Food Bioscience
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2024
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IF 4.8
Jindan Xiao,Liuming Xie,Bing Zheng,Wenjie Ma,Yi Chen,Jianhua Xie,Xiaobo Hu,Qiang Yu
Autophagy is pivotal for the management of intestinal homeostasis, modulation of intestinal immunity response and anti-microbial protection. Previous studies have documented the protective function of Polygonatum cyrtonema Saponin (PCS) against intestinal injury, but whether PCS modulated autophagy and its associated responses remained unknown. A model of dextran sodium sulfate (DSS)- elicited intestinal injury was employed to confirm this hypothesis. The results showed that PCS effectively relieved the typical symptoms of DSS-induced weight reduction, shortened colon length, and augmented disease activity index score, down-regulated organ indices, reduced hepatic oxidative stress, and inhibited excessive inflammatory mediators. Meanwhile, PCS intervention ameliorated the intestinal barrier dysfunction via promoting the differentiation of goblet cells and augmenting the expression of tight junction proteins (TJs). It also suppressed apoptosis in intestinal cells by altering the Bcl-2/Bax ratios and diminishing the expressions of Caspase-9 and Caspase-3. Additionally, PCS remarkably enhanced autophagy by modulating the PI3K/AKT/mTOR signal pathway. More importantly, the classical autophagy inducer rapamycin augmented the beneficial effects of PCS. In contrast, the autophagy inhibitor 3-methyladenine essentially eliminated the above effects, revealing a role for autophagy in the response. Further studies have demonstrated that PCS intervention improved the diversities of the intestinal flora, increased occupancy of beneficial bacteria in Lachnospiraceaeae and Akkermansia , which was closely associated with autophagy. Taken together, these findings demonstrated that PCS is a potential supplier of prebiotics by modulating immunity, repairing intestinal mucosal injury, regulating autophagy and intestinal flora, and autophagy is a key target for PCS-mediated intestinal barrier protection.
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JOURNAL OF NUTRITIONAL BIOCHEMISTRY
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2024
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IF 4.8
Suizhi Cheng,Jin Chen,Qianhui Li,Yuhong Nie,Ting Ni,Caiting Peng,Xi Luo,Yasin Pazilat,Shumin Zhang,Jiancai Tang,Zhenzhong Liu
Recent research has revealed that N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) constitutes a significant risk factor in the development of esophageal cancer. Several investigations have elucidated the beneficial impact of folic acid (FA) in safeguarding esophageal epithelial cells against MNNG-induced damage. Therefore, we hypothesized that FA might prevent MNNG-induced proliferation of esophageal epithelial cells by interfering with the PI3K/AKT/mTOR signaling pathway. In vivo experiments, we found that FA antagonized MNNG-induced proliferation of rat esophageal mucosal epithelial echinocytes and activation of the PI3K/AKT/mTOR signaling pathway. In our in vitro experiments, it was observed that acute exposure to MNNG for 24 h led to a decrease in proliferative capacity and inhibition of the PI3K/AKT/mTOR signaling pathway in an immortalized human normal esophageal epithelial cell line (Het-1A), which was also ameliorated by supplementation with FA. We successfully established a Het-1A-T-cell line by inducing malignant transformation in Het-1A cells through exposure to MNNG. Notably, the PI3K/AKT2/mTOR pathway showed early suppression followed by activation during this transition. Next, we observed that FA inhibited cell proliferation and activation of the PI3K/AKT2/mTOR signaling pathway in Het-1A-T malignantly transformed cells. We further investigated the impact of 740Y-P, a PI3K agonist, and LY294002, a PI3K inhibitor, on Het-1A-T-cell proliferation. Overall, our findings show that FA supplementation may be beneficial in safeguarding normal esophageal epithelial cell proliferation and avoiding the development of esophageal cancer by decreasing the activation of the MNNG-induced PI3K/AKT2/mTOR signaling pathway.
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JOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE
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2024
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IF 3.3
Wanyu Yan,Cong Chen,Yuanru Zheng,Jingwen Xu,Yihai Wang,Xiangjiu He
BACKGROUND Apples are among the most nutritionally valuable fruits and have a history of use in traditional Chinese medicine. Triterpenoids, the primary bioactive compounds found in apples, demonstrate significant antitumor activity. RESULTS Following enrichment and optimization, the total content of major triterpenoids in total triterpenoids from apple peels (ATT) reached 5.76 g kg −1 . The growth of MDA-MB-231 xenograft tumors was significantly inhibited after treatment with ATT. Network pharmacology analysis conclusively identified a close association between the antitumor effect of ATT and the phosphatidylinositol 3-kinase–protein kinase B (PI3K-Akt) signaling pathway. Experimental validation using MDA-MB-231 cells and a xenograft nude mouse model confirmed that ATT suppressed tumor cell proliferation effectively by modulating the PI3K-Akt signaling pathway, which was consistent with the findings from network pharmacology. The total triterpenoids from apple peels also induced cell apoptosis by mediating the PI3K-Akt signaling pathway. CONCLUSION The total triterpenoids from apple peels can inhibit tumor cell proliferation and induce cell apoptosis effectively through the PI3K-Akt signaling pathway, suggesting that ATT holds promise as a prospective therapeutic agent for breast cancer treatment. © 2024 Society of Chemical Industry.
研究领域:
药理学
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肿瘤学
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分子生物学
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PubMed
高影响因子
NEW JOURNAL OF CHEMISTRY
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2025
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IF 2.5
Yanru Liu,Ya Hu,Xiaoxia Xie,Gongjun Yang,Fang Feng
Wen-Pi-Tang (WPT), a Traditional Chinese Medicine (TCM) prescription, is commonly used to treat chronic renal failure. However, the material basis and potential mechanisms of WPT against chronic renal failure have not been clarified. UHPLC-Q-Exactive Orbitrap-MS was utilized in this work to investigate the chemical components of WPT and their prototypes or metabolites in vivo. 227 chemical compounds were identified in the WPT. Meanwhile, 56 exogenous components (24 prototype components and 32 metabolic components) were examined in rat plasma. Meanwhile, network pharmacology revealed that liquiritigenin-O-sulfate, 3-keto-18β-glycyrrhetinic acid, 22-hydroxy-18-β-glycyrrhetinic acid, and hydroxyliquiritigenin (B ring)-O-sulfate with related targets AKT1, EGFR, STAT3, ESR1, SRC, MAPK3, MTOR, and PIK3CA were considered as the effective components and core targets. Furthermore, the findings suggested that the therapeutic effects of WPT on chronic renal failure may be substantially influenced by the PI3K-Akt, HIF-1, and FoxO signaling pathways. The outcomes of molecular docking and molecular dynamics simulations indicate that the key targets have strong binding capacities with effective components. Our study offers a comprehensive method for examining the molecular foundation and underlying mechanisms of WPT against chronic renal failure, opening up new therapeutic opportunities.
研究领域:
中药学
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药理学
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代谢组学
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高影响因子
BURNS
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2024
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IF 3.2
Meiyue Yang,Zhibo Yang,Xiangjun Huang,Xiaoping Li,Fangqin Chou,Shuiqing Zeng
The aim of this study was to explore the effect and mechanism of formononetin (FMNT) in thermal-injured fibroblast proliferation, apoptosis, and oxidative stress. After the thermal injury, HSF cells showed inhibited proliferation, migration, and ECM synthesis, whereas increased apoptosis, ROS production, and inflammation. Specifically, after thermal injury, cell viability, migration distance, and protein levels of Collage I, Collage III, α-SMA, MMP1, and MMP3 were reduced; cell apoptosis rate and TUNEL-positive cell numbers were increased; the levels of Bax and Cleaved caspase-3 showed to be elevated, while Bcl-2 level showed to be reduced. Moreover, the thermal injured-HSF cells showed increased levels of ROS, MDA, LDH, TNF-α, and IL-1β, and decreased GSH, SOD, GSH-Px, and CAT. FMNT levels can partially eliminate the effects of thermal injury on HSF cells, as shown by promoting thermal injured-HSF cell proliferation and migration, and inhibiting cell apoptosis, ROS production, and inflammation. FMNT exerted no significant effect on normal HSF cells. Additionally, the level of the P13K/AKT/mTOR signaling-related proteins (p-P13K, p-AKT, and p-mTOR) was reduced in thermal injured-HSF cells, whereas FMNT could promote p-P13K, p-AKT, and p-mTOR levels. FMNT can partially alleviate the thermal injury-induced inhibition of fibroblast proliferation and migration; FMNT also inhibited the apoptosis, ROS level, and inflammation in thermal-injured cells. The effects of FMNT may be mediated by regulating the P13K/AKT/mTOR pathway.
研究领域:
药理学
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细胞生物学
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伤口愈合
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高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Yan Zhu,Shiyuan Yang,Jia Zhou,Zixiao Zhang,Yue Hu,Qingyu Xu,Yuning Zhou,Yuanjin Xu
The healing process of diabetic wounds is notably impeded due to reduced cellular functions, impaired vascularization, and persistent malignant inflammation, posing a significant obstacle in clinical management. Herein, a novel injectable multifunctional composite hydrogel (CMCSMF/QCT-Cu) with photo−/glucose-/ROS-responsivity was fabricated for enhancing diabetic wound healing which could be adapted to the local irregular anatomical shape as well as the microenvironment of high glucose and oxidative stress. Furthermore, experimental evidence has demonstrated that the CMCSMF/QCT-Cu composite hydrogel displays superior mechanical properties, with a storage modulus exceeding 700 Pa and an average adhesion strength of approximately 12.5 kPa, thereby enabling the hydrogel to effectively prevent external irritation and exhibit rapid hemostatic effects after injection. Moreover, this composite hydrogel exerted excellent collective functions including remodeling the homeostasis of fibroblast, accelerated angiogenesis and regulating immune microenvironment, ultimately accelerating diabetic wound healing, while the immunoregulatory effect may be attributed to the activation of the PI3K-AKT signaling pathway. Overall, the innovative multifunctional composite hydrogel presents a promising potential clinical therapy for enhancing diabetic wound healing.
研究领域:
生物材料学
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再生医学
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药理学
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PubMed
高影响因子
FITOTERAPIA
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2025
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IF 2.6
Ren-Fen Ma,Xin-Cheng Zhuang,Qian Wu,Hua Zhang
An intensive phytochemical study on the aerial parts of Euphorbia wallichii afforded ten lathyrane-type diterpenoids, including six formerly unreported ones ( 1 – 4 , 6 and 8 ). Their structures were determined via comprehensive spectroscopic analyses, and the absolute stereochemistries were assigned on the basis of electronic circular dichroism technique. Among these diterpenoids, compound 2 exhibited the best inhibitory activity on NO production and its potential anti-inflammatory mechanism was then explored by network pharmacology analysis. Further experimental validation demonstrated that diterpenoid 2 could exert its anti-inflammatory effect by suppressing pro-inflammatory factors and modulating PI3K/Akt/mTOR signaling pathway. In short, the present work confirms the promising potential of E. wallichii as a source of natural anti-inflammatory agents.
研究领域:
植物化学
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药理学
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药物化学
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天然产物研究
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2025
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IF 5.4
Huanchen Yao,Dayang Wang,Jiashuo Ye,Hailin Cong,Bing Yu
Ethnopharmacological relevance Lung cancer is a common respiratory cancer worldwide, which seriously threatens people's lives. The current treatment of lung cancer is not satisfactory. Traditional Chinese medicine records that Hedyotis diffusa Willd (HDW) has effects that include clearing heat and detoxifying, promoting diuresis and dehumidification, relieving pain and resolving masses, and exhibiting anti-cancer properties. It has shown extraordinary therapeutic value in the clinical practice of traditional Chinese medicine. It is commonly used to treat various tumors, inflammation, and other diseases. Aim of the study The purpose of this experiment is to isolate the components with anti-lung cancer effects from HDW and to explore its anti-lung cancer effect and mechanism through network pharmacology and in vitro cell experiments in order to find more effective and less side effects—anticancer drugs. Materials and methods We used ethanol to extract HDW preliminarily and then used ethyl acetate, n-butanol, petroleum ether, and water to extract it, obtaining the ethyl acetate fraction with the highest inhibition rate on lung cancer H1299 cells. The silica gel column purification, TOF, and nuclear magnetic resonance analysis yielded the Fisetin, which has an inhibitory effect on H1299 cells. The mechanism and application of Fisetin in inhibiting lung cancer were explored by network pharmacology and in vitro cell experiments. Results Using network pharmacology to explore the mechanism of Fisetin inhibiting lung cancer, 115 Fisetin targets, and 26,857 lung cancer targets were obtained, and 90 GO functions and 19 KEGG pathways were obtained (P < 0.01). Molecular docking results demonstrated that target protein-drug binding was stable. Afterward, the toxicity of Fisetin to H1299 cells was verified by in vitro cell experiments. MTT, live-dead staining, and confocal microscopy all showed that Fisetin had a good inhibitory effect on H1299 cells and had good cell compatibility. Through Western blot analysis, Fisetin can reduce the protein content of PI3K, MTOR, HIF1A and VEGFA. And it can reduce the mRNA expression levels of HIF1A and VEGFA. Moreover, Fisetin can also increase the expression of tumor suppressor molecule PTEN protein and mRNA in H1299 cells. Conclusions Fisetin and HDW can successfully stop lung cancer H1299 cells from growing. The mechanism of Fisetin may be related to the inhibition of PI3K/MTOR/HIF1A/VEGFA signaling pathway.
研究领域:
药理学
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肿瘤学
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生物信息学
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细胞生物学
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药物化学
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高影响因子
Human Cell
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2025
·Vol. 39
·期 1
·1-17
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IF 3.1
Guo Yan,Liu Ying,Zhou Mingkai,Zhao Yulan
Mitochondrial dysfunction is a key contributor to septic cardiomyopathy, driving myocardial inflammation and apoptosis. This study found that Sushi-repeat containing protein X-linked 2 (Srpx2) is associated with mitochondrial damage and is downregulated in the myocytes of lipopolysaccharide (LPS)-treated rats. Sprague Dawley rats were intraperitoneally injected with LPS (10 mg/kg) to establish a septic cardiomyopathy model. Adeno-associated viruses (8.5 × 10 11 vg/mL) containing Srpx2-overexpressing plasmids were injected into rats through their tail vein. Srpx2 overexpression improved hemodynamics and decreased myocardial damage in LPS-treated rats. H9C2 cells were treated with LPS (10 μg/mL) to establish an in vitro septic model. The cells were then transfected with Srpx2-overexpressing plasmids. Srpx2 overexpression ameliorated mitochondrial damage, which was evidenced by restoring mitochondrial morphology, enhancing the complex activities, and elevating ATP and mitochondrial membrane potential levels in cardiomyocytes. Srpx2 overexpression reduced mitochondrial reactive oxygen species levels and superoxide generation in cardiomyocytes. Srpx2 overexpression decreased cleaved caspase-3 and 9 protein levels. Tumor necrosis factor-α and interleukin-1 beta levels were also reduced in cardiomyocytes with Srpx2 overexpression, suggesting reversal of inflammation. The RNA-sequencing data indicated that Srpx2 might regulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway to protect cardiomyocytes. Srpx2 overexpression increased the p-PI3K and p-AKT protein levels. The treatment of H9C2 cells with 10 μM LY294002, a PI3K/AKT pathway inhibitor, reversed the protective effects of Srpx2 against mitochondrial damage and apoptosis. In conclusion, Srpx2 alleviates mitochondrial damage by activating the PI3K/AKT pathway, thereby reducing apoptosis and inflammation in septic cardiomyopathy. Graphical abstract
研究领域:
心脏病学
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分子生物学
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免疫学
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线粒体研究
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信号转导
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高影响因子
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
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2025
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IF 3.1
Man Tian,Yu Huiyong,Li Lei,Nie Weicheng,Wang Chengxiang
Multidrug-resistant Klebsiella pneumoniae (MDR-KP) infections present a global health crisis, with escalating resistance to last-line antibiotics. Traditional Chinese medicines (TCMs) demonstrate multi-component synergy against resistant pathogens. This study deciphered the antibacterial mechanisms of bioactive TCM components targeting MDR-KP through integrative pharmacology and experimental validation. Four core TCMs ( Scutellaria baicalensis , Forsythia suspensa , Lonicera japonica , Aloe vera ) were screened via Chinese Pharmacopoeia and TCMSP database. Network pharmacology identified core components and enriched pathways. Clinically isolated MDR-KP strains (resistant to meropenem, polymyxin E, and tigecycline) were characterized. Synergistic effects were evaluated using checkerboard assays, biofilm quantification, and membrane permeability assays. Molecular docking and RT-qPCR analyzed target interactions, while ELISA and CCK-8 assessed anti-inflammatory activity and cytotoxicity. Consequently, luteolin, wogonin, and kaempferol were identified as key components targeting PI3K/AKT and MAPK pathways. Their triple combination (2/4/8 μg/mL) exhibited potent synergy (FIC = 0.38), reducing biofilm biomass by 68% (p < 0.001) and extracellular polysaccharide thickness from 15.1 μm to 3.1 μm (p < 0.001). Flow cytometry confirmed a 144.8% increase in membrane permeability. Molecular docking revealed high-affinity binding to PI3K (− 6.78 kcal/mol), AKT1 (− 6.60 kcal/mol), and MAPK1 (− 7.24 kcal/mol), with RT-qPCR showing significant downregulation of these genes (p < 0.001). The combination suppressed LPS-induced TNF-α and IL-6 release by 72% and 65%, respectively, while maintaining 95.5% cell viability at therapeutic concentrations. In Conclusion, this study unveils a triple-action mechanism of luteolin-wogonin-kaempferol against MDR-KP, simultaneously disrupting resistance pathways, biofilms, and hyperinflammation. The regimen offers a safe, multi-target therapeutic strategy for combating drug-resistant infections.
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American Journal of Translational Research
·
2025
·Vol. 17
·期 10
·7749
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IF 1.6
Xiaowen Li,Ruikang Guo,Lingling Liang,Hao Liang,Guangqi Zhou,Qinglan Lu,Yonghui Huang,Zhen Qi,Xiaojie Li
Objective: Periodontitis, a prevalent oral disease leading to alveolar bone defects, remains a primary cause of tooth loss in adults. The biologic mechanisms driving bone loss in periodontitis are still poorly understood, limiting the development of genetic treatment. This study investigates potential therapeutic targets for alveolar bone loss by analyzing transcriptomic data related to the osteogenic differentiation of induced pluripotent stem cells (iPSCs). Methods: Using in vitro and in vivo models, we examined the role of neuropeptide Y receptor Y1 (NPY1R) and the PI3K-AKT-mTOR (PAM) signaling pathway in osteogenic differentiation and bone loss. A combination of bioinformatics, molecular biology, and histologic techniques was employed to pinpoint key signaling events that influence bone remodeling in periodontitis and to identify potential intervention points. Results: Transcriptomic profiling during iPSC osteogenic differentiation revealed significant upregulation of neuropeptide Y (NPY) and NPY1R. Suppression of NPY1R reduced the osteogenic capacity of iPSCs. Activation of the PAM pathway was observed during osteogenesis, and treatment with LY294002, a PAM pathway inhibitor, led to decreased osteogenic activity. In vivo experiments using a rat periodontitis model confirmed increased expression of NPY1R and activation of the PAM pathway, suggesting a role in bone repair processes. Conclusion: The NPY/NPY1R axis and the PAM signaling pathway appear to regulate bone regeneration and may be involved in preventing alveolar bone loss in periodontitis. These findings provide a new direction for therapy targeting bone defects associated with periodontal disease.
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MOLECULAR IMMUNOLOGY
·
2021
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IF 4.407
Limei Ao,Han Gao,Lifen Jia,Shimin Liu,Jie Guo,Bingzhen Liu,Qiumei Dong
Matrine (Mat) is an alkaloid of tetracycline quinazine, and previous studies have demonstrated its specific effect on relieving rheumatoid arthritis (RA). However, the effect of Mat on joint synovial angiogenesis in the pathogenesis of RA has not been elucidated. In this study, body weight, joint swelling, arthritis index (AI) score, histopathological changes, immunohistochemical, and western blot- were used in collagen-induced arthritis (CIA) rats to detect pro-inflammatory factors and, - expression levels of key cytokines and proteins along the hypoxia-inducible factor (HIF)-endothelial growth factor (VEGF)-angiopoietin (Ang) axis and VEGF-phosphoinositide 3-kinase (PI3K) / protein kinase B (Akt) pathway. In vitro experiments were conducted to observe the effect of Mat on the proliferation, migration and lumen formation of RA-fibroblast-like synovial cells (FLS) and human umbilical vein endothelial cells (HUVECs). Results showed that Mat reduced the degree of paw swelling and AI score in CIA rats, joint synovial tissue proliferation, inflammatory cell infiltration, and neovascularization; moreover, it down-regulated the expression levels of inflammatory factors interleukin-1β, interferon-γ, and pro-angiogenic factors VEGF, placental growth factor, HIF-α, Ang-1, Ang-2, Tie-2, and phosphorylation-Akt in the ankle joint of CIA rats. In addition, the in vitro experiments showed that Mat inhibited the proliferation and migration of RA-FLS and inhibited the proliferation and lumen formation of HUVECs. Therefore, Mat exerts an anti-angiogenesis effect by regulating the HIF-VEGF-Ang axis and inhibiting the PI3K/Akt signaling pathway. This inhibits the pathogenesis and improve the symptoms of RA, and may be offered as a candidate drug for the treatment of RA.
研究领域:
药理学
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免疫学
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病理学
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分子生物学
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高影响因子
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