JOURNAL OF ETHNOPHARMACOLOGY
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2026
·
IF 6.8
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.
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PubMed
高影响因子
MOLECULES
·
2026
·Vol. 31
·期 11
·1933
·
IF 5.1
Yanlong Li,Anning Zhan,Xiaobing Zhang,Yu Duan,Jiawen Tang,Hua Bai,Qi Wang
Objective: The present study investigates the effect of 1,8-cineole on improving lipid metabolism disorder by regulating oxidative stress and inflammation via the TLR4/MyD88/NF-κB pathway. 1,8-Cineole is a monoterpene compound widely found in the essential oils of many plants and has been reported to possess anti-inflammatory and antioxidant activities. However, its role in regulating lipid metabolism disorders remains unclear. This study aimed to investigate the effects of 1,8-cineole on lipid metabolism and explore the potential mechanisms related to oxidative stress and inflammation. Methods: Cell viability was assessed by MTT assay to determine the optimal PA concentration for inducing lipid accumulation and the non-cytotoxic range of 1,8-cineole in HepG2 and AML-12 cells. Lipid droplets were visualized by Oil Red O staining, while triglyceride (TG) and total cholesterol (TC) levels were quantified using enzymatic kits. Oxidative stress markers (ROS by DCFH-DA fluorescence; MDA by TBA method; CAT activity by ammonium molybdate method) and inflammatory cytokines (TNF-α, IL-6, IL-1β, IL-18 by ELISA) were measured. Western blotting analyzed key proteins in the TLR4/MyD88/NF-κB pathway (TLR4, MyD88, p-P65, p-IκBα). Pathway-specific inhibitors were employed for mechanistic validation. Results: 1,8-Cineole (up to 1000 μg/mL) showed no cytotoxicity. It significantly attenuated PA-induced lipid droplet accumulation, reduced TG and TC levels (p< 0.05), and ameliorated oxidative stress by decreasing ROS and MDA while enhancing CAT activity in AML-12 cells (p< 0.01). Furthermore, 1,8-cineole suppressed pro-inflammatory cytokine release (TNF-α, IL-6, and IL-1β;p< 0.01), whereas no significant effect was observed on IL-18 levels. Downregulated TLR4/MyD88/NF-κB pathway activation. Inhibition of TLR4 or NF-κB mirrored these protective effects. Conclusions: 1,8-Cineole alleviates PA-induced lipid metabolism disorders, oxidative stress, and inflammation in hepatocytes, likely through suppression of the TLR4/MyD88/NF-κB signaling pathway.
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高影响因子
Journal of Translational Medicine
·
2025
·Vol. 23
·期 1
·1385
·
IF 7.5
Gong Jiaxin,Wei Feng,Wu Tianyu,Zhang Ningzhi,Zhang Yongqiao,Cui Zhaoqiang,Ge Junbo
Background Obesity-related cardiac injury is a serious global condition associated with excessive fat intake, which is strongly linked to chronic low-degrade inflammation. Pyroptosis, a pro-inflammatory form of cell death, has been implicated in obesity recently. L-Fucose (Fuc), a sulfated polysaccharide with anti-inflammatory and antioxidant properties, remains unexplored in the area of pyroptosis and obesity-related cardiac injury. Methods Six-week-old wide type C57BL/6 mice were subjected to high-fat diet (HFD) feeding for 20 weeks to induce obesity with or without Fuc gavaging, followed by assessment of metabolic related indicators. Echocardiography, histopathological analysis and enzymatic assays were used to assess cardiac function. The level of pro-inflammatory cytokines was detected by ELISA, qRT-PCR and CD68 staining. Pyroptosis-related protein including NLRP3, GSDMD, pro-caspase-1, cleaved-caspase-1, IL-1β, and ASC were evaluated by western blot. Oxidative stress was detected by ROS level. Cardiac mitochondrial structure was assessed by electron microscopy and mitotracker staining. Mitochondrial function was measured by mitochondrial membrane potential (MMP) and oxygen consumption rate (OCR) assay. Molecular docking and molecular dynamics (MD) simulations were conducted to look for the potential target of Fuc. Cellular thermal shift assay (CETSA) and western blot were used to investigate the interaction between Fuc and its target. Palmitic acid (PA) induced lipotoxicity model in AC16 cells was used to further confirm the protective effects of Fuc and its downstream signaling pathway against inflammation, pyroptosis and mitochondrial injury in vitro. Results In vivo, Fuc treatment alleviated obesity-related weight gain, hyperlipidemia, elevated systolic blood pressure and cardiac diastolic dysfunction. It also reduced the expression of pro-inflammatory cytokines and pyroptosis-related proteins, the level of oxidative stress, and mitochondrial abnormalities in the myocardium. Moreover, the vitro lipotoxicity model further confirmed the protective effect of Fuc. The molecular docking analysis identified TLR4 as the key target of Fuc. Fuc reduced the level of TLR4 and its downstream proteins MyD88 and p-NF-κB, while activating TLR4/MyD88/NF-κB pathway by TLR4 agonist Neoseptin3 reversed the protective function of Fuc in vitro. Conclusions These findings demonstrated that Fuc mitigated cardiac inflammation, pyroptosis and mitochondrial injury by inhibiting the TLR4/MyD88/NF-κB pathway, highlighting its potential as a therapeutic agent for obesity-associated cardiac injury.
研究领域:
心脏病学
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分子生物学
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免疫学
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代谢性疾病
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药理学
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PubMed
高影响因子
CARBOHYDRATE POLYMERS
·
2025
·
IF 12.5
Chun-Jie Bao,Meng-Qiu Liu,Ya-Nan Liu,Li-Qiang Zhao,Yu-Xuan Li,Xin-Lan Zhang,Fang Zhang,Sheng Guo,Er-Xin Shang,Jia-Lun Duan,Jin-Ao Duan
Current studies on plant-derived adjuvants focus on heterogeneous or partially characterized polysaccharides, while the adjuvanticity of structurally defined, arabinogalactan (AG)-rich polysaccharide in cancer nanovaccine settings remains unexplored. Here, we identify and characterize NLBPE1, a homogeneous AG-rich polysaccharide isolated from Lycium barbarum , which features an atypical arabinose-bridged structure. Unlike canonical AG-I or AG-II motifs, NLBPE1 contains galactose side chains connected to the rhamnogalacturonan backbone via → 5)- α -Ara f -(1 → linkages, forming a structurally distinct AG topology. Mechanistic studies demonstrate that NLBPE1 activates dendritic cells through the TLR4–IKK–NF-κB signaling axis, promoting antigen uptake, cross-presentation, and proinflammatory cytokine release. When co-formulated in a PLGA-based nanovaccine with a model antigen, NLBPE1 markedly enhances CD8 + T cell priming, leading to effective tumor control in vivo . Moreover, combination with anti-PD-1 immune checkpoint blockade yields synergistic antitumor responses in a melanoma model. Together, these findings establish NLBPE1 as a structurally and mechanistically distinct polysaccharide adjuvant with translational potential for next-generation cancer nanovaccine strategies.
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高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2025
·Vol. 26
·期 20
·10073
·
IF 4.9
Mei Feng,Xinxiang Chen,Fan Huang,Lin Chen,Can Liu,Wei Li,Yinyan Li,Shaobin Chen,Zhen Deng,Zhengyi Wei,Yuan Luo,Xiyong Yu,Aiping Qin
Alpinetin, a distinctive plant-derived dihydroflavonoid from cardamom seeds, represents an under-explored chemical scaffold compared to common flavonoids like quercetin or kaempferol. While many flavonoids have shown general cardioprotective potential, the structural specificity of alpinetin may confer unique pharmacological advantages. Inspired by its historical use in traditional Chinese medicine for cardiac discomfort, this study systematically investigated its efficacy against acute myocardial infarction (AMI). In a rat AMI model, alpinetin demonstrated superior infarct size reduction and functional recovery relative to other tested flavonoids. It significantly attenuated key AMI pathologies—including inflammatory infiltration, CD68+ macrophage activation, IL-6/TNF-α release, collagen deposition, and cardiomyocyte apoptosis—more effectively than common flavonoid benchmarks. Mechanistically, alpinetin selectively targeted the TLR4/MyD88/NF-κB signaling axis with notable potency, a pathway not robustly modulated by other flavonoids in the screening. These findings not only validate the traditional wisdom of cardamom but also establish alpinetin as a structurally and mechanistically distinct flavonoid with high translational promise, offering a new candidate for the targeted treatment of ischemic heart disease.
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高影响因子
Advanced Science
·
2026
·
IF 14.1
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.
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高影响因子
BRITISH JOURNAL OF PHARMACOLOGY
·
2019
·Vol. 176
·期 14
·2627-2641
·
IF 6.583
Zheng Xu,Chunpeng Zou,Weihui Yu,Sujing Xu,Lan Huang,Zia Khan,Jingying Wang,Guang Liang,Yi Wang
Background and Purpose Hypertension adversely affects the kidney and is the second leading cause of kidney failure. Overproduction of angiotensin II greatly contributes to the progression of hypertensive kidney disease. Angiotensin II has recently been shown to activate STAT3 in cardiovascular cells. However, the underlying mechanisms of STAT3 activation by angiotensin II and downstream functional consequences in the kidneys are not fully understood. Experimental Approach C57BL/6 mice were treated with angiotensin II by subcutaneous infusion for 1 month to develop nephropathy. Mice were treated with either adeno-associated virus expressing STAT3 shRNA or STAT3 inhibitor, S3I-201. Human archival kidney samples from five patients with hypertension and five individuals without hypertension were also examined. In vitro, STAT3 was blocked using siRNA or STAT3 inhibitor S3I-201 in the renal proximal tubular cell line, NRK52E, after exposure to angiotensin II. Key Results Angiotensin II activated STAT3 in kidney epithelial cells through engaging toll-like receptor 4 (TLR4) and JAK2, which was independent of IL-6/gp130 and angiotensin AT 1 receptors. Angiotensin II-mediated STAT3 activation increased fibrotic proteins and resulted in renal dysfunction. Both STAT3 inhibition by the low MW compound S3I-201 and TLR4 deficiency normalized renal fibrosis and dysfunction caused by Ang II in mice, without affecting hypertension. Conclusions and Implications Our study reveals a novel mechanism of STAT3 activation, induced by angiotensin II, in kidney tissues and highlights a translational significance of a STAT3 inhibitor as potential therapeutic agent for hypertensive kidney disease.
研究领域:
肾病学
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药理学
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分子生物学
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心血管疾病
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高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 3
·1-10
·
IF 2.447
Jing Li,Yu-Shan Mao,Fen Chen,Dong-Xia Xia,Tin-Qi Zhao
Insulin resistance is the main sign of type 2 diabetes mellitus and is often accompanied by the infiltration of inflammatory factors. These inflammatory factors are mainly produced and secreted by macrophages. The purpose of the current study was to explore the relationship between macrophages and insulin resistance, and to determine its underlying mechanism. The insulin resistance of macrophages was induced by palmitic acid (PA) in vitro. The glucose uptake rate of macrophages, the expression levels of inflammatory cytokines and the expression levels of insulin resistance‑related proteins were detected. The protein expression levels of Krüppel‑like factor 4 (KLF4), toll‑like receptor 4 (TLR4), NF‑κB and Galectin‑3 (Gal‑3) were detected via western blotting and recovery experiments were performed by combining the Gal‑3 and TLR4 inhibitors GB1107 and TAK242. The results revealed that PA‑induced macrophages demonstrated insulin resistance. Additionally, KLF4 protein was inhibited and the sugar uptake rate was significantly lower than that of the control group. Western blotting and immunofluorescence assays revealed that the expression of Gal‑3 in PA‑induced macrophages was significantly upregulated. The addition of the Gal‑3 inhibitor GB1107 significantly increased glucose utilization and reduced insulin resistance in PA‑treated cells. Inhibitor of TLR4 inhibited the protein expression level of the TLR4/NF‑κB pathway. In conclusion, PA promoted the TLR4/phosphorylated‑NF‑κB signaling pathway by inhibiting KLF4, promoted the upregulation of Gal‑3 expression and improved the insulin resistance of macrophages.
研究领域:
免疫学
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内分泌学
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分子生物学
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糖尿病研究
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PubMed
高影响因子
PHYTOMEDICINE
·
2023
·
IF 7.9
Yeye Hu,Ziliang He,Ji Zhang,Chaohua Zhang,Yanting Wang,Wei Zhang,Fenglun Zhang,Weiming Zhang,Fenglin Gu,Weicheng Hu
Background Piper nigrum essential oil (PnEO) possesses pleasant aroma, unique flavor, and various bioactivities; however, its role against colitis remains unclear. Purpose In this study, we investigated the role of PnEO in relieving colitis and explored its potential mechanisms in a mouse model of dextran sulfate sodium (DSS)–induced colitis. Methods Initially, we identified and quantified the components of PnEO by gas chromatography-mass spectrometry (GC–MS). Subsequently, we investigated the protective role of PnEO (50 and 200 mg/kg) in DSS-induced colitis in mice by evaluating disease activity index (DAI) scores and colon length, and performing histological analyses. Eyeball blood was collected and cytokines were determined using ELISA kits. The anti-inflammatory mechanisms of PnEO were analyzed by western blot (WB) and immunohistochemistry (IHC). The intestinal barrier function was evaluated according to tight junction (TJ) protein mRNA levels. We used 16S rRNA gene sequencing to analyze the intestinal microflora of mouse cecal contents. Results Supplementation with PnEO (50 and 200 mg/kg) increased colon length and improved colon histopathology . PnEO regulated inflammatory responses by downregulating TLR4/MAPKs activation, thereby reducing the release of cytokines and mediators. Moreover, it also protected the intestinal barrier through enhancing the expression of claudin-1, claudin-3, occludin , ZO-1, and mucin 2 . 16S rRNA gene sequencing revealed that PnEO (200 mg/kg) decreased the abundance of Akkermansia in the gut microbiome . Conclusion PnEO treatment (50 and 200 mg/kg) relieved DSS-induced colitis by inhibiting TLR4/MAPK pathway and protecting intestinal barrier, and high-dose PnEO exhibited better effects. Moreover, PnEO (200 mg/kg) regulated key compositions of the gut microbiome, which indicated that it had therapeutic potential for sustaining gut health to lower the risk of colitis.
研究领域:
药理学
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免疫学
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胃肠病学
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微生物学
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PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 7
·3735
·
IF 4.9
Jing Sun,Zhengtian Zhao,Jiaqi Lu,Wen An,Yiming Zhang,Wei Li,Li Yang
The unsatisfactory efficacy of immunotherapy for colorectal cancer (CRC) remains a major challenge for clinicians and patients. The tumor microenvironment may promote CRC progression by upregulating the expression of hypoxia-inducing factor (HIF) and PD-L1. Therefore, this study explored the expression and correlation of HIF-1α and PD-L1 in the CRC microenvironment. The expression and correlation of HIF-1α and PD-L1 in CRC were analyzed using bioinformatics and Western blotting (WB). The hypoxia and inflammation of the CRC microenvironment were established in the CT26 cell line. CT26 cells were stimulated with two hypoxia mimics, CoCl2and DFO, which were used to induce the hypoxic environment. Western blotting was used to assess the expression and correlation of HIF-1α and PD-L1 in the hypoxic environment.LPS stimulated CT26 cells to induce the inflammatory environment. WB and bioinformatics were used to assess the expression and correlation of TLR4, HIF-1α, and PD-L1 in the inflammatory environment. Furthermore, the impact of curcumin on the inflammatory environment established by LPS-stimulated CT26 cells was demonstrated through MTT, Transwell, molecular docking, network pharmacology and Western blotting assays. In this study, we found that the HIF-1α/PD-L1 pathway was activated in the hypoxic and inflammatory environment and promoted immune escape in CRC. Meanwhile, curcumin suppressed tumor immune escape by inhibiting the TLR4/HIF-1α/PD-L1 pathway in the inflammatory environment of CRC. These results suggest that combination therapy based on the HIF-1α/PD-L1 pathway can be a promising therapeutic option and that curcumin can be used as a potent immunomodulatory agent in clinical practice.
研究领域:
肿瘤学
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免疫学
·
分子生物学
·
癌症治疗
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PubMed
高影响因子
BIOCHEMICAL GENETICS
·
2025
·
IF 1.6
Li Qiaoxia,Zhang Yongyan,Shen Haoyu,Wang Ziqian,Huang Jiezhuang,Tang Shuli,Chen Peiyue,Zhi Zhifu
Intrauterine adhesions (IUA) is one of the most prevalent gynecological conditions affecting women of childbearing age. The active ingredient curcumin (CUR), derived from turmeric, is a promising candidate for the treatment of IUA. Nevertheless, the mechanism of action remains undetermined. This study investigates the role and mechanism of CUR in the treatment of IUA through network pharmacology, molecular docking, and molecular biology experiments. IUA-related targets were sourced from the GeneCards database. CUR-related targets were obtained from Herb and SwissTarget Prediction. Cytoscape version 3.10.2 was employed to construct PPI networks and to identify core targets. GO and KEGG enrichment analyses were conducted using the DAVID database. Additionally, molecular docking was employed to evaluate the interaction between CUR and core targets. Finally, the mechanism and targets of CUR in IUA were validated through animal experiments. A total of 122 common target points for CUR and IUA were identified. Topological analysis and KEGG analysis identified 20 core target points, encompassing multiple pathways, including inflammation and the PI3K/AKT signaling pathway. Molecular docking results demonstrated that CUR exhibits a strong binding affinity for the core target points. In vivo experiments indicate that CUR significantly alleviates the fibrosis and epithelial-mesenchymal transition (EMT) processes of the endometrium in IUA rats while inhibiting the overexpression of TGF-β1 in the uterine tissue of IUA rats and the activation of the PI3K/AKT and TLR4/NLRP3 signaling pathways. CUR can inhibit fibrosis and the EMT process in the endometrium of IUA rats, and its mechanism may be associated with the inhibition of the PI3K/AKT and TLR4/NLRP3 signaling pathways.
研究领域:
药理学
·
分子生物学
·
生殖医学
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高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2025
·
IF 8.5
Donglin Sui,Mingxin Li,Chunqing Ai,Shugang Li,Hong Chang,Yixuan Li,Shouhao Zhao,Huan Li,Xiaomeng Ren
This study aimed to investigate the therapeutic efficacy of Larimichthys Crocea Isinglass polysaccharide (CIP) in ameliorating DSS-induced colitis. CIP, a complex polysaccharide composed of six monosaccharides with a molecular weight of 3.97 kDa. Specifically, CIP treatment mitigated weight loss and histopathological damage in the colon, increased colon length, and by inhibiting the TLR4/MyD88/NF-κB pathway significantly downregulated the secretion levels of pro-inflammatory cytokines TNF-α, IL-6, and IL-1β, while simultaneously upregulating the anti-inflammatory cytokine IL-10 and inhibition of the oxidative stress-related enzyme inducible nitric oxide synthase (iNOS). Additionally, CIP treatment enhanced intestinal barrier function by increasing the expression of intestinal tight junction proteins (TJs) and MUC2, and it promoted the production of short-chain fatty acids (SCFAs). Concurrently, CIP modulated the composition of the intestinal microbiota, inhibiting the proliferation of potentially harmful bacteria such as Bacteroidota and Campylobacter . Taken together, these findings suggest that CIP exhibits promising attributes as a functional food constituent, with a particular efficacy in modulating and maintaining intestinal health.
研究领域:
免疫学
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营养学
·
肠道健康研究
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PubMed
高影响因子
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