Ginsenoside Rb1 alleviates atherosclerosis by modulating vascular smooth muscle cell proliferation, foam cell formation, and autophagy
Bibliographic record
Abstract
BACKGROUND: Atherosclerosis features chronic inflammation and lipid accumulation; vascular smooth muscle cells (VSMCs) contribute by proliferating and becoming foam cells via oxidized LDL (ox-LDL) uptake through lectin-like ox-LDL receptor-1 (LOX-1). PURPOSE: To test whether ginsenoside Rb1 limits neointima formation and atherosclerosis by inhibiting VSMC proliferation and foam formation via c-JUN/AP-1-dependent regulation of LOX-1, with autophagy as a supportive mechanism. STUDY DESIGN: In vivo carotid ligation models (complete in C57BL/6 J; partial in ApoE-/-) with perivascular Rb1 in F-127 hydrogel, plus in vitro analyses in A7R5 VSMCs. METHODS: Lesion burden was quantified histologically. VSMC proliferation (EdU, cell-cycle proteins), lipid accumulation (Oil Red O, BODIPY), intracellular cholesterol, and Dil-ox-LDL uptake were measured. Network pharmacology/docking nominated targets; biotin-Rb1 pull-down validated binding. c-JUN phosphorylation/AP-1 activity, LOX-1 expression, and autophagy markers (LC3-II, p62) were assessed; AP-1 was inhibited with T5224. RESULTS: Rb1 reduced ligation-induced neointima in C57BL/6 J mice and decreased plaque size and lipid content in ApoE-/- carotids. In VSMCs, Rb1 suppressed proliferation, lowered ox-LDL uptake and total cholesterol, downregulated LOX-1. Network analyses identified JUN among the top Rb1 targets; docking predicted binding and pull-down confirmed direct interaction with c-JUN (and PTGS2). Rb1 decreased c-JUN phosphorylation and AP-1 activity; AP-1 blockade with T5224 recapitulated reductions in LOX-1 and ox-LDL uptake. Rb1 increased LC3-II and decreased p62, consistent with enhanced autophagy. CONCLUSION: Rb1 mitigates atherosclerosis by inhibiting VSMC proliferation and foam formation through suppression of c-JUN/AP-1-mediated LOX-1 transcription and activation of autophagy. These actions support Rb1 as a promising phytotherapeutic for plaque attenuation and stabilization.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".