PHYTOTHERAPY RESEARCH
·
2026
·
IF 8.1
Shuanggong Liu,Jie Zhao,Shuhang Dong,Yang Zhang,Yachao Zhao,Ning Ran,Guowei Yang,Changliang Peng,Xu Yang,Guangxu Song,Yingze Zhang,Dongjin Wu
Intervertebral disc degeneration (IVDD) is a major cause of chronic low back pain and is driven by oxidative stress, inflammation, and ferroptosis. While mitophagy regulates ferroptosis in other diseases, its role in IVDD remains unclear. The potential of scutellarein, a flavonoid with antioxidant properties, to treat IVDD has not yet been explored. Primary human nucleus pulposus (HNP) cells were treated with tert-butyl hydroperoxide (TBHP) to establish an in vitro IVDD model. Mitophagy was inhibited by cyclosporin A (CsA) treatment. Radiographic and histopathological analyses were performed in a rodent IVDD model. Key markers (IL-1β, ACSL4, GPX4, PINK1, LC3, and PI3K/mTOR) were assessed. Scutellarein preserved the NPC phenotype, reduced inflammation, and suppressed ferroptosis by activating PINK1/Parkin-mediated mitophagy. It restored mitochondrial function and inhibited the PI3K/AKT/mTOR pathway. In vivo, scutellarein attenuated IVDD progression; downregulated the expression of IL-1β and ACSL4; and upregulated the expression of collagen II, GPX4, PINK1, and LC3. Scutellarein mitigates IVDD by inducing mitophagy to inhibit ferroptosis and restore mitochondrial function, highlighting its therapeutic potential.
✓ 已验证
DOI
PubMed
高影响因子
Journal of Hazardous Materials Advances
·
2026
·
IF 9.1
Xin-Ru Zhang,Yue-Hua Chen,Gui-Zhong Xin,Cheng Qian,Mu Zhang,Xiao-Wei Zhang,Zi-Xuan Ding,Fang-Tong Liu,Hui Zhang,Rui-Bo Sun,Tian-Qi Zhang,Hong-Juan Hou,Kang Ting-Guo,Hui-Peng Song
The aquatic toxicity mechanism of methyl eugenol (ME), an emerging insect sex pheromone-based pesticide, remains unclear. To address this issue, we established a strategy termed "1N (network toxicology) + 2T (toxicity assessment, transcriptomics) + 3M (metabolomics, molecular docking, mechanism verification)" to systematically investigate its toxicity, focusing on ferroptosis as a potential core mechanism. Toxicity assessment determined the 96-hour LC₅₀ of ME in zebrafish to be 2.536 mg/L and it caused marked histopathological damage in liver and gill tissues. Furthermore, integrated transcriptomic and metabolomic analysis revealed the co-enrichment of dysregulated genes and altered metabolites in ferroptosis-related pathways. Subsequently, network toxicology identified CDK1, TP53, CHEK2, and CTNNB1 as key ferroptosis-related targets of ME, and molecular docking confirmed their stable binding via hydrogen bonds with lysine residues. For mechanism verification, the ferroptosis inhibitor ferrostatin-1 (Fer-1) significantly reduced ME-induced mortality, alleviated tissue damage, and mitigated oxidative stress and lipid peroxidation. These findings demonstrated that ferroptosis was the primary toxicity mechanism of ME in zebrafish. Our study provides scientific evidence for the ecological risk assessment of ME and presents the "1N+2T+3M" strategy as an applicable framework for evaluating other pesticides.
✓ 已验证
DOI
高影响因子
JOURNAL OF FOOD AND DRUG ANALYSIS
·
2025
·Vol. 33
·期 2
·119
·
IF 3
Quan Liao,Zhenzhen Guo,Chenchun Ding,Renjie Zuo,Guoyan Liu
Chronic atrophic gastritis (CAG) is precancerosis with limited treatment options. This study investigated the therapeutic effects of velvet antler (VA), a traditional natural medicine, on CAG, with a focus on ferroptosis. In vivo experiments demonstrated the efficacy of VA in alleviating CAG, and network pharmacology analysis revealed its involvement in related terms, including inflammation, oxidative stress, and cell proliferation. Analyses further confirmed the modulation of ferroptosis by VA, particularly via the Keap1-Nrf2/HO-1/GPX4 pathway. In vitro assays supported these findings, demonstrating the ability of VA to reduce methylnitronitrosoguanidine-induced inflammation, oxidative stress, and ferroptosis in GES-1. This study provides a basis for exploring VA as a potential treatment for CAG, and offers new therapeutic strategies targeting ferroptosis.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2025
·
IF 4.7
Zhun Li,Sixia Yang,Wei Liu,Long Ling,Hailan Hu,Yanming Cao,Shouyu Xiang
Salidroside, one of the main active compounds extracted from Rhodiola, has shown promising potential for the treatment of osteoporosis. Our previous study demonstrated that salidroside alleviated cognitive dysfunction in senescence-accelerated mouse prone 8(SAMP8) mice. In this study, we further investigated the effect of salidroside on osteoporosis in SAMP8 mice and explored the mechanism. The results of micro-computed tomography(micro-CT) and histology showed that salidroside significantly increased trabecular bone formation and improved bone microstructure in senile osteoporotic SAMP8 mice, and upregulated the protein expression levels of phosphatidylinositol-3-kinase(PI3K), glutathione peroxidase 4(GPX4), and Runt-related transcription factor 2(RUNX2) in the distal femur. Cell-based assays, including the Cell Counting Kit-8(CCK-8) assay, senescence-associated β-galactosidase (SA-β-galactosidase) staining, alkaline phosphatase (ALP) staining, Alizarin Red staining, and lipid peroxide detection, demonstrated that salidroside significantly promoted the proliferation and osteogenic differentiation of senile osteoporotic bone marrow stromal cells (BMSCs) and decreased lipid peroxide levels. Furthermore, real-time polymerase chain reaction (RT-PCR) and Western blotting analysis showed that salidroside increased protein and gene expression levels of solute carrier family 7 member 11(SLC7A11), GPX4, and ferroptosis suppressor protein 1(FSP1). Additionally, salidroside also increased the phosphorylation of PI3K, AKT, and mTOR, an effect reversed by LY294002.In conclusion, our investigation showed that salidroside could prevent ferroptosis, promote proliferation, and enhance osteogenic differentiation in senile osteoporotic BMSCs, thereby alleviating senile osteoporosis in SAMP8 mice. The PI3K/AKT/mTOR signaling pathway might play a crucial role in this mechanism. These findings suggest that salidroside has the potential to prevent senile osteoporosis and may serve as a candidate for therapeutic development.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
·
2025
·
IF 3.3
Ruirui Dong,Gaoying Wang,Yingxian Shi,Jianyi Gao,Wen Hu,Ting Zhang
Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse fetal outcomes, while current biomarkers such as total bile acid remain suboptimal. This study aimed to identify novel biomarkers and clarify metabolic pathways underlying ICP through integrated metabolomic and proteomic analyses. Placental profiles were obtained from ICP model rats and healthy controls, with differential metabolites and proteins validated in human placental and serum samples. Multiomics integration revealed prominent dysregulation of lipid metabolism, particularly fatty acid degradation and biosynthesis, highlighting lipids as central players in ICP. Palmitic acid and acyl-CoA synthetase long chain family member 1 (ACSL1) were central to these pathways, markedly elevated in ICP, and showed high diagnostic value (area under the curve 0.794 and 0.825), with combined detection reaching 0.894. Both markers also stratified patients by disease severity, suggesting their potential use for disease monitoring and risk classification. Moreover, ferroptosis was implicated in ICP pathophysiology, supported by validations in both patient placental tissues and taurocholic acid (TCA)-treated trophoblast cells, showing reduced glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11) together with increased six-transmembrane epithelial antigen of prostate 3 (STEAP3), transferrin receptor protein 1 (CD71), and acyl-CoA synthetase long-chain family member 4 (ACSL4). In summary, palmitic acid and ACSL1 represent promising biomarkers for ICP diagnosis and classification, while ferroptosis contributes to ICP-related placental dysfunction. These findings provide comprehensive evidence linking altered lipid metabolism and ferroptosis to ICP, offering new insights for clinical diagnosis and potential therapeutic strategies.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
·
2026
·
IF 6.5
Huimin Qiu,Xinqi Tan,Quan Sheng,Na Yang,Chunming Jiang,Lulu Wang
Metabolic dysfunction-associated steatohepatitis (MASH) frequently induces renal injury, forming a “liver-kidney axis” vicious cycle. Current therapies primarily target hepatic lesions, failing to interrupt the cross-organ injury cascade, creating an urgent need for novel strategies. To explore dapagliflozin’s therapeutic efficacy and core mechanism in MASH and associated renal injury, we utilized in vitro models (free fatty acid [FFA]-induced HepG2 hepatocyte MASH model, HK2 renal tubular epithelial cell injury model, Transwell co-culture system) and an in vivo MASH mouse model induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD). Results showed dapagliflozin dose-dependently improved dysregulated lipid metabolism, suppressed inflammation, and alleviated fibrosis in vitro and in mouse liver/kidney tissues, while upregulating SIRT1/PPARα and downregulating SREBP-1c to restore lipid homeostasis. Molecularly, dapagliflozin specifically bound to ferroptosis key regulator solute carrier family 7 member 11 (SLC7A11), upregulated its abnormally reduced expression, and inhibited PI3K/AKT pathway hyperactivation—an effect mediated via a “liver-kidney axis” paracrine mechanism with β-hydroxybutyrate (β-HB) as the key mediator. Additionally, SLC7A11 knockdown in cells conversely confirmed that the lipid-lowering effect of dapagliflozin is mediated by SLC7A11.Collectively, dapagliflozin forms hydrogen bonds with SLC7A11, modulates the SIRT1/PPARα/SREBP-1c axis, and inhibits PI3K/AKT, thereby exerting therapeutic effects on MASH and associated renal injury.
✓ 已验证
DOI
PubMed
高影响因子
Current Medical Science
·
2026
·
IF 2
Liu Xiao-cui,Liu Ya-ge,Lv Yong-ning,Deng Bin
Objective This study aimed to investigate the protective effects of berberine (BBR) on pancreatic β-cells and explore its underlying molecular mechanisms via a proteomics-based approach. Methods Using db/db mice as a diabetes model, BBR was administered at doses of 100 mg/kg and 200 mg/kg for 8 weeks. The protective effects were assessed through fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), pancreatic histopathological analysis, and TUNEL staining. Proteomic analysis employing the data-independent acquisition (DIA) method identified differentially expressed proteins (DEPs), whereas Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to identify potential pathways. Molecular docking, surface plasmon resonance (SPR), and immunohistochemistry (IHC) were performed to validate key target proteins. Results BBR significantly reduced blood glucose levels, improved insulin resistance, enhanced insulin secretion, and reversed pathological changes in pancreatic tissue, thereby alleviating β-cell damage. Proteomic analysis identified 171 DEPs, implicating the AGE/RAGE signaling pathway as a key mechanism through which BBR exerts its protective effects. The results of molecular docking, SPR and IHC confirmed that BBR markedly inhibited the activation of the AGE/RAGE pathway. Conclusions These findings suggest that BBR alleviates pancreatic β-cell damage, potentially through regulation of the AGE/RAGE pathway, providing insights into its therapeutic potential for diabetes management.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD AND CHEMICAL TOXICOLOGY
·
2022
·
IF 5.572
Wenyue Qiu,Xinting Zhang,Xiaoyue Pang,Jianjia Huang,Shuilian Zhou,Rongmei Wang,Zhaoxin Tang,Rongsheng Su
Asiatic acid (AA), a triterpenoid compound isolated from Centella asiatica , has anti-inflammatory, antioxidant and anticancer biological characteristics . To explore the effect of AA on LPS-induced acute kidney injury (AKI) in broilers, a total of 60 one-day-old broilers were randomly divided into 6 groups, including the normal group, AKI model group, AKI + AA 15 mg/kg group, AKI + AA 30 mg/kg group, AKI + AA 60 mg/kg group and normal + AA 60 mg/kg group. Hematoxylin-eosin staining was used to observe the histopathology in kidney tissue, and the mRNA and protein expressions related to oxidative stress and ferroptosis were tested by qPCR and western blotting respectively. AA mitigated vacuolar degeneration and enlarged glomerular space caused by LPS in kidney tissue. Additionally, AA significantly increased the mRNA levels of Nrf2, HO-1, NQO1, GCLC, GCLM , GPX4 , SLC7A11 and FTH1 , and decreased the mRNA levels of Keap1 and PTGS2 in LPS-induced AKI. Likewise, AA significantly upregulated the protein expressions of Nrf2, HO-1, NQO1, GPX4, SLC7A11 and FTH1, and downregulated the protein expressions of Keap1 and PTGS2 in LPS-induced AKI. These results suggested that AA alleviated LPS-induced AKI by inhibiting oxidative stress and ferroptosis through targeting regulation of the Nrf2 pathway in broilers.
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Nana Li,Lei Dong,Yuanyuan Shen,Yongling Wang,Liansheng Chang,Hongwei Wu,Yuqiao Chang,Menghao Li,Dan Li,Zhaoyi Li,Mei He,Cheng Li,Yao Wei,Haiqin Xie,Feng Wang
In recent years, studies have shown a close relationship between cardiomyocyte death and ferroptosis. Clioquinol (CQ) can inhibit ferroptosis. Porous lipid-poly (lactic-co-glycolic acid) (PLGA) microbubbles (MBs) were prepared by double emulsification (W 1 /O/W 2 ) using 1,2-dioctadecanoyl-sn-glycero-3-phophocholine and PLGA as raw materials. Porous lipid-PLGA MBs were used as carriers to prepare CQ/PLGA MBs containing CQ. CQ/PLGA had the advantages of high drug loading, good biocompatibility, and sustained release. Our results showed that CQ/PLGA improved the effect of CQ and reduced its cytotoxicity. Under low-frequency ultrasound with certain parameters, CQ/PLGA showed steady-state cavitation, which increased the membrane permeability of mouse cardiomyocyte HL-1 to a certain extent and further prevented the process of ferroptosis in mouse cardiomyocyte HL-1.
✓ 已验证
DOI
PubMed
高影响因子
ACS Pharmacology & Translational Science
·
2021
·
IF 0
Xue-Yan Dai,Shi-Yong Zhu,Mu-Zi Li,Milton Talukder,Yi Zhao,Jin-Long Li
Di(2-ethylhexyl) phthalate (DEHP) is a synthetic chemical and widely used as a plasticizer. Humans can be exposed to DEHP through direct contact or environmental contamination. Lycopene (Lyc) has been discussed as a potential effector in the prevention and therapy of various diseases. 140 male mice were assigned into control, vehicle control, Lyc (5 mg/kg BW/d), DEHP (500 and 1000 mg/kg BW/d, respectively), and DEHP + Lyc groups and treated with an oral gavage that lasted 28 d. The ultrastructural results showed that DEHP induced pathological changes and mitochondrial injuries. We further revealed that DEHP exposure destroyed the Fe2+ imbalance homeostasis and, consequently, increases of lipid peroxidation and inhibition of cysteine/glutamate antiporter, all of which were involved in the process of ferroptsis. Moreover, the supplementation of Lyc significantly inhibited the ferroptsis changes mentioned above. Altogether, these results indicated that DEHP exposure triggered splenic cell death via ferroptosis; meanwhile, they also shed new evidence on a potential clue for the intervention and prevention of DEHP-related diseases.
✓ 已验证
产品关联
DOI
PubMed
Journal of Inflammation-London
·
2023
·Vol. 20
·期 1
·1-11
·
IF 5.1
Zhao Ziwen,Xu Zhao,Chang Jingwen,He Liwei,Zhang Zijin,Song Xiaoyu,Hou Xianbang,Fan Fangtian,Jiang Zhijun
Background Ferroptosis in alveolar and bronchial epithelial cells is one of the main mechanisms underlying the development of chronic obstructive pulmonary disease (COPD). Sodium pyruvate (NaPyr) is a natural antioxidant in the body, exhibiting anti-inflammatory and antioxidant activities. NaPyr has been used in a Phase II clinical trial as a novel therapy for COPD; however, the mechanism underlying NaPyr-mediated therapeutic benefits in COPD is not well understood. Objective We aimed to assess the protective effects of NaPyr and elucidate its potential mechanism in cigarette smoke extract (CSE)-induced ferroptosis.To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, we expose a human bronchial epithelial cells to CSE. Methods To minic the inflammatory response and ferroptosis triggered by cigarette smoke in COPD in an invitro cell based system, the A549 (human lung carcinoma epithelial cells) and BEAS-2B (bronchial epithelial cells) cell lines were cultured, followed by treatment with CSE. To measure cellular viability and iron levels, we determined the levels of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species (ROS), mitochondrial superoxide (MitoSOX), membrane potential (MMP), and inflammatory factors (tumor necrosis factor [TNF] and interleukin [IL]-8), and examined CSE-induced pulmonary inflammation and ferroptosis. To clarify the molecular mechanisms of NaPyr in COPD therapy, we performed western blotting and real-time PCR (qPCR) to determine the expression of glutathione peroxidase 4 (GPX4), nuclear factor E2-related factor 2 (Nrf2), and cyclooxygenase 2 (COX2). Results We found that NaPyr effectively mitigated CSE-induced apoptosis and improved apoptosis induced by erastin, a ferroptosis inducer. NaPyr significantly decreased iron and MDA levels and increased GSH levels in CSE-induced cells. Furthermore, NaPyr suppressed ferroptosis characteristics, such as decreased levels of ROS, MitoSOX, and MMP. NaPyr significantly increases the expression levels of GPX4 and Nrf2, indicating that activation of the GPX4/Nrf2 axis could inhibit ferroptosis in alveolar and bronchial epithelial cells. More importantly, NaPyr inhibited the secretion of downstream inflammatory factors, including TNF and IL-8, by decreasing COX2 expression levels to suppress CSE-induced inflammation. Conclusion Accordingly, NaPyr could mitigate CSE-induced ferroptosis in alveolar and bronchial epithelial cells by activating the GPX4/Nrf2 axis and decreasing COX2 expression levels. In addition, NaPyr reduced the secretion of inflammatory factors (TNF and IL-8), affording a novel therapeutic candidate for COPD. Graphical Abstract
✓ 已验证
DOI
PubMed
高影响因子
Advanced Therapeutics
·
2023
·Vol. 6
·期 7
·2200356
·
IF 4.6
Haixia Liu,Xianxian Yao,Weichu Zhu,Jiaxin Zhang,Shuangping Ma,Daru Lu,Wuli Yang
Colorectal cancer is one of the most common causes of cancer-related deaths worldwide. Ferroptosis is a non-apoptotic form of regulated cell death that can be triggered by excessive lipid peroxidation and provides an alternative cancer treatment option. To design ferroptosis-targeted nanomedicine, a new type of nanoparticle is synthesized. The antineoplastic agent simvastatin (SIM) and specifically designed short hairpin RNA (shRNA) are co-loaded into zeolitic imidazolate framework-8 (ZIF-8) nanoparticles coated with poly(carboxybetaine methacrylate) (PCBMA). The constructed shRNA/ZIF-8@PCBMA-SIM nanoparticles effectively eliminate human colorectal carcinoma cells in vivo, showing superior cytotoxicity against tumors owing to their improved targeting ability and the high retention of antineoplastic agents delivered at tumor sites. Furthermore, SIM and shRNA downregulate the expression of ferroptosis-related enzymes 3-hydroxy-3-methylglutaryl-CoA reductase and glutathione peroxidase 4, thus, triggering ferroptosis in cancer cells. Given that SIM is already approved for clinical use, and shRNA offers high potency to downregulate the cystine/glutamate antiporter (x-CT) system protein (subunit SLC7A11), shRNA/ZIF-8@PCBMA-SIM nanoparticles show great clinical potential to treat colorectal cancer via ferroptosis. This presents an alternative therapy that addresses the limitations of chemotherapy.
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）