Scientific Reports
·
2025
·Vol. 15
·期 1
·40525
·
IF 3.9
Ma Chunli,Wang Linghong,Cao Lili,Zhao Linyun,Zhang Xin,Ma Chengyou,Lian Hua,Bao Xiufang,Eerde Mutu,Buren Qiqige,Tong He,Dai Lili,Amu Guleng,Bao Yulong,Hong Mei,Wang Li
Acute liver injury (ALI) is a prevalent hepatic condition that poses significant risks to both life and overall health. Traditional Mongolian medicine utilizes Honghua Qinggan Thirteen-Flavor Pills (HHQG) as a primary formula for dispelling liver heat, illustrating both an extensive application in clinical settings and notable therapeutic effectiveness for treating liver ailments such as hepatitis and liver failure. Nevertheless, the molecular mechanisms underpinning the hepatoprotective properties of HHQG remain inadequately understood.We employed a CCl 4 -induced mouse model of liver injury alongside network pharmacology analysis, molecular docking studies, and cellular assays to dissect the effects and mechanisms of action of HHQG. Our findings demonstrated that HHQG significantly improved CCl 4 -induced liver injury in mice, reducing pathological damage and inflammatory factors. Network pharmacology identified 184 overlapping targets, 6 key genes, and 5 key active components in HHQG. Molecular docking confirmed the binding affinity of these components to RASD1. Gene expression analysis in liver tissue revealed a positive correlation between mRNA expression of RASD1 and NLRP3. Cell experiments demonstrated the role of RASD1 in regulating NLRP3 inflammasome and inflammatory factors. Pretreatment of HHQG attenuated LPS-induced inflammatory response and the activation of PKCδ-NF-κB signaling pathway. In the CCl 4 -induced liver injury model, HHQG significantly reduced NLRP3, RASD1, and PKCδ-NF-κB expression.This study revealed that HHQG effectively mitigates CCl 4 -induced liver injury by inhibiting the activation of NLRP3 inflammasome by regulating the PKCδ-NF-κB signaling pathway via RASD1. These findings provide novel theoretical support for the rational application of HHQG as a potential hepatoprotective agent.
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PHYTOTHERAPY RESEARCH
·
2025
·
IF 6.3
Xian Zheng,Yuanyue Jiang,Wenbo Wang,Kekang Sun,Libin Zhou,Yanru Zhang,Jie Cui,Haiyan Yu,Wenbin Dong,Baofei Yan
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon, characterized by recurrent flare-ups and limited effectiveness of available drug therapies. Asiatic acid (AA), a triterpenoid compound extracted from Centella asiatica , has shown promising pharmacological activities and therapeutic potential in several inflammation-related diseases. However, AA's efficacy in treating UC and its precise mechanisms of action remain to be fully explored. This study aimed to provide a comprehensive assessment of AA's therapeutic effects on UC and to investigate its underlying mechanisms, with a focus on gut microbiota interactions. In our study, a dextran sulfate sodium-induced UC mouse model was used to evaluate AA's therapeutic potential and explore its impact on gut microbiota composition and function. We further used an antibiotic cocktail and fecal microbiota transplantation assays to substantiate the role of gut microbiota in AA's mechanisms of action. A metabolomic analysis was also conducted to identify key metabolic pathways and gut microbiota-derived metabolites involved in AA's effects. Our findings demonstrated that AA significantly alleviates symptoms of UC, including reducing weight loss, slowing disease progression, mitigating colonic inflammation, and restoring immune balance. Mechanistically, the beneficial effects of AA were strongly linked to alterations in the gut microbiota and its metabolites, particularly γ-glutamyltyrosine. This metabolite was found to regulate the cyclic adenosine monophosphate/protein kinase A/nuclear factor kappa-B signaling pathway, which plays a crucial role in inflammatory responses. Overall, these findings strongly suggest that AA holds promise as a therapeutic agent for UC by modulating the gut microbiota and influencing critical inflammatory pathways.
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YONSEI MEDICAL JOURNAL
·
2021
·
IF 2.759
Chunting Hu,Chen Li,Qiaoya Ma,Ruili Wang,Ya He,Hui Wang,Guogang Luo
Purpose Ischemic brain injury results in high mortality and serious neurologic morbidity. Here, we explored the role of SNHG15 in modulating neuronal damage and microglial inflammation after ischemia stroke. Materials and Methods The hypoxia/ischemia models were induced by middle cerebral artery occlusion in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro. Quantitative real-time PCR (qRT-PCR) and Western blot were conducted to determine the levels of SNHG15, miR-302a-3p, and STAT1/NF-κB. Moreover, gain- or loss-of functional assays of SNHG15 and miR-302a-3p were conducted. MTT assay was used to evaluate the viability of HT22 cells, and the apoptotic level was determined by flow cytometry. Furthermore, enzyme-linked immunosorbent assay was performed to detect oxidative stress and inflammatory mediators in the ischemia cortex and OGD/R-treated BV2 microglia. Results The SNHG15 and STAT1/NF-κB pathways were both distinctly up-regulated, while miR-302a-3p was notably down-regulated in the ischemia cortex. Additionally, overexpressing SNHG15 dramatically enhanced OGD/R-mediated neuronal apoptosis as well as the expression of oxidative stress and inflammation factors from microglia. In contrast, knocking down SNHG15 or overexpressing miR-302a-3p relieved OGD/R-mediated neuronal apoptosis and microglial activation. Moreover, the rescue experiment testified that overexpressing miR-302a-3p also attenuated SNHG15 up-regulation-induced effects. In terms of the mechanisms, SNHG15 sponged miR-302a-3p and activated STAT1/NF-κB as a competitive endogenous RNA, while miR-302a-3p targeted STAT1 and negatively regulated the STAT1/NF-κB pathway. Conclusion SNHG15 was up-regulated in the hypoxia/ischemia mouse or cell model. The inhibition of SNHG15 ameliorates ischemia/hypoxia-induced neuronal damage and microglial inflammation by regulating the miR-302a-3p/STAT1/NF-κB pathway.
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NEUROCHEMICAL RESEARCH
·
2018
·Vol. 43
·期 5
·1058-1066
·
IF 2.772
Nong Xiaolian,Lan Yuyan
Reactive astrocyte-mediated neuroinflammatory responses in the spinal dorsal horn have been reported to play a pivotal role in pathological pain. Chronic constriction injury (CCI) enhances the activation of nuclear factor kappa B (NF-κB), which is involved in neuropathic pain (NP). Picroside II (PII), a major active component of Picrorhiza scrophulariiflora, has been investigated for its anti-oxidative, anti-inflammatory, and anti-apoptotic activities. Here, we explored the analgesic effects of PII on a model of CCI-induced NP and investigated the levels of the GFAP protein and the mRNA and protein levels of pro-inflammatory cytokines in the spinal cord, including interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). CCI significantly induced mechanical allodynia and thermal hyperalgesia. Intraperitoneal administration of PII remarkably reversed the CCI-induced mechanical allodynia and thermal hyperalgesia and reduced the mRNA and protein levels of IL-1β, IL-6, and TNF-α in the spinal cord. Additionally, according to the in vitro data, the PII treatment inhibited LPS-induced increases in the mRNA and protein levels of IL-1β, IL-6, and TNF-α and suppressed the NF-κB pathway by inhibiting the phosphorylation of NF-κB/p65 and the degradation of inhibitor of NF-κB (IκB) in astrocytes without toxicity to astrocytes. Overall, the analgesic effect of PII correlated with the inhibition of spinal reactive astrocyte-mediated neuroinflammation through the NF-κB pathway in rats with NP.
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ACTA BIOCHIMICA ET BIOPHYSICA SINICA
·
2026
·Vol. 58
·期 9
·
IF 4.5
Jingjing Chen,Lu Zhou,Xiguang Liu,Mengxin Li,Sijie Zhao,Jun Wang,Qian Dong,Xinran Li,Zibo Dong,Huizhen Chen
Chronic intermittent hypoxia (CIH) is an alternating state of recurrent hypoxia and reoxygenation triggered by disorders such as sleep apnea, leading to systemic oxidative stress and organ damage. In this study, we investigate the protective effect and mechanism of atraric acid (AA), a secondary metabolite produced by lichens, against CIH-induced liver injury. By establishing a CIH mouse model (10 h/d, oxygen cycling 5%-21% for 4 weeks) and an in vitro model of AML-12 cell hypoxia/reoxygenation (H/R), we perform H&E staining, biochemical assays (ALT/AST/MDA/CAT/T-AOC/GSH-Px), qPCR, western blotting, immunofluorescence and flow cytometry (JC-1 detection of the mitochondrial membrane potential) analyses. The results show that AA significantly reduces alanine aminotransferase (ALT)/aspartate aminotransferase (AST) levels, inhibits the elevation of hepatic malondialdehyde (MDA), restores the activities of catalase (CAT), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) in CIH mice, ameliorates mitochondrial dysfunction, activates autophagy, and reduces the expression levels of inflammatory factors. Mechanistically, AA reduces the release of downstream proinflammatory factors by blocking NF-κB nuclear translocation through the inhibition of IκBα phosphorylation. The activation of autophagic flow by AA is accompanied by a significant increase in LC3BII/I protein expression. Furthermore, autophagy blockade impedes the role of AA in alleviating inflammatory oxidative stress and mitochondrial dysfunction in the CIH-induced injury model, confirming that autophagy activation is necessary for the protective effect of AA. In conclusion, the present study reveals that AA alleviates oxidative stress and mitochondrial dysfunction, as well as NF-κB signaling, through the activation of autophagy, providing a novel therapeutic strategy for CIH-associated liver injury.
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Journal of Applied Biomedicine
·
2023
·Vol. 21
·期 4
·193-199
·
IF 1.3
Hongji Wang,Lisha Chen,Juping Xing,Xiangchao Shi,Changshui Xu
Naringin inhibits inflammation and oxidative stress, the P2 purinoreceptor X4 receptor (P2X4R) is associated with glial cell activation and inflammation, the purpose of this study is to investigate the effects of naringin on P2X4 receptor expression on satellite glial cells (SGCs) and its possible mechanisms. ATP promoted the SGC activation and upregulated P2X4R expression; naringin inhibited SGC activation, decreased expression of P2X4R, P38 MAPK/ERK, and NF-κB, and reduced levels of Ca2+, TNF-α, and IL-1β in SGCs in an ATP-containing environment. These findings suggest that naringin attenuates the ATP-induced SGC activation and reduces P2X4R expression via the Ca2+-P38 MAPK/ERK-NF-κB pathway.
研究领域:
神经科学
·
药理学
·
细胞生物学
·
炎症研究
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Chemical Biology & Drug Design
·
2024
·Vol. 103
·期 1
·e14437
·
IF 3.2
Junde Xu,Keshuang Tang,Zhiran Ju
The adverse effects caused by nonselective and selective cyclooxygenase-2 (COX-2) inhibitors remain a challenge for current anti-inflammatory medications. A balanced inhibition of COX-1/−2 represents a promising strategy for the development of novel COX-2 inhibitors. In this study, we present the design and synthesis of a novel series of firocoxib analogues incorporating an amide bond to facilitate essential hydrogen bonding with amino residues in COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX-1 and COX-2 enzymes. Among them, compound 9d demonstrated potent and balanced inhibition. Inhibition of COX enzymes by 9d in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages resulted in the suppression of the NF- κ B signaling pathway to reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, nitric oxide (NO), and reactive oxygen species (ROS). The remarkable in vitro anti-inflammatory activity exhibited by 9d positions it as a promising candidate for further development as a novel lead compound for inflammation treatment.
研究领域:
药理学
·
药物化学
·
炎症研究
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JOURNAL OF ETHNOPHARMACOLOGY
·
2024
·
IF 4.8
Mengqin Yi,Zhenglang Zhang,Zhenhui Luo,Anqi Luo,Hekun Zeng,Peiyang Li,Tingting Wang,Jingwen Yang,Hong Nie
Ethnopharmacological relevance PolyphyllinVI (PPⅥ) is the main bioactive component of Chonglou which is a traditional Chinese herbal with various effects, including antitumor, anti-inflammatory, and analgesia. Aim of the study This study aimed to investigate the properties and mechanisms of the analgesia of PPⅥ by using neuropathic pain (NPP) mice. Materials and methods The potential targets and mechanisms of PPⅥ in alleviating NPP were excavated based on the network pharmacology. Subsequently, the construction of a spared nerve injury (SNI) mice model was used to evaluate the effect of PPⅥ on NPP and the expression of the P2X3 receptor. We identified the signaling pathways of PPⅥ analgesia by RNA sequencing. Results The results of network pharmacology showed that BCL2, CASP3, JUN, STAT3, and TNF were the key targets of the analgesic effect of PPⅥ. PPⅥ increased the MWT and TWL of SNI mice and decreased the level of P2X3 receptors in the dorsal root ganglion (DRG) and spinal cord (SC). Additionally, PPⅥ reduced the release of pro-inflammatory mediators (TNF-α, IL-1β, and IL-6) in the DRG, SC, and serum. Based on the KEGG enrichment of differentially expressed genes (DEGs) identified by RNA-Seq, PPVI may relieve NPP by regulating the AMPK/NF-κB signaling pathway. Western blotting results showed that the AMPK signaling pathway was activated, followed by inhibition of the NF-κB signaling pathway. Conclusion PPⅥ increased the MWT and TWL of SNI mice maybe by inhibiting the expression of the P2X3 receptor and the release of inflammatory mediators. The properties of the analgesia of PPⅥ may be based on the AMPK/NF-κB pathway.
研究领域:
药理学
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神经科学
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民族药理学
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分子生物学
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CURRENT MEDICINAL CHEMISTRY
·
2024
·
IF 3.5
Liu Wei,Zheng Yi-nan,Jiang Shuang,Ren Shen,Tang Shan,Zhang Jing,Wang Zi,Li Wei
Background: Based on the Maillard reaction principle of red ginseng, this
study innovatively synthesized a new amino acid derivative by combining arginine with
lactose through simulated synthesis and was separated and purified through repeated silica
gel and polyacrylamide gel (Bio-gel P-II) column chromatography.
Purpose: The work was aimed at elucidating the synthesis of a novel amino acid derivative
and investigating the intestinal protective activity of the novel amino acid derivative
and possible molecular mechanism by establishing the intestinal injury model induced
by cisplatin in mice.
Methods: The purity and molecular weight of the amino acid derivatives were determined
to be by electrospray ionization mass spectrometry (ESI-MS). Subsequently, by
establishing cisplatin (20 mg/kg)-induced intestinal injury in vivo for 10 days and IEC-6
cell model. The biochemical indexes and histopathological analysis were used to evaluate
the oxidative stress and inflammatory and pathological changes of intestinal tissue in
mice. The protein expression levels of p-Nuclear transcription factor-κB (p-NF-κB),
cleaved caspase 3/caspase 3, cleaved caspase 9/caspase-9, Bcl-2, Bax, cytochrome C,
phosphatidylinositol 3-kinase (PI3K), Protein Kinase B (Akt), p-PI3K, p-Akt were quantified
through immunofluorescence staining and western blot analysis.
Results: The new amino acid derivatives of chemical structure were identified to be 1-
(arginine-Nαgroup)-1-deoxy-4-O-(β-D-galactopyranosyl)-D-fructose, named Argininylfructosyl-
galactose (AFGA, C18H34N4O12). The results showed that pretreatment with a
single AFGA dose remarkably alleviated cisplatin-evoked intestinal oxidative stress injury,
and the levels of reactive oxygen species (ROS) were lessening in IEC-6 cells
(p<0.05, p<0.01) and could effectively reduce the secretion of TNF-α and IL-1β in
serum and the expression level of NF-κB protein in intestinal tissues (p<0.01). Meantime,
AFGA also significantly suppressed the caspase 3, caspase 9, cytochrome C and
Bax protein expression in intestinal tissue in mice (p<0.01), and regulated the PI3K/Akt
pathway (p<0.05, p<0.01). Importantly, the molecular docking results of AFGA also
suggested a better binding ability with the above-mentioned related target proteins.
Conclusion: The results clearly revealed AFGA as a potential multifunctional therapeutic
agent with a clear protective effect against cisplatin-induced intestinal injury may be
related to the PI3K/Akt signaling pathway.
研究领域:
药理学
·
毒理学
·
分子生物学
·
生物化学
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CHEMICAL ENGINEERING JOURNAL
·
2026
·
IF 13.2
Liang Xia,Ru Tang,Yi Chen,Ning Ma,Lili Xiao,Xiaoyan Chen,Xiaoyin Mao,Keyi Li,Yanmei Feng,Jingjing Liu,Amin Zhang
Noise-induced hearing loss (NIHL) is a prevalent condition caused by irreversible cochlear hair cell damage resulting from an oxidative stress imbalance. To combat this, we engineered a yolk-shell shaped hollow Prussian blue nanozyme, loaded with N -acetylcysteine (NAC) and surface-modified with reactive oxygen species (ROS)-responsive liposomes, which was then incorporated into a tissue-adhesive hydrogel (HN@TK-Lipo gel ). This system establishes a dual-modal antioxidant mechanism, where the nanozyme acts as a continuous ROS scavenger and NAC replenish intrinsic antioxidant capacity. The hydrogel exhibits superior adhesiveness, effectively overcoming rapid drainage challenges in the middle ear. In vitro, HN@TK-Lipo gel demonstrated potent antioxidative capabilities, successfully scavenging intracellular ROS and preserving mitochondrial function. Crucially, in an NIHL animal model, the hydrogel treatment significantly alleviated auditory threshold shifts and minimized hair cell apoptosis and ribbon synapse loss. Transcriptomic analysis (RNA-seq) uncovered that the hydrogel exerts its protective effects by specifically downregulating inflammation-related pathways. Further mechanistic validation confirmed that HN@TK-Lipogel elicits an enhanced therapeutic effect by robustly upregulating antioxidant defenses (NRF2/SOD2) and suppressing lipid peroxidation (4-HNE) via the regulation of the identified NF-κB and MAPK signaling cascades. This biomaterial combines targeted delivery with enhanced catalytic and biological functions, improving the safety and effectiveness of inner ear therapy. Therefore, this nanozyme hydrogel system offers a promising therapeutic strategy for auditory medicine.
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ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
·
2026
·
IF 6.6
Ziyi Guo,Zengguang Zhu,Hongyue Ma,Houqiang Du,Rong Tan,Weiwei Wang,Shaoguo Ru,Pengfei Cui
Phenanthrene (PHE) is a common marine pollutant, but whether it induces autophagy-related responses in bivalves and how such responses contribute to cellular adaptation under pollutant stress remain incompletely understood. Here, using multimodal imaging, ultrastructural analysis, proteomics, and gene-expression assays, we found evidence consistent with the engagement of an E3 ubiquitin ligase-NF-κB-autophagy regulatory axis in hemocytes of the Pacific oyster Crassostrea gigas following phenanthrene exposure. Confocal laser scanning microscopy, Cyto-ID flow-cytometry screening, and transmission electron microscopy revealed increased autophagy-related signals and the presence of autophagic vesicle-like structures in PHE-exposed hemocytes. The proteomics results showed that protein levels of HUWE1, TRIM36, and ATG7 were significantly upregulated. The expression of axis-related genes was significantly upregulated after PHE exposure, while CAPE-mediated inhibition of NF-κB attenuated the PHE-associated induction of LC3 and p62/SQSTM1 transcripts, supporting the involvement of NF-κB signaling in the autophagy-related transcriptional response. Similar upregulation of axis-related transcripts in RAW264.7 macrophages supported a comparable direction of transcriptional response, but did not establish conserved pathway activation or causality. Together with changes in hemocyte number, apoptosis rate, phagocytic capacity, and ROS levels, these findings are consistent with a cellular adaptation response under PHE stress. This study provides integrated evidence for autophagy-associated stress responses in Pacific oysters exposed to phenanthrene and offers a mechanistic framework for future validation of pollutant tolerance in marine bivalves.
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SOUTH AFRICAN JOURNAL OF BOTANY
·
2026
·
IF 3.1
Xian Dong Lv,Meiherinisa Maitituersun,Fei Li
This study established HPLC fingerprints of PCAE 70% and RLQ, supported by the 2020 edition of the Chinese Pharmacopeia and relevant literature, and performed network pharmacology prediction for the common constituents. • Multi-index regression analysis of uniform design data was conducted by partial least squares, by which seven active components were optimized and determined as six important active components, and their rationality was experimentally validated. • The entropy weight method was employed to unify heterogeneous data from in vitro and in vivo experiments, and the integrated important active component combination was subjected to in vivo activity validation through a mouse urinary tract infection model. • This study suggests that the active components centered on gallic acid, myricitrin, and quercitrin may constitute the major pharmacodynamic material basis of Polygonum capitatum against UTI, and preliminarily explored the underlying mechanism. Ethnopharmacological relevance As a cornerstone herb in the traditional medicine of the Miao ethnic group in Guizhou Province, Polygonum capitatum has long been used to treat diseases of the urinary system. Documented in Miao medical theory as cold in nature and bitter-pungent in taste, and as acting on the kidney and bladder meridians, it is traditionally used to clear heat, promote diuresis, relieve stranguria, and detoxify, thereby relieving pain. The aqueous extract of this herb is the sole component of Relinqing Granules (RLQ), a clinically widespread formulation. Despite its broad clinical application, the underlying material basis of its pharmacological activity remains to be fully elucidated. Materials and methods The target compounds were identified through literature investigation, and their presence in both the Polygonum capitatum 70% aqueous ethanol extract (PCAE 70%) and RLQ was subsequently verified. The common constituents shared by the two were identified by comparing the fingerprint chromatograms with reference standards, and network pharmacology was employed to predict the potential targets of these components. The constituents were then combined through uniform design to evaluate their antibacterial, anti-inflammatory, and antioxidant activities, optimized via partial least squares regression and the entropy weight method, and ultimately validated in a mouse model of UTI. Results A total of seven common constituents were identified: gallic acid, protocatechuic acid, catechin, myricitrin, quercitrin, quercetin, and kaempferol. Network pharmacology predicted that these constituents might exert anti-UTI effects through modulation of the PI3K-Akt signaling pathway. The optimal ratio combination demonstrated significant antibacterial activity against Escherichia coli and Staphylococcus aureus , while another optimal ratio enhanced catalase activity and modulated the expression of AKT-1/Nrf 2 / HO-1/NF-κB 3 in zebrafish. Following data integration using the entropy weight method, mouse validation results revealed decreased TNF-α/IL-1β levels and increased IL-10 levels, with superior efficacy compared to PCAE 70% and RLQ, without dose-dependent differences. The results implied that gallic acid, myricitrin, and quercitrin represent the potential principal active components of P. capitatum. Conclusion The optimized combination dominated by gallic acid, myricitrin, and quercitrin, identified from P. capitatum , exhibited antibacterial, anti-inflammatory, and antioxidant performance superior or equivalent to existing preparations, holding significant theoretical and practical value. Download: Download high-res image (228KB) Download: Download full-size image Graph A illustrates the experimental procedure for determining the in vitro antibacterial activity of target drugs by the MTT method; Graph B illustrates the experimental procedure for the acute toxicity assay in zebrafish; Graph C illustrates the mechanism diagram of drug administration in the zebrafish oxidative stress model; Graph D illustrates the simplified experimental procedure and mechanism diagram before drug administration in the mouse UTI model.
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