabolites in the cecum were analyzed.Results DYY significantly reduced symptom scores and decreased CRP level, while also regulating parameters in CBC and biochemical profiles. The treatment ameliorated tissue damage in the kidney, spleen, tongue, lung, liver, stomach, and colon. DYY downregulated citrullinated histone H3 (Cit H3), polyclonal peptidylarginine deiminase 4 (PADI4), and MPO expressions in the lung, stomach, and colon. Furthermore, it modulated inflammatory responses, suppressed the interleukin-23 (IL-23)/janus kinase-2 (JAK2)/signal transduction and transcription activator-3 (STAT3) signaling pathway and enhanced antioxidant activity. DYY administration significantly increased total SCFA content. The intervention restored gut microbiota diversity and abundance, while ameliorating metabolic dysregulation.Conclusion Systemic pathophysiological alterations were observed in rats with damp-heat syndrome. The comprehensive protective effects of DYY involved suppression of neutrophil extracellular traps (NETs) formation through downregulation of PADI4 expression, modulation of inflammatory responses, inhibition of the IL-23/JAK2/STAT3 signaling pathway, restoration of intestinal microecological balance and metabolic homeostasis, and enhancement of antioxidant.
✓ 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）