Isoandrographolide

Isoandrographolide at a Glance

Isoandrographolide is a minor ent-labdane diterpenoid of andrographis (Andrographis paniculata), the “king of bitters” whose activity is usually attributed to its marker compound andrographolide. Structurally, isoandrographolide is a cyclized relative of andrographolide — the same diterpene skeleton with an additional ether ring — and it sits alongside neoandrographolide, 14-deoxyandrographolide and dozens of other labdanes in the plant’s diterpenoid fraction ^{1,3Reference 1Pramanick S et al. · 2006Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysisView study →Reference 3Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}.

It is not a headline constituent, and its evidence base is correspondingly thin. What exists is a small cluster of preclinical mouse studies showing an anti-fibrotic, anti-inflammatory effect in the kidney and lung, with lower cellular toxicity than andrographolide itself in the comparisons that were run ^{4,5Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}. There is no human data, no characterized pharmacokinetics for the isolated molecule, and no established use. This page reports what the isolate work shows and marks where it stops.

A Minor Andrographis Diterpenoid

Andrographis produces a large family of ent-labdane diterpenoid lactones — one phytochemical review of the plant catalogues more than fifty ^{3Reference 3Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}. Andrographolide dominates that family both by abundance (roughly 0.3–5% of the dry aerial parts, richest in the leaf) and by research attention; it is the compound extracts are standardised to. Isoandrographolide is one of the minor members of the same series.

Chemically it is best understood as a transformation product of andrographolide: the two share the labdane carbon skeleton, but in isoandrographolide the side chain has cyclized to form an additional oxygen-containing (ether/tetrahydrofuran) ring. It was long known from the laboratory rearrangement of andrographolide before being isolated from the plant, and its structure and stereochemistry — the (8R,12S) configuration — were settled by X-ray crystallography in 2006, in the same report that described the new diterpenoid andropanolide ^{1Reference 1Pramanick S et al. · 2006Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysisView study →}. It should not be confused with andrographolide (the parent) or neoandrographolide (a glucoside of a related deoxy-diterpenoid) — these are distinct molecules with their own, larger evidence bases.

The genuine isolate signal for isoandrographolide is narrow but real: in two independent mouse studies it behaved as an anti-fibrotic, anti-inflammatory agent, suppressing the NLRP3 inflammasome in silica-induced lung disease and the AKT/GSK-3β/β-catenin axis in obstruction-induced kidney disease ^{4,5Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}. Both are isolated-molecule, animal-model results. Beyond this, isoandrographolide-specific pharmacology is essentially uncharacterised — the broader “anti-inflammatory / anticancer” reputation of the andrographis diterpenoids belongs to andrographolide, and should not be transferred to this minor isomer without its own evidence.

What It's Used For

The isoandrographolide literature is small enough to summarise directly: two preclinical fibrosis studies, both using the purified molecule in mice, from groups working on andrographis diterpenoids ^{4,5Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}. No human trials exist.

Evidence by IndicationStrength of support · Beta

Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here rests on isolated-molecule mouse studies only, so the ceiling is low.

01Anti-fibrotic — lung (silicosis)Shaky20%One mouse study; NLRP3 inflammasome inhibition ^{4Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →}

02Anti-fibrotic — kidneyShaky18%One mouse study; AKT/GSK-3β/β-catenin suppression ^{5Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}

Mechanisms

Both mechanistic stories come from the same two anti-fibrosis papers; they are consistent (an anti-inflammatory, anti-EMT profile) but rest on a very small body of isolated-molecule animal work.

Pharmacokinetics

No pharmacokinetic data exist for isoandrographolide specifically — its oral absorption, bioavailability, metabolism and half-life have not been characterised. The only relevant context is class-level: the parent compound andrographolide has poor/low oral bioavailability, a recurring limitation that tempers translation of its preclinical potency ^{2Reference 2Zeng B et al. · 2022Clinical trialAndrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researchesView study →}. Whether isoandrographolide’s extra ether ring changes that is unknown. This gap matters — the mouse anti-fibrosis effects ^{4,5Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →} have not been shown to survive oral dosing of the isolate in a way that would reach human fibrotic tissue.

Clinical Trials

There are no clinical trials of isoandrographolide — completed, ongoing or planned. All evidence is preclinical.

Last checked: July 2026.

Major Natural Sources

Isoandrographolide is, on current evidence, an andrographis-specific minor diterpenoid. It has not been reported at meaningful levels elsewhere, and its concentration in the plant has not been quantified.

Source (botanical)	Part	Level	Notes
Andrographis (Andrographis paniculata)	Aerial parts	Minor (not quantified)	A trace member of the diterpenoid fraction, far below andrographolide 1,3Reference 1Pramanick S et al. · 2006Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysisView study →Reference 3Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →

Discovery & Synthesis

Isoandrographolide was known from chemistry before botany: it was first described as a cyclization/rearrangement product of andrographolide obtained under acid/base treatment in the laboratory. Its definitive structure and (8R,12S) stereochemistry were established by X-ray crystallographic analysis in 2006 by Pramanick and colleagues, who isolated it from Andrographis paniculata leaves alongside the then-new diterpenoid andropanolide ^{1Reference 1Pramanick S et al. · 2006Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysisView study →}. It is thus best understood as a naturally occurring cyclized isomer of the plant’s marker diterpenoid rather than a separately biosynthesised headline compound.

There is no notable commercial production: isoandrographolide is prepared for research either by isolation from andrographis or by transformation of the far more abundant andrographolide, and it is sold only as a reference/research chemical.

Patents: not yet researched.

Toxicity & Safety

Isoandrographolide carries a low flag, but this reflects absence of characterised hazard rather than a clean safety dossier — the toxicology of the isolated molecule has not been studied in its own right. The one relevant datapoint is comparative: in the renal-fibrosis work, isoandrographolide showed lower cellular toxicity than andrographolide at active concentrations ^{5Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}. That is reassuring in direction but is a single in-vitro/animal comparison, not a safety clearance.

Safety at a Glance

✅ Low / no toxicity

• No specific toxicity signal reported, and lower cellular toxicity than andrographolide in the one paired comparison run ^{5Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}.
• Human safety is unknown. There is no clinical, repeat-dose or reproductive-toxicity data for isoandrographolide; “low” here means uncharacterised, not proven safe.
• Do not infer safety (or activity) from andrographis or andrographolide. This is a distinct minor isomer with its own, near-absent evidence base; any use would be experimental.

Reproductive note (prose only). No reproductive or developmental-toxicity data exist for isolated isoandrographolide. Whether the andrographolide-class cautions apply to this isomer is unknown, and any pregnancy/lactation decision belongs to the herb or product page where intake is actually decided — not to this molecule page.

Dosage

There is no human dose for isoandrographolide. It is not used clinically and has no established intake. The only figures on record are experimental doses in mice from the two anti-fibrosis studies ^{4,5Reference 4Song Z et al. · 2022AnimalIsoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in miceView study →Reference 5Guan Z et al. · 2022AnimalIsoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathwayView study →}, which do not translate to a human amount and are not reproduced here as if they were guidance. Human exposure, if any, is indirect and negligible — as a trace constituent of whole andrographis preparations that are themselves standardised to andrographolide, not to this minor isomer.

These are research observations, not a personal recommendation.

References

1. Pramanick S, Banerjee S, Achari B, et al. (2006). Andropanolide and isoandrographolide, minor diterpenoids from Andrographis paniculata: structure and X-ray crystallographic analysis. Journal of Natural Products. https://pubmed.ncbi.nlm.nih.gov/16562845/
2. Zeng B, Wei A, Zhou Q, et al. (2022). Andrographolide: a review of its pharmacology, pharmacokinetics, toxicity and clinical trials and pharmaceutical researches. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/34818697/
3. Hossain MS, Urbi Z, Sule A, Rahman KM (2014). Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacology. The Scientific World Journal. https://pubmed.ncbi.nlm.nih.gov/25950015/
4. Song Z, Wang L, Cao Y, et al. (2022). Isoandrographolide inhibits NLRP3 inflammasome activation and attenuates silicosis in mice. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/35063750/
5. Guan Z, Wang Y, Xu H, et al. (2022). Isoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3β/β-cat signaling pathway. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/36067652/