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Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling.

ABSTRACT: Eucommia ulmoides Oliver staminate flower (ESF) tea enjoys a good reputation in folk medicine and displays multiple bioactivities, such as antioxidant and antifatigue properties. However, the underlying biological mechanisms remain largely unknown. In this study, we aimed to investigate whether ESF tea can mitigate cellular oxidative stress. Crude ethyl alcohol extract and its three subfractions prepared by sequential extraction with chloroform, n-butyl alcohol and residual water were prepared from ESF tea. The results of antioxidant activity tests in vitro manifested n-butyl alcohol fraction (n-BUF) showed the strongest antioxidant capacity (DPPH: IC50 = 24.45 ± 0.74 μg/mL, ABTS: IC50 = 17.25 ± 0.04 μg/mL). Moreover, all subfractions of ESF tea, especially the n-BUF, exhibited an obvious capacity to scavenge the reactive oxygen species (ROS) and stimulate the NRF2 antioxidative response in human keratinocytes HaCaT treated by H2O2. Using ultra-high-performance liquid chromatography, we identified geniposidic acid (GPA) as the most abundant component in ESF tea extract. Furthermore, it was found that GPA relieved oxidative stress in H2O2-induced HaCaT cells by activating the Akt/Nrf2/OGG1 pathway. Our findings indicated that ESF tea may be a source of natural antioxidants to protect against skin cell oxidative damage and deserves further development and utilization.

SUBMITTER: Cheng S

PROVIDER: S-EPMC9739628 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling

Cheng Shuo S Jia Huiling H Zhang Yisen Y Zhou Juanjuan J Chen Xue X Wu Lifang L Wang Jun J

Molecules (Basel, Switzerland) 20221205 23

<i>Eucommia ulmoides</i> Oliver staminate flower (ESF) tea enjoys a good reputation in folk medicine and displays multiple bioactivities, such as antioxidant and antifatigue properties. However, the underlying biological mechanisms remain largely unknown. In this study, we aimed to investigate whether ESF tea can mitigate cellular oxidative stress. Crude ethyl alcohol extract and its three subfractions prepared by sequential extraction with chloroform, n-butyl alcohol and residual water were pre ...[more]

PMID: 36500666

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Project description:Eucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein-protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson-Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.

Project description:BackgroundNatural rubber produced by plants, known as polyisoprene, is the most widely used isoprenoid polymer. Plant polyisoprenes can be classified into two types; cis-polyisoprene and trans-polyisoprene, depending on the type of polymerization of the isoprene unit. More than 2000 species of higher plants produce latex consisting of cis-polyisoprene. Hevea brasiliensis (rubber tree) produces cis-polyisoprene, and is the key source of commercial rubber. In contrast, relatively few plant species produce trans-polyisoprene. Currently, trans-polyisoprene is mainly produced synthetically, and no plant species is used for its commercial production.ResultsTo develop a plant-based system suitable for large-scale production of trans-polyisoprene, we selected a trans-polyisoprene-producing plant, Eucommia ulmoides Oliver, as the target for genetic transformation. A full-length cDNA (designated as EuIPI, Accession No. AB041629) encoding isopentenyl diphosphate isomerase (IPI) was isolated from E. ulmoides. EuIPI consisted of 1028 bp with a 675-bp open reading frame encoding a protein with 224 amino acid residues. EuIPI shared high identity with other plant IPIs, and the recombinant protein expressed in Escherichia coli showed IPI enzymatic activity in vitro. EuIPI was introduced into E. ulmoides via Agrobacterium-mediated transformation. Transgenic lines of E. ulmoides overexpressing EuIPI showed increased EuIPI expression (up to 19-fold that of the wild-type) and a 3- to 4-fold increase in the total content of trans-polyisoprenes, compared with the wild-type (non-transgenic root line) control.ConclusionsIncreasing the expression level of EuIPI by overexpression increased accumulation of trans-polyisoprenes in transgenic E. ulmoides. IPI catalyzes the conversion of isopentenyl diphosphate to its highly electrophilic isomer, dimethylallyl diphosphate, which is the first step in the biosynthesis of all isoprenoids, including polyisoprene. Our results demonstrated that regulation of IPI expression is a key target for efficient production of trans-polyisoprene in E. ulmoides.

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Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling.

Publications

Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling

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Geniposidic Acid from Eucommia&nbsp;ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling.

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Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

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Geniposidic Acid from Eucommia ulmoides Oliver Staminate Flower Tea Mitigates Cellular Oxidative Stress via Activating AKT/NRF2 Signaling.