Selective Activation of Human Pregnane X Receptor, Glucocorticoid Receptor, and Constitutive Androstane Receptor by Individual Ginkgolides
Bibliographic record
Abstract
Pregnane X receptor (PXR), glucocorticoid receptor (GR), and constitutive androstane receptor (CAR) regulate the expression of genes involved in diverse biological functions. Ginkgolide A, ginkgolide B, ginkgolide C, and ginkgolide J are structurally‐related terpene trilactones present in Ginkgo biloba extract. In the present study, we compared the effect of individual ginkgolides on the function of human PXR (hPXR), human GR (hGR), and human CAR (hCAR). As assessed in a cell‐based luciferase reporter gene assay, none of the ginkgolides activated hGR or hCAR (wild‐type and its SV23, SV24, and SV25 splice variants). Whereas ginkgolide A and ginkgolide B activated hPXR to a greater extent than ginkgolide C, ginkgolide J had no effect. Among the ginkgolides investigated, only ginkgolide A and ginkgolide B bound to the ligand‐binding domain of hPXR, recruited steroid receptor coactivator‐1, and increased hPXR target gene (CYP3A4) expression. In conclusion, the individual ginkgolides regulate the function of nuclear receptors in a chemical‐dependent and receptor‐selective manner. This study identifies ginkgolide A and ginkgolide B as naturally‐occurring agonists of hPXR, provides mechanistic insight into the structure‐activity relationship of ligand‐activation of hPXR, and suggests that specific ginkgolides may modulate the biological actions mediated by this receptor. [Supported by CIHR and MSFHR]
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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 | 0.000 | 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) | 0.001 | 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".