Food Frontiers
·
2026
·Vol. 7
·期 6
·e70370
·
IF 6.3
Jingzheng Li,Honglin Jiang,Jianwen He,Wen Yao
Lactation represents one of the most metabolically demanding physiological states in mammals, characterized by heightened bioenergetic flux that increases electron transport chain (ETC) activity. This metabolic feature renders the maternal liver highly susceptible to mitochondrial redox imbalance under heat stress (HS). Baicalin (BAI), a nature food-derived flavonoid from Scutellaria baicalensis , is known for its antioxidant and hepatoprotective properties, but its mechanism in lactational HS has not been fully elucidated. Here, we demonstrate that BAI exerts its hepatoprotective effects by targeting the Sirt3–NDUFS1 axis to preserve mitochondrial complex I redox homeostasis in lactating mammals. Using a lactational HS mouse model and AML-12 hepatocytes, we demonstrate that BAI attenuates HS-induced hepatic injury, oxidative stress, and mitochondrial dysfunction. Mechanistically, BAI restored the expression of the mitochondrial deacetylase Sirt3, which was suppressed by HS. This led to deacetylation of the complex I core subunit NDUFS1, thereby rescuing complex I activity and limiting mitochondrial reactive oxygen species (mtROS) overproduction. BAI also attenuated secondary excessive Pink/PARKIN-dependent mitophagy triggered by mitochondrial respiratory failure, revealing coordinated recovery of electron transport function and downstream mitochondrial quality control. Pharmacological inhibition of Sirt3 abolished the protective effects of BAI on mitochondrial respiration and redox balance, confirming Sirt3 dependence. These findings reveal a BAI–Sirt3–NDUFS1 axis maintaining mitochondrial complex I redox homeostasis, thereby enhancing maternal hepatic resilience to HS. Distinct from previous Sirt3 research in nonreproductive disease models, this work establishes a natural nutritional target strategy specialized for HS lactating subjects, with great potential for maternal nutritional intervention and functional food development.
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DOI
高影响因子
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
·
2022
·Vol. 149
·期 2
·683-699
·
IF 4.322
Shen Chongxing,Yue Xiaofeng,Dai Linyong,Wang Jianwu,Li Jinjin,Fang Qiang,Zhi Yi,Shi Chunmeng,Li Weibing
Background Bladder cancer has a high rate of recurrence and drug resistance due to the lack of effective therapies. IR-780 iodide, a near-infrared (NIR) mitochondria-targeting fluorescent agent, has been demonstrated to achieve higher selectivity than other drugs in different tumor types and exhibited tumor-killing effects in some cancers. However, this therapeutic strategy is rarely studied in bladder cancer. Material and methods The accumulation of IR-780 in bladder cancer was measured by NIR imaging. Human bladder cell lines (T24, 5637, and TCCSUP) were treated with IR-780 or combined IR-780 and hyperbaric oxygen (HBO). Cell viability, cell apoptosis, cellular ATP production, mitochondrial reactive oxygen species (ROS), and plasma membrane potential were detected. Mitochondrial complex I protein NDUFS1 was measured by western blot. To confirm the anti-tumor efficacy of IR-780 + HBO, mouse bladder cell line (MB49) tumor-bearing mice were established and tumor size and weight were recorded. Besides, cell apoptosis and tumor size were assessed in drug-resistant bladder cancer cells (T24/DDP) and xenografts to evaluate the effect of IR-780 + HBO on drug-resistant bladder cancer. Results IR-780 selectively accumulated in bladder cancer (bladder cancer cells, transplanted tumors, and bladder cancer tissue from patients) and could induce cancer cell apoptosis by targeting the mitochondrial complex I protein NDUFS1. The combination with HBO could significantly enhance the anti-tumor effect of IR-780 in vitro by promoting cancer cell uptake and inducing excessive mitochondrial ROS production, while suppressing tumor growth and recurrence in animal models without causing apparent toxicity. Moreover, this combination antitumor strategy was also demonstrated in drug-resistant bladder cancer cells (T24/DDP) and xenografts. Conclusion We identified for the first time a combination of IR-780 and HBO (IR-780 + HBO), which exhibits mitochondria-targeting and therapeutic capabilities, as a novel treatment paradigm for bladder cancer.
研究领域:
肿瘤学
·
药理学
·
分子生物学
·
细胞生物学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2024
·
IF 6.6
Pilong Shi,Yuetong Sha,Xinran Wang,Tao Yang,Jiawei Wu,Jiajun Zhou,Kai Liu,Xue Guan,Song Wang,Yongsheng Liu,Jingquan Gao,Hongli Sun,Tao Ban,Yonggang Cao
Purpose Myocardial ischemia-reperfusion injury (MI/RI) is associated with increased oxidative damage and mitochondrial dysfunction, resulting in an elevated risk of mortality. MI/RI may be alleviated by protecting cardiomyocytes from oxidative stress. Lutein, which belongs to a class of carotenoids, has proven to be effective in cardiovascular disease treatment due to its remarkable antioxidant properties, but its application is limited due to its poor stability and low bioavailability in vivo.Methods In this study, a delivery system was developed based on distearoyl phosphatidyl ethanolamine (DSPE)-thiol-ketone (TK)-PEG2K (polyethylene glycol 2000) (abbreviated as DTP) and PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver lutein (abbreviated as lutein@DTPP) to damaged myocardium. First, lutein, lutein@DTP, or lutein@DTPP were injected through the tail vein once a day for 3 days and then MI/RI model rats were established by exposing rats to ischemia for 45 min and reperfusion for 6 h. We employed a range of experimental techniques including qRT-PCR, Western blotting, transmission electron microscopy, immunohistochemistry, immunofluorescence, flow cytometry, immunoprecipitation, molecular docking, and molecular dynamics simulations.Results Lutein@DTPP exhibited good myocardial targeting and ROS-responsive release. Our data suggested that lutein@DTPP effectively suppresses ferroptosis in cardiomyocytes. Mechanistically, we observed an upregulation of mouse double minute-2 (MDM2) in the hearts of MI/RI models and cardiomyocytes exposed to hypoxia/reoxygenation (H/R) conditions. In addition, NADH-ubiquinone oxidoreductase 75 kDa Fe-S protein 1 (NDUFS1) translocation from the cytosol to the mitochondria was inhibited by MDM2 upregulation. Notably, no significant variation in the total NDUFS1 expression was observed in H/R-exposed cardiomyocytes following treatment with siMDM2. Further study indicated that lutein facilitates the translocation of NDUFS1 from the cytosol to mitochondria by directly binding and sequestering MDM2, thereby improving mitochondrial function and inhibiting ferroptosis.Conclusion Lutein@DTPP promoted the mitochondrial translocation of NDUFS1 to restore mitochondrial function and inhibited the ferroptosis of cardiomyocytes by directly binding and sequestering MDM2.
研究领域:
心血管疾病
·
纳米技术
·
药理学
·
细胞生物学
·
分子生物学
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产品关联
DOI
PubMed
高影响因子
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