Characterizing the mechanism for ginsenoside-induced cytotoxicity in cultured leukemia (THP-1) cellsThis article is one of a selection of papers published in this special issue (part 2 of 2) on the Safety and Efficacy of Natural Health Products.
Bibliographic record
Abstract
Pure ginsenoside standards (saponins Rh2, PD, and PT), along with an Rh2-enhanced North American ginseng ( Panax quinquefolius ) leaf extract (LFRh2), were tested for cytotoxic activity in cultured THP-1 leukemia cells. Thermal treatment of ginseng leaf resulted in production of both Rh2 and Rg3 content that was confirmed by liquid chromatography – mass spectrometry (LC-MS). Flow cytometry of cells stained with annexin V – fluorescein isothiocyanate and propidium iodide showed that the LFRh2 significantly (p ≤ 0.05) increased apoptosis (18% ± 0.4%) after 23 h at a concentration that inhibited cell viability by 50% (LC50 (72 h) = 52 μg/mL. In comparison, a similar significant (p ≤ 0.05) increase in apoptotic cell numbers occurred at 41 h of exposure for pure ginsenoside standards, PD (LC50 (72 h) = 13 μg/mL), PT (LC50 (72 h) = 19 μg/mL), and Rh2 (LC50 (72 h) = 15 μg/mL). Although no further increase in apoptosis was observed in THP-1 cells after exposure to increasing concentrations of LFRh2 and pure Rh2, PD, and PT standards, a significant (p < 0.05) increase in the percentage of necrotic cells did occur after exposure of cells to different ginsenosides at elevated concentrations. THP-1 caspase-3 activity was greatest (p ≤ 0.05) with Rh2 (7.6 ± 1.1 nmol/L pNA), followed by LFRh2 (5.9 ± 1.0 nmol/L pNA) and PT (5.0 ± 0.8 nmol/L pNA), whereas PD was similar to control cells. We define for the first time the proportion of apoptotic to necrotic events that characterize the relative cytotoxicity and reduced cell proliferation of different ginsenosides in cultured THP-1 cells. Moreover, thermal treatment of North American ginseng leaf produced a marked transformation of ginsenoside, largely attributable to an increase in Rh2 content. This change was associated with cytotoxic properties in THP-1 cell that were related to alterations in cell membrane properties, which were also obtained with the pure ginsenosides PD, PT, and Rh2.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| 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 | 0.001 |
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".