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Ling-Yang-Gou-Teng-decoction prevents vascular dementia through inhibiting oxidative stress induced neurovascular
Xin Zhao1, Jinyu Liu1, Shijun Yang1
1Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China.
Insights
Ling-Yang-Gou-Teng decoction (LG) improved cognitive function and protected brain pathology in a rat model of vascular dementia (VaD). LG works by reducing oxidative stress and preserving nitric oxide bioavailability, thereby maintaining neurovascular coupling sensitivity.
Area of Science:
- Neuroscience
- Pharmacology
- Traditional Chinese Medicine
Background:
- Vascular dementia (VaD), often stemming from lacunar stroke (LS), is a prevalent cognitive disorder.
- Oxidative stress-induced neurovascular coupling (NVC) dysfunction is a key factor in VaD pathogenesis.
- Currently, no specific pharmaceutical treatments exist for VaD.
Purpose of the Study:
- To investigate the underlying therapeutic mechanisms of Ling-Yang-Gou-Teng decoction (LG) in a rat model of VaD.
- To evaluate the effects of LG on cognitive function, brain pathology, and NVC in VaD.
Main Methods:
- VaD was induced in rats via micro-thrombi and hypercholesterolemia.
- Rats were administered varying dosages of LG.
- Neurovascular coupling (NVC) sensitivity was assessed by measuring cerebral blood velocity (CBV) in response to electroencephalograph (EEG) changes.
- Behavioral tests, brain pathology, and oxidative stress markers were analyzed.
Main Results:
- LG administration improved exploratory, learning, and memory functions in VaD rats.
- LG treatment alleviated vascular and neural pathological changes in the cerebral cortex and hippocampus.
- LG maintained NVC sensitivity, evidenced by increased ΔCBV and an elevated ΔCBV/ΔqEEG ratio.
- Mechanistically, LG exhibited antioxidant effects by decreasing NOX2 and increasing SOD3 expression, while also modulating nitric oxide synthase (NOS) expression to restore NO bioavailability.
Conclusions:
- LG demonstrates potential in preventing VaD by mitigating oxidative stress and preserving nitric oxide bioavailability.
- These actions contribute to the maintenance of neurovascular coupling sensitivity, offering a protective effect against VaD.
- LG's therapeutic effects are linked to its antioxidant properties and ability to restore NO bioavailability.
Ethnopharmacological Relevance:
Vascular dementia (VaD) is the common cognitive disorder derived mainly from lacunar stroke (LS). The oxidative stress induced neurovascular coupling (NVC) dysfunction involves in the pathogenesis of VaD. Currently, there is no specific drug for VaD. Ling-Yang-Gou-Teng -Decoction (LG), a well-known traditional Chinese formula, has been used for preventing VaD in clinic.
Aim Of The Study:
In this study, we aimed to investigate the underlying mechanism of LG on VaD in rats.
Materials And Method:
VaD was replicated with autologous micro-thrombi against the background of hypercholesterolemia induced with high fatty diet. PTX (68.90 mg/kg/day), LG with three dosages (2.58, 8.14, 25.80 g/kg/day) was orally administrated to VaD rats, respectively. The NVC sensitivity was defined as the ratio of the microcirculative cerebral blood velocity (CBV) to the electroencephalograph (EEG) before and after penicillin stimulation. Behavioral performance, pathological changes of brain and oxidation related molecules were detected to assess the effects of LG on VaD.
Results:
LG exhibited beneficial effects on the VaD, which was demonstrated as improved exploratory, learning and memory abilities, relieved vascular or neural pathological changes in cerebral cortex or hippocampus. LG maintained NVC sensitivity, which was confirmed as significantly increased ΔCBV and the elevated ratio of ΔCBV/ΔqEEG. The underlying mechanisms of LG was associated with antioxidant effects, which was confirmed as significantly decreased nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) expression, and increased superoxide dismutase 3 (SOD3) expression. LG also reduced iNOS, increased nNOS and eNOS expression to restore NO bioavailability.
Conclusions:
The results suggested that LG prevented VaD may associate with inhibiting oxidative stress, protecting NO bioavailability, and then maintaining NVC sensitivity.
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