BIOCHEMICAL PHARMACOLOGY
·
2024
·
IF 5.3
Shan Meng,Xin Chen,Jikai Zhao,Xinyi Huang,Yuting Huang,Tao Huang,Zijun Zhou,Wenpu Ren,Tao Hong,Jinfeng Duan,Liming Yu,Huishan Wang
Fibronectin type III domain-containing protein 5 (FNDC5) exerts potential anti-arrhythmic effects. However, the function and mechanism of FNDC5 in diabetes-associated atrial fibrillation (AF) remain unknown. In this study, bioinformatics analysis, in vivo and in vitro experiments were conducted to explore the alteration and role of FNDC5 in diabetes-related atrial remodeling and AF susceptibility. RNA sequencing data from atrial samples of permanent AF patients and diabetic mice exhibited significantly decreased FNDC5 at the transcriptional level, which was in line with the protein expression in diabetic mice as well as high glucose and palmitic acid (HG+PA) injured atrial myocytes. Diabetic mice exhibited adverse atrial remodeling and increased AF inducibility. Moreover, reduced atrial FNDC5 was accompanied with exacerbated NOD-like receptor pyrin domain containing 3 (NLRP3) activation and disturbed mitochondrial fission and fusion processes, as evidenced by decreased expressions of optic atrophy 1 (OPA-1), mitofusin (MFN-1, MFN-2) and increased phosphorylation of dynamin-related protein 1 (Ser616). These effects were validated in HG+PA-treated atrial myocytes. Critically, FNDC5 overexpression remarkably enhanced cellular antioxidant capacity by upregulating the expressions of superoxide dismutase (SOD1, SOD2) level. In addition, HG+PA-induced mitochondrial dysfunction was ameliorated by FNDC5 overexpression as evidenced by improved mitochondrial dynamics and membrane potential. Moreover, NLRP3 inflammasome-mediated inflammation was reduced by FNDC5 overexpression, and AMPK signaling might serve as the key down-stream effector. The present study demonstrated that reduced atrial FNDC5-AMPK signaling contributed to the pathogenesis of diabetes- associated AF by impairing mitochondrial dynamics and activating the NLRP3 inflammasome. These findings provide promising therapeutic avenues for diabetes-associated AF.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Science & Nutrition
·
2026
·Vol. 14
·期 4
·e71768
·
IF 5
Yunyun Zhi,Keli Zhou,Xueqing Huang,Yonghui Li,Ye Zhu,Yiqiang Xie,Shouzhong Ren
Gastric mucosal injury refers to the pathological changes characterized by congestion, edema, bleeding and erosion of the gastric mucosa caused by various factors. This condition is a significant feature of gastritis in which the inflammatory response plays a critical role in its pathogenesis. The herbal pair Daphniphyllum calycinum – Polygonum hydropiper (DCPH), known for its anti‐inflammatory and antioxidant properties, has been shown to alleviate gastric mucosal injury. This study aimed to elucidate the mechanism by which DCPH alleviates gastric mucosal injury by integrating network pharmacology with both in vivo and in vitro experimental validation. The results indicated that DCPH treatment significantly increased the antioxidant capacity of the cells and decreased the expression of inflammation‐related factors. DCPH suppressed macrophage M1 polarization while inducing apoptosis in damaged cells. Furthermore, DCPH diminished structural gastric mucosal damage and gastric inflammation. DCPH promotes autophagy by upregulating the expression of LC3II/I and Beclin1, and downregulating P62 accumulation, thereby inhibiting the TLR4/NF‐κB/NLRP3 signaling pathway and M1 polarization, and reducing the release of inflammatory factors. However, these effects can be reversed by the autophagy inhibitor chloroquine (CQ). In conclusion, DCPH alleviates gastric mucosal injury via regulating autophagy and targeting TLR4/NF‐κB/NLRP3, thereby offering insights for the treatment of gastrointestinal diseases. The schematic diagram illustrated the proposed mechanism of DCPH in mouse macrophages. DCPH promotes autophagy to suppress the TLR4/NF‐κB/NLRP3 pathway and M1 polarization, thereby attenuating cellular oxidative stress and inflammation.
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Qi Lou,Lu Pan,Shengjin Xiang,Yueting Li,Jiahui Jin,Jingyang Tan,Baoshan Huang,Kaihui Nan,Sen Lin
Introduction Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED).Methods The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael’s addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction.Results After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission.Conclusion NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Diabetology & Metabolic Syndrome
·
2023
·Vol. 15
·期 1
·1-13
·
IF 4.8
Li Tianrong,Yang Jingjing,Tan Anjun,Chen Hewen
Background Irisin plays a key role in metabolic diseases, including type 2 diabetes mellitus (T2DM). However, the mechanism underlying the link between irisin and the development of T2DM, particularly in pancreatic islet β-cells, remains unknown.Methods In vitro, Min6 cells were treated with high glucose (HG) to generate T2DM cell models. GSDMD-N staining, Western blotting assays, and ELISA were performed to measure the expression levels of GSDMD, caspase 1, IL-1β, and IL-18. Next, the NLRP3 stimulator, ATP, was used to assess the effect of irisin on NLRP3 inflammasome. To evaluate the function of the Nrf2-TrX/TXNIP signaling axis, the Nrf2 inhibitor ML385 was used. For in vivo assessment, we first established T2DM model mice. Then, hematoxylin and eosin (H&E) staining was performed to observe the islet morphology, and the immunofluorescence technique was used to examine the mass of α and β cells. To confirm the role of the Nrf2-TrX/TXNIP signaling axis, ML385 was injected into the mice. Immunofluorescence of Nrf2, caspase 1, and GSDMD was detected in the islet cells of the model mice to verify the results.Results We found that irisin treatment significantly decreased the expression of GSDMD-N (P31) and cleaved caspase-1 (p20), decreased caspase1 activity, and inhibited the secretion of IL-1β and IL-18 in HG-treated Min6 cells. We also found that irisin inhibited oxidative stress and NLRP3 expression by activating the Nrf2-TrX/TXNIP signaling axis. Additionally, in the T2DM model mice, irisin enhanced the function of islet cells, decreased insulin resistance, and preserved the morphology of pancreatic islets.Conclusion We showed in this study that irisin can be used for treating pyroptosis in HG-induced islet β-cells and T2DM model mice. We also found that irisin inhibits pyroptosis and oxidative stress by inhibiting the NLRP3-GSDMD pathway and activating the Nrf2-TrX/TXNIP signaling axis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2019
·
IF 3.845
Li Wei,He Weiming,Xia Ping,Sun Wei,Shi Ming,Zhou Yao,Zhu Weiwei,Zhang Lu,Liu Buhui,Zhu Jingjing,Zhu Yiye,Zhou Enchao,Sun Minjie,Gao Kun
Abelmoschus manihot (L.) Medik. (Malvaceae) is a herb used in traditional Chinese medicine to treat some kidney diseases. To date, the detailed mechanisms by which A. manihot improves some kinds of renal disease are not fully understood. In this study, we established Adriamycin-induced NRK-52E cells, the normal rat kidney epithelial cell line, injury, and Sprague-Dawley rats with Adriamycin-induced nephropathy to evaluate the role and mechanisms of total extracts of A. manihot flower (TEA) both in vitro and in vivo. We found that TEA ameliorated Adriamycin-induced cellular morphological changes, cell viability, and apoptosis through the suppression of protein oxidation and ERK1/2 signaling. However, this anti-oxidative stress role of TEA was independent of ROS inhibition. Adriamycin activated ERK1/2 signaling followed by activation of NLRP3 inflammasomes. TEA suppressed NLRP3 inflammasomes via inhibition of ERK1/2 signal transduction; decreased proteinuria and attenuated renal tubule lesions; and inhibited the expression of NLRP3 in tubules in rats with Adriamycin nephropathy. Collectively, TEA protects renal tubular cells against Adriamycin-induced tubule injury via inhibition of ROS-ERK1/2-NLRP3 inflammasomes.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
·
2024
·
IF 5.7
Jingqi Yang,Xiaoyu Xia,Ming Du,Shuzhen Cheng,Beiwei Zhu,Xianbing Xu
Inflammatory bowel disease (IBD) etiology is intricately linked to oxidative stress and inflammasome activation. Natural antioxidant nobiletin (NOB) contains excellent anti-inflammatory properties in alleviating intestinal injury. However, the insufficient water solubility and low bioavailability restrict its oral intervention for IBD. Herein, we constructed a highly efficient NOB-loaded yeast microcapsule (YM, NEFY) exhibiting marked therapeutic efficacy for dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) at a low oral dose of NOB (20 mg/kg). We utilized the metal polyphenol network (MPN) formed by self-assembly of epigallocatechin gallate (EGCG) and FeCl3 as the intermediate carrier to improve the encapsulation efficiency (EE) of NOB by 4.2 times. These microcapsules effectively alleviated the inflammatory reaction and oxidative stress of RAW264.7 macrophages induced by lipopolysaccharide (LPS). In vivo, NEFY with biocompatibility enabled the intestinal enrichment of NOB through controlled gastrointestinal release and macrophage targeting. In addition, NEFY could inhibit NLRP3 inflammasome and balance the macrophage polarization, which favors the complete intestinal mucosal barrier and recovery of colitis. Based on the oral targeted delivery platform of YM, this work proposes a novel strategy for developing and utilizing the natural flavone NOB to intervene in intestinal inflammation-related diseases.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Functional Foods
·
2024
·
IF 3.8
Shengchen Ding,Jun Chen,Guangming Chen,Weiyi Tian,Junping Zheng,Haiming Hu,Lu Cao,Xiaowei Yao,Baifei Hu,Hongtao Liu
This study aimed to isolate oligosaccharides from P. sibiricum , analyze its structure, and elucidate the pharmacological mechanism for colitis improvement. First, a homogeneous oligosaccharide PSO-A was isolated and its structure was characterized. Then, the colitis model was induced with 3 % dextran sulfate sodium (DSS) and intervened with PSO-A. The results show that PSO-A was an agavin-type acetylated fructooligosaccharide with a molecular weight of 2.12 kDa. PSO-A consisted of (2 → 6)-β-D-Fru f residue backbone with an internal α-D-Glc p residue and (2 → 1)-β-D-Fru f residue side chains. Further, PSO-A increased mucin content, protected intestinal barrier integrity of colitis mice, and significantly inhibited the levels of inflammatory factors. Moreover, the protein expressions of NLRP3, ASC, and Caspase-1 in colitis mice was statistically inhibited by PSO-A. In summary, PSO-A could alleviate colitis by inhibiting NLRP3 inflammasome pathway, which provides a basis for the development and application of P. sibiricum oligosaccharides as drug or functional food to relieve colitis.
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2025
·
IF 5.4
Lei Yan,Qin Zeng,Wenru Wang,Ying Liang,Rui Lang,Jingyi Zhan,Jiayi Yang,Renhuan Yu,Xinhui Wang
Ethnopharmacological relevance Jianpi Qushi Heluo formula (JQHF) is an evidence-based herbal formula based on "Fangji Huangqi Decoction" in the classic of traditional Chinese medicine (TCM) synopsis of the Golden Chamber. Its effectiveness in reducing idiopathic membranous nephropathy (IMN) proteinuria, edema and other clinical symptoms and improving kidney injury has been confirmed by clinical trials and animal experiments. These results demonstrate the critical significance of reducing podocyte injury by regulating mitophagy through integrating ethnopharmacology. Aim of the study This study aimed to explore the protective effects of JQHF on podocyte injury in IMN, focusing on its role in promoting PINK1-dependent mitophagy to inhibit reactive oxygen species (ROS) mediated activation of the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome. Materials and Methods The main components of JQHF were identified by ultra-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MSE). Passive Heymann nephritis (PHN) was induced in rats using anti-Fx1A antiserum, while podocyte injury in vitro was stimulated with sublytic complement C5b-9 (sC5b-9). The PHN rats were treated with JQHF, and autophagy inhibitor 3-methyladenine (3-MA) combined with JQHF was used for pathway verification, and Benazepril served as a positive control. In vitro, podocytes were exposed to palmitic acid (PA, a ROS inducer) and N-acetylcysteine (NAC, a ROS scavenger). Further, we silenced the expression of PINK1 in podocytes model and intervened with JQHF-containing serum. Renal function was assessed through biochemical analyses and histopathology. Mitochondrial function was measured by detecting mitochondrial membrane potential (MMP), ROS levels as well as mitochondrial ultrastructure. The expression of podocyte structural proteins (desmin, nephrin, podocin) and inflammasome-related markers (NLRP3, caspase-1, IL-1β, IL-6) was analyzed to assess podocyte injury and inflammasome activation. Results (1) In vitro, in contrast to the control group, PA intervention caused increased ROS accumulation, reduced MMP, upregulated NLRP3 and caspase-1 expression, as well as elevated expression of inflammatory factors IL-1β and IL-6. The expression of nephrin and podocin was notably reduced. By contrast, NAC reversed these effects. (2) In vivo, JQHF effectively ameliorated mitochondrial damage, reduced NLRP3 expression and mitigated podocyte injury in PHN rats. The protective effects of JQHF were diminished by 3-MA, confirming the involvement of autophagy. (3) In vitro, JQHF-containing serum attenuated C5b-9-induced podocyte injury, improved mitochondrial dysfunction, and inhibited ROS-mediated activation of NLRP3 inflammasome. Silencing PINK1 significantly reversed these protective effects. Conclusion JQHF can alleviate podocyte damage, that through inhibiting ROS-mediated NLRP3 inflammasome activation by improving PINK1-mediated mitophagy.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Huiping Ou,Zhanpan Wu,Jinhua Ning,Qiufeng Huang,Wancun Wang,Guochun Yang,Yingxun Zhou,Anguo Hou,Peng Li,Lingyun Chen,Wen Bin Jin
Introduction: A series of oridonin hybrids were synthesized and evaluated for anti-inflammatory potential, focusing on their ability to inhibit NO production in RAW264.7 cells and their therapeutic prospects for NLRP3-driven disorders.Methods: Anti-inflammatory activity was assessed by measuring NO inhibition in LPS-stimulated RAW264.7 cells. The most active compound, 4c, was further analyzed using ELISA and WB to evaluate its effects on inflammatory proteins (p-NF-κB, p-IκB, NLRP3, IL-6, IL-1β, COX-2, iNOS). In vivo efficacy was tested in a murine acute lung injury model, with RT‒qPCR and WB used to assess inflammatory markers in lung tissues. Molecular docking predicted 4c’s binding mode with NLRP3, while RNA-seq and RT‒qPCR identified differentially expressed genes.Results: Compound 4c significantly inhibited NO production and suppressed key inflammatory proteins in vitro. In vivo, it alleviated acute lung injury, reduced IL-6 and TNF-α mRNA levels, and inhibited NLRP3, p-NF-κB, and IL-6 protein expression. Docking suggested covalent binding to NLRP3. RNA-seq revealed 4c upregulated Trdc, Stfa2, and Gsta2 while downregulating Spib, Csf2, and Nr4a1.Discussion: Compound 4c demonstrates potent anti-inflammatory effects via NLRP3 pathway inhibition and modulation of inflammatory genes. These findings highlight oridonin hybrids, particularly 4c, as promising candidates for NLRP3-driven inflammatory disorders, warranting further investigation.
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2022
·
IF 5.195
Zhenhua Bian,Yuwen Qin,Lin Li,Lianlin Su,Chenghao Fei,Yu Li,Minmin Hu,Xiaowei Chen,Wei Zhang,Chunqin Mao,Xiaohang Yuan,Tulin Lu,De Ji
Ethnopharmacological relevance the fruit of Schisandra chinensis (Turcz.) Baill. (SC) is an important traditional Chinese herbal medicine, which has been widely used in traditional Chinese medicine (TCM) for treating intestinal diseases . It is also traditionally used as health product and medicine in Russia and other countries. However, the effect of SC ethanol extract on anti-ulcerative colitis (UC) has not been systematically studied yet. Aim of the study We investigated the protective effects and underlying action mechanisms of SC extract (SCE) for UC treatment. Materials and methods An animal model of UC induced by dextran sulfate sodium (DSS) was established. After oral administration of SCE, the Disease Activity Index (DAI) was calculated, the length of colon measured, levels of proinflammatory factors determined, and histopathology carried out to assess the therapeutic efficacy of SCE on UC. The effects of SCE on the toll-like receptor 4/nuclear factor-kappa B/nucleotide-binding and oligomerization domain-like receptor family pyrin domain containing 3 inflammasome (TLR4/NF-κB/NLRP3 inflammasome) signaling pathway were evaluated by western blotting . High-throughput sequencing was done to reveal the effect of SCE on the change of the gut microbiota (GM) in mice with DSS-induced colitis. Results SCE significantly reduced the DAI score, restored colon-length shortening, and ameliorated colonic histopathologic injury in mice with DSS-induced colitis. SCE inhibited the inflammatory response by regulating the TLR4/NF-κB/NLRP3 inflammasome pathway in mice with UC. SCE also maintained gut barrier function by increasing the levels of zonula occludens (ZO)-1 and occludin . 16S rRNA sequencing showed that SCE could reverse the GM imbalance caused by UC. Conclusions SCE can ameliorate DSS-induced colitis, and that its effects might be associated with suppression of the TLR4/NF-κB/NLRP3 inflammasome pathway and GM regulation, which may provide significant supports for the development of potential candidates for UC treatment.
✓ 已验证
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zijun Zhou,Yinli Xu,Xiong Xiao,Tao Huang,Jikai Zhao,Yuting Huang,Guoxin Zhang,Bo Xing,Qiusheng Zhao,Zijun Cao,Zhishang Wang,Zongtao Yin,Liming Yu,Huishan Wang
Background and purpose Our previous clinical study showed that berberine could reduce the occurrence of postoperative atrial fibrillation (AF), but the underlying mechanism remains unknown. Additionally, the effect of SIRT6 in the pathogenesis of AF and whether the anti-arrhythmic effects of berberine are associated with SIRT6 regulation remain uncovered. This study aimed to investigate the role of SIRT6 in the occurrence of AF and the pharmacological effect of berberine on atrial remodeling and AF susceptibility with a focus on SIRT6-AMPK signaling. Methods Bioinformatics tools and human atrial sample analysis were conducted to investigate the potential mechanisms. Murine AF model was induced by angiotensin II (Ang II) infusion with or without the treatment of berberine and the adeno-associated virus carrying SIRT6 or SIRT6-specific short hairpin RNA. The protective effect and the underlying mechanisms were examined. Results NLRP3 inflammasome-mediated inflammatory signaling in atrial tissue was activated, and SIRT6 activity was inhibited in AF patients. Berberine dose-dependently improved atrial structural and electrical remodeling in Ang II-induced mice. Moreover, berberine enhanced atrial antioxidative stress capacity and reduced NLRP3 inflammasome activation. SIRT6 overexpression mimicked these actions. Berberine-mediated SIRT6-AMPK signaling activation was inhibited by SIRT6 knockdown, and berberine-mediated inhibition of NLRP3 inflammasome signaling was compromised. Conclusion These results demonstrate that activation of SIRT6-AMPK signaling protects against Ang II-induced atrial remodeling and AF susceptibility. Berberine prevents Ang II-induced atrial injury by inhibiting NLRP3 inflammasome activation through the SIRT6-AMPK signaling pathway. Its potential as a preventive or therapeutic agent warrants further clinical investigation.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Advanced Science
·
2026
·
IF 14.1
Weidong Wang,Yimin Gong,Jianing Li,Tianze Wu,Mingli Deng,Yannan Yang
The clinical translation of cancer vaccines remains limited by the inability to effectively coordinate innate and adaptive immunity. Leveraging the metabolism pattern of the immune system, herein, we report a glucose metabolism-modulatory nanobiohybrid vaccine with superior antitumor immunity via orchestrating cross-presentation-enhanced adaptive immunity and proinflammatory signaling-mediated innate immunity. This nanobiohybrid vaccine is constructed by a nanoscale hydrogen-bonded organic framework (HOF) co-encapsulating glucose oxidase (GOx), and a model antigen, ovalbumin (OVA) (denoted OVA/GOx@HOF). OVA/GOx@HOF enables a GOx-mediated enzyme reaction that consumes glucose and produces H 2 O 2 within dendritic cells (DCs) in controlled kinetics, which disrupts intracellular glucose metabolism and causes redox imbalance but minimally impacts cell viability. These effects induce autophagic machinery in DCs that promotes antigen cross-presentation, thereby boosting cytotoxic T cell response. Meanwhile, through RNA sequencing, we found that OVA/GOx@HOF stimulates innate immunity through an NF-κB signaling-mediated and endogenous hydrogen sulfide (H 2 S)-enhanced NLRP3 inflammasome pathway, leading to significant DC maturation. In a melanoma tumor model, this nanobiohybrid vaccine effectively inhibits tumor growth and metastasis, and can be applied to encapsulate neoantigens to generate a potent personalized cancer vaccine. Our findings suggested the remarkable potential of enzyme-driven nanobiohybrid materials as a metabolism-modulatory platform for cancer vaccines.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）