Isobicyclogermacrenal ameliorates hippocampal ferroptosis involvement in neurochemical disruptions and neuroinflammation induced by sleep deprivation in rats.
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Abstract
Background: Sleep deprivation (SLD) is a widespread condition that disrupts physiological functions and may increase mortality risk. Valeriana officinalis, a traditional medicinal herb known for its sedative and hypnotic properties, contains isobicyclogermacrenal (IG), a newly isolated active compound. However, research on the therapeutic potential of IG for treating SLD remains limited.
Methods: In this study, IG was extracted and characterized from Valeriana officinalis, and an SLD model was established in rats using p-chlorophenylalanine (PCPA). Behavioral tests and pathological studies were conducted to assess the effects of IG on SLD, and transcriptomic and metabolomic analyses were utilized to investigate its underlying mechanisms.
Results: IG administration significantly improved the cognitive performance of SLD rats in behavioral tests and ameliorated histological injuries in the hippocampus and cerebral cortex. IG treatment increased the levels of brain-derived neurotrophic factor (BDNF) and neurotransmitters such as serotonin (5-HT) in SLD rats. Additionally, IG directly targets TFRC, thereby improving iron metabolism in the hippocampus. Comprehensive transcriptomic and metabolomic analyses revealed that the improvements from IG stemmed from the mitigation of abnormalities in iron metabolism, cholesterol metabolism, and glutathione metabolism, leading to reduced oxidative stress, ferroptosis, and neuroinflammation in the hippocampus caused by SLD.
Conclusions: Collectively, these findings suggest that IG has the potential to ameliorate neurological damage and cognitive impairment caused by SLD, offering a novel strategy for protection against the adverse effects of SLD.
期刊介绍：
Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.
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