Chlorogenic acid promotes the Nrf2/HO-1 anti-oxidative pathway by activating p21Waf1/Cip1 to resist dexamethasone-induced apoptosis in osteoblastic cells
Bibliographic record
Abstract
In a previous study, p21 Waf1/Cip1 (p21) promoted activation of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway, which has an important role in regulating apoptosis triggered by oxidative stress and inhibiting development of osteoporosis. Chlorogenic acid (CGA) has a strong protective effect on osteoporosis, closely related to activating the Nrf2/HO-1 pathway. However, whether CGA can resist apoptosis by regulating p21 and consequently promote activation of the Nrf2/HO-1 pathway needs further investigation. MC3T3-E1 cells were treated with dexamethasone (Dex), with or without CGA pre-treatment. Cell proliferation and cytotoxicity were measured using MTT assay and LDH release assay, respectively, and apoptosis assessed by flow cytometry. CGA significantly attenuated mitochondrial apoptosis and reversed down-regulation of p21 in osteoblastic MC3T3-E1 cells exposed to Dex. Additionally, CGA decreased Keap1 expression and promoted activation of the Nrf2/HO-1 pathway, quenching intracellular reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ) and mitochondrial superoxide overproduction boosted by Dex. Importantly, depletion of p21 by siRNA blocked activation of the Nrf2/HO-1 pathway, enhanced oxidative stress and increased apoptosis induced by CGA in MC3T3-E1 cells challenged with Dex. Therefore, CGA promoted the Nrf2/HO-1 anti-oxidative pathway by activating p21 to prevent Dex-induced mitochondrial apoptosis in osteoblastic cells. This pathway has potential as a therapeutic target for prevention and treatment of osteoporosis.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".