PHYTOMEDICINE
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2024
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IF 6.7
Canchao Jia,Minjuan Yang,Guanlin Xiao,Zhihao Zeng,Lingjie Li,Yangxue Li,Jieyi Jiang,Aili Xu,Jinyan Qiu,Ruiyin Tang,Dongmei Li,Dezheng Jia,Canhui Xie,Guangying Wu,Dake Cai,Xiaoli Bi
Backgrounds Idiopathic pulmonary fibrosis (IPF) is a persistent and advanced pulmonary ailment. The roles of innate immunity and adaptive immunity are pivotal in the evolution of IPF. An ill-adjusted interaction between epithelial cells and immune cells is responsible for initiating the epithelial–mesenchymal transition (EMT) process and sustaining chronic inflammation, thereby fostering fibrosis progression. The intricacy of IPF pathogenesis has hindered the availability of efficacious agents. Elephantopus scaber Linn. (ESL) is a canonical Chinese medicine with significant immunoregulatory effects, and its aqueous extract has been proven to attenuate IPF symptoms in bleomycin (BLM)-induced mice. However, the underlying mechanism through which ESL relieves IPF remains unclear. Aim To validate whether ESL reverses IPF by mediating the immune response and EMT. Methods : Ultra-performance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS) and UPLC were used to identify the components and determine the concentrations of the specific compounds in the ESL. Network pharmacology and molecular docking were applied to predict the potential mechanism underlying the anti-IPF effect of ESL. BLM-induced IPF mice were used to validate the anti-IPF effect of ESL, and lung tissue was collected to test putative pathways involved in inflammation and EMT via immunohistochemistry (ICH), real-time quantitative polymerase chain reaction (RT–qPCR) and Western blotting. Results Sixty-one compounds were identified, and thirteen main ingredients were quantified in the ESL. In silico experiments predicted that the IPF-mediated reversal of adverse effects by ESL would be related to interruption of the Toll-like receptor 4 (TLR4)/nuclear factor-k-gene binding (NF- ĸ B) inflammatory pathway and the transforming growth factor-beta l (TGF-β1)/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/forkhead box O3 (FOXO3a) fibrosis pathway. In vivo experiments showed that ESL alleviates BLM-induced lung inflammation and fibrosis by reducing neutrophil aggregation and fibroblast foci, similar to the effects of the positive control drug pirfenidone (PFD). ESL markedly inhibited the transcription of TNF-α, IL-1 β, and IL-6, which are downstream genes of the NF-κB signaling pathway. Furthermore, the protein levels of TLR4 and p-NF- κ B were correspondingly inhibited in response to ESL treatment. Additionally, ESL reverses BLM-induced changes in the expression of EMT-related biological characteristic indicators (collagen I [COLIA1], E-cadherin, and alpha smooth muscle actin [ α -SMA]) at the messenger ribonucleic acid (mRNA) level and markedly inhibits the expression of EMT-related upstream proteins (TGF- β 1, p-PI3K, p-Akt, and p-FOXO3a). Conclusion Our research suggested that ESL attenuates BLM-induced IPF through mediating the EMT process via the TGF-β1/PI3K/Akt/FOXO3a signaling pathway and inhibiting inflammation through the TLR4/NF-κB signaling pathway, highlighting that ESL can serve as an immunoregulator for relieving the abnormal immune response and reversing the EMT in IPF.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Pin Gong,Xufeng Wang,Yewen Han,Hui Long,Wenjuan Yang,Fuxin Chen,Mengjiao Cui,Wenjun Zhai,Benzhong Zheng,Xuefeng Chen
This study devised optimal conditions to extract Eucommia ulmoides leaf (EUL) polysaccharides using a cellulase and pectinase composite enzyme system based on one-way experiments and response surface methodology. Crude EUL polysaccharides (EULPs) were extracted and purified using a DEAE chromatography column. The polysaccharides EUL-w, EUL1, EUL2, and EUL3 were obtained by elution with water, 0.1 mol/L NaCl, 0.2 mol/L NaCl, and 0.3 mol/L NaCl, respectively. The EUL-w fraction had the highest hypoglycemic activity based on its α-amylase and α-glucosidase activities. The preliminary structure of purified EUL-w1 was elucidated. In vitro hypoglycemic activity studies and metabolomics analyses suggested that EUL-w1 modulated glucose metabolism by mediating the AMPK/PI3K/Akt signaling pathway. Our findings provide novel insights and data support for the utilization of EULPs as an emerging food resource in functional foods.
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INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2024
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IF 7.7
Yadan Zhang,Xiaoyu Zhang,Tianhan Kai,Lin Zhang,Anping Li
Plant-derived exosome-like nanovesicles (ELNs) are nano-sized vesicles extracted from edible plants. Lycium ruthenicum Murray (LRM) has been gaining increasing attention due to its nutritional and medicinal value, but the ELNs in LRM has not been reported. In this study, LRM-ELNs were obtained, and the proteins, lipids, microRNAs (miRNAs) and active components in LRM tissues and LRM-ELNs was analyzed by LC-MS/MS, LC-MS, high-throughput sequencing techniques, and physical and chemical analysis. LRM-ELNs can be uptaken by PC12 cells through macropinocytosis and caveolin-mediated endocytosis primarily. Transcriptomic and western blot experiments indicate that LRM-ELNs can inhibit Aβ-induced apoptosis in PC12 cells through the MAPK and PI3K/AKT signaling pathways, with miRNAs playing a crucial role. These results indicate that LRM-ELNs have the protection effect on PC12 cells and can be considered as dietary supplements for alleviating neurodegenerative diseases.
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JOURNAL OF IMMUNOLOGY
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2024
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IF 3.6
Gao Along,Lin Yuhua,Chai Yiwen,Han Jugan,Wu Liting,Ye Jianmin
Chemokines play crucial roles in the regulation of immune cell migration and development. The CXCL12/CXCR4 axis has been extensively studied in mammals, but its regulatory mechanism in teleost fish remains unclear. In this study, we used Nile tilapia (Oreochromis niloticus) as a teleost model to investigate the mediation of the CXCL12/CXCR4 axis in IgM+ B cells. Our findings demonstrate that the CXCL12/CXCR4 axis exhibits chemotactic activity on IgM+ B cells and promotes the phagocytosis of IgM+ B cells. Blocking CXCR4 severely impairs the chemotaxis and phagocytosis of IgM+ B cells in vitro and reduces the percentages and numbers of IgM+ B cells that migrate to peripheral blood after pathogen infection in vivo. This reduction in migration leads to a decrease in the inflammatory response, an increase in tissue bacterial load, and a decrease in survival rate. We also discovered that the evolutionarily conserved PI3K-AKT signaling pathway and Girdin are involved in the immune response during Streptococcus agalactiae infection. Inhibitors of the PI3K-AKT signaling pathway prevent the chemotaxis and phagocytosis of IgM+ B cells, impair the expression and phosphorylation levels of related proteins in vitro, and prevent IgM+ B cells chemotaxis into the peripheral blood after pathogen infection in vivo. Furthermore, CXCR4 blocking significantly downregulates the expression of AKT and Girdin. Overall, our study reveals the regulatory mechanism of the CXCL12/CXCR4 axis on IgM+ B cells via the PI3K-AKT signaling pathway in tilapia, suggesting that the functions of the CXCL12/CXCR4 axis in B cells may be conserved between mammals and teleost fish.
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EUROPEAN JOURNAL OF PHARMACOLOGY
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2024
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IF 4.2
Jingjing Lin,Lu Deng,Ailin Qi,Hong Jiang,Di Xu,Yuehui Zheng,Zixuan Zhang,Xiaoman Guo,Beilei Hu,Peijun Li
Hypoxic-ischemic encephalopathy (HIE) is a brain damage caused by perinatal hypoxia and blood flow reduction. Severe HIE leads to death. Available treatments remain limited. Oxidative stress and nerve damage are major factors in brain injury caused by HIE. Catalpol, an iridoid glucoside found in the root of Rehmannia glutinosa, has antioxidant and neuroprotective effects. This study examined the neuroprotective effects of catalpol using a neonatal rat HIE model and found that catalpol might protect the brain through inhibiting neuronal ferroptosis and ameliorating oxidative stress. Behavior tests suggested that catalpol treatment improved functions of motor, learning, and memory abilities after hypoxic-ischemic injury. Catalpol treatment inhibited changes to several ferroptosis-related proteins, including p-PI3K, p-AKT, NRF2, GPX4, SLC7A11, SLC3A2, GCLC, and GSS in HIE neonatal rats. Catalpol also prevented changes to several ferroptosis-related proteins in PC12 cells after oxygen-glucose deprivation. The ferroptosis inducer erastin reversed the protective effects of catalpol both in vitro and in vivo . We concluded that catalpol protects against hypoxic-ischemic brain damage (HIBD) by inhibiting ferroptosis through the PI3K/NRF2/system Xc-/GPX4 axis.
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Biomaterials Advances
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2024
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IF 5.5
Longbiao Wan,Feng Liu,Ao Wang,Yan He,Jiali Pan,Liu Ye,Xu Jie,Chun Xu,Wu Fei,Qingsong Ye
Tissue engineering (TE) is commonly suggested as a promising remedy for the worldwide shortage of organ donors required for transplantation. Scholars are investigating organic and biocompatible materials as the principal options for regeneration to replicate the natural extracellular matrix. Hydrogels exhibit swift gel formation and outstanding biocompatibility, thus presenting considerable promise in tissue regeneration. The objective of this study was to investigate the role of a novel biomaterial complex, comprising gelatin (Gel), hyaluronic acid (HA) and exosomes (Exo), in promoting bone regeneration and elucidate its underlying molecular mechanism. The experimental results demonstrated that the Gel/HA/Exo complex could significantly enhance the proliferation and differentiation of osteoblasts, as well as the deposition and mineralization of bone matrix. Further mechanistic studies demonstrated that TGF-β in exosomes enhanced the biological activity of osteoblasts by activating the PI3K/Akt pathway, thus promoting the fracture healing process. The results of in vivo experiments indicated that the application of Gel/HA/Exo complexes significantly accelerated the fracture healing rate and improved the quality of healing, exhibiting good biocompatibility and controlled degradation properties. Consequently, the present study concluded that the Gel/HA/Exo complex not only has potential clinical applications, but also provides an important theoretical and experimental basis for the development of novel bone regeneration therapeutic strategies.
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Journal of Taibah University for Science
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2024
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IF 2.8
Lingyu Wang,Ruolan Li,Meiyan Li,Jiayi Sun,Jia Liu,Min Xie,Yunhui Chen,Songqi Tang
This study aimed to investigate the inhibitory effect of Zuojin Pill (ZJP) on KYSE 150 cells and xenograft tumours of the digestive tract cancer – esophageal cancer (EC) and its underlying mechanism. Initially, in vivo research demonstrated that oral administration of ZJP effectively inhibited the growth of EC tumours, and in vitro studies revealed that ZJP suppressed the proliferation, migration, and invasion of cells. Then, network pharmacology prediction identified the core target, active ingredient, and involvement of the PI3K-Akt signalling pathway in ZJP treatment of EC. Cell studies validated that ZJP affected the expression of core targets, and its active ingredients inhibited the proliferation of cells. Additionally, ZJP was shown to induce cell apoptosis, decrease mitochondrial membrane potential, and increase the level of intracellular oxidative stress. Further experimental verifications suggested that the inhibitory effects of ZJP on EC might be attributed to the modulation of PI3 K/Akt signalling pathways.
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CELL PROLIFERATION
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2020
·Vol. 53
·期 8
·e12871
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IF 5.753
Hongping Yu,Pei Liu,Daoyu Zhu,Junhui Yin,Qianhao Yang,Yigang Huang,Yixuan Chen,Changqing Zhang,Youshui Gao
Objectives Osteonecrosis of the femoral head (ONFH), largely caused by alcohol abuse, is a refractory bone disease characterized by the impaired capacity of osteogenic differentiation of bone mesenchymal stem cells (BMSCs), as well as the disordered adipocyte accumulation. Chrysophanic acid (CPA) is a natural anthraquinone which has lipid regulation and bone protection capacity. The aim of this study was to reveal the potential function of CPA and the underlying mechanisms for the alcohol-induced ONFH. Materials and Methods The effects of alcohol and CPA on BMSCs were investigated by cell proliferation, induced differentiation assays and immunofluorescent staining. Meanwhile, the function of PI3K/AKT and AMPK pathway was investigated in the process of osteogenic and adipogenic differentiation, respectively. Furthermore, we established the rat model of alcohol-induced ONFH to reveal the pharmacotherapeutic effect of CPA in vivo using radiographical and histopathological methods. Results In vitro, alcohol significantly inhibited the proliferation and osteogenic differentiation of BMSCs but stimulated the adipogenic differentiation. However, CPA could counteract the anti-osteogenesis of alcohol partly via PI3K/AKT pathway and retard the promotion of alcohol-induced adipogenesis via AMPK pathway. In vivo, radiographical and histopathological findings showed that CPA could alleviate alcohol-induced ONFH and substantially restore the bone volume. Conclusions We demonstrated that CPA ameliorated alcohol-induced ONFH possibly via regulating the differentiation tendency of BMSCs. Hence, CPA may become a beneficial herb extract to alleviate alcohol-induced ONFH.
研究领域:
药理学
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骨科
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干细胞研究
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Journal of Food Measurement and Characterization
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2024
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IF 2.9
Meng Wenya,Xue Yuhan,Zhang Jing,Wang Ye,Hou Hu,Li Jing,Dong Ping
Fish sperm extracts have been shown to have various activities, but it has not been effectively developed and utilized at present due to the lack of effective methods for preparing edible grade products. This study proposed a method for preparing edible fish sperm DNA from Alaska pollock (PSD) and evaluated the hepatoprotective effect of the extracted DNA. Firstly, the preparation conditions of fish sperm DNA were optimized by response surface methodology. Under the ideal conditions that the ratio of solid to liquid was 3:1, the pH of extractant was 7.5, the purified solvent was saturated sodium carbonate solution and absolute ethanol was twice the volume of purified solvent, the yield of PSD was (13.657 ± 0.577) µg/mg. To evaluate the liver protective effects of the extracted DNA, the digestion products by three digestion enzymes (pepsin, DNase I and DNase II) compared using an alcohol-induced HepG2 cell model. The DNase I hydrolysis product was more effective in preventing cell alcohol damage, as shown by reducing the content of lipid peroxides. Transcriptomics and metabolomics data revealed that the DNase I hydrolysis product activated the Nrf2/HO-1 pathway through the PI3K/Akt signaling pathway and regulated abnormal lipid synthesis through the steroidogenic pathway. This study will provide an important basis for the evaluation and analysis of the hepatoprotective effect of fish sperm DNA in vivo. Overall, our findings will promote the comprehensive utilization of fish sperm and other aquatic wastes, and provide scientific guidance for the development of functional nucleic acid foods.
研究领域:
食品科学
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分子生物学
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生物化学
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INTERNATIONAL IMMUNOPHARMACOLOGY
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2026
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IF 5.6
Lei Zhu,Guan Zhang,Jiasai Kang,Xinru Xu,Haoshu Zhang,Yingying Pu,Yong Huang,Dewen Tong,Qian Du
Background Folium Isatidis (Da Qing Ye), a traditional Chinese medicine, exhibits broad-spectrum antiviral and immunomodulatory properties and has been widely used in treating respiratory diseases. Porcine circovirus type 2 (PCV2), a widespread swine virus, causes respiratory disease complex in piglets and leads to substantial economic losses in the global swine industry. This study aimed to evaluate the anti-PCV2 activity of Folium Isatidis . Materials and methods The anti-PCV2 activity of Folium Isatidis was first validated through both in vivo and in vitro experiments. Potential targets of Folium Isatidis were identified using TCMSP, BATMAN-TCM, and SwissTargetPrediction databases, and intersected with PCV2-related targets. Mechanism exploration involved PPI network analysis, GO annotation, and KEGG enrichment. Molecular docking analyzed component-target interactions, followed by experimental validation of the core component. Finally, the anti-PCV2 effect of the core component was verified through in vitro and in vivo experiments. Results A total of 135 overlapping targets between Folium Isatidis components and PCV2-related disease targets were identified. Key targets, including AKT1 and TNF-α, were implicated in the therapeutic effects of Folium Isatidis against PCV2. Isovitexin was identified to be the core component that directly binds to AKT1 and TNF-α, thereby inhibiting the PI3K/AKT signaling pathway and regulating TNF-α expression and activity to suppress PCV2 replication and alleviate PCV2-induced lung injury. Conclusions Our study reveals that Isovitexin, the core anti-PCV2 component of Folium Isatidis , exerts its effect by inhibiting the PI3K/AKT pathway and modulating TNF-α, thereby outlining a novel therapeutic strategy for combating PCV2 infection and associated respiratory injuries.
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JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY
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2026
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IF 3.4
Yanliang Li,Siqiang Niu,Haipeng Wang,Jianhua Li
Gemcitabine (GEM) resistance remains a major challenge in the treatment of gallbladder cancer (GBC). This study investigated the synergistic effect of curcumin (CUR) combined with the probiotic Lactobacillus rhamnosus GG (LGG) in reversing chemoresistance through modulation of the gut microbiota. In GEM-resistant GBC-SD cells, the CUR–LGG combination significantly inhibited cell proliferation, suppressed migration and invasion, and induced apoptosis, as demonstrated by CCK-8, wound healing, Transwell, and flow cytometry assays. Western blot analysis revealed corresponding regulation of proliferation markers (Ki67, PCNA), apoptosis-related proteins (Bcl-2, Bax, cleaved Caspase-3), and epithelial–mesenchymal transition markers. In xenograft models, the combined treatment markedly suppressed tumor growth and altered gut microbial composition, increasing beneficial bacteria ( Lactobacillus , Bifidobacterium ) while reducing pathogenic taxa. LC–MS analysis further demonstrated restoration of bile acid homeostasis, characterized by elevated primary bile acids (GCA, CDCA) and decreased secondary bile acids (DCA, LCA). Mechanistically, the intervention significantly inhibited PI3K/AKT signaling, as confirmed by Western blot and immunohistochemistry. Bioinformatic analysis further identified PI3K/AKT as a central regulatory pathway. These findings indicate that probiotic-assisted CUR therapy reverses GEM resistance by remodeling the gut microbiota and its metabolic outputs, thereby suppressing oncogenic signaling pathways. This strategy provides a promising microbiota-based approach for improving therapeutic outcomes in GBC.
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BIOCHEMICAL PHARMACOLOGY
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2026
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IF 6.5
Huimin Qiu,Xinqi Tan,Quan Sheng,Na Yang,Chunming Jiang,Lulu Wang
Metabolic dysfunction-associated steatohepatitis (MASH) frequently induces renal injury, forming a “liver-kidney axis” vicious cycle. Current therapies primarily target hepatic lesions, failing to interrupt the cross-organ injury cascade, creating an urgent need for novel strategies. To explore dapagliflozin’s therapeutic efficacy and core mechanism in MASH and associated renal injury, we utilized in vitro models (free fatty acid [FFA]-induced HepG2 hepatocyte MASH model, HK2 renal tubular epithelial cell injury model, Transwell co-culture system) and an in vivo MASH mouse model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Results showed dapagliflozin dose-dependently improved dysregulated lipid metabolism, suppressed inflammation, and alleviated fibrosis in vitro and in mouse liver/kidney tissues, while upregulating SIRT1/PPARα and downregulating SREBP-1c to restore lipid homeostasis. Molecularly, dapagliflozin specifically bound to ferroptosis key regulator solute carrier family 7 member 11 (SLC7A11), upregulated its abnormally reduced expression, and inhibited PI3K/AKT pathway hyperactivation—an effect mediated via a “liver-kidney axis” paracrine mechanism with β-hydroxybutyrate (β-HB) as the key mediator. Additionally, SLC7A11 knockdown in cells conversely confirmed that the lipid-lowering effect of dapagliflozin is mediated by SLC7A11.Collectively, dapagliflozin forms hydrogen bonds with SLC7A11, modulates the SIRT1/PPARα/SREBP-1c axis, and inhibits PI3K/AKT, thereby exerting therapeutic effects on MASH and associated renal injury.
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