Ashwagandha Root
An extract of ashwagandha root, supplied as a dry powder for use in dietary supplements.
- Tested in
- C. elegans, whole organism (BioSēq™)
- Exposure
- 48 hours (acute exposure)
- Genes measured
- 11,865
Certificate of Analysis and supplier documents reviewed: the ingredient meets its specifications.
An extract of ashwagandha root, supplied as a dry powder for use in dietary supplements.
What we check. The Certificate of Analysis and supplier documents: identity and standardisation, purity and contaminants (heavy metals, microbial limits, residual solvents and pesticides), and source documentation (supplier, origin, batch and date of manufacture).
No acute toxicity observed at the dose tested.
Survival during the 48-hour BioSēq™ exposure at the dose tested.
About the acute assessment. Acute toxicity is read from the survival of the worms during the 48-hour BioSēq™ exposure itself, so no separate study is run. It informs dose selection; it is not a regulatory safety study, and no safety claim is made from it.
443 worm genes responded, in both directions, at the tested dose.
| Criterion | Requirement | Result | |
|---|---|---|---|
| Breadth of response | At least 100 genes change (adjusted p < 0.05, more than 1.4-fold); 250 or more is a broad response | 443 genes changed (broad response) | ✓ Met |
| Bidirectional modulation | Genes move both up and down (each direction at least 10%) | 239 up, 204 down | ✓ Met |
| Coherent pathway response | At least one pathway group with strong or moderate evidence | 17 pathway groups | ✓ Met |
How to read it. Each dot is one gene. Left–right shows the size and direction of the change; higher means more statistically confident. The shaded band and the dashed line mark the cut-offs (more than 1.4-fold, adjusted p below 0.05). Labelled genes are the strongest changes with a human counterpart.
Change bands. Moderate: 1.4–2-fold · Strong: 2–4-fold · Very strong: 4-fold or more. Very large ratios occur for genes that are almost silent without treatment; values are shrunk estimates (DESeq2 apeglm).
Note: unchanged genes are thinned (every 4th) to keep the file small.
Also strongly changed, no human counterpartcyp-35B3 (very strong increase); cyp-35B2 (very strong increase); ora-1 (very strong increase); F57H12.6 (very strong increase); W02D7.11 (very strong decrease); T22F3.11 (very strong decrease); C23G10.11 (very strong decrease); C35C5.9 (very strong decrease); Y51H4A.5 (very strong decrease)
Naming. A worm gene that matches one human gene shows that gene; one that matches several shows the largest human gene family, with “+N” for further matches.
Selection. The 10 largest increases and 10 largest decreases among changed genes with a human counterpart and a baseline expression of at least 50 reads.
| Worm gene | Human | Direction | Band | Fold change | log2FC | Adjusted p |
|---|---|---|---|---|---|---|
| hsp-70 | HSPA family | up | Very strong | 52.3-fold | +5.71 | 1.6e-62 |
| hsp-16.41 | HSPB family +2 | up | Very strong | 49.9-fold | +5.64 | 1.2e-20 |
| hsp-16.2 | HSPB family +2 | up | Very strong | 31.1-fold | +4.96 | 4.7e-33 |
| dhs-26 | DHRS1 | up | Very strong | 16.1-fold | +4.01 | 1.3e-17 |
| col-80 | SFTPD | up | Very strong | 12.6-fold | +3.66 | 2.4e-69 |
| gpdh-1 | GPD family | up | Very strong | 12.4-fold | +3.63 | 1.2e-08 |
| col-93 | SFTPD | up | Very strong | 9.6-fold | +3.26 | 3.9e-07 |
| Y39B6A.1 | HRNR | up | Very strong | 8.0-fold | +3.00 | 8.4e-08 |
| pgph-3 | PGP +1 | up | Very strong | 5.9-fold | +2.56 | 1.5e-10 |
| hmit-1.1 | SLC family | up | Very strong | 5.8-fold | +2.54 | 1.3e-08 |
| fmo-2 | FMO family | down | Very strong | 6.3-fold | -2.65 | 2.8e-05 |
| cpr-2 | CTSB +1 | down | Very strong | 5.9-fold | -2.57 | 1.4e-03 |
| lec-2 | LGALS family +3 | down | Very strong | 4.3-fold | -2.10 | 1.7e-37 |
| tbx-43 | TBX21 +3 | down | Strong | 3.6-fold | -1.84 | 3.8e-04 |
| tbx-38 | TBX21 +3 | down | Strong | 3.4-fold | -1.78 | 1.4e-03 |
| ech-7 | ECHS1 | down | Strong | 3.3-fold | -1.71 | 1.2e-17 |
| nnt-1 | NNT | down | Strong | 3.2-fold | -1.67 | 9.3e-20 |
| skr-5 | SKP1 | down | Strong | 3.1-fold | -1.64 | 3.2e-03 |
| tbx-37 | TBX21 +3 | down | Strong | 2.9-fold | -1.52 | 1.9e-02 |
| dhp-1 | DPYSL family +2 | down | Strong | 2.8-fold | -1.51 | 1.1e-07 |
A biological signature led by NF-κB inflammatory signalling and TGF-β/BMP signalling.
A master switch for inflammatory gene programs.
Signals that regulate tissue growth, repair and remodelling.
Enzymes that chemically modify and clear foreign compounds.
Chaperones and clearance systems that keep proteins correctly folded.
Factors that switch genes on and off and mark DNA for long-term control.
Signals that tell cells how much food and energy is available.
Common responsesDetoxification (Phase I/II), Protein quality control (proteostasis), Gene regulation & epigenetics and Nutrient-sensing (insulin/mTOR) signalling are seen with most ingested ingredients; here, detoxification was stronger than in most ingredients tested.
How mechanisms are chosen. Pathway groups that are statistically significant (adjusted p below 0.05) are ranked by the BioSēq™ mechanistic priority score, which weighs how central the group is to the overall response; groups with strong or moderate evidence come first. Engagement is the pipeline's evidence rating (strength and consistency across pathway libraries). Direction: more or less active when the regulators and at least 60% of the group's changed genes agree; otherwise reshaped, meaning parts of the group went up and parts went down. The table lists every mechanism with strong or moderate evidence; ● marks the six shown above. L5 and L6 draw on all of them.
| Mechanism | In 4.1 | Engagement | Direction | Genes up / down | Priority score | Adjusted p | Seen in panel | Stronger than |
|---|---|---|---|---|---|---|---|---|
| NF-κB inflammatory signalling | ● | Strong | Reshaped | 4 / 29 | 0.75 | 3.3e-10 | 70% | 100% |
| TGF-β/BMP signalling | ● | Emerging | More active | 32 / 15 | 0.69 | 4.5e-03 | 84% | 100% |
| Detoxification (Phase I/II) | ● | Moderate | Reshaped | 33 / 49 | 0.89 | 1.8e-36 | 100% | 93% |
| Protein quality control (proteostasis) | ● | Strong | Reshaped | 16 / 66 | 0.83 | 5.5e-22 | 100% | 86% |
| Gene regulation & epigenetics | ● | Strong | Reshaped | 8 / 40 | 0.77 | 3.3e-10 | 100% | 16% |
| Nutrient-sensing (insulin/mTOR) signalling | ● | Moderate | Reshaped | 26 / 18 | 0.77 | 7.2e-05 | 93% | 82% |
| Cellular transport (vesicle trafficking) | Strong | More active | 39 / 2 | 0.76 | 4.6e-03 | 100% | 36% | |
| Glucose & energy metabolism | Moderate | Reshaped | 17 / 10 | 0.74 | 2.6e-09 | 100% | 71% | |
| Host-defense response | Moderate | Reshaped | 47 / 39 | 0.72 | 8.3e-17 | 100% | 61% | |
| Nerve-cell signalling | Moderate | More active | 36 / 16 | 0.72 | 3.0e-04 | 100% | 18% | |
| Tissue structure (extracellular matrix) | Strong | More active | 110 / 35 | 0.71 | 9.6e-27 | 100% | 100% | |
| Muscle function | Strong | More active | 36 / 10 | 0.71 | 6.2e-04 | 100% | 32% | |
| Amino acid & nucleotide metabolism | Strong | Reshaped | 10 / 20 | 0.68 | 1.9e-05 | 93% | 66% | |
| Fat (lipid) metabolism | Moderate | Less active | 40 / 90 | 0.67 | 1.6e-13 | 100% | 93% | |
| Programmed cell turnover | Moderate | Reshaped | 47 / 45 | 0.66 | 1.9e-03 | 93% | 89% | |
| Membrane transport | Strong | Less active | 11 / 41 | 0.61 | 2.6e-09 | 100% | 66% | |
| Inflammatory signalling | Moderate | Reshaped | 61 / 80 | 0.60 | 1.1e-07 | 100% | 70% |
Benchmark (prelim-2026.10): 22 studies from 14 independent ingredient groups on standard food, run on the current BioSēq™ engine. Related studies (same experiment or same molecule) count once, and the ingredient's own group is left out. The score is the share of the ingredient's changed human genes that fall in the mechanism, which does not depend on how large the overall response is. A common response is significant in at least 85% of the groups and is never shown as leading. Stands out: stronger than at least 80% of the other groups, and still so in at least 90% of 500 resamples of the panel.
Reading the map. Left: the key human genes or gene families from the changed worm genes (▲ up, ▼ down). Middle: the key mechanisms from 4.1. Right: the health domains each mechanism is linked to; L5 develops these.
Draft mapping. Mechanism-to-domain links combine the pipeline's curated health-domain map with a NemaLife mapping drafted for review.
| Mechanism | Draft mapping (for review) | Pipeline health-domain map |
|---|---|---|
| NF-κB inflammatory signalling | Immune Function | — |
| TGF-β/BMP signalling | — | — |
| Detoxification (Phase I/II) | Stress Resilience & Detox, Metabolic Health | Metabolic Health, Stress Resilience & Detox |
| Protein quality control (proteostasis) | Stress Resilience & Detox, Longevity & Cellular Aging | — |
| Gene regulation & epigenetics | Longevity & Cellular Aging | — |
| Nutrient-sensing (insulin/mTOR) signalling | Longevity & Cellular Aging, Metabolic Health | Longevity & Cellular Aging |
Strongest signals in Metabolic health and Immune health.
Pathways that process sugars, fats and energy.
Genes of innate and adaptive immune defense and inflammation.
Genes and pathways linked to how cells and organisms age.
Genes for cell division, DNA repair and tissue renewal.
Genes that help cells adapt to stress and clear unwanted compounds.
Themes describe biology seen in C. elegans; they are not human health claims. L6 carries the formal mechanistic claim language.
How themes are chosen. One theme per health area with a strong signal. The text combines a plain description of the area with the mechanisms from L4 that point to it (for gut health, also the digestive-gene signature and digestive pathways). The full health-area profile follows in 5.2.
Conserved in humans. At least one gene behind the theme has a human counterpart supported by four or more of the six OrthoList 2 prediction programs.
How the signal level is set. Every mechanism with strong or moderate evidence (L4) is linked to health areas (draft mapping, for review). A mechanism counts 1 toward its main area and 0.5 toward a second one. Strong signal: 1.5 or more (for example the area's main mechanism plus one other); Signal: less; Not seen: none. Gut health also counts the digestive-gene signature (1): five or more changed genes whose human counterparts are specific to digestive tissues (Human Protein Atlas: stomach, duodenum, small intestine, colon and rectum), with at least 80% moving the same way. Switched on counts with the benefit, switched off against it. This study: 6 switched on, 10 switched off (no signature). It also counts digestive pathways (0.5): digestive-function pathways significant in the pathway analysis (for example protein digestion and absorption, pancreatic or gastric secretion), with five or more of their genes changed and at least 80% moving the same way. The two lines can share genes. This study: 10 pathways, 42 genes switched on, 22 switched off (no consistent direction). An area whose support moved mostly against the beneficial direction is shown as Not seen (marked opposite direction in this table) and gives no benefit theme. Areas are ordered by their total support, then by the size of their main mechanism (changed genes). Stronger than: the share of the other BioSēq™ panel ingredients with a lower combined mechanism score for the area.
| Health area | Level | Linked evidence | Area score | Stronger than |
|---|---|---|---|---|
| Metabolic health | Strong signal | Glucose & energy metabolism, Amino acid & nucleotide metabolism, Detoxification (Phase I/II), Nutrient-sensing (insulin/mTOR) signalling, Fat (lipid) metabolism | 0.48 | 100% |
| Immune health | Strong signal | NF-κB inflammatory signalling, Host-defense response, Inflammatory signalling | 0.42 | 79% |
| Healthy aging | Strong signal | Gene regulation & epigenetics, Nutrient-sensing (insulin/mTOR) signalling, Protein quality control (proteostasis) | 0.47 | 38% |
| Cell renewal & repair | Strong signal | Cellular transport (vesicle trafficking), Programmed cell turnover | 0.11 | 21% |
| Stress resilience & detox | Strong signal | Detoxification (Phase I/II), Protein quality control (proteostasis) | 0.31 | 93% |
| Skin & tissue | Signal | Tissue structure (extracellular matrix) | 0.23 | 64% |
| Heart & circulation | Signal | Muscle function, Fat (lipid) metabolism | 0.21 | 93% |
| Brain & nerve health | Signal | Nerve-cell signalling | 0.08 | 18% |
| Muscle & performance | Signal | Muscle function | 0.19 | 43% |
| Gut health | Signal | Host-defense response | 0.14 | 18% |
Four mechanistic claims are supported by this study.
* Supported by preclinical pathway evidence (C. elegans, BioSēq™)
How mechanistic claims are chosen. One mechanistic claim per benefit theme in 5.1. Each is anchored to a key mechanism from L4 that sits behind that theme and is not used by another claim, so every claim traces back to the same mechanism, engagement and direction shown in L4. Wording follows direction. “Activates” or “suppresses” is used only when the pathway model and at least 60% of the mechanism’s genes agree (more or less active in L4). All four mechanisms here were reshaped, with parts of the group up and parts down, so the claims use “engages” or “modulates”. Mechanistic claims describe biology, not health outcomes; functional product wording belongs in the private functional claim advisory. TGF-β/BMP signalling was more active but has only emerging engagement and no benefit theme in 5.1, so it carries no claim.
| Mechanistic claim | Benefit theme (L5) | Mechanism (L4) | Engagement | Direction | Genes up / down |
|---|---|---|---|---|---|
| Modulates cellular nutrient-sensing (insulin/mTOR) signalling | Metabolic balance (metabolic health) | Nutrient-sensing (insulin/mTOR) signalling | Moderate | Reshaped | 26 / 18 |
| Modulates gene programs linked to NF-κB inflammatory signalling | Immune & inflammatory balance (immune health) | NF-κB inflammatory signalling | Strong | Reshaped | 4 / 29 |
| Engages cellular protein quality-control (proteostasis) pathways | Cellular maintenance (healthy aging) | Protein quality control (proteostasis) | Strong | Reshaped | 16 / 66 |
| Engages cellular detoxification (Phase I/II) pathways | Cellular stress adaptation (stress resilience & detox) | Detoxification (Phase I/II) | Moderate | Reshaped | 33 / 49 |
Mechanistic claim wording is a draft (claim library v0.1) for regulatory review before any public use.