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JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY · 2025 · IF 6.2

Pachymic Acid Ameliorates Fructose-Driven Hyperuricemic Nephropathy in Mice by Suppressing Ferroptosis via Activating Nrf2/GPX-4 Pathway

Cong Zhang,Yangkun Xiong,Mingyang Gong,Haixia Zhao,Shan Li,Xin Chen,Xiaochuan Ye,Zhenpeng Qiu

Hyperuricemic nephropathy, a common subtype of chronic kidney disease (CKD), has become an important global public health issue and is closely related to the dramatic increase in fructose consumption. Pachymic acid, the primary active ingredient of the edible fungal herb Poria cocos, has demonstrated the protective capacity against renal injury, but its beneficial effect on hyperuricemic nephropathy remains unclear. In this study, a fructose-diet-induced hyperuricemia nephropathy mouse model was established to reveal the efficacy of pachymic acid in inhibiting hyperuricemic nephropathy the progression. Our results showed that pachymic acid restored abnormal renal function indexes and pathological manifestations such as tubular dilatation and glomerular fibrosis in fructose-fed mice. Transcriptome sequencing results showed marked alterations in glutathione metabolism and ferroptosis signaling pathways in the kidneys of fructose-fed mice after pachymic acid treatment. Mechanistically, pachymic acid activated the Nrf2/GPX-4 signaling pathway by directly binding to Nrf2 and promoting its nuclear translocation, thereby inhibiting ferroptosis, oxidative stress, and inflammatory responses in the kidneys of fructose-fed mice. Consistent results were observed in uric acid-treated HK-2 cells. Notably, both Nrf2 inhibitor ML385 and GPX-4 inhibitor RSL3 treatments reversed the protective effects of pachymic acid against renal injury by suppressing ferroptosis in vitro and in vivo. Summary, our study provides compelling evidence that pachymic acid ameliorates renal injury in fructose-fed mice by inhibiting ferroptosis through targeted activating an Nrf2/GPX-4 pathway, suggesting that dietary supplementation with Poria cocos or pachymic acid might be an effective strategy for CKD prevention, particularly in the subtype of fructose-diet-driven hyperuricemic nephropathy.

研究领域: 药理学 · 肾脏病学 · 生物化学 · 分子生物学 · 营养学 · 药物化学
✓ 已验证 产品关联 DOI PubMed 高影响因子
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COLLOIDS AND SURFACES B-BIOINTERFACES · 2023 · IF 5.8

Multifunctional Fe3O4-PEI@HA nanoparticles in the ferroptosis treatment of hepatocellular carcinoma through modulating reactive oxygen species

Ziwei Liang,Yuhui Wang,Jiapu Wang,Tao Xu,Shilong Ma,Qi Liu,Liqin Zhao,Yan Wei,Xiaojie Lian,Di Huang

Ferroptosis is a novel form of regulated cell death induced by iron-dependent lipid peroxidation imbalance. It has emerged as a promising antitumor therapeutic strategy in recent years. In this work, we successfully synthesized a complex magnetic nanocube Fe 3 O 4 modified with PEI and HA by the thermal decomposition method. While loading a ferroptosis inducer RSL3 inhibited cancer cells through the ferroptosis signal transduction pathway. The drug delivery system could actively target tumor cells through an external magnetic field and HA-CD44 binding. Zeta potential analysis showed that Fe 3 O 4 [email protected] nanoparticles were more stable and uniformly dispersed in tumor acidic environment. Moreover, cellular experiments demonstrated that Fe 3 O 4 [email protected] nanoparticles could significantly inhibit the proliferation of hepatoma cells without a cytotoxic effect on normal hepatic cells. In addition, Fe 3 O 4 [email protected] played a vital role in ferroptosis by accelerating ROS production. The expression of ferroptosis-related genes Lactoferrin, FACL 4, GPX 4 and Ferritin was significantly suppressed with increasing treatment of Fe 3 O 4 [email protected] nanocubes. Therefore, this ferroptosis nanomaterial has great potential in Hepatocellular carcinoma (HCC) therapy.

CAS / MDL: 1078-61-1
研究领域: 纳米技术 · 癌症生物学 · 药学 · 分子生物学 · 生物医学工程
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Materials Today Bio · 2024 · IF 8.7

Hyperthermia/glutathione-triggered ferritin nanoparticles amplify the ferroptosis for synergistic tumor therapy

Yiting Chen,Xinhong Li,Kuankuan Luo,Tao Wang,Tongyao Liu,Enhao Lu,Rui Wang,Yu Luo,Xianyi Sha

Breast cancer is the most diagnosed malignancy in women globally, and drug resistance is among the major obstacles to effective breast cancer treatment. Emerging evidence indicates that photothermal therapy and ferroptosis are both promising therapeutic techniques for the treatment of drug-resistant breast tumors. In this study, we proposed a thermal/ferroptosis/magnetic resonance imaging (MRI) triple functional nanoparticle (I@P-ss-FRT) in which ferritin, an iron storage material with excellent cellular uptake capacity, was attached via disulfide bonds onto polydopamine coated iron oxide nanoparticle (I@P) as photothermal transduction agent and MRI probe. I@P-ss-FRT converted the near-infrared light (NIR) into localized heat which accelerated the release of ferrous ions from ferritin accomplished by glutathione reduction and subsequently induced ferroptosis. The drug-resistant cancer cell lines exhibited a more significant uptake of I@P-ss-FRT and sensitivity to PTT/ferroptosis compared with normal cancer cell lines. In vivo , I@P-ss-FRT plus NIR displayed the best tumor-killing potential with inhibitory rate of 83.46 %, along with a decline in GSH/GPX-4 content and an increase in lipid peroxides generation at tumor sites. Therefore, I@P-ss-FRT can be applied to combat drug-resistant breast cancer.

CAS / MDL: 70-18-8 62-31-7 66-71-7
研究领域: 肿瘤学 · 纳米技术 · 诊疗学 · 生物医学工程
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