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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS · 2024 · IF 2.5

Naringenin protects against septic cardiomyopathy in mice by targeting HIF-1α

Jiajia Pan,Lijun Meng,Rujun Li,Zicheng Wang,Wenjie Yuan,Yucheng Li,Lin Chen,Qinhao Shen,Weili Liu,Li Zhu

Myocardial dysfunction is a prevalent complication of sepsis (septic cardiomyopathy) with a high mortality rate and limited therapeutic options. Naringenin, a natural flavonoid compound with anti-inflammatory and antioxidant properties, holds promise as a potential treatment for sepsis-induced myocardial dysfunction. This study investigated the pharmacological effects of naringenin on septic cardiomyopathy. In vivo and in vitro experiments demonstrated that naringenin improved cardiomyocyte damage. Network pharmacology and database analysis revealed that HIF-1α is a key target protein of naringenin. Elevated expression of HIF-1α was observed in damaged cardiomyocytes, and the HIF-1α inhibitor effectively protected against LPS-induced cardiomyocyte damage. Molecular docking studies confirmed the direct binding between naringenin and HIF-1α protein. Importantly, our findings demonstrated that naringenin did not provide additional attenuation of cardiomyocyte injury on the biases of HIF-1α inhibitor treatment. In conclusion, this study proves that naringenin protects against septic cardiomyopathy through HIF-1α signaling. Naringenin is a promising therapeutic candidate for treating septic cardiomyopathy.

研究领域: 药理学 · 心脏病学 · 分子生物学
✓ 已验证 DOI PubMed 高影响因子
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NEUROSCIENCE LETTERS · 2022 · IF 3.197

Apelin-13 reduces lipopolysaccharide-induced neuroinflammation and cognitive impairment via promoting glucocorticoid receptor expression and nuclear translocation

Sheng Hu,Pei Shen,Bin Chen,Shao-Wen Tian,Yong You

Neuroinflammation is usually associated with cognitive decline, which is involved in neurodegenerative diseases. Apelin , a neuropeptide, exerts various biological roles in central nervous system. Recent evidence showed that apelin-13, an active form of apelin, suppresses neuroinflammation and improves cognitive decline in diverse pathological processes. However, the underlying mechanism of apelin-13 in neuroinflammation remains largely unknown. The present study aimed to determine underlying mechanism of apelin-13 on neuroinflammation-related cognitive decline. The lipopolysaccharide (LPS) intracerebroventricular (i.c.v.) to is used to establish a rat model of neuroinflammation-related cognitive decline. The results showed that apelin-13 inhibits LPS-induced neuroinflammation and improves cognitive impairment. Apelin-13 upregulates the GR level and nuclear translocation in hippocampus of rats. Moreover, glucocorticoid receptor inhibitor RU486 prevents apelin-13-mediated neuroprotective actions on cognitive function. Taken together, apelin-13 could exert a protective effect in neuroinflammation-mediated cognitive impairment via the activation of GR expression and nuclear translocation.

CAS / MDL: 84371-65-3
研究领域: 神经科学 · 药理学 · 神经炎症 · 认知功能
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Frontiers in Nutrition · 2023 · IF 5

Anti-inflammatory effects and molecular mechanisms of bioactive small molecule garlic polysaccharide

Shao Xin,Li Jialong,Zhang Huidan,Zhang Xuhui,Sun Chongzhen,Ouyang Xin,Wang Yong,Wu Xiyang,Chen Chunbo

Although garlic polysaccharides have been found to possess anti-inflammatory activities, anti-inflammatory study on small molecule water-soluble garlic polysaccharide (WSGP) is few. In this study, a novel WSGP with a molecular weight of 1853 Da was isolated by DEAE-52 and Sephadex G-100 column and the chemical composition was identified by monosaccharide composition and methylation analysis. Furthermore, the antioxidant effects of WSGP and the potential molecular mechanisms on LPS-induced inflammatory responses in RAW264.7 macrophage cells were investigated. The results showed that WSGP has strong antioxidant activity, such as DPPH, hydroxyl, superoxide anion, ABTS radical scavenging capacity, Fe2+ chelating ability and reducing power. Meanwhile, WSGP could considerably suppress the manufacturing of NO and the mRNA and protein expression degrees of IL-6, TNF-α, and IL-1β in LPS inspired RAW264.7 macrophages WSGP could significantly suppress the production of NO and the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α in LPS stimulated RAW264.7 macrophage cells (p < 0.05). In addition, the phosphorylated IκB-α, p65, and STAT3 proteins were significantly increased in LPS-induced macrophages, while this trend was significantly reversed by WSGP treatment in a concentration-dependent manner (p < 0.05). Consequently, WSGP supplementation might reduce LPS-induced inflammatory responses by suppressing proinflammatory cytokines and NF-κB and STAT3 pathway activation. The finding of this research would give scientific guidelines for the judicious use of small molecular garlic polysaccharide in anti-inflammatory treatments.

研究领域: 免疫学 · 药理学 · 分子生物学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES · 2025 ·Vol. 26 ·期 24 ·12057 · IF 4.9

Flavonoid-Rich Extract from Bombyx batryticatus Alleviate LPS-Induced Acute Lung Injury via the PI3K/MAPK/NF-κB Pathway

Wenkai Li,Sifan Song,Wenyong Li,Jing Chen

Treating acute lung injury (ALI) presents significant challenges due to adverse drug reactions. This study systematically explored the protective effects and mechanisms of a flavonoid-rich extract fromBombyx batryticatus(FBB), a traditional Chinese medicine, in combating ALI. Through UPLC-MS/MS analysis, we identified 163 flavonoid components in FBB for the first time, including flavonoids, flavonols, and chalcones. Unlike single-component flavonoid therapies, FBB provides synergistic regulation across multiple targets and pathways. Network pharmacology predictions, supported by experimental validation, revealed that FBB primarily suppresses the expression of inflammatory factors (IL-1β, IL-6, TNF-α) and oxidative stress markers (iNOS, COX-2) by modulating the PI3K/Akt, MAPK, and NF-κB signaling pathways. FBB inhibits pro-inflammatory responses and upregulates chemokine receptors like Ccr1 and Ccr2, along with IL-2Rb, at the transcriptional level. This suggests its potential to promote inflammation resolution and tissue repair through immune microenvironment remodeling, rather than mere immunosuppression. Additionally, FBB demonstrated significant anti-apoptotic effects both in vitro and in vivo, effectively reducing pulmonary edema and vascular permeability. Its complex composition and multi-pathway synergistic mechanisms offer broader regulatory potential and unique therapeutic advantages in treating ALI compared to single flavonoid compounds or conventional hormone drugs like dexamethasone (DEX). This study reveals a novel mechanism by which FBB, a multi-component natural drug, exerts therapeutic effects in ALI, providing a theoretical and experimental foundation for developing flavonoid-based compound preparations from traditional Chinese medicine.

CAS / MDL: 314-13-6
✓ 已验证 产品关联 DOI PubMed 高影响因子
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CELLULAR SIGNALLING · 2026 · IF 4.7

Chlorogenic acid (CGA) exerts antidepressant-like effects by regulating SIRT1/FoxO3a/PINK1/Parkin pathway in LPS-induced depressive mice

Xinmiao Piao,Jinfang Song,Jingjing Piao,Yuhan Shang,Yang Jin,Ranji Cui,Bingjin Li

A growing focus in nutritional psychiatry is examining dietary interventions as a therapeutic strategy for depression. Chlorogenic acid (CGA), a naturally occurring polyphenol, has demonstrated promising anti-inflammatory and neuroprotective effects. This study aimed to elucidate the underlying molecular targets and mechanisms responsible for CGA's antidepressant-like actions. The potential targets and pathways of CGA related to FoxO3a were initially predicted using network pharmacology and molecular docking. In vitro, the protective effects of CGA were investigated in H 2 O 2 -stimulated HT-22 cells by assessing cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and the expression of mitophagy-related proteins. In vivo, a depression model was established in male mice via intraperitoneal injection of lipopolysaccharide (LPS). The antidepressant efficacy of CGA was evaluated through a behavioral test battery. Microglial activation was detected via immunofluorescence. Furthermore, mitochondrial ultrastructure was examined by transmission electron microscopy (TEM), and the expression of mitophagy-related proteins was additionally validated by Western blotting. Finally, the direct interaction between SIRT1 and FoxO3a was examined by co-immunoprecipitation. In vitro, CGA pretreatment improved HT-22 cells viability under H 2 O 2 -induced oxidative stress, reduced ROS levels, and restored mitochondrial membrane potential. In vivo, CGA reduced neuroinflammation by lowering the levels of proinflammatory cytokines interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), inhibited microglial activation, and alleviated depressive-like behaviors in LPS-treated mice. Additionally, CGA activated the sirtuin 1 (SIRT1) / forkhead box O3a (FoxO3a) / PTEN-induced kinase 1 (PINK1) / Parkin signaling pathway, promoting hippocampal mitophagy. The antidepressant-like effects of CGA were suppressed upon SIRT1 antagonism with EX527. This study suggests that CGA may serve as a potential therapeutic agent for depression.

✓ 已验证 DOI PubMed 高影响因子
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Research · 2026 · IF 12.9

Engineering a Gram-Negative Bactericidal Hydrogel: CuxTe Nanozyme Functions as a Specific Killer by Hijacking LPS and Flagella Biosynthesis

Jianguo Niu,Yuhao Xue,Wenqi Wang,Wei Zhang,Min Wang,Jiaqi Qin,Dongliang Yang,Xianwen Wang

The treatment of gram-negative bacterial infections remains a formidable challenge due to their resilient outer membrane and adaptive evasion mechanisms. Herein, we present a multifunctional nanozyme hydrogel, copper telluride@cationic guar gum (Cu x Te@CG), which acts as a gram-negative-specific bactericidal platform. This hydrogel integrates the unique enzymatic and physical properties of urchin-like Cu x Te nanozymes with the biocompatible and adhesive cationic guar gum (CG) matrix. The Cu x Te@CG hydrogel exhibits synergistic oxidase- and glutathione peroxidase-like activities, catalyzing the generation of reactive oxygen species (ROS) while depleting bacterial glutathione, thereby inducing lethal oxidative stress. Crucially, transcriptome sequencing revealed that the platform specifically targets Pseudomonas aeruginosa by down-regulating key genes involved in lipopolysaccharide (LPS) biosynthesis and flagellar assembly, compromising their primary defense and motility structures. This targeted interference with LPS and flagella amplifies the ROS-mediated attack, leading to enhanced and specific killing of gram-negative pathogens ( Escherichia coli , P. aeruginosa , and Klebsiella pneumoniae ), effective biofilm disruption, and inhibition. In a P. aeruginosa -infected burn wound model, the Cu x Te@CG hydrogel markedly accelerated healing by eliminating bacteria, promoting angiogenesis, and modulating inflammation, all while demonstrating excellent biosafety. This work establishes the Cu x Te@CG hydrogel as a robust and targeted therapeutic strategy for combating stubborn gram-negative infections.

✓ 已验证 产品关联 DOI PubMed 高影响因子
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JOURNAL OF ETHNOPHARMACOLOGY · 2026 · IF 6.8

Aurantio-obtusin ameliorates prediabetes in a gut microbiota-dependent manner via regulating LPS-TLR4 axis and Akt/GLUT4 signaling

Xiang Chen,Mengting Li,Miaomiao Xia,Yumeng Yang,Rui Liu,Ling Ma,Mao Luo

Ethnopharmacological relevance Cassiae Semen, the dried seeds of Cassia obtusifolia L., has traditionally been used in East Asian medicine to manage metabolic disorders, including hyperglycemia and dyslipidemia. Aurantio-obtusin (AO), a bioactive anthraquinone compound, exhibits diverse pharmacological activities, derived from Cassiae Semen, a traditional herb used for metabolic disorders; however, its protective efficacy against prediabetes remains poorly understood. Aim of the study This study aimed to investigate the effects of AO on prediabetes and to elucidate the underlying mechanisms, with particular emphasis on gut microbiota-mediated regulation of metabolic homeostasis. Materials and methods Mice were subjected to prediabetes by a combination of a high-fat diet and streptozotocin. Metabolic parameters, liver function, oxidative stress, inflammatory responses, insulin signaling, and gut microbiota composition were assessed. Fecal microbiota transfer and models simulating antibiotic-induced germ-free conditions were utilized to investigate the function of gut microbiota. Results AO exhibited a marked improvement in glucose tolerance, lipid profiles, and insulin sensitivity among prediabetic mice. Furthermore, AO demonstrated a protective effect against liver damage, as suggested by the notable reductions in serum levels of alanine aminotransferase and aspartate aminotransferase. Oxidative stress was markedly suppressed, as indicated by decreased malondialdehyde levels, along with enhanced antioxidant defenses, including superoxide dismutase, catalase, and reduced glutathione. Additionally, AO preserved intestinal barrier integrity, reduced endotoxemia, and suppressed Toll-like receptor 4-mediated inflammatory signaling, accompanied by restoration of the PI3K/Akt/GLUT4 pathway. Notably, depletion of gut microbiota completely abolished the metabolic benefits of AO. Conclusion Collectively, this study substantiates the ethnomedical value of Cassiae Semen, demonstrating that AO improves prediabetes through the regulation of intestinal barrier function, oxidative stress, inflammation, and insulin signaling, which is dependent on gut microbiota.

✓ 已验证 DOI PubMed 高影响因子
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POULTRY SCIENCE · 2025 · IF 4.2

Naringenin's Rescue of Broiler Spleen from LPS-Triggered Pyroptosis and Inflammation: Decoding the AMPK/PINK1/Parkin-Driven Mitophagy Pathway

Yu Xia,Yidan Wang,Jiahui Xue,Jiahong Chu,Yanhe Zhang,Fuze She,Huijie Chen,Shu Li

Naringenin (Nar) is known to maintain mitochondrial homeostasis, antioxidation and anti-inflammation. Damaged mitochondria can promote excessive Reactive oxygen species (ROS) production, triggering pyroptosis and inflammation process in immune tissues. PTEN induced putative kinase 1 (PINK1)/E3 ubiquitin ligase PARK2 (Parkin)-mediated mitophagy contributes to removing damaged mitochondria. This study aims to investigate detailed mechanism of Nar against Lipopolysaccharide (LPS)-induced injury in broiler spleens and the role of mitophagy in this process. We used LPS as a stimulus and treated with Nar to establish relevant models in vivo and in vitro . Our findings demonstrated Nar increased the expression levels of Phospho-Adenosine 5 ’ -monophosphate (AMP)-activated protein kinase (p-AMPK)/AMPK, PINK1, Parkin and Microtubule-Associated Protein 1A/1B Light Chain 3 (LC3), and reduced the level of Sequestosome 1 (P62), leading to a reduction in levels of factors associated with mitochondrial fission, mtDNA release, pyroptosis, and inflammation. Conversely, Nar treatment enhanced the levels of factors related to mitochondrial fusion, energy metabolism, and anti-inflammatory response. Moreover, an increase was observed in ΔΨm, ATP content, and ATPase activity. Molecular docking analysis and cellular thermal shift assay (CETSA) supported the interaction between Nar and AMPK. In summary, Nar enhanced LPS-induced mitophagy and alleviated mitochondrial homeostasis imbalance and oxidative stress in broiler spleens through its interaction with AMPK, resulting in alleviating pyroptosis and inflammation.

CAS / MDL: 67604-48-2
研究领域: 兽医学 · 免疫学 · 分子生物学 · 线粒体生物学 · 药理学
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Biochemistry and Biophysics Reports · 2025 · IF 2.2

Duchesnea indica (Andr.) Focke extracts exerted anti-inflammatory effect via inhibiting MAPK/ERK pathway in LPS-stimulated RAW264.7 cells

Haipeng Feng,Qianqian Qiao,Jingyan Zhang,Kang Zhang,Lei Wang,Jianxi Li

Duchesnea indica (Andr.) Focke ( DIF ), a medicinal plant from the Rosaceae family, possesses therapeutic properties such as heat-clearing and detoxification, dispersion of stasis detumescence, blood-cooling, and hemostatic effect. The latest research unveiled a diverse array of pharmacologically active compounds from DIF, showcasing a broad spectrum of pharmacological effects. However, there was limited attention given to the comprehensive investigation of its high molecular weight compounds, particularly polysaccharides. In this study, DIF extracts were prepared by water-extraction and alcohol-precipitation method and the pharmacological effect was detected. The results demonstrated that the total polysaccharide content, reducing sugar content, total flavonoid content, and total polyphenol content in DIF extracts were 32.62 ± 0.91 %, 13.41 ± 0.18 %, 1.07 ± 0.07 %, and 12.16 ± 0.27 %, respectively. Although the total antioxidant activity of DIF extracts were significantly low than that of the vitamin C group, its ability to scavenge ABTS, DPPH, and superoxide anion radicals was similar to that of the vitamin C group. Furthermore, DIF extracts demonstrated significant inhibition on NO and MDA levels while simultaneously enhancing SOD activity in LPS-stimulated RAW264.7 cells. Finally, DIF extracts significantly reduced the mRNA level of pro-inflammation cytokines interleukin ( IL )-6, IL-1β, inducible nitric oxide synthase ( iNOS ), cyclooxygenase-2 ( COX-2 ) and tumor necrosis factor ( TNF ) -α , and directly inhibited the phosphorylation level of extracellular regulated kinase and mitogen-activated protein kinase ( ERK-MAPK ) pathway. Taken together, these results indicated that DIF extracts exhibited an anti-inflammatory and antioxidant effect in LPS-induced RAW264.7 mouse macrophages by directly inhibiting ERK-MAPK signaling pathway. Based on these findings, DIF extracts provided new insights into the treatment and prevention of diseases related to oxidative stress and inflammation.

CAS / MDL: 117-39-5
研究领域: 药理学 · 免疫学 · 天然产物化学 · 分子生物学 · 炎症与感染 · 抗氧化研究 · 信号转导
✓ 已验证 产品关联 DOI PubMed 高影响因子
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Energy Technology · 2020 ·Vol. 8 ·期 6 ·2000023 · IF 3.404

Li2S–Li3PS4 (LPS) Composite Synthesized by Liquid-Phase Shaking for All-Solid-State Lithium–Sulfur Batteries with High Performance

Huize Jiang,Yu Han,Hui Wang,Yuhao Zhu,Qingpeng Guo,Haolong Jiang,Chunman Zheng,Kai Xie

Compared with traditional lithium–sulfur batteries, all-solid-state lithium–sulfur batteries assembled with inorganic solid electrolytes can not only effectively eliminate the shuttle effect but also drastically improve the safety performance. Due to the low ionic conductivity of the active materials, the construction of the interface between the active materials and the solid electrolytes in the composite cathode is crucial to the performance of the battery. Herein, Li 2 S– Li 3 PS 4 (LPS) composite materials are prepared by the in situ growth of solid electrolytes on the surface of the active material Li 2 S through the method of liquid-phase shaking. After heat treatment at 320 °C for 1 h, the 45Li 2 S–55LPS-320 exhibits a high ionic conductivity of 1.11 × 10 −4 S cm −1 , much higher than that of commercial Li 2 S. Without additional electrolytes, the Li 2 S–LPS composite mixed with a conductive agent is directly used as the cathode material. The composite cathode with high active material Li 2 S, whose content is up to 50%, delivers a discharge specific capacity of 674.3 mAh g −1 after 30 cycles at a current density of 0.2 mA cm −2 at 60 °C, with Coulombic efficiency being 100%.

✓ 已验证 DOI 高影响因子
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Advanced Science · 2026 · IF 14.1

Mesoporous Catalytic-Adsorptive Nanoregulator Orchestrates Biofilm eDNA/LPS Disassembly and TLR9/TLR4 Immune Reprogramming to Resolve Diabetic Foot Infections

Junfeng Song,Yang Song,Xirui Huang,Xingjin Li,Lifei Gao,Yixiang Wang,Tianbao Zhu,Xiaomin Li,Shuai Wang,Tiancong Zhao,Dongyuan Zhao

Chronic diabetic foot infections are severely hindered by tough biofilms and a self-fueling hyperinflammatory microenvironment, primarily orchestrated by the synergistic interplay between extracellular DNA (eDNA) and lipopolysaccharides (LPS) which facilitates the assembly of impenetrable biofilm architectures while inducing cross-inflammatory activation through the TLR4/9 axis. Conventional therapies often fail to resolve these “dual traps” of structural resistance and immunological interference. Herein, we developed a multifunctional mesoporous nano-regulator composed of Colistin (CT) and m-aminophenol formaldehyde (mAPF) framework, hence termed CT/mAPF to implement a “triad-strategy”: biofilm disruption, bacterial eradication, and debris neutralization. The CT/mAPF nano-regulator achieves potent bactericidal activity (99.99%) and initiates ROS-mediated oxidative fragmentation of eDNA to destroy the biofilm scaffold. Crucially, the platform effectively neutralizes LPS and degrades eDNA, leading to the simultaneous silencing of TLR4 and TLR9 signaling pathways. This dual-targeting approach weakens the eDNA/LPS-mediated synergistic inflammatory response, and suppresses pro-inflammatory cytokines ( IL-6 , IL-1β , TNF-α ). In diabetic mouse models, CT/mAPF significantly accelerated bacterial clearance and wound closure through enhanced angiogenesis and collagen maturation. This integrated strategy resolves the cycle of chronic infection and inflammation, offering a robust strategy for Gram-negative bacteria-infected diabetic wound management.

✓ 已验证 DOI PubMed 高影响因子
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MOLECULES · 2026 ·Vol. 31 ·期 18 ·3247 · IF 5.1

Carboxyl Amidation of Chlorogenic Acid Improves Anti-Inflammatory Activity and Biosafety via Potent AKR1B1 Inhibition in LPS-Induced Macrophages

Faliu Yang,Chunmei Guang,Huan Chen,Hongwei Hou

Persistent inflammation driven by excessive AKR1B1 activation contributes to the progression of multiple chronic inflammatory diseases. Natural chlorogenic acid (CGA) exhibits anti-inflammatory activity but suffers from poor membrane permeability, while its laurate ester derivative (CGL) shows clear dose-dependent cytotoxicity in macrophages. Here, we synthesized a novel chlorogenic acid amide derivative (CGAA) by selective amidation of the aliphatic carboxyl group on the quinic acid moiety of CGA, fully preserving the chiral polyphenol scaffold. Structural identity was confirmed by HSQC, HMBC, FTIR and HR-ESI-MS. CCK-8 assays demonstrated that CGAA maintained > 95% viability of RAW264.7 cells at 100 μM, displaying markedly superior cellular safety relative to CGL. In LPS-stimulated RAW264.7 macrophages, CGAA dose-dependently suppressed NO, TNF-α and IL-6 production and exhibited stronger antioxidant activity than both CGA and CGL. Temperature-gradient CETSA, DARTS and enzymatic assays established direct binding and potent inhibition of AKR1B1 by CGAA (IC50= 7.85 μM). Molecular docking revealed that the newly introduced amide forms an additional hydrogen bond with ILE-260, enhancing ligand–target affinity. This carboxyl-amidation strategy simultaneously improves the cellular safety and AKR1B1 inhibitory potency of CGA, providing a rational approach for developing low-toxicity polyphenol-based anti-inflammatory leads.

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