Objective:

2

To evaluate active components of Tianma Gouteng Yin (TMGTY) and its mechanisms in treating hypertension-associated vascular cognitive impairment (VCI).

Methods:

2

Network pharmacology and molecular docking were used to identify major active ingredients and potential targets of TMGTY in treating hypertension-associated VCI. An

in vivo

model was established using spon

taneously hypertensive rats subjected to unilateral common carotid artery occlusion and a high-salt diet. Rats were randomly divided into 7 groups by a simple randomization method: control

model

sham

low-

medium-

and high-dose TMGTY

and nimodipine groups (

n

=6). After 28 days of oral administration

blood pressure

behavioral studies

pathological staining

and molecular mechanisms were assessed via tail artery blood pressure monitoring

the morris water maze test

HE staining

immunofluorescence staining

ELISA

and Western blotting.

Results:

2

Network analysis identified quercetin

kaempferol

beta-sitosterol

and stigmasterol as key ingredients. Pathway enrichment analysis identified the NF-κB signaling pathway as a key pathway through which TMGTY antagonizes the development of hypertension combined with VCI. Core targets included glyceraldehyde-3-phosphate dehydrogenase (GAPDH)

interleukin 6 (IL-6)

insulin (INS)

tumor necrosis factor (TNF)

and tumor protein p53 (TP53)

and molecular docking confirmed stable binding to TNF and INS.

In vivo

experiments demonstrated that TMGTY significantly enhanced cognitive performance and reduced blood pressure. Furthermore

it lowered the levels of pro-inflammatory factors (IL-1β

IL-6

TNF-α

Ang-Ⅱ) and malondialdehyde (MDA)

while elevating superoxide dismutase (SOD) expression (

P

<

0.05 or

P

<

0.01). Immunofluorescence staining further revealed that TMGTY treatment reduced the number of Iba1- and CD16-labeled microglia in the hippocampal CA1 region

thereby alleviating neuroinflammation. Additionally

TMGTY inhibited the expression levels of p-NF-κB p65/NF-κB p65 proteins and attenuated neuroinflammation.

Conclusion:

2

TMGTY exerts multi-component

multi-target effects on hypertension-associated VCI

mitigating neuroinflammation and oxidative stress via modulation of NF-κB signaling pathway.