Abstract
Hops, the dried female clusters from Humulus lupulus L., have traditionally been used as folk medicines for treating insomnia, neuralgia, and menopausal disorders. However, its pharmacological action on iron overload induced nerve damage has not been investigated. This study aims to evaluate the protective effects of hops extract (HLE) and its active constituent xanthohumol (XAN) on nerve injury induced by iron overload in vivo and in vitro, and to explore its underlying mechanism. The results showed that HLE and XAN significantly improved the memory impairment of iron overload mice, mainly manifested as shortened latency time, increased crossing platform times and spontaneous alternation ratio, and increased the expression of related proteins. Additionally, HLE and XAN significantly increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) activities, and remarkably decreased malondialdehyde (MDA) level in hippocampus. Also, HLE and XAN apparently reduced reactive oxygen species (ROS) content of PC12 cells induced by iron dextran (ID), and improved the oxidative stress level. Moreover, HLE and XAN significantly upregulated the expression of nuclear factor E2-related factor (Nrf2), NAD(P)H quinone oxidoreductase (NQO1), heme oxygenase-1 (HO-1), SOD, phosphorylated AKT (p-AKT), and phosphorylated GSK3β (p-GSK3β) both in hippocampus and PC12 cells. These findings demonstrated the protective effect of HLE and XAN against iron-induced memory impairment, which is attributed to its antioxidant profile by activation of AKT/GSK3β and Nrf2/NQO1 pathways. Also, it was suggested that hops could be a potential candidate for iron overload-related neurological diseases treatment.
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Abbreviations
- HLE:
-
Hops extract
- XAN:
-
Xanthohumol
- ID:
-
Iron dextran
- MWM:
-
Morris water maze
- BDNF:
-
Brain-derived neurotrophic factor
- ERK:
-
Extracellular regulated protein kinases
- CREB:
-
cAMP-response element binding protein
- AKT:
-
Protein kinase B
- GSK-3β :
-
Glycogen synthase kinase-3β
- Nrf2:
-
Nuclear factor E2-related factor
- SOD:
-
Superoxide dismutase
- GSH-PX:
-
Glutathione peroxidase
- MDA:
-
Malondialdehyde
- NQO1:
-
NAD(P)H:quinone oxidoreductase 1
- HO-1:
-
Heme oxygenase-1
- Aβ :
-
Amyloid β-protein
- ROS:
-
Reactive oxygen species
- H-A:
-
Huperzine-A
- PRRSV:
-
Porcine reproductive and respiratory syndrome virus
- SAMP8:
-
Senescence-accelerated prone mice
- BCA:
-
Bicinchoninic acid
- LDH:
-
Lactate dehydrogenase
- SDS-PAGE:
-
Sodium dodecylsulfate polyacrylamide gel electrophoresis
- PVDF:
-
Polyvinylidine difluoride
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- ECL:
-
Enhanced chemiluminescence
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (82174079, 82004015), and Project of Science and Technology Commission of Shanghai Municipality (21S21902600).
Funding
National Natural Science Foundation of China, 82174079, Xin Hailiang, 82004015, Xia Tian-Shuang, Project of Science and Technology Commission of Shanghai Municipality, 21S21902600, Xin Hailiang.
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XH-L, SX-L, and XT-S designed the experiments; SX-L performed the experiments; SX-L and XT-S analyzed the data, wrote and revised the manuscript; JY-P helped to organize figures, WN-N contributed to the documents download, XL-C, HT and XH-L reviewed the manuscript.
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Appendix 1
Appendix 1
HPLC profile of Humulus lupulus L. (9-xanthohumol, 13-cohumulone, 14-humulone, 15-adhumulone, 17-colupulone, 18-lupulone, 19-adlupulone)
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Xiao-Lei, S., Tian-Shuang, X., Yi-Ping, J. et al. Humulus lupulus L. extract and its active constituent xanthohumol attenuate oxidative stress and nerve injury induced by iron overload via activating AKT/GSK3β and Nrf2/NQO1 pathways. J Nat Med 77, 12–27 (2023). https://doi.org/10.1007/s11418-022-01642-1
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DOI: https://doi.org/10.1007/s11418-022-01642-1