Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats

Huang, Yi; Wu, Honggang; Hu, Yisong; Zhou, Chenhui; Wu, Jiawei; Wu, Yen-Ting; Wang, Haifeng; Lenahan, Cameron; Huang, Lei; Nie, Sheng; Gao, Xiang; Sun, Jie

doi:10.3390/antiox11071259

Cited by 63 publications

(42 citation statements)

References 59 publications

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“…SCD1 has been reported as a ferroptosis suppressor via the regulation of monounsaturated fatty acid synthesis in ovarian cancer cells [ 43 ]. Additionally, PGC1α has been proven to attenuate oxidative stress and ferroptosis through the regulation of an Nrf2-dependent antioxidative system in subarachnoid hemorrhage in rats [ 55 ]. The results of our present study are consistent with these previous reports and provide solid mechanistic evidence to support the crucial function of MITF in the control of ferroptosis.…”

Section: Discussionmentioning

confidence: 99%

Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF

Wang

Zhang

Chen

et al. 2022

Cells

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Melanoma is the most lethal form of skin cancer, resulting from the malignant transformation of epidermal melanocytes. Recent revolutionary progress in targeted therapy and immunotherapy has prominently improved the treatment outcome, but the survival of melanoma patients remains suboptimal. Ferroptosis is greatly involved in cancer pathogenesis and can execute the outcome of immunotherapy. However, the detailed regulatory mechanisms of melanoma cell ferroptosis remain elusive. Herein, we report that Wnt/β-catenin signaling regulates ferroptosis and melanoma immunotherapy efficacy via the regulation of MITF. First of all, we found that Wnt/β-catenin signaling was prominently suppressed in melanoma cell ferroptosis. Then, we proved that targeting β-catenin exacerbated melanoma cell ferroptosis by promoting the generation of lipid peroxidation both in vitro and in vivo. Subsequent mechanistic studies revealed that MITF mediated the effect of Wnt/β-catenin signaling on melanoma cell ferroptosis, and PGC1α and SCD1 were documented as two main effectors downstream of Wnt/β-catenin-MITF pathway. Ultimately, pharmacological inhibition of β-catenin or MITF increased the efficacy of anti-PD-1 immunotherapy in preclinical xenograft tumor model by promoting ferroptosis. Taken together, Wnt/β-catenin signaling deficiency exacerbates ferroptosis in melanoma via the regulation of MITF. Targeting Wnt/β-catenin-MITF pathway could be a promising strategy to potentiate ferroptosis and increase the efficacy of anti-PD-1 immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF

Wang

Zhang

Chen

et al. 2022

Cells

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“…By increasing the expression of SIRT-1, it reduces the autophagy and mitochondrial antioxidant potential as well as the overproduction of ROS, so that oxidative stress injury is inhibited [ 15 ]. Puerarin’s neuroprotective effects on rat subarachnoid hemorrhage (SAH)-induced early brain damage (EBI) were studied by Huang et al, and they found that puerarin plays an antioxidant effect by activating the AMPK/PGC1α/Nrf2 pathway, which helps to restore nerve injury caused by SAH [ 16 ].…”

Section: Antioxidantmentioning

confidence: 99%

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

Wang

et al. 2022

Antioxidants

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As a kind of medicine and food homologous plant, kudzu root (Pueraria lobata (Willd.) Ohwi) is called an “official medicine” in Chinese folk medicine. Puerarin is the main active component extracted from kudzu root, and its structural formula is 8-β-D-grapes pyranose-4, 7-dihydroxy isoflavone, with a white needle crystal; it is slightly soluble in water, and its aqueous solution is colorless or light yellow. Puerarin is a natural antioxidant with high health value and has a series of biological activities such as antioxidation, anti-inflammation, anti-tumor effects, immunity improvement, and cardio-cerebrovascular and nerve cell protection. In particular, for the past few years, it has also been extensively used in clinical study. This review focuses on the antioxidant activity of puerarin, the therapy of diverse types of inflammatory diseases, various new drug delivery systems of puerarin, the “structure-activity relationship” of puerarin and its derivatives, and pharmacokinetic and clinical studies, which can provide a new perspective for the puerarin-related drug research and development, clinical application, and further development and utilization.

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“…Ferroptosis is a new form of iron-dependent programmed cell death. Previous studies have shown that neuronal ferroptosis occurs in SAH and that the infiltration of transferrin into the brain parenchyma might play an important role in neuronal ferroptosis after SAH ( 48 , 91 , 92 ). Liu et al.…”

Section: Astrocytes Are Involved In the Pathophysiological Process Th...mentioning

confidence: 99%

The role of the astrocyte in subarachnoid hemorrhage and its therapeutic implications

Zhao²,

Yao³

et al. 2022

Front. Immunol.

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Subarachnoid hemorrhage (SAH) is an important public health concern with high morbidity and mortality worldwide. SAH induces cell death, blood−brain barrier (BBB) damage, brain edema and oxidative stress. As the most abundant cell type in the central nervous system, astrocytes play an essential role in brain damage and recovery following SAH. This review describes astrocyte activation and polarization after SAH. Astrocytes mediate BBB disruption, glymphatic–lymphatic system dysfunction, oxidative stress, and cell death after SAH. Furthermore, astrocytes engage in abundant crosstalk with other brain cells, such as endothelial cells, neurons, pericytes, microglia and monocytes, after SAH. In addition, astrocytes also exert protective functions in SAH. Finally, we summarize evidence regarding therapeutic approaches aimed at modulating astrocyte function following SAH, which could provide some new leads for future translational therapy to alleviate damage after SAH.

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Puerarin Attenuates Oxidative Stress and Ferroptosis via AMPK/PGC1α/Nrf2 Pathway after Subarachnoid Hemorrhage in Rats

Cited by 63 publications

References 59 publications

Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF

Targeting Wnt/β-Catenin Signaling Exacerbates Ferroptosis and Increases the Efficacy of Melanoma Immunotherapy via the Regulation of MITF

Pharmacological Activity, Pharmacokinetics, and Clinical Research Progress of Puerarin

The role of the astrocyte in subarachnoid hemorrhage and its therapeutic implications

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