FASEB JOURNAL
·
2026
·Vol. 40
·期 19
·e72301
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IF 4.3
Xiaodie Chen,Huiqun Huang,Yutong Yang,Xiangyu Chen,Nan Xiao,Chenghui Li,Yanbin Pan,Yongan Deng,Xiaodong Duan,Shuting Zeng,Simin Yang,Chengkai Chen,Yixuan Huang,Yuliang Zhou,Yubin Yang,Zunpeng Shu,Li Zhang
Cardiac aging is a major risk factor for cardiovascular diseases, with an imbalance in mitochondrial dynamics homeostasis being a pivotal aspect. Although Astragaloside IV (AS-IV) has been shown to delay aging, its specific effects on cardiac aging and the link to mitochondrial dynamics remain unclear. This study aimed to elucidate the role and regulatory mechanism of AS-IV in delaying cardiac aging by using naturally aged mouse models and D-galactose (D-gal)-induced H9c2 cell senescence models. The results demonstrated that AS-IV reduced the expression of senescence markers (p16 INK4a , p21, and p53), β-galactosidase (SA-β-gal), and senescence-associated secretory phenotype (SASP) factors ( Il6 , Il1b , and Tnfa ) while also significantly ameliorating aging-induced cardiac dysfunction and myocardial fibrosis. Furthermore, AS-IV significantly enhanced mitochondrial morphology and function in cardiomyocytes. This improvement was demonstrated by increased mitochondrial membrane potential, elevated ATP production, and reduced ROS levels. Mechanistically, AS-IV upregulated SIRT3 and promoted its interaction with DRP1, leading to the inhibition of DRP1 acetylation. This action suppressed excessive mitochondrial fission and thereby improved mitochondrial dynamics. Transfection with SIRT3-siRNA attenuated the beneficial effects of AS-IV. In conclusion, this study demonstrates that AS-IV mitigates cardiac aging by activating SIRT3 to mediate DRP1 deacetylation, which in turn improves mitochondrial dynamics. These findings provide a strong theoretical and experimental foundation for the potential application of AS-IV in preventing and treating age-related cardiovascular diseases. Graphical This study demonstrates that AS-IV upregulates and activates the deacetylase SIRT3, thereby prompting the deacetylation of DRP1, a key mitochondrial fission protein. This modification inhibits the excessive activation and mitochondrial localization of DRP1, thereby correcting aging-associated mitochondrial hyper-fission and restoring dynamic balance. The reestablished mitochondrial homeostasis effectively improves mitochondrial structure and function, ultimately conferring protective effects against cardiac aging.
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MOLECULAR AND CELLULAR BIOCHEMISTRY
·
2026
·
IF 4.7
Gao Jie,Lv Xiaoyu,Zhao Pingping,Pan Bingjing,Liu Jingfang
Diabetic kidney disease (DKD) is a major microvascular complication of diabetes. The glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide exerts renoprotective effects beyond glucose control; however, the underlying mechanisms remain incompletely understood. The protective effects and mechanisms of liraglutide were investigated using in vitro (HK-2 cells under glucolipotoxic conditions) and in vivo (DKD rat) models. Key molecular and functional assessments included the evaluation of oxidative stress, apoptosis, mitochondrial function (dynamics (MFN1, MFN2, FIS1, and DRP1), mitophagy (PINK1, PARKIN, LC3II/I, and P62), and ultrastructure), and histone acetylation (H3K9/14/18/27ac). The critical role of the NQO1/SIRT3 pathway was validated using pharmacological inhibition and genetic silencing (shRNA/AAV). Both in vitro and in vivo, a multifaceted injury phenotype, including oxidative stress, apoptosis, mitochondrial dysfunction, and histone hyperacetylation, was induced, accompanied by downregulation of the NQO1/SIRT3 pathway. Disruption of this pathway further exacerbated these injuries. Conversely, liraglutide treatment effectively counteracted this phenotype, improving metabolic parameters (blood glucose, blood insulin, and blood lipids), renal function (blood urea nitrogen, serum creatinine, and urine albumin-to-creatinine ratio) and histopathology. Liraglutide attenuated oxidative stress and apoptosis, restored mitochondrial function and mitophagy, and reduced histone hyperacetylation. These protective effects were consistently associated with the restoration of NQO1/SIRT3 expression. Genetic or pharmacological disruption of the NQO1/SIRT3 axis significantly attenuated the efficacy of liraglutide, and combined inhibition completely abolished its effects. Our findings demonstrate that liraglutide attenuates DKD by activating the NQO1/SIRT3 pathway, which coordinates the enhancement of mitochondrial function and the restoration of epigenetic homeostasis. This study revealed that the NQO1/SIRT3 pathway is a critical mechanistic mediator of the renoprotective effect of liraglutide.
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Autophagy
·
2021
·
IF 16.016
Yabin Gong,Ning Tang,Panrao Liu,Yingjie Sun,Shanxin Lu,Weiwei Liu,Lei Tan,Cuiping Song,Xusheng Qiu,Ying Liao,Shengqing Yu,Xiufan Liu,Shu-Hai Lin,Chan Ding
Lacking a self-contained metabolism network, viruses have evolved multiple mechanisms for rewiring the metabolic system of their host to hijack the host’s metabolic resources for replication. Newcastle disease virus (NDV) is a paramyxovirus, as an oncolytic virus currently being developed for cancer treatment. However, how NDV alters cellular metabolism is still far from fully understood. In this study, we show that NDV infection reprograms cell metabolism by increasing glucose utilization in the glycolytic pathway. Mechanistically, NDV induces mitochondrial damage, elevated mitochondrial reactive oxygen species (mROS) and ETC dysfunction. Infection of cells depletes nucleotide triphosphate levels, resulting in elevated AMP:ATP ratios, AMP-activated protein kinase (AMPK) phosphorylation, and MTOR crosstalk mediated autophagy. In a time-dependent manner, NDV shifts the balance of mitochondrial dynamics from fusion to fission. Subsequently, PINK1-PRKN-dependent mitophagy was activated, forming a ubiquitin chain with MFN2 (mitofusin 2), and molecular receptor SQSTM1/p62 recognized damaged mitochondria. We also found that NDV infection induces NAD+-dependent deacetylase SIRT3 loss via mitophagy to engender HIF1A stabilization, leading to the switch from oxidative phosphorylation (OXPHOS) to aerobic glycolysis. Overall, these studies support a model that NDV modulates host cell metabolism through PINK1-PRKN-dependent mitophagy for degrading SIRT3.Abbreviations: AMPK: AMP-activated protein kinase; CCCP: carbonyl cyanide 3-chlorophenylhydrazone; ECAR: extracellular acidification rate; hpi: hours post infection LC-MS: liquid chromatography-mass spectrometry; mito-QC: mCherry-GFP-FIS1[mt101–152]; MFN2: mitofusin 2; MMP: mitochondrial membrane potential; mROS: mitochondrial reactive oxygen species; MOI: multiplicity of infection; 2-NBDG: 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose; NDV: newcastle disease virus; OCR: oxygen consumption rate; siRNA: small interfering RNA; SIRT3: sirtuin 3; TCA: tricarboxylic acid; TCID50: tissue culture infective doses.
研究领域:
病毒学
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细胞生物学
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分子生物学
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肿瘤学
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代谢
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高影响因子
Frontiers in Aging Neuroscience
·
2021
·
IF 5.75
Zhang Miao,Hu Yuan,Zhang Jiahui,Zhang Junjian
Vascular dementia (VD) and Alzheimer's disease (AD) are the most prevalent types of late-life dementia. Chronic cerebral hypoperfusion (CCH) contributes to both AD and VD. Recently, accumulating evidence has indicated that fingolimod (FTY720) is neuroprotective in acute cerebral ischemic stroke animal models, and the drug is now being used in clinical translation studies. However, fewer studies have addressed the role of FTY720 in chronic cerebral hypoperfusion (CCH)-related brain damage. In the present study, to investigate whether FTY720 can improve CCH-induced spatial memory loss and its underlying mechanism, two-vessel occlusion (2VO) rats were administered intraperitoneal FTY720 (1 mg/kg) for 7 consecutive weeks from post-operative day 8. Spatial memory was tested using the Morris Water Maze (MWM), and the rats' brains were harvested to allow molecular, biochemical, and pathological tests. We found that FTY720 treatment significantly reduced the escape latency and increased the target quadrant swimming time of the 2VO rats in the MWM task. The improvement in memory performance paralleled lower levels of pro-inflammatory cytokines and Iba-1 positive cells in the hippocampus of the 2VO rats, indicating that FTY720 had a beneficial effect in mitigating neuroinflammation. Furthermore, we found that FTY720 alleviated mitochondrial dysfunction in 2VO rats, as manifested by lower malondialdehyde levels, higher ATP content, and upregulation of ATP synthase activity in the hippocampus after treatment. FTY720 had no effect on the CCH-induced decrease in the activity of hippocampal Sirtuin-3, a master regulator of mitochondrial function and neuroinflammation. In summary, the results showed that FTY720 can improve CCH-induced spatial memory loss. The mechanism may involve Sirtuin-3-independent regulation of mitochondrial dysfunction and neuroinflammation in the hippocampus. The present study provides new clues to the pathological mechanism of CCH-induced cognitive impairment.
研究领域:
神经科学
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药理学
·
痴呆症
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2026
·
IF 5.6
Xiaohui Yang,Jie Li,Yilang Zhong,Yuanjiayi Shen,Chenqin Xu,Zhouyu Nie,He Wang,Rui Cao,Miaomiao Wang,Jinyu Zhang,Chao Ma,Tongkai Cai,Chenglin Jia,Ruilian Wang,Hao Yin,Jian Chen,Yongbing Cao
Background Candida auris ( C. auris ) is an emerging multidrug-resistant fungal pathogen. Current antifungals are often insufficient, creating a need for host-directed strategies. Sirtuin 3 (SIRT3) is a mitochondrial deacetylase that regulates redox homeostasis, but its role in antifungal macrophage defense is not well defined. We examined how SIRT3 shapes macrophage responses to C. auris . We also evaluated ethyl caffeate (EC) as a host-directed modulator. Methods We used murine macrophages with Sirt3 knockdown or overexpression. We quantified phagocytosis, intracellular fungal survival, mitochondrial ROS dynamics, and macrophage cell integrity using imaging, flow cytometry, CFU assays, and LDH release. We profiled infection-induced transcriptional programs by RNA-seq and performed pathway analyses. We tested EC both in vitro and in systemic infection models in Drosophila and mice. We assessed pathway markers by immunoblotting and immunofluorescence. We used the SIRT3 inhibitor 3-TYP to test inhibition sensitivity. Results SIRT3 deficiency impaired macrophage antifungal function and was accompanied by redox imbalance. mtROS regulation was disrupted in a biphasic pattern, with an early spike followed by late depletion. Transcriptomics linked SIRT3-dependent programs to FOXO and PI3K–AKT signaling. In macrophages, SIRT3 status tracked with FOXO3A acetylation and AKT phosphorylation. EC showed weak direct antifungal activity in vitro but improved outcomes in systemic infection models. EC treatment increased SIRT3 abundance and was associated with reduced FOXO3A acetylation and restrained infection-associated AKT activation. These functional and signaling effects were largely sensitive to SIRT3 inhibition by 3-TYP. Conclusion This study connects SIRT3-dependent redox control to FOXO3A–AKT signaling during C. auris infection. It also supports EC as a host-directed candidate that improves antifungal defense in vivo while limiting inflammatory injury.
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Frontiers in Pharmacology
·
2024
·
IF 4.4
Jiemei Shi,Min Liu,Jiajie Zhao,Ye Tan,Chunhui Jiang
Introduction: Mitochondrial dysfunction and oxidative stress play important roles in diabetic retinal vascular injuries. Honokiol (HKL) is a small-molecule polyphenol that exhibits antioxidant effects and has a beneficial effect in diabetes. This study aimed to explore the potential ability of HKL to ameliorate vascular injury in diabetic retinopathy (DR) and its possible mechanisms of action.Methods: The effect of HKL was evaluated in vascular injury in an in vivo type 2 diabetic (db/db) mouse model. In vitro, retinal microvascular endothelial cells were treated with high glucose (HG) to simulate the pathological diabetic environment. Cell viability, expression of apoptosis-related proteins, cellular reactive oxygen species, mitochondrial membrane potential, and morphological changes in the mitochondria were examined.Results: The diabetic mice exhibited severe retinal vascular damage, including vascular leakage in vivo and capillary endothelial cell apoptosis in vitro. HKL reversed the retinal vascular leakage in the diabetic mice. In vitro, HKL improved retinal capillary endothelial cell viability, decreased apoptosis, and reversed the HG-induced increased cellular oxidative stress and mitochondrial fragmentation. The sirtuin 3 (SIRT3) inhibitor 3-TYP blocked all the in vivo and in vitro protective effects of HKL against diabetic retinal vascular leakage and capillary endothelium and eliminated the decrease in oxidative stress levels and reduction of mitochondrial fragmentation.Discussion: In conclusion, these findings suggest that HKL inhibits vascular injury in DR, which was likely achieved through SIRT3-mediated mitochondrial fusion. This study provides a potential new strategy for the treatment of DR.
研究领域:
药理学
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糖尿病学
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眼科学
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细胞生物学
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Redox Biology
·
2024
·
IF 10.7
Yue-Yue Guo,Nan-Nan Liang,Xiao-Yi Zhang,Ya-Hui Ren,Wen-Zheng Wu,Zhi-Bing Liu,Yi-Zhang He,Yi-Hao Zhang,Yi-Chao Huang,Tao Zhang,De-Xiang Xu,Shen Xu
Increasing evidences demonstrate that environmental stressors are important inducers of acute kidney injury (AKI). This study aimed to investigate the impact of exposure to Cd, an environmental stressor, on renal cell ferroptosis. Transcriptomics analyses showed that arachidonic acid (ARA) metabolic pathway was disrupted in Cd-exposed mouse kidneys. Targeted metabolomics showed that renal oxidized ARA metabolites were increased in Cd-exposed mice. Renal 4-HNE, MDA, and ACSL4, were upregulated in Cd-exposed mouse kidneys. Consistent with animal experiments, the in vitro experiments showed that mitochondrial oxidized lipids were elevated in Cd-exposed HK-2 cells. Ultrastructure showed mitochondrial membrane rupture in Cd-exposed mouse kidneys. Mitochondrial cristae were accordingly reduced in Cd-exposed mouse kidneys. Mitochondrial SIRT3, an NAD + -dependent deacetylase that regulates mitochondrial protein stability, was reduced in Cd-exposed mouse kidneys. Subsequently, mitochondrial GPX4 acetylation was elevated and mitochondrial GPX4 protein was reduced in Cd-exposed mouse kidneys. Interestingly, Cd-induced mitochondrial GPX4 acetylation and renal cell ferroptosis were exacerbated in Sirt3 −/− mice. Conversely, Cd-induced mitochondrial oxidized lipids were attenuated in nicotinamide mononucleotide (NMN)-pretreated HK-2 cells. Moreover, Cd-evoked mitochondrial GPX4 acetylation and renal cell ferroptosis were alleviated in NMN-pretreated mouse kidneys. These results suggest that mitochondrial GPX4 acetylation, probably caused by SIRT3 downregulation, is involved in Cd-evoked renal cell ferroptosis.
研究领域:
毒理学
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肾脏生理学
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细胞生物化学
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JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
·
2026
·
IF 3.5
Ruya Mei,Rong Zhang,Zhengyang Li,Jie Luo,Xinyue Zhang,Tong Zhang,Guanglei Lv,Juhua Zhang,Bingqing Liang,Yuzhong Yan
Background and Aim Mitochondrial dysfunction in macrophages drives pro-inflammatory M1 polarization in ulcerative colitis (UC). We developed a colon-targeted, mitochondria-directed nanoplatform (KSF@SS31@S100Ns) to restore mitochondrial fitness and alleviate UC. Methods Kaempferol-loaded silk fibroin (SF) nanoparticles were conjugated with SS-31 peptide and coated with pH-sensitive Eudragit S100. Physicochemical properties, release profile, and uptake were characterized. Mitochondrial function, macrophage polarization, and SIRT3/FOXO3a signaling were assessed in LPS-stimulated RAW264.7 cells. Efficacy and mechanisms were evaluated in a DSS-induced colitis mouse model. Results Nanoparticles showed uniform size (~307 nm), high stability, and pH-dependent release. SS-31 enhanced macrophage uptake and mitochondrial localization. In vitro, KSF@SS31Ns restored mitochondrial membrane potential and ATP, reduced ROS, promoted mitophagy, and shifted macrophages toward the M2 phenotype via SIRT3/FOXO3a activation. In vivo, oral KSF@SS31@S100Ns accumulated in inflamed colons, reduced disease severity, suppressed pro-inflammatory cytokines, elevated IL-10, restored tight-junction proteins, and increased M2 macrophages. Conclusions KSF@SS31@S100Ns effectively treats experimental colitis by restoring mitochondrial homeostasis, reprogramming macrophage polarization, and repairing the intestinal barrier, offering a translational nanotherapeutic strategy for UC. Graphical IBD by KSF@SS-31@S100N treatment repair
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International Journal of Biological Sciences
·
2026
·Vol. 22
·期 4
·1775-1792
·
IF 10
Shen Siman,Ying Chen,Fu Xinglin,Zeng Xiaobian,Guo Xiuli,Wu Han,Zhang Liangqing,Xu Li
Background: Persistently elevated glycolysis is increasingly recognized as a driving force in diabetic kidney disease (DKD). As a product of glycolysis, lactate can induce histone lactylation, an emerging epigenetic mechanism associated with post-transcriptional modification. However, the molecular mechanism and clinical impact of histone lactylation in DKD remain largely understood.Methods and Results: Spatial transcriptomics analysis revealed upregulation of glycolytic genes in tubular epithelial cells (TECs), thus leading to elevated levels of renal lactate accumulation. PKM2 deficiency lowered the lactate production during the fibrotic process and decreased histone lactylation. Mechanistically, ChIP-seq & RNA-seq results showed lactate promoted histone H4 lysine 12 lactylation (H4K12la), which in turn enhanced RUNX1 transcription. RUNX1 subsequently activated HK1 and SLC2A1, which accelerated glycolysis and renal fibrosis of DKD. Further, SIRT3 expression was significantly decreased in the renal tubular cells in DKD. Furthermore, insufficient SIRT3 is functionally promote renal fibrosis by directly deacetylating RUNX1 at H4K12, leading to attenuated glycolytic process, and subsequently robust glycolytic ability and increased production of lactate.Conclusion: Thus, the study links RUNX1-mediated glycolysis to SIRT3-mediated histonelactylation epigenetic reprogramming in promoting the fibrotic process, providing better understanding of epigenetic regulation of DKD pathogenesis, and new therapeutic strategy for DKD.
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Food & Function
·
2019
·Vol. 10
·期 5
·2752-2765
·
IF 3.241
Li-Ming Yu,Xue Dong,Xiao-Dong Xue,Jian Zhang,Zhi Li,Hong-Jiang Wu,Zhong-Lu Yang,Yang Yang,Hui-Shan Wang
Mitochondrial dysfunction contributed greatly to myocardial ischemia-reperfusion (MI/R)-induced cardiomyocyte apoptosis. Naringenin is a flavonoid exhibiting potential protective effects on myocardial mitochondria under stress conditions. However, the detailed down-stream signaling pathway involved remains uncovered. This study was designed to elucidate naringenin's mitochondrial protective actions during MI/R with a focus on AMPK-SIRT3 signaling. Sprague-Dawley rats were administered with naringenin (50 mg kg−1 d−1) and subjected to MI/R surgery in the presence or absence of compound C (0.25 mg kg−1, Com.C, an AMPK inhibitor) co-treatment. An in vitro study was performed on H9c2 cardiomyoblasts subjected to simulated ischemia-reperfusion treatment. Before the treatment, the cells were administered with naringenin (80 μmol L−1) with or without SIRT3 siRNA/AMPK1α siRNA transfection. Naringenin improved post-reperfusion left ventricular systolic pressure and the instantaneous first derivative of left ventricular pressure, and reduced the infarction size and myocardial apoptosis index by suppressing mitochondrial oxidative stress damage (as evidenced by decreased mitochondrial cytochrome c release and oxidative markers) and enhancing mitochondrial biogenesis [as evidenced by increased NRF1, TFAM and oxidative phosphorylation subunit complexes (II, III and IV)]. These protective actions were abolished by Com.C (in vivo) or SIRT3 siRNA (in vitro) administration. Further investigation revealed that Com.C (in vivo) or AMPK1α siRNA (in vitro) markedly suppressed PGC-1α and SIRT3 levels while SIRT3 siRNA (in vitro) inhibited SIRT3 expression without significantly changing AMPK phosphorylation and PGC-1α levels. Taken together, we found that naringenin directly inhibits mitochondrial oxidative stress damage and preserves mitochondrial biogenesis, thus attenuating MI/R injury. Importantly, AMPK-SIRT3 signaling played a key role in this process.
研究领域:
心脏病学
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药理学
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分子生物学
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Frontiers in Pharmacology
·
2025
·
IF 4.8
Hongtao Zhang,Yi Huang,Songhong Yang,Feipeng Gong,Yuncheng Gu,Qin Xie,Yanrong Ye,Xingmei Lu,Lingyun Zhong
Introduction: Sand-fired aconite slices (SFAS) demonstrate anti-heart failure effects, but the mechanism remains unclear. This study investigated myocardial mitochondrial energy metabolism as a therapeutic mechanism of SFAS in doxorubicin-induced chronic heart failure (CHF) rats.Methods: The CHF rat model was established via the intraperitoneal injection of doxorubicin (DOX). Following successful model production, rats were randomly assigned to nine groups. After drug administration, their cardiac function was assessed, and their cardiac tissue morphology and myocardial mitochondria were examined. Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), norepinephrine (NE), malondialdehyde (MDA), superoxide dismutase (SOD), free fatty acid (FFA), sodium-potassium-ATPase (Na+-k+-ATPase), calcium-magnesium-ATPase (Ca2+-Mg2+-ATPase), and adenosine triphosphate (ATP) levels were quantified using enzyme-linked immunosorbent assays (ELISAs). Fatty acid translocase (CD36), carnitine palmitoyl transferase 1 (CPT1), adenosine 5′-monophosphate-activated protein kinase (AMPK), phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK), peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α), and Sirtuin 3 (SIRT3) protein expression levels were assessed by Western blot.Results: SFAS significantly improved cardiac function in CHF rats. It increased the left ventricular ejection fraction (LVEF) (from 34.22% ± 2.03%–83.68% ± 2.34%; P < 0.001) and left ventricular shortening fraction (LVFS) (from 17.06% ± 1.08%–53.86% ± 2.82%; P < 0.001) and decreased ANP (from 551.29 ± 14.63 pg/mL to 291.96 ± 11.28 pg/mL; P < 0.05), BNP (from 743.15 ± 18.03 pg/mL to 478.75 ± 10.57 pg/mL; P < 0.001), and NE levels (from 1,105.36 ± 21.79 pg/mL to 672.67 ± 6.70 pg/mL; P < 0.001). Additionally, it decreased MDA production (from 8.89 ± 0.36 nmol/mL to 5.11 ± 0.35 nmol/mL; P < 0.05) and increased SOD activity (from 264.82 ± 4.26 pg/mL to 529.64 ± 10.27 pg/mL; P < 0.001), Na+-K+-ATPase levels (from 7.19 ± 0.65 μmol/mL to 14.08 ± 0.28 μmol/mL; P < 0.001), Ca2+-Mg2+-ATPase levels (from 0.86 ± 0.03 μmol/mL to 1.40 ± 0.02 μmol/mL; P < 0.05), CD36 levels (P < 0.05), and CPT1 levels (P < 0.01). Moreover, it improved mitochondrial structural damage and reduced the level of oxidative stress in cardiomyocytes. Furthermore, SFAS promoted FFA oxidation (from 1,477.49 ± 7.60 μmol/mL to 768.87 ± 82.53 μmol/mL; P < 0.05) and ATP production (from 2,869.85 ± 298.26 nmol/mL to 5,483.17 ± 120.03 nmol/mL; P < 0.001) and increased p-AMPK, PGC-1α, and SIRT3 levels (P < 0.05 and P < 0.01).Conclusion: By activating the AMPK/PGC-1α/SIRT3 signaling pathway, SFAS ameliorated the impaired fatty acid oxidation pathway and enhanced mitochondrial function and antioxidant capacity in cardiomyocytes, ultimately reducing myocardial damage and restoring cardiac function in CHF rats.
研究领域:
心血管药理学
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中医药学
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线粒体生物学
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代谢紊乱
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高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
·
2026
·
IF 5.7
Zhen Zhou,Yongfen Bao,Rongjie Li,Rui Yang,Qingyu Peng,Tianci Lu,Binyu Wang,Ming Zhang,Jie Xu,Ying Xiang,Shigang Shan,Liqiong Huang
Background Preeclampsia (PE) is a severe hypertensive disorder in pregnancy, and disruption of placental energy homeostasis, particularly mitochondrial dysfunction, plays a critical role in its pathogenesis. Melatonin (MEL) and Metformin (MET), an effect associated through the AMP-activated protein kinase/Sirtuin 3 (AMPK/SIRT3) signaling pathway. However, the precise mechanisms remain unclear. Materials and methods The PE rat model was established in Sprague–Dawley (SD) rats by lipopolysaccharide (LPS) injection after confirmation of pregnancy. Pathological changes, protein expression, inflammatory and angiogenic factors, and mitochondrial status in placental tissue and HTR-8/SVneo trophoblasts were assessed by histology, immunohistochemistry, Western blotting, ELISA, RT-qPCR, reactive oxygen species (ROS) detection, transmission electron microscopy, and measurements of mitochondrial membrane potential and cytosolic calcium. Results Both MEL and MET individually activated the AMPK/SIRT3 signaling pathway, thereby enhancing mitochondrial function and placental energy homeostasis, while attenuating LPS-induced oxidative stress and inflammatory damage in placental tissue and trophoblast cells. Conclusions MEL and MET, when administered together, improve placental mitochondrial dysfunction and inflammatory injury in PE, which is associated with activation of the AMPK/SIRT3 signaling pathway, suggesting a potential therapeutic strategy for preeclampsia using clinically available agents.
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