Ferroptosis pathways: Unveiling the neuroprotective power of cistache deserticola phenylethanoid glycosides.

Autor: Zhang X; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Liu Z; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Li Z; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Qi L; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Huang T; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Li F; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Li M; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Wang Y; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Ma Z; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China., Gao Y; School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, 510006, Guangzhou, China; Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, 100850, Beijing, China. Electronic address: gaoyue@bmi.ac.cn.
Jazyk: angličtina
Zdroj: Journal of ethnopharmacology [J Ethnopharmacol] 2024 Oct 28; Vol. 333, pp. 118465. Date of Electronic Publication: 2024 Jun 27.
DOI: 10.1016/j.jep.2024.118465
Abstrakt: Ethnopharmacological Relevance: Cistanche deserticola is a kind of parasitic plant living in the roots of desert trees. It is a rare Chinese medicine, which has the effect of tonifying kidney Yang, benefiting essence and blood and moistening the intestinal tract. Cistache deserticola phenylethanoid glycoside (PGS), an active component found in Cistanche deserticola Ma, have potential kidney tonifying, intellectual enhancing, and neuroprotective effects. Cistanche total glycoside capsule has been marketed to treat vascular dementia disease.
Aim of the Study: To identify the potential renal, intellectual enhancing and neuroprotective effects of PGS and explore the exact targets and mechanisms of PGS.
Materials and Methods: This study systematically investigated the four types of pathways leading to ferroptosis through transcriptome, metabolome, ultrastructure and molecular biology techniques and explored the molecular mechanism by which multiple PGS targets and pathways synergistically exert neuroprotective effects on hypoxia.
Results: PGS alleviated learning and memory dysfunction and pathological injury in mice exposed to hypobaric hypoxia by attenuating hypobaric hypoxia-induced hippocampal histopathological damage, impairing blood‒brain barrier integrity, increasing oxidative stress levels, and increasing the expression of cognitive proteins. PGS reduced the formation of lipid peroxides and improved ferroptosis by upregulating the GPX-4/SCL7A311 axis and downregulating the ACSL4/LPCAT3/LOX axis. PGS also reduced ferroptosis by facilitating cellular Fe 2+ efflux and regulating mitochondrial Fe 2+ transport and effectively antagonized cell ferroptosis induced by erastin (a ferroptosis inducer).
Conclusions: This study demonstrated the mechanism by which PGS prevents hypobaric hypoxic nerve injury through four types of ferroptosis pathways, achieved neuroprotective effects and alleviated learning and memory dysfunction in hypobaric hypoxia mice. This study provides a theoretical basis for the development and application of PGS.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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