TrueBioactives™ASHWAGANDHA ROOT · TB-2026-10-001
L1 · Identity

Ingredient identity.

Certificate of Analysis and supplier documents reviewed: the ingredient meets its specifications.

1.1

Is the ingredient documented?

Ingredient

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
Identity & standardisationMeets specification
Botanical or chemical identity test and the assay for the standardised marker compound.
Purity & contaminantsMeets specification
Heavy metals, microbial limits, residual solvents and pesticides.
Source documentationConfirmed
Supplier, origin, batch and date of manufacture.
Details & method

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).

L2 · Toxicity · ToxRadar™

Safety screening.

No acute toxicity observed at the dose tested.

2.1

Is there acute toxicity at the dose tested?

Acute toxicity

Not observed

Survival during the 48-hour BioSēq™ exposure at the dose tested.

Readout: Survival
Details & method

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.

L3 · Bioactivity · BioSēq™

In vivo bioactivity.

443 worm genes responded, in both directions, at the tested dose.

3.1

Did the ingredient produce a meaningful biological response?

C. elegansworm genes changed
443
▲ 239switched on▼ 204switched off
Very strongtranslat­ability
Humancounterpart genes
623
▲ 288switched on▼ 307switched off
+28 matched both ways
Details & method
CriterionRequirementResult
Breadth of responseAt least 100 genes change (adjusted p < 0.05, more than 1.4-fold); 250 or more is a broad response443 genes changed (broad response)✓ Met
Bidirectional modulationGenes move both up and down (each direction at least 10%)239 up, 204 down✓ Met
Coherent pathway responseAt least one pathway group with strong or moderate evidence17 pathway groups✓ Met
Changed gene
Adjusted p below 0.05 and a change of more than 1.4-fold versus vehicle (DESeq2); 11,865 genes measured. This includes 1 gene switched on or off from near zero (1 on, 0 off; more than 1,000-fold). They are counted here and shown in the gene lists, but the pathway analysis (L4) leaves them out because their exact fold change cannot be estimated.
Human counterpart
Human gene predicted from the same ancestral gene (OrthoList 2). 28 human genes are matched from both a switched-on and a switched-off worm gene.
Translatability
A qualitative read of how fully the changed worm genes map onto human biology, based on the human counterparts predicted by OrthoList 2.
3.2

Which genes moved, and how strongly?

020406080100120-5-4-3-2-1012345678hsp-70lec-2hsp-16.2hsp-16.41dhs-26fmo-2cpr-2← switched off · change (log scale) · switched on →confidence ↑
Details & method

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.

3.3

Which key genes changed, and what are their human counterparts?

▲ Switched on

  1. hsp-70HSPA familyVery strong
  2. hsp-16.41HSPB family +2Very strong
  3. hsp-16.2HSPB family +2Very strong
  4. dhs-26DHRS1Very strong
  5. col-80SFTPDVery strong
  6. gpdh-1GPD familyVery strong
  7. col-93SFTPDVery strong
  8. Y39B6A.1HRNRVery strong
  9. pgph-3PGP +1Very strong
  10. hmit-1.1SLC familyVery strong

▼ Switched off

  1. fmo-2FMO familyVery strong
  2. cpr-2CTSB +1Very strong
  3. lec-2LGALS family +3Very strong
  4. tbx-43TBX21 +3Strong
  5. tbx-38TBX21 +3Strong
  6. ech-7ECHS1Strong
  7. nnt-1NNTStrong
  8. skr-5SKP1Strong
  9. tbx-37TBX21 +3Strong
  10. dhp-1DPYSL family +2Strong

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)

Details & method

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 geneHumanDirectionBandFold changelog2FCAdjusted p
hsp-70HSPA familyupVery strong52.3-fold+5.711.6e-62
hsp-16.41HSPB family +2upVery strong49.9-fold+5.641.2e-20
hsp-16.2HSPB family +2upVery strong31.1-fold+4.964.7e-33
dhs-26DHRS1upVery strong16.1-fold+4.011.3e-17
col-80SFTPDupVery strong12.6-fold+3.662.4e-69
gpdh-1GPD familyupVery strong12.4-fold+3.631.2e-08
col-93SFTPDupVery strong9.6-fold+3.263.9e-07
Y39B6A.1HRNRupVery strong8.0-fold+3.008.4e-08
pgph-3PGP +1upVery strong5.9-fold+2.561.5e-10
hmit-1.1SLC familyupVery strong5.8-fold+2.541.3e-08
fmo-2FMO familydownVery strong6.3-fold-2.652.8e-05
cpr-2CTSB +1downVery strong5.9-fold-2.571.4e-03
lec-2LGALS family +3downVery strong4.3-fold-2.101.7e-37
tbx-43TBX21 +3downStrong3.6-fold-1.843.8e-04
tbx-38TBX21 +3downStrong3.4-fold-1.781.4e-03
ech-7ECHS1downStrong3.3-fold-1.711.2e-17
nnt-1NNTdownStrong3.2-fold-1.679.3e-20
skr-5SKP1downStrong3.1-fold-1.643.2e-03
tbx-37TBX21 +3downStrong2.9-fold-1.521.9e-02
dhp-1DPYSL family +2downStrong2.8-fold-1.511.1e-07
L4 · Pathways · BioSēq™

What moved, and which way.

A biological signature led by NF-κB inflammatory signalling and TGF-β/BMP signalling.

4.1

What is this ingredient's biological signature?

Leading mechanism
Stands out

NF-κB inflammatory signalling

A master switch for inflammatory gene programs.

Immune health
Leading mechanism
Stands out

TGF-β/BMP signalling

Signals that regulate tissue growth, repair and remodelling.

Supporting
Stands out

Detoxification (Phase I/II)

Enzymes that chemically modify and clear foreign compounds.

Stress resilience & detoxMetabolic health
Supporting

Protein quality control (proteostasis)

Chaperones and clearance systems that keep proteins correctly folded.

Stress resilience & detoxHealthy aging
Supporting

Gene regulation & epigenetics

Factors that switch genes on and off and mark DNA for long-term control.

Healthy aging
Supporting

Nutrient-sensing (insulin/mTOR) signalling

Signals that tell cells how much food and energy is available.

Healthy agingMetabolic health

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.

Details & method

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.

MechanismIn 4.1EngagementDirectionGenes up / downPriority scoreAdjusted pSeen in panelStronger than
NF-κB inflammatory signalling●StrongReshaped4 / 290.753.3e-1070%100%
TGF-β/BMP signalling●EmergingMore active32 / 150.694.5e-0384%100%
Detoxification (Phase I/II)●ModerateReshaped33 / 490.891.8e-36100%93%
Protein quality control (proteostasis)●StrongReshaped16 / 660.835.5e-22100%86%
Gene regulation & epigenetics●StrongReshaped8 / 400.773.3e-10100%16%
Nutrient-sensing (insulin/mTOR) signalling●ModerateReshaped26 / 180.777.2e-0593%82%
Cellular transport (vesicle trafficking)StrongMore active39 / 20.764.6e-03100%36%
Glucose & energy metabolismModerateReshaped17 / 100.742.6e-09100%71%
Host-defense responseModerateReshaped47 / 390.728.3e-17100%61%
Nerve-cell signallingModerateMore active36 / 160.723.0e-04100%18%
Tissue structure (extracellular matrix)StrongMore active110 / 350.719.6e-27100%100%
Muscle functionStrongMore active36 / 100.716.2e-04100%32%
Amino acid & nucleotide metabolismStrongReshaped10 / 200.681.9e-0593%66%
Fat (lipid) metabolismModerateLess active40 / 900.671.6e-13100%93%
Programmed cell turnoverModerateReshaped47 / 450.661.9e-0393%89%
Membrane transportStrongLess active11 / 410.612.6e-09100%66%
Inflammatory signallingModerateReshaped61 / 800.601.1e-07100%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.

4.2

How do the gene changes connect to health domains?

KEY GENES (L3)MECHANISMS (L4)HEALTH DOMAINS (L5)▲ HSPA family▲ HSPB family▼ LGALS family▲ CRYAA▲ CRYAB▲ DHRS1▲ ACP2▼ FMO family▼ SKP1▲ FOXA3NF-κB inflammatory signallingTGF-β/BMP signallingDetoxification (Phase I/II)Protein quality control (proteostasis)Gene regulation & epigeneticsNutrient-sensing (insulin/mTOR) signallingHealthy agingStress resilience & detoxMetabolic healthImmune health
Details & method

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.

MechanismDraft mapping (for review)Pipeline health-domain map
NF-κB inflammatory signallingImmune Function—
TGF-β/BMP signalling——
Detoxification (Phase I/II)Stress Resilience & Detox, Metabolic HealthMetabolic Health, Stress Resilience & Detox
Protein quality control (proteostasis)Stress Resilience & Detox, Longevity & Cellular Aging—
Gene regulation & epigeneticsLongevity & Cellular Aging—
Nutrient-sensing (insulin/mTOR) signallingLongevity & Cellular Aging, Metabolic HealthLongevity & Cellular Aging
L5 · Benefit signals

From pathways to benefit themes.

Strongest signals in Metabolic health and Immune health.

5.1

What does the biology suggest?

Metabolic health
✓ Conserved in humans

Metabolic balance

Pathways that process sugars, fats and energy.

Built onGlucose & energy metabolism · Amino acid & nucleotide metabolism · Detoxification (Phase I/II) · Nutrient-sensing (insulin/mTOR) signalling · Fat (lipid) metabolism
Immune health
✓ Conserved in humans

Immune & inflammatory balance

Genes of innate and adaptive immune defense and inflammation.

Built onNF-κB inflammatory signalling · Host-defense response · Inflammatory signalling
Healthy aging
✓ Conserved in humans

Cellular maintenance

Genes and pathways linked to how cells and organisms age.

Built onGene regulation & epigenetics · Nutrient-sensing (insulin/mTOR) signalling · Protein quality control (proteostasis)
Cell renewal & repair
✓ Conserved in humans

Cell renewal

Genes for cell division, DNA repair and tissue renewal.

Built onCellular transport (vesicle trafficking) · Programmed cell turnover
Stress resilience & detox
✓ Conserved in humans

Cellular stress adaptation

Genes that help cells adapt to stress and clear unwanted compounds.

Built onDetoxification (Phase I/II) · Protein quality control (proteostasis)

Themes describe biology seen in C. elegans; they are not human health claims. L6 carries the formal mechanistic claim language.

Details & method

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.

5.2

Which health areas does the biology point to?

Metabolic health
Strong signal
Glucose & energy metabolismAmino acid & nucleotide metabolism+3
Immune health
Strong signal
NF-κB inflammatory signallingHost-defense response+1
Healthy aging
Strong signal
Gene regulation & epigeneticsNutrient-sensing signalling+1
Cell renewal & repair
Strong signal
Cellular transportProgrammed cell turnover
Stress resilience & detox
Strong signal
DetoxificationProtein quality control
Skin & tissue
Signal
Tissue structure
Heart & circulation
Signal
Muscle functionFat metabolism
Brain & nerve health
Signal
Nerve-cell signalling
Muscle & performance
Signal
Muscle function
Gut health
Signal
Host-defense response
Details & method

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 areaLevelLinked evidenceArea scoreStronger than
Metabolic healthStrong signalGlucose & energy metabolism, Amino acid & nucleotide metabolism, Detoxification (Phase I/II), Nutrient-sensing (insulin/mTOR) signalling, Fat (lipid) metabolism0.48100%
Immune healthStrong signalNF-κB inflammatory signalling, Host-defense response, Inflammatory signalling0.4279%
Healthy agingStrong signalGene regulation & epigenetics, Nutrient-sensing (insulin/mTOR) signalling, Protein quality control (proteostasis)0.4738%
Cell renewal & repairStrong signalCellular transport (vesicle trafficking), Programmed cell turnover0.1121%
Stress resilience & detoxStrong signalDetoxification (Phase I/II), Protein quality control (proteostasis)0.3193%
Skin & tissueSignalTissue structure (extracellular matrix)0.2364%
Heart & circulationSignalMuscle function, Fat (lipid) metabolism0.2193%
Brain & nerve healthSignalNerve-cell signalling0.0818%
Muscle & performanceSignalMuscle function0.1943%
Gut healthSignalHost-defense response0.1418%
L6 · Mechanistic claims · BioSēq™

From biology to mechanistic claims.

Four mechanistic claims are supported by this study.

6.1

Which mechanistic claims does the evidence support?

Metabolic health

Modulates cellular nutrient-sensing (insulin/mTOR) signalling*

Based onNutrient-sensing (insulin/mTOR) signalling · L4, moderate, reshaped
Immune health

Modulates gene programs linked to NF-κB inflammatory signalling*

Based onNF-κB inflammatory signalling · L4, strong, reshaped
Healthy aging

Engages cellular protein quality-control (proteostasis) pathways*

Based onProtein quality control (proteostasis) · L4, strong, reshaped
Stress resilience & detox

Engages cellular detoxification (Phase I/II) pathways*

Based onDetoxification (Phase I/II) · L4, moderate, reshaped

* Supported by preclinical pathway evidence (C. elegans, BioSēq™)

Details & method

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 claimBenefit theme (L5)Mechanism (L4)EngagementDirectionGenes up / down
Modulates cellular nutrient-sensing (insulin/mTOR) signallingMetabolic balance (metabolic health)Nutrient-sensing (insulin/mTOR) signallingModerateReshaped26 / 18
Modulates gene programs linked to NF-κB inflammatory signallingImmune & inflammatory balance (immune health)NF-κB inflammatory signallingStrongReshaped4 / 29
Engages cellular protein quality-control (proteostasis) pathwaysCellular maintenance (healthy aging)Protein quality control (proteostasis)StrongReshaped16 / 66
Engages cellular detoxification (Phase I/II) pathwaysCellular stress adaptation (stress resilience & detox)Detoxification (Phase I/II)ModerateReshaped33 / 49

Mechanistic claim wording is a draft (claim library v0.1) for regulatory review before any public use.