International Journal of Biological Sciences
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2024
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IF 8.2
Suyun Yu,Rui Deng,Wei Wang,Defang Zou,Liang He,Zhonghong Wei,Yanhong Pan,Xiaoman Li,Yuanyuan Wu,Aiyun Wang,Wenxing Chen,Yang Zhao,Yin Lu
The thermo-sensory receptor, transient receptor potential channel 5 (TRPC5), a non-selective calcium ion (Ca 2+ )-permeable ion channel, has been implicated in cancer initiation and progression. However, its specific role in gastrointestinal cancer remains unclear. This study demonstrates that TRPC5 is significantly overexpressed in gastrointestinal tumors and is inversely associated with patient prognosis. TRPC5 overexpression triggers a substantial elevation in intracellular Ca 2+ levels ([Ca 2+ ]i), driving actin cytoskeleton reorganization and facilitating filopodia formation. Furthermore, kaempferol, a compound sourced from traditional Chinese medicine, is identified as a TRPC5 inhibitor that effectively suppresses its activity, thereby impeding gastrointestinal cancer metastasis. These findings underscore the potential of TRPC5 as a therapeutic target for metastasis inhibition, with kaempferol emerging as a promising natural inhibitor that could be optimized for clinical use in preventing cancer metastasis.
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高影响因子
FOOD HYDROCOLLOIDS
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2025
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IF 12.4
Wenjuan Qu,Xinyue Deng,Yuhan Li,Cunshan Zhou,Haile Ma
In order to enhance the stability and bioavailability of fat-soluble kaempferol (Kae), the zein-pectin nanoemulsions were synthesized by a novel dual-frequency pulsed ultrasound (DFPU) technology to improve the loading effect of Kae. The effects of ultrasonic operating parameters on the nanoemulsions were examined, along with the influence of DFPU treatment on the structure, stability, digestion, and intracellular uptake of the nanoemulsions in this study. The results indicated that both emulsion encapsulation and DFPU treatment significantly enhanced the protection and delivery of Kae. Compared to the unsonicated emulsion, the emulsifying activity index, stability index, Kae embedding rate, and hydroxyl radical scavenging rate increased by 133.81%, 4.18%, 19.20%, and 19.73%, respectively, while the particle size decreased by 94.43% after DFPU treatment. DFPU treatment notably improved the stability of the nanoemulsions during long-term storage, high temperature, and salt concentration conditions, as well as the retention of Kae by 15.59% in intestinal digestives. Furthermore, DFPU treatment significantly enhanced the Caco-2 intracellular absorption rate, transport rate and bioavailability of Kae by 7.67%, 9.96% and 14.67%, respectively at a dosage of 0.6 mg/mL, which was attributed to the significant downregulation of mRNA expression levels of tight junction protein Occludin and efflux proteins MDR1 and BCRP by 21.27%, 51.05%, and 62.26%, respectively. This downregulation enhanced the intracellular transport capacity of Kae while reducing its exocytosis, thereby improving cellular utilization. The mechanism of improving the intracellular bioavailability of kaempferol was elucidated. This study offers a promising nanoemulsion for the efficient oral delivery of fat-soluble active ingredients, fully facilitating its antioxidant activity.
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Frontiers in Microbiology
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2026
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IF 4.5
Jiawei Huang,Qianqian Wang,Xiaowen Guo,Yuanyuan Niu,Junhong Huang,Boyi Zhang,Zixuan Guo,Zilong Wang,Shuying Feng
Background: Mulberry leaf (Morus alba L.) is an edible plant that has been found to have medicinal effects in the treatment of hyperuricemia (HUA). The bioactive compounds of mulberry leaf and their mechanisms of action have not been determined yet.Methods: In-silico methodologies were used to identify bioactive compounds and to determine the underlying mechanisms of mulberry leaf. In order to verify the biochemical mechanism and intestinal microbiota, in vivo experiments were conducted.Results: Kaempferol was identified as the principal bioactive compound, while the key targets were AKT1 and TNF. Molecular docking and dynamics simulations revealed that AKT1-kaempferol and TNF-kaempferol complexes showed strong and stable binding pattern after a 100 ns simulation. In vivo studies demonstrated that kaempferol exerted significant anti-HUA effects. Specifically, kaempferol reduces AKT expression and phosphorylation, which may in turn reduces the oxidative stress and inflammatory pathways and signal transmission of the kidneys. Meanwhile, the application of kaempferol attenuated gut microbiota dysbiosis caused by HUA.Conclusion: Kaempferol may regulate UA metabolism and inflammatory injury by modulating the AKT signaling pathway, and exert its effects on the gut-kidney axis and restoring gut microbiota composition.
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Frontiers in Pharmacology
·
2020
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IF 4.225
Yao He,Sun Jingyu,Wei Jie,Zhang Xin,Chen Bing,Lin Yajun
Over recent years, an increasing number of studies have confirmed that the occurrence and development of vascular pathological changes are closely related to oxidative stress and the inflammatory response of the vascular endothelium. Kaempferol is the most common flavonoid compound found in fruits and vegetables. Our present research identified that kaempferol had the capability to protect the vascular endothelium in a mouse model of vascular injury and explored the specific mechanisms underlying these effects by investigating oxidative stress, the extent of cardiovascular injury, and inflammatory markers such as NF-κB, TNF-α, IL-6, and the Nrf2/HO-1 signaling pathway. Analysis showed that kaempferol reduced oxidative stress and inflammation mediated by H2O2 and paraquat, respectively, both in vitro and in vivo. Furthermore, kaempferol suppressed the levels of TNF-α and IL-6, and the activation of NF-κB, in aortic tissues and human umbilical vein endothelial cells (HUVECs). Finally, we observed that kaempferol corrected the levels of antioxidants and elevated the protein levels of Nrf2 and HO-1 in aortic tissues and HUVECs. Collectively, our findings prove that kaempferol protects blood vessels from damage induced by oxidative stress and inflammation and that the Nrf2/HO-1 signaling pathway plays a key role in mediating these effects.
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高影响因子
MICROCHEMICAL JOURNAL
·
2023
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IF 4.8
Qian Tan,Chao Chen,Cuixia Lin,Jiahui Zhang,Saiwen Liu,Jin Zhang
Kaempferol (KA), which is a biologically active natural polyphenol compound with considerable medicinal value, can be used to fight various diseases. Herein, a β-cyclodextrin/fullerene-graphene oxide/Nickel-metal–organic framework (β-CD/C 60 -GO/Ni-MOF) composite-based electrochemical sensor was developed to detect KA; the composite was characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, and X-ray photoelectron (XPS) spectroscopy. The biocompatibility and host–guest recognition performance of β-cyclodextrin (β-CD); the porosity and the catalytic performance of the nickel-metal–organic framework (Ni-MOF); and the excellent electrical conductivity of fullerene-graphene oxide (C 60 -GO) work together to considerably improve the detection performance of the sensor for KA. The sensor has an extensive linear range (0.5–50 μM) and a low detection limit (58 nM) with an electrochemically active specific surface area of 0.0971 cm 2 ; furthermore, the redox mechanism of KA in the sensor is explained. For the detection of actual natural samples of broccoli containing KA, satisfactory recovery rates and accuracy were observed; the recovery rate was 96.4 %–101.1 %.
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高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
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2024
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IF 4.8
Pan Su,Liming Liu,Yuhang Gong,Shuaijun Peng,Xiangli Yan,Ming Bai,Erping Xu,Yucheng Li
Background The pathogenesis of depression is largely influenced by dyshomeostasis of neuroinflammation regulated by microglia M1/M2 polarization, and NLRP3 inflammasome acts critical roles in shifting microglia polarization. Kaempferol (Kae), a major flavonoid in edible plants, possesses anti-inflammation and anti-depression capacity, but its underlying cellular and molecular mechanisms of antidepressive effect have not yet fully explored. Methods In vivo studies with lipopolysaccharide (LPS)-induced depressive mice were carried out to evaluate antidepressant effect of Kae. In vitro, BV2 microglia cell line stimulated by LPS along with IFN-γ to detect pharmacological effects of Kae on microglia polarization and NLRP3. Based on two depression-related GEO datasets (GSE54570 and GSE54568) and the potential targets of Kae obtained from GeneCards database, enrichment analysis and protein–protein interaction (PPI) network construction reveal potential therapeutic targets of Kae for depression. Then the precise antidepressant mechanisms of Kae were verified by western blot and immunofluorescent staining in vivo and vitro . Results Our results showed that Kae significantly improves LPS-induced depressive behaviors and alleviates neuroinflammation in prefrontal cortex. Moreover, Kae obviously shifted microglia polarization to M2 phenotype, and also suppressed NLRP3 in prefrontal cortex and BV2. Enrichment analysis and PPI network construction suggested PPARγ and STAT1 signaling are related to regulation of NLRP3 in depression. Furtherly, Kae remarkably enhanced PPARγ activation and inhibited nuclear translocation of p-STAT1 in microglia of prefrontal cortex and BV2. Importantly, pre-incubation with PPARγ antagonist T0070907 or overexpression with CA STAT1 (constitutively active STAT1) both prevented pharmacologic effects of Kae on shifting microglia polarization and suppressing NLRP3 in BV2. Noteworthily, T0070907 significantly blocked the inhibitory effect of Kae on STAT1 while overexpression with CA STAT1 abolished the effect of Kae on PPARγ activation in BV2. Above results suggested that pharmacologic effects of Kae on microglia polarization and NLRP3 are dependent on the balance of counter-regulatory PPARγ and STAT1 signaling. Conclusion Our results indicated that the shifting microglia polarization and suppression of NLRP3 via tilting the balance of PPARγ and STAT1 signaling may be the antidepressant mechanism of Kae, which provides a novel perspective for elucidating antidepressive effect of Kae.
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高影响因子
RSC Advances
·
2019
·Vol. 9
·期 59
·34607-34616
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IF 3.049
Xiaojie Wang,Li Li,Genyi Zhang
The barrier function of intestinal tract is essential to gut health, and the expression of tight junction (TJ) proteins in human epithelial colorectal adenocarcinoma (Caco-2) cells, mimicking the intestinal stem cell proliferation and differentiation, was investigated after treatment by the mycotoxin of deoxynivalenol (DON) and phenolic compound of kaempferol (KAM). The results showed that DON (5 μM) significantly reduced the expression of claudin-4 while kaempferol (100 μM) increased the expression of claudin-3 during Caco-2 cell proliferation. After being cultured for 11 days, the DON treatment, unexpectedly, augmented the expression of claudin-4 with an increased TEER. For differentiated Caco-2 cells after a 21 day culture, both the TEER and claudin-4 levels were significantly reduced by DON while KAM pretreatment alleviated the damage caused by DON accompanying an increase of TEER, claudin-3, and ZO-1. Thus, kaempferol and DON differentially affected the expression of tight junction proteins at different stages of Caco-2 cell proliferation and differentiation, and an increase of the integrity of TJ after KAM pretreatment indicates KAM has the potential to protect the integrity of the barrier function of the intestinal epithelium for improved health.
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International Journal of Food Engineering
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2023
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IF 1.6
Danni Song,Changqing Xie,Rong Yang,Aijinxiu Ma,Honghui Zhao,Fengmao Zou,Xiangrong Zhang,Xu Zhao
Kaempferol (KPF) is a flavonoid compound, which has a variety of pharmacological activities, and widely exists in daily diet. However, its application is limited due to poor solubility. Citric acid (CA) is a common food additive with high solubility. In this study, solid dispersion (SD) was prepared with CA as the carrier to improve the solubility of KPF. KPF-CA-SD (weight ratio 1:20) was obtained by ultrasonic for 20 min at 40 °C. The in vitro dissolution of KPF in SD was increased from about 50% to more than 80%. The physicochemical characterizations were analyzed by X-ray diffraction, differential scanning calorimetry, Fourier transform infrared spectroscopy, and scanning electron microscope. In hyperuricemia mice, KPF-SD (equivalent to 100 mg/kg KPF) can effectively reduce serum uric acid and exert nephroprotective effects. In conclusion, the preparation of SD with CA might provide a safe and effective selection to facilitate application of KPF in food and medicine.
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高影响因子
Journal of Functional Foods
·
2021
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IF 4.451
Ge Fang,Chuanjing Cheng,Manqian Zhang,Xiaoyao Ma,Shengnan Yang,Xiaotao Hou,Jiagang Deng,Yuanyuan Hou,Gang Bai
Kaempferol and quercetin, as dietary flavonoids, are beneficial to diabetes risk reduction. Clarifying the mechanism of dietary flavonoids in improving glucose metabolism may meet the functional and nutritional requirements. In this paper, PCA revealed two glucuronides, kaempferol-3-glucuronide (K-3-G) and quercetin-3-glucuronide (Q-3-G), which were the primary metabolites. Target prediction, enzymatic activity, and AKT plasma translocation assays indicated that K-3-G and Q-3-G could target the AKT PH domain. Fluorescence spectrometry was used to measure the dissociation constants of K-3-G (K D = 27.6 μM) and Q-3-G (K D = 10.8 μM). Molecular docking provided interaction insights for K-3-G and Q-3-G with the AKT PH domain. K-3-G and Q-3-G activated the AKT/GSK3β phosphorylation, thereby improving glucose consumption. Our study demonstrates that the glucuronide metabolites of flavonoids directly target the AKT PH domain and activate AKT/GSK3β signal pathway, thereby improving glucose metabolism.
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高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2024
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IF 4.8
Xiaoliang Li,Mingyan Zhou,Zhe Zhu,Zhe Wang,Xuguang Zhang,Lu Lu,Zhenrui Xie,Bingshu Wang,Yipeng Pan,Junqing Zhang,Jian Xu
Ethnopharmacological relevance Alpinia officinarum Hance ( A . officinarum ), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A . officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A . officinarum , has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated. Aim of the study This investigation aims to elucidate the anti-HCC effects of kaempferol derived from A . officinarum and to delve into its underlying mechanistic pathways. Materials and Methods Using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum . HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A . officinarum . The cytotoxicity and proliferation of kaempferol and A . officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples. Results UPLC-MS/MS was employed to detect five active compounds in A . officinarum , such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A . officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC. Conclusions Collectively, our results revealed that kaempferol from A . officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.
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高影响因子
INFLAMMATION RESEARCH
·
2024
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IF 4.8
Su Pan,Li Zibo,Yan Xiangli,Wang Baoying,Bai Ming,Li Yucheng,Xu Erping
Objective and design Mast cells (MCs), as the fastest immune responders, play a critical role in the progression of neuroinflammation-related diseases, especially in depression. Quercetin (Que) and kaempferol (Kae), as two major diet-derived flavonoids, inhibit MC activation and exhibit significant antidepressant effect due to their anti-inflammatory capacity. The study aimed to explore the mechanisms of inhibitory effect of Que and Kae on MC activation, and whether Que and Kae suppress hippocampal mast cell activation in LPS-induced depressive mice. Subjects and treatment In vitro assays, human mast cells (HMC-1) were pretreated with Que or Kae for 1 h, then stimulated by phorbol 12-myristate 13-acetate (PMA) and 2,5-di-t-butyl-1,4-benzohydroquinone (tBHQ) for 3 h or 12 h. In vivo assays, Que or Kae was administered by oral gavage once daily for 14 days and then lipopolysaccharide (LPS) intraperitoneally injection to induce depressive behaviors. Methods The secretion and expression of TNF-α were determined by ELISA and Western blotting. The nuclear factor of activated T cells (NFAT) transcriptional activity was measured in HMC-1 stably expressing NFAT luciferase reporter gene. Nuclear translocation of NFATc2 was detected by nuclear protein extraction and also was fluorescently detected in HMC-1 stably expressing eGFP-NFATc2. We used Ca 2+ imaging to evaluate changes of store-operated calcium entry (SOCE) in HMC-1 stably expressing fluorescent Ca 2+ indicator jGCamP7s. Molecular docking was used to assess interaction between the Que or Kae and calcium release-activated calcium modulator (ORAI). The hippocampal mast cell accumulation and activation were detected by toluidine blue staining and immunohistochemistry with β-tryptase. Results In vitro assays of HMC-1 activated by PtBHQ (PMA and tBHQ), Que and Kae significantly decreased expression and secretion of TNF-α. Moreover, NFAT transcriptional activity and nuclear translocation of NFATc2 were remarkably inhibited by Que and Kae. In addition, the Ca 2+ influx mediated by SOCE was suppressed by Que, Kae and the YM58483 (ORAI inhibitor), respectively. Importantly, the combination of YM58483 with Que or Kae had no additive effect on the inhibition of SOCE. The molecular docking also showed that Que and Kae both exhibit high binding affinities with ORAI at the same binding site as YM58483. In vivo assays, Que and Kae significantly reversed LPS-induced depression-like behaviors in mice, and inhibited hippocampal mast cell activation in LPS-induced depressive mice. Conclusions Our results indicated that suppression of SOCE/NFATc2 pathway-mediated by ORAI channels may be the mechanism of inhibitory effect of Que and Kae on MC activation, and also suggested Que and Kae may exert the antidepressant effect through suppressing hippocampal mast cell activation.
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高影响因子
Food & Function
·
2020
·Vol. 11
·期 8
·7266-7279
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IF 4.171
Xiaojie Wang,Li Li,Genyi Zhang
Deoxynivalenol (DON) is one of the most widely distributed mycotoxins in the food chain, and the protective effect of kaempferol (KAM) pretreatment against the barrier dysfunction induced by DON in a Caco-2 cell model was investigated using a proteomic approach. The results showed that after KAM pretreatment, both the numbers of down- and up-regulated differentially expressed proteins were significantly lower than those in the DON group. Gene ontology analysis revealed that differentially expressed proteins were enriched in cell adhesion molecule binding, cell junction, and cell junction assembly. Further study demonstrated that KAM pretreatment affected the expression and assembly of tight junction and adherens junction proteins through the PKA pathway and MAPK/ERK pathway to improve the barrier integrity of the Caco-2 cell monolayer, and nutraceutical approach based on bioactive phytochemicals to improve the body's immunity might be an effective strategy to combat the adverse effects of mycotoxins on intestinal barrier function.
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高影响因子
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