PHYTOMEDICINE
·
2024
·
IF 6.7
Yunyi Xu,Qionghua Ding,Yuhuan Xie,Qingqing Zhang,Yangyu Zhou,Hairui Sun,Rui Qian,Liqun Wang,Xuxi Chen,Ying Gao,Yuqin Yao,Yue Xiao
Background Silicosis, an interstitial lung disease caused by inhalation of silica particles, poses a significant health concern globally. Green tea polyphenol (TP) stands out as a promising therapeutic candidate, yet its specific protective effects and in-depth mechanisms against silicosis have not been thoroughly investigated. Purpose This study aimed to systematically assess the protective potential of TP against silicosis and to elucidate the underlying mechanisms of its action. Methods A combination of physiological, transcriptomic, molecular, and computational techniques was employed. HPLC was used to identify the components of TP, and its antioxidant properties were tested with DPPH and ABTS assays. The effects of TP on lung injury were assessed in silicosis mice using histopathology, qRT-PCR, and western blot. Transcriptomic analysis was applied to explore the differentially expressed genes and pathways in response to TP intervention. In vitro studies with mouse alveolar macrophages (MH-S) examined TP's effects on cell viability, proliferation, apoptosis, and inflammation responses. Integrated qRT-PCR, western blot, immunohistochemistry, and molecular docking were performed to confirm the molecular mechanism underlying the protective effects of TP against silicosis. Results TP effectively attenuated pulmonary inflammation and fibrosis in silicosis mice, as evidenced by significant reductions in inflammation and fibrotic markers. Moreover, TP's therapeutic benefits were linked to its cytoprotective effects on alveolar macrophages, notably its ability to protect MH-S cells from silica particle-induced apoptosis, inhibition of proliferation, and inflammatory response, underscoring its targeted protective effects at the cellular level. Mechanistically, TP exerted its anti-silicosis activity by targeting key pathways implicated in inflammatory responses, notably through the inhibition of the IL-17/NF-κB p65 signaling cascade. Molecular docking simulations corroborated these findings, demonstrating favorable binding affinities between TP's bioactive components (EGC, ECG, and EGCG) and crucial proteins (IL-17A, IL-17F, p65, TNF-α, IL-6, and IL-1β) involved in the IL-17/NF-κB p65 signaling pathway. This pathway inhibition led to a significant decrease in the production of pro-inflammatory cytokines, such as TNF-α, IL-6, and IL-1β, thus mitigated silicosis. Conclusion TP demonstrates efficacy in alleviating silica particle-induced lung injury by suppressing inflammation through the IL-17/NF-κB p65 signaling pathway, underscoring its potential as a valuable natural compound for silicosis management.
研究领域:
肺科学
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药理学
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免疫学
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分子生物学
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毒理学
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产品关联
DOI
PubMed
高影响因子
AMERICAN JOURNAL OF CHINESE MEDICINE
·
2023
·Vol. 51
·期 08
·2157-2173
·
IF 5.7
Zhenfeng Liu,Wuming Zhou,Qingyang Liu,Zhirong Huan,Qiubo Wang,Xin Ge
Hemorrhagic shock (HS) is the leading cause of death in trauma patients. Inflammation following HS can lead to cardiac damage. Pachymic acid (PA), a triterpenoid extracted from Poria cocos , has been found to possess various biological activities, including anti-inflammatory and anti-apoptotic properties. Our research aims to investigate the protective effects of PA against HS-induced heart damage and the underlying mechanisms involved. Male Sprague-Dawley rats were intraperitoneally injected with PA (7.5 or 15 mg/kg) daily for three days. Subsequently, we created a rat model of HS by drawing blood through a catheter inserted into the femoral artery followed by resuscitation. The results revealed that HS led to abnormalities in hemodynamics, serum cardiac enzyme levels, and cardiac structure, as well as induced cardiac apoptosis. However, pretreatment with PA effectively alleviated these effects. PA-pretreatment also suppressed mRNA and protein levels of interleukin (IL)-1 β , IL-6, and tumor necrosis factor α (TNF- α ) in the heart tissues of HS rats. Additionally, PA-pretreatment reduced inflammatory cell infiltration and M1 macrophage polarization while exaggerating M2 polarization in HS rat hearts. The study observed a decreased proportion of the expression of of M1 macrophages (CD86 + ) and their marker (iNOS), along with an increased proportion of the expression of M2 macrophages (CD206 + ) and their marker (Arg-1). Notably, PA-pretreatment suppressed NF- κ B pathway activation via inhibiting NF- κ B p65 phosphorylation and its nuclear translocation. In conclusion, PA-pretreatment ameliorates HS-induced cardiac injury, potentially through its inhibition of the NF- κ B pathway. Therefore, PA treatment holds promise as a strategy for mitigating cardiac damage in HS.
研究领域:
药理学
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免疫学
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心脏病学
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病理生理学
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分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF HYDROGEN ENERGY
·
2024
·
IF 8.1
Shucan Qin,Qianqian Peng,Weizhen Kong,Rong Xue,Chongqing Xu,Jianming Shi,Yanrong Liu,Yunqian Ma
Integrating sulfide oxidation reaction (SOR) with hydrogen evolution reaction (HER) by electrochemical means to simultaneously valorize sulfion and produce hydrogen is an efficient cleaner production method. Currently, we reported on the fabrication of one succulent-like phosphorus-doped transition metal selenide bifunctional catalyst supported on nickel foam (P–CoSe/NF) for SOR and HER. The unique structure has a significant surface area that allows many active sites to be exposed, enabling the catalyst to have an excellent activity up to 100 mA cm −2 at only 0.362 V. The H 2 Faraday efficiency reaches 97.4% and the rate of sulfur evolution is 26.24 mg h −1 . The durability test demonstrates that the bifunctional catalyst possesses excellent anti-sulfur properties. The Density Functional Theory calculations demonstrate that phosphorus as a dopant is believed to confer an optimal electronic structure and local coordination environment by tuning d electron number. The calculate S 8 ∗ to S 8 was confirmed to have a low energy barrier, indicating the self-cleaning tendency caused by phosphorus doping. This work presents a promising approach utilizing anti-sulfur single-atom-doped transition metal selenide catalysts in electrochemical reaction, representing a significant advancement in achieving low-cost and high value-added using waste resources.
研究领域:
电化学
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材料科学
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催化
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可再生能源
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环境科学
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产品关联
DOI
高影响因子
Nutrients
·
2024
·Vol. 16
·期 22
·3854
·
IF 4.8
Yannan Zhang,Sijuan Huang,Shuai Zhang,Zhihui Hao,Jianzhong Shen
Background: Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common chronic functional gastrointestinal disorder that causes diarrheal and intestinal barrier disruptions. Although pomegranate peel extract (PPE) has been reported for the treatment of diarrheal and intestinal inflammation, its effectiveness and mechanisms specifically for the treatment of IBS-D remain unknown. Objectives: This study aimed to explore the therapeutic effect of PPE on IBS-D and elucidate its underlying mechanisms. Methods: A high-fat diet, restraint stress, and senna gavage were combined to establish a rat model mimicking IBS-D, to evaluate the therapeutic effects of PPE. Network pharmacology analysis, serum medicinal chemistry, and transcriptomics were employed to investigate potential downstream signaling pathways. Findings were further validated through molecular docking and Western blot analysis. Results: The findings revealed that PPE significantly improved the symptoms of IBS-D, ameliorated intestinal inflammation, and promoted intestinal barrier function. The target genes in the MAPK and NF-κB signaling pathways were significantly enriched and down-regulated. Molecular docking and Western blot assays were performed to verify that PPE had a high affinity for the protein candidates in these pathways, and significantly down-regulated the expression of p-IκB, p-p65, p-JNK, p-p38, and p-ERK1/2. Conclusions: The present study is the first to demonstrate that PPE alleviates diarrheal and intestinal damage in IBS-D, potentially by inhibiting MAPK and NF-κB signaling pathways. These findings suggest that PPE may provide a novel therapeutic option for IBS-D.
CAS / MDL:
研究领域:
胃肠病学
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药理学
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分子生物学
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动物模型
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功能基因组学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF MOLECULAR MEDICINE-JMM
·
2024
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IF 4.8
Wang Pengtao,Tao Wei,Li Qiujie,Ma Wanting,Jia Wei,Kang Yuting
Indole-3-aldehyde (I3A) is an intestinal microbial metabolite that regulates inflammation in various inflammatory diseases; however, its role in chronic obstructive pulmonary disease (COPD) remains unclear. This study aimed to investigate the anti-inflammatory effects and molecular mechanisms of I3A in COPD. We constructed in vivo models using cigarette smoke (CS)-stimulated mice and in vitro models using cigarette smoke extract (CSE)-stimulated MH-S cells. The results demonstrated that I3A significantly alleviated bronchial obstruction in mice with COPD and reduced the expression of inflammatory factors such as TNF-α, IL-1β, and IL-6. Additionally, I3A decreased the levels of matrix metalloproteinases MMP2, MMP12, and inhibited the NF-κB p65/NLRP3 pathways. Further investigation revealed that I3A inhibited NF-κB activity by suppressing p65 phosphorylation and nuclear translocation in CSE-stimulated MH-S cells. The activation of the NF-κB and NLRP3 signaling pathways is mediated by histone deacetylase 5 (HDAC5) and HDAC6, both of which are inhibited by I3A. Subsequent experiments indicated that aryl hydrocarbon receptor (AHR) knockdown attenuated the inhibitory effect of I3A on pro-inflammatory cytokines and the HDACs/NF-κB/NLRP3 signaling pathways, highlighting the dependence of I3A's anti-inflammatory effects on the AHR receptor. Key messages
I3A effectively reduced lung inflammation in COPD mice by inhibiting the NF-κB pathway.
In CSE-stimulated MH-S cells, I3A suppressed p65 phosphorylation and nuclear translocation, thereby inhibiting NF-κB activity.
The activation of the NF-κB/NLRP3 pathways by HDAC5 and HDAC6 was diminished by I3A.
Through the activation of the AHR receptor, I3A suppressed the activities of HDAC5/6, leading to a decrease in inflammatory factor levels.
Graphical abstract
研究领域:
呼吸病学
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免疫学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 4
·619
·
IF 5.1
Kaijie Shang,Zhiheng Zhao,Hua Chen,Xiaonan Bian,Xianquan Zhong,Xiaoping Hu,Xue Lin,Lu Wang
The consumption of wampee has traditionally been utilized to alleviate gastrointestinal inflammation and associated disorders; however, its exact mechanism has remained unknown. The aim of this study was to elucidate the therapeutic efficacy and underlying mechanism of wampee polyphenol extract (WPE) in dextran sulfate sodium (DSS)-induced ulcerative colitis (UC). The findings revealed that WPE alleviated diverse symptoms of UC, regulated various inflammatory cytokines, and effectively protected the colon tissue structure and barrier integrity, thereby inhibiting LPS translocation. Moreover, WPE restored the richness and diversity of gut microbiota and optimized its structure at the phylum and genus levels, causing a notable improvement in short- chain fatty acid (SCFA) metabolism, particularly acetic acid, propionic acid, and butyric acid. Consequently, WPE was demonstrated to effectively suppress the LPS-induced TLR4-p38 MAPK/NF-κB signaling pathway by modulating gut microbiota and SCFA metabolism. These findings provided a theoretical basis for the use of wampee as a potential functional natural food for UC.
研究领域:
营养学
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胃肠病学
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免疫学
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微生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
FASEB JOURNAL
·
2025
·Vol. 39
·期 16
·e70906
·
IF 4.2
Lina Wei,Lei Wang,Yang Yu,Xiaozhou Sun,Liang Liu,Jing Han,Yongji Wang,Yinan Guo
Pediatric bacterial pneumonia continues to pose a significant global health burden, often resulting in serious complications. Recent studies have emphasized the pivotal role of the gut-lung axis in the progression of respiratory diseases, wherein disruptions in gut microbiota can aggravate pulmonary inflammation. This research investigates the underlying mechanisms by which Ma-Xing-Shi-Gan Decoction (MXSG), a classical formula in traditional Chinese medicine, influences the gut-lung axis in the context of childhood bacterial pneumonia. Clinical data indicated pronounced alterations in intestinal microbial composition and a marked decline in short-chain fatty acid (SCFA) levels among affected pediatric patients—changes that coincided with dysfunctional gut-lung signaling. In a murine model of bacterial pneumonia, MXSG administration restored microbial diversity, elevated SCFA production, and attenuated inflammatory responses by suppressing the HDAC3/NF-κB signaling cascade. Key bioactive constituents of MXSG—namely, quercetin, osajin, nobiletin, and solasodine—were identified as critical regulators, modulating lipid metabolism and promoting SCFA biosynthesis. These results highlight the therapeutic promise of MXSG in reestablishing gut-lung homeostasis and shed light on its mechanistic potential in the treatment of pediatric bacterial pneumonia. Graphical This schematic illustrates how MXSG restores gut microbiota diversity and SCFA levels, suppresses HDAC3/NF-κB signaling, and alleviates lung inflammation in pediatric bacterial pneumonia. Integrated multi-omics and mouse model experiments reveal that MXSG modulates the gut-lung axis and provides a novel mechanism for its clinical efficacy.
研究领域:
中医药学
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微生物学
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免疫学
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药理学
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分子生物学
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儿科学
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呼吸疾病
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 17
·8678
·
IF 4.9
Yamin Zhang,Jiajia Lin,Xiaomei Xu,Xuehua Lu,Lisha Li,Yuezhen Yang,Wenjin Lin
This study aimed to compare the therapeutic effects of fresh (CMF) and dried (CMD) Centipeda minima against allergic rhinitis (AR), elucidate their underlying molecular mechanisms, and identify the bioactive compounds responsible for their immunomodulatory actions. An ovalbumin-induced AR mouse model was treated with CMF or CMD extracts, followed by evaluation of nasal symptoms, serum biomarkers (IgE, histamine, cytokines), and nasal mucosa histopathology. Transcriptomics and widely targeted metabolomics were integrated with network pharmacology to identify differentially expressed genes and bioactive components, which were further validated in RAW264.7 and RBL-2H3 cells. CMF and CMD exhibited distinct anti-AR mechanisms: CMF predominantly suppressed Th2 responses (reducing IgE, IL-6, and histamine while elevating IL-10), whereas CMD enhanced Th1 activity (increasing IFN-γ). Metabolomic analysis revealed CMF was rich in amino acids while CMD contained higher flavonoids, with neocnidilide and 6-gingerol identified as key bioactive compounds that modulated TNF-α, IL-6, and IL-10 via NF-κB and JAK-STAT pathways. These findings demonstrate that CMF and CMD exert complementary anti-inflammatory effects through Th2 inhibition and Th1 activation, respectively, providing a molecular basis for the traditional use of Centipeda minima and highlighting its bioactive compounds as potential therapeutics for inflammatory diseases.
研究领域:
药理学
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免疫学
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民族药理学
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分子生物学
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植物学
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生物医学
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产品关联
DOI
PubMed
高影响因子
FOOD RESEARCH INTERNATIONAL
·
2024
·
IF 7
Chengyu Jin,Chu Chu,Xianghai Zhu,Yuanchao Lu,Ningxiang Yu,Qin Ye,Yuanxiang Jin,Xianghe Meng
Camellia oleifera Abel ( C. oleifera ) is a multifunctional oilseed, which is rich in many biological active substances with health-promoting properties, especially polyphenols. Previous research revealed that camellia oil phenolics exhibited anti-inflammatory effect, which originated from seed. Thus, we aimed to explore the components of camellia seed phenolics and its potential mechanism of anti-inflammation. Initially, fractional extraction was processed to prepare the phenolics from camellia seed kernels, and we compare four different fractions of phenolics under the LPS-induced Caco-2/RAW264.7 coculturing model. Results showed that free phenolics (FP) had best effect on alleviating pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and TNF-α) compared to esterified-bound phenolics (EP), glycosylated-bound phenolics (GP) and insoluble-bound phenolics (IP). Furthermore, FP reduced inflammation by suppressing the PI3K/Akt/NF-κB signaling pathway and effectively inhibited LPS-induced intestinal permeability increase, tight junction related proteins loss (ZO-1, claudin-1). Same results obtained, as the transepithelial electrical resistance (TEER) and alkaline phosphatase (AKP) activity of high-dose FP treated group was high than model group. Finally, molecular docking was used for evaluating the anti-inflammatory effect for phenolic monomer. KGRG (kaempferol −3-O-(2-O-glucopyranosyl-6-O-rhamnopyranosyl)-glucopyranoside), KXR (kaempferol 3-O-(2′’-xylopyranosyl)-rutinoside) and leucoside (kaempferol 3-O-sambubioside) show lower binding energy docking with NF-κB, PI3K and Akt protein, indicating better interactions, which might be effective constituents against inflammation. Subsequently, five major polyphenols were obtained to validate the docking results, especially, indicating the best anti-inflammatory activities of KGRG. Overall, this research sheds insights on the therapy of phenolics from C. oleifera seed towards LPS-induced intestinal inflammation model in vitro and its related mechanism.
研究领域:
药理学
·
分子生物学
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营养保健品
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2024
·
IF 4.4
Chencen Lai,Shuo Zhang,Zhiyu Chen,Xiaoyu Fu,Min Zhang,Pengjiao Wang,Xiuli Gao
Pyroptosis induced by oxidative stress is a significant contributor to mental health disorders, including depression (+)-Catechin (CA), a polyphenolic compound prevalent in various food sources, has been substantiated by prior research to exhibit potent antioxidant properties and potential antidepressant effects. Nonetheless, the precise antidepressive mechanisms and effects of CA remain incompletely elucidated. In this study, we employed corticosterone (CORT) and PC12 cells to develop a cellular model of depression, aiming to investigate the protective effects of CA against CORT-induced cellular damage. Our objective was to elucidate the underlying mechanisms of protective action. We utilized transcriptomic analysis to identify differentially expressed genes and employed bioinformatics approaches to predict the potential mechanisms of CA’s protective effects in PC12 cells. These transcriptomic predictions were subsequently validated through western blot analysis. The findings indicated that CA possesses the capacity to mitigate oxidative stress and suppress pyroptosis in PC12 cells via the activation of the PI3K/AKT signaling pathway. This activation subsequently modulates the Nrf2/HO1/NF-κB pathways, thereby providing protection to PC12 cells against damage induced by CORT. Furthermore, we investigated the interaction between CA and the Keap1 protein employing molecular docking and protein thermal shift assays. We propose that CA can activate Nrf2 through two mechanisms to decrease reactive oxygen species (ROS) levels and inhibit pyroptosis: one mechanism involves the activation of the PI3K/AKT signaling pathway, and the other involves direct binding to Keap1, leading to an increase in p-Nrf2.
研究领域:
神经科学
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药理学
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细胞生物学
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分子生物学
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生物信息学
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DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF HISTOCHEMISTRY
·
2024
·Vol. 68
·期 3
·4034
·
IF 2.1
Lan Wang,Zhenyu Fan,Haijin Wang,Shougui Xiang
Subarachnoid hemorrhage (SAH) is a devastating stroke caused by ruptured intracranial aneurysms, leading to blood accumulation around the brain. Early brain injury (EBI) within 72 h post-SAH worsens prognosis, primarily due to intense neuroinflammation. Microglia, pivotal in central nervous system defense and repair, undergo M1 to M2 polarization post-SAH, with M1 exacerbating neuroinflammation. Propofol (PPF), an anesthetic with anti-inflammatory properties, shows promise in mitigating neuroinflammation in SAH by modulating microglial activation. It likely acts through microRNAs like miR-140-5p, which attenuates microglial activation and inflammation by targeting TREM-1 and the NF-κB pathway. Understanding these mechanisms could lead to new therapeutic approaches for SAH-related EBI. In this study, BV-2 cell was used to establish in vitro model of SAH, and the expression of miR-140-5p and TREM-1 was detected after modeling. Microglial activity, apoptosis, the inflammatory pathway and response, oxidative damage, and M1/M2 polarization of microglia were evaluated by drug administration or transfection according to experimental groups. Finally, the targeting relationship between miR-140-5p and TREM-1 was verified by dual luciferase reporter assays, and the effect of PPF on the miR-140-5p/TREM-1/NF-κB signaling cascade was evaluated by RT ‒ qPCR or Western blotting. PPF effectively mitigates apoptosis, neuroinflammation, oxidative damage, and M1 microglial polarization in SAH. In SAH cells, PPF upregulates miR-140-5p and downregulates TREM-1. Mechanistically, PPF boosts miR-140-5p expression, while TREM-1, a downstream target of miR-140-5p, inhibits NF-κB signaling by regulating TREM-1, promoting M1 to M2 microglial polarization. Reduced miR-140-5p or increased TREM-1 counters PPF's therapeutic impact on SAH cells. In conclusion, PPF plays a neuroprotective role in SAH by regulating the miR-140-5p/TREM-1/NF-κB signaling axis to inhibit neuroinflammation and M1 polarization of microglia.
研究领域:
神经科学
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药理学
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炎症
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
NEUROSCIENCE
·
2024
·
IF 2.9
Tao Ye,Ning Zhang,Yunting He,Chunyan Chen,Qiqi Zha,Anbang Zhang,Xiuqi Sun,Xuemei Wu
Cerebral ischemia–reperfusion injury is frequently associated with neuroinflammation. The modulation of microglial polarization presents a promising approach for addressing cerebral ischemia–reperfusion injury. While electroacupuncture preconditioning has demonstrated efficacy in the management of ischemic stroke, the underlying therapeutic mechanisms remain inadequately understood. The investigation focused on elucidating the relationship between alterations in the TLR4/NF-κB/TXNIP/NLRP3 signaling pathway and microglial polarization subsequent to EA pretreatment. Established a middle cerebral artery occlusion (MCAO) rat model following electroacupuncture (EA) treatment at the Baihui (GV 20) acupoint. Male Sprague-Dawley rats were randomly assigned to the sham, Ischemia/Reperfusion (I/R), I/R + EA groups (n = 6). The results of Nissl Staining and TUNEL Stainingl showed that the number of curative neurons increased significantly after pretreatment, indicating an improvement in neuron formation and an increase in the number of austenite. The level of apoptosis in brain tissue in the I/R group was significantly higher than that in the sham operation group. Electroacupuncture pretreatment can effectively inhibit apoptosis occurrence. In addition, electric acupuncture pretreatment protects rat blood–brain barrier integrity and mitochondrial function. After treatment, the number of M1-type microglia decreased, while the number of M2-type microglia increased. These results suggest that EA preconditioning may alleviate neurological deficits and neuronal apoptosis caused by cerebral I/R injury, while maintaining the integrity of the blood–brain barrier and promoting microglial polarization through the TLR4/NF-κB/TXNIP/NLRP3 signaling pathway. Our findings establish a new molecular mechanism and theoretical foundation for electroacupuncture therapy of ischemic stroke.
研究领域:
神经科学
·
免疫学
·
药理学
·
中医
✓ 已验证
DOI
PubMed
高影响因子
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