Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis

Zhang, Heping; Zhou, Wei; Li, Jianling; Qiu, Zhaohui; Wang, Xiaotong; Xu, Hui; Wang, Huadong; Lu, Daxiang; Qi, Renbin

doi:10.1007/s12035-022-03014-y

Cited by 18 publications

(8 citation statements)

References 33 publications

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“…Senegenin has been shown to have antioxidative effects [ 22 ]. To investigate whether it exerts an antioxidative effect in addition to its antifibrotic effect, we examined the levels of ROS in the lung tissues of different groups of mice and found that medium and high doses of senegenin significantly reduced the levels of ROS in the lung tissues of mice with pulmonary fibrosis ( Figure 2 A).…”

Section: Resultsmentioning

confidence: 99%

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway

Zeng,

Luo,

Sang

et al. 2024

Antioxidants

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Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc–1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin.

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Section: Resultsmentioning

confidence: 99%

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway

Zeng,

Luo,

Sang

et al. 2024

Antioxidants

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“…Salidroside, [ 357 , 358 ] edaravone, [ 359 ] senegenin, [ 360 ] tetrahydroxy stilbene glycoside (TSG), [ 361 ] ginkgolide B, [ 362 ] forsythoside A, [ 363 ] deferoxamine, [ 364 ] insamgobonhwan, [ 365 ] γ ‐glutamylcysteine ( γ ‐GC), [ 366 ] a novel lipoic acid‐niacin dimer N2L, [ 367 ] eriodictyol, [ 368 ] selenium (Se), [ 369 , 370 ] clioquinol, [ 371 ] GW7647, [ 372 ] α ‐Lipoic acid, [ 373 ] OABL, [ 374 ] CMS121, [ 375 ] Fer‐1, [ 173 ] Lip‐1, [ 173 ] coenzyme Q10, [ 376 ] 7,8‐dihydroxyflavone (7,8‐DHF), [ 377 ] 2′,6′‐dihydroxy‐4′‐methoxy dihydrochalcone (DHMDC), [ 378 ] kojic acid, [ 379 ] crocin, [ 380 ] celecoxib, [ 381 ] allicin, [ 382 ] centella asiatica, [ 383 ] and ellagic acid [ 384 ] alleviate AD through inhibiting ferroptosis (Table 2 ).…”

Section: Pharmacological Inhibition Of Ferroptosis To Treat Nds and S...mentioning

confidence: 99%

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Wang

et al. 2023

Advanced Science

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Emerging evidence suggests that ferroptosis, a unique regulated cell death modality that is morphologically and mechanistically different from other forms of cell death, plays a vital role in the pathophysiological process of neurodegenerative diseases, and strokes. Accumulating evidence supports ferroptosis as a critical factor of neurodegenerative diseases and strokes, and pharmacological inhibition of ferroptosis as a therapeutic target for these diseases. In this review article, the core mechanisms of ferroptosis are overviewed and the roles of ferroptosis in neurodegenerative diseases and strokes are described. Finally, the emerging findings in treating neurodegenerative diseases and strokes through pharmacological inhibition of ferroptosis are described. This review demonstrates that pharmacological inhibition of ferroptosis by bioactive small‐molecule compounds (ferroptosis inhibitors) could be effective for treatments of these diseases, and highlights a potential promising therapeutic avenue that could be used to prevent neurodegenerative diseases and strokes. This review article will shed light on developing novel therapeutic regimens by pharmacological inhibition of ferroptosis to slow down the progression of these diseases in the future.

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“…Furthermore, the expression of ACSL4 and PEBP1 proteins decreased after senegenin treatment. These results indicate that senegenin remarkably attenuates the oxidative damage caused by Aβ25-35 and also affects the expression of ferroptosis-related proteins, thus significantly protecting PC12 cells against Aβ25-35-induced cytotoxicity [ 114 ].…”

Section: Models To Study Ferroptosis In Neurodegenerationmentioning

confidence: 99%

Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases

et al. 2023

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Ferroptosis is a type of regulated cell death promoted by the appearance of oxidative perturbations in the intracellular microenvironment constitutively controlled by glutathione peroxidase 4 (GPX4). It is characterized by increased production of reactive oxygen species, intracellular iron accumulation, lipid peroxidation, inhibition of system Xc-, glutathione depletion, and decreased GPX4 activity. Several pieces of evidence support the involvement of ferroptosis in distinct neurodegenerative diseases. In vitro and in vivo models allow a reliable transition to clinical studies. Several in vitro models, including differentiated SH-SY5Y and PC12 cells, among others, have been used to investigate the pathophysiological mechanisms of distinct neurodegenerative diseases, including ferroptosis. In addition, they can be useful in the development of potential ferroptosis inhibitors that can be used as disease-modifying drugs for the treatment of such diseases. On the other hand, in vivo models based on the manipulation of rodents and invertebrate animals, such as Drosophila melanogaster, Caenorhabditis elegans, and zebrafish, have been increasingly used for research in neurodegeneration. This work provides an up-to-date review of the main in vitro and in vivo models that can be used to evaluate ferroptosis in the most prevalent neurodegenerative diseases, and to explore potential new drug targets and novel drug candidates for effective disease-modifying therapies.

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Senegenin Rescues PC12 Cells with Oxidative Damage Through Inhibition of Ferroptosis

Cited by 18 publications

References 33 publications

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway

Pharmacological Inhibition of Ferroptosis as a Therapeutic Target for Neurodegenerative Diseases and Strokes

Research Models to Study Ferroptosis’s Impact in Neurodegenerative Diseases

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