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Can a Rubia extract protect hypoperfused rat brains?

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In 70 SD rats with 2VO hypoperfusion, 30-day RY-A gavage improved cognition and raised ferroptosis-guard proteins (SLC7A11, GPX4) via System Xc-/GSH/GPX4.

Source

Neuroprotective effects of ethanol extraction from <i>Rubia yunnanensis</i> Diels on chronic cerebral hypoperfusion: modulation of the System Xc-/GSH/GPX4 axis to alleviate oxidative stress and ferroptosis

Cheng J, Ma X, Tao J, et al. · Frontiers in pharmacology · 2025

doi.org/10.3389/fphar.2025.1552228Read the full paper ↗8 citationscc by

Study at a glance

Design
Animal / in-vitro — CCH (2VO) rat model with RY-A gavage, behavior/CBF/histology plus serum chemistry, RNA-seq, metabolomics, and Western blot
N
N=70 · 70 male Sprague-Dawley rats (260 ± 20 g, 8 weeks); Sham n=12; 52 successful 2VO models
Population
Male Sprague-Dawley rats with bilateral carotid 2-vessel occlusion chronic cerebral hypoperfusion
Outcome
Cognition (Morris water maze), cerebral blood flow, histology, ferroptosis/oxidative-stress proteins (SLC7A11, GPX4, etc.)

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What they did

After 2VO CCH modeling, treated rats with RY-A gavage for 30 days, then Morris water maze, CBF, HE staining, serum medicinal chemistry, RNA-seq, metabolomics, assay kits, and Western blots.

What they found

RY-A attenuated neurological damage and improved cognition. UHPLC-HRMS found 511 blood-entry compounds. RY-A increased SLC7A11, SLC3A2, GSS, and GPX4, boosted antioxidant enzymes, and authors conclude it inhibited ferroptosis by activating System Xc-/GSH/GPX4 and balancing iron.

The limits

What it doesn't show

Rat 2VO data do not prove RY-A treats human vascular dementia; doses and 511 compounds are preclinical leads, not a clinical trial.

Key terms

CCH
Chronic cerebral hypoperfusion, a driver of vascular dementia models.
2VO
Two-vessel occlusion (bilateral carotid) rat CCH model.
RY-A
Ethanol extract of Rubia yunnanensis Diels.
Ferroptosis
Iron-dependent cell death opposed here by GPX4/System Xc-.
System Xc-/GSH/GPX4
Cystine/glutamate antiporter–glutathione–GPX4 antioxidant axis.

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Total rats used:

Common questions

How many rats?

70 male Sprague-Dawley rats; Sham n=12.

Treatment duration?

30 days of RY-A gavage.

How many blood-entry compounds?

511 identified by UHPLC-HRMS.

Proposed mechanism?

Activate System Xc-/GSH/GPX4, limit oxidative stress and ferroptosis.

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