Withania somnifera · PhytoNexus

01 Identity and provenance

Accepted binomial: Withania somnifera
Common names: Ashwagandha
Family (APG IV): Solanaceae
Part used: Root
Verification tier: Tier 2 · Verified Clinical columns reviewed and a source is on record.
Reviewer note (2026 audit): Reference not supplied - claim unverified against primary literature.

02 Constituent chemistry

Chemical class	Marker compound	Synthetic analogue in use
Withanolides	Withaferin A, Withanolide A Root	Hydrocortisone, Prednisolone

The analogue column is what makes the interaction reasoning tractable: where a constituent has a marketed structural counterpart, the counterpart's interaction profile is the starting hypothesis for the plant.

Looking up structures and physicochemical properties from PubChem…

03 Stated application

Reported activity: Reduce anxiety, antiinflammatory ,
antioxidant
Marketed in: Tablet: himalaya, zandu
Churna: Dabur , Baidyanath
Reported adverse effects: Stomach upset
Nausea and vomiting
Diarrhea

04 Interaction matrix

Source column, verbatim: Sedative , antidiabetic drugs
Normalised onto 2 canonical drug classes below.

Curated from the reviewed source

Drug class	Severity	Mechanism type	Provenance	Expected effect
Antidiabetic drugs (insulin, sulfonylureas, biguanides, GLP-1, SGLT2) Endocrine	3Major	PD-additive	curated B	Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events rep…	why ▾
Chemistry of this pair. Withanolides modulate the hypothalamic-pituitary axis, GABA-A signalling and thyroid hormone output. Class mechanism. Hypoglycaemic botanicals act through insulin secretagogue, insulin-sensitising, alpha-glucosidase-inhibiting or glucose-transport routes. Added to a titrated pharmacological regimen the effects summate rather than plateau. Expected Symptomatic hypoglycaemia, sweating, tremor, confusion; severe events reported with insulin and sulfonylureas. Management Increase self-monitoring frequency for 2 weeks after starting or stopping. Anticipate a downward dose adjustment of insulin or sulfonylurea. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “antidiabetic drugs” Find evidence for this pair Map this mechanism
Sedatives, hypnotics and benzodiazepines CNS	3Major	PD-additive	curated B	Excess sedation, psychomotor and driving impairment, falls, respiratory d…	why ▾
Chemistry of this pair. Withanolides modulate the hypothalamic-pituitary axis, GABA-A signalling and thyroid hormone output. Class mechanism. Valepotriate, kavalactone, apigenin, sesquiterpene and alkaloid constituents act at GABA-A, adenosine and histamine sites, summating with prescribed CNS depression. Some also inhibit CYP3A4 and raise benzodiazepine exposure. Expected Excess sedation, psychomotor and driving impairment, falls, respiratory depression when combined with opioids. Management Warn against driving and machine operation. Avoid triple combinations with opioids. Reduce hypnotic dose in older adults. Onset rapid Evidence B - reviewed clinical column, source pending Matched on “sedative” Find evidence for this pair Map this mechanism

Predicted from constituent chemistry

These edges are not clinical findings. Each one is a rule inference: a constituent class in this plant is known to act on a target that the drug class also acts on. They are shown because a blank cell reads as “safe”, and for a Tier 1 entry a blank cell only means “not yet looked at”. Treat them as a literature-search agenda, not as a warning.

Drug class	Severity	Mechanism type	Provenance	Expected effect
Immunosuppressants (ciclosporin, tacrolimus, mycophenolate) Transplant	4Contraindicated	PK-CYP3A4/P-gp + PD-antagonistic	predicted D	Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hy…	why ▾
Chemistry of this pair. Withanolides modulate the hypothalamic-pituitary axis, GABA-A signalling and thyroid hormone output. Class mechanism. These are narrow-therapeutic-index CYP3A4 and P-glycoprotein substrates. Botanical induction collapses trough levels; inhibition causes toxic accumulation. Immunostimulant botanicals separately oppose the therapeutic goal. Expected Acute graft rejection with inducers; nephrotoxicity, neurotoxicity and hypertension with inhibitors; autoimmune flare with immunostimulants. Management Treat as contraindicated in transplant recipients. Any exposure requires immediate trough level measurement and transplant team notification. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism
Thyroid hormones and antithyroid drugs Endocrine	2Moderate	PK-absorption + PD-modulation	predicted D	Iatrogenic hyper- or hypothyroidism, unexplained TSH drift, loss of euthy…	why ▾
Chemistry of this pair. Withanolides modulate the hypothalamic-pituitary axis, GABA-A signalling and thyroid hormone output. Class mechanism. Guggulsterone stimulates thyroid function and T4-to-T3 conversion; goitrogenic glucosinolates and lithospermic acid suppress it; high-fibre and cation-rich botanicals bind levothyroxine in the gut and reduce absorption. Expected Iatrogenic hyper- or hypothyroidism, unexplained TSH drift, loss of euthyroid control. Management Separate levothyroxine from fibre and mineral products by 4 hours. Recheck TSH 6-8 weeks after any botanical change. Onset unspecified Evidence D - in silico rule prediction only Find evidence for this pair Map this mechanism

05 Hazard register

The audit recorded no hazard beyond the interaction profile. The controlled-vocabulary field reads not assessed, which means the assessment has not been done rather than that it came back clear.

06 Confusable material

These entries could be mistaken for this one in trade, in the herbarium, or in a prescription. Powdered material is often indistinguishable, so the check is macroscopic, microscopic and chromatographic rather than nominal.

Withania coagulans

Paneer dodi

Solanaceae

Same genus (Withania)

07 Mechanism map

Chemistry sorts to the left, pharmacology to the right. Dashed edges are predicted. Drag nodes, scroll to zoom, export at 3× for a figure.

species

chemical class

marker compound

drug class

expected effect

hazard

08 Open literature

Abstract-scoped query built from this binomial, its common names and its marker compounds, run live against Europe PMC, PubMed and OpenAlex, then ranked locally against an evidence hierarchy.

Checking openFDA spontaneous reports…

09 Isomechanistic neighbours

Species whose interaction profile overlaps this one, ranked by shared severity weight rather than by count — a shared contraindication counts for more than a shared minor signal. Practical use: these are the plants you should not stack with this one, because the mechanisms summate.

Species	Family	Shared classes	Jaccard
Withania coagulans Paneer dodi	Solanaceae	4	1.00
Echinacea purpurea Echinacea	Asteraceae	3	0.23
Azadirachta indica Neem	Meliaceae	2	0.40
Tinospora cordifolia Guduchi	Menispermaceae	2	0.33
Picrorhiza kurroa Kutki	Plantaginaceae	2	0.33
Berberis aristata Daruharidra	Berberidaceae	2	0.40

10 References and notes

No citation is on record for this entry. That is itself the finding: the audit flagged it, and it is why the entry does not carry an A evidence grade.

Curator notes

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