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Ferroptosis-Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin.

ABSTRACT: The search for safe and effective ferroptosis-inhibitors has become an important topic. Geraniin, an ellagitannin bearing hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) groups, was observed to inhibit erastin-induced ferroptosis in bone marrow-derived mesenchymal stem cells (bmMSCs). To determine the mechanism, geraniin was further analyzed using UV-vis spectra and several colorimetric assays, where its IC₅₀ values were always much lower than that of the Trolox positive control. When interacted with several free radicals, geraniin gave no radical adduct formation (RAF) peak in the ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry. In conclusion, geraniin exhibits ferroptosis-inhibitory potential towards erastin-treated bmMSCs; such potential may mainly stem from its strong lipid peroxidation (LPO)-inhibition, Fe²⁺ -chelating, and antioxidant actions. Geraniin gives neither dimer nor radical adduct, owing to the bulky HHDP (or DHHDP) group; thus, it is considered as a safe and effective ferroptosis-inhibitor.

SUBMITTER: Chen B

PROVIDER: S-EPMC8340064 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

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Ferroptosis-Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin.

Chen Ban B Li Xican X Liu Jie J Li Yuling Y Dai Wanjian W Chen Yingci Y Chen Dongfeng D

ChemistryOpen 20210215 8

The search for safe and effective ferroptosis-inhibitors has become an important topic. Geraniin, an ellagitannin bearing hexahydroxydiphenoyl (HHDP) and dehydrohexahydroxydiphenoyl (DHHDP) groups, was observed to inhibit erastin-induced ferroptosis in bone marrow-derived mesenchymal stem cells (bmMSCs). To determine the mechanism, geraniin was further analyzed using UV-vis spectra and several colorimetric assays, where its IC<sub>50</sub> values were always much lower than that of the Trolox po ...[more]

PMID: 33590718

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Project description:BackgroundPhytophthora nicotianae is a fungal soil-borne pathogen that damages various plant species. Mancozeb and Zineb, fungicides containing manganese (Mn) and zinc (Zn) as the main components, are widely used to control the diseases caused by Phytophthora. However, the inhibition mechanism is still unclear. The purpose of this study was to examine the effects of Mn and Zn on P. nicotianae and to determine possible inhibitory mechanisms of Mn and Zn on sporangiogenesis of P. nicotianae.MethodsThe mycelial growth, sporangium generation, zoosporogenesis and zoospore germination of P. nicotianae were observed under Mn and Zn treatments. The gene (csn4 and csn7) expression levels of P. nicotianae in different growth stages were examined. Csn4 and csn7 gene expression, superoxide dismutase (SOD) activity, catalase (CAT) activity and malondialdehyde (MDA) content were tested at the stage of sporangiogenesis under different Mn and Zn concentrations.ResultsMycelial growth of P. nicotianae was significantly inhibited by Mn from ≥1 mg/L concentration and by Zn from ≥10 mg/L. The sporangia production, sporangia release, and zoospore germination of P. nicotianae were significantly reduced by Mn at all concentrations, while treatment with Zn from ≥0.5 mg/L concentration significantly inhibited the same processes. At the same concentration, the inhibition rate of Mn on the growth process of P. nicotianae was higher than that of Zn. The csn4 and csn7 gene transcription of P. nicotianae were significantly reduced by all treatments with Mn and Zn at the stage of sporangiogenesis. With the increase of Mn concentration, the activities of SOD and CAT increased to maxima and then decreased, and the content of MDA gradually increased during sporangiogenesis of P. nicotianae. The sporangia production of P. nicotianae was significantly positively correlated with the expression levels of the genes csn4 and csn7.ConclusionThe inhibitory effect of Mn on the growth process of P. nicotianae was stronger than that of Zn, especially on sporangiogenesis and zoosporogenesis. A possible mechanism of the inhibitory effect on sporangiogenesis of P. nicotianae was that Mn and Zn acted by inhibiting the expression levels of the genes csn4 and csn7 and by affecting antioxidant enzyme activity (further resulting in lipid peroxidation) in the sporangium of P. nicotianae.

Dataset Information

Ferroptosis-Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin.

Publications

Ferroptosis-Inhibitory Effect and Possible Mechanisms of Ellagitannin Geraniin.

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