Neoandrographolide

Neoandrographolide at a Glance

Neoandrographolide is a labdane diterpenoid glucoside from andrographis (Andrographis paniculata), the intensely bitter “king of bitters” of Ayurvedic and Chinese herbal medicine. It is one of the plant’s three principal diterpenoids, sitting alongside the marker compound andrographolide and 14-deoxy-11,12-didehydroandrographolide. Chemically it stands apart from those two: it carries a sugar (glucose) group, which makes it a glycoside rather than a free diterpene lactone.

Its clearest isolate signals are anti-inflammatory — it suppresses nitric-oxide and prostaglandin output in activated macrophages — and hepatoprotective, where in one classic comparison the glucoside actually outperformed the parent andrographolide. Both of these are real, cited findings for the pure molecule, and both are almost entirely in-vitro and rodent work.

The honest headline is the same one that governs the whole andrographis family: the substantial human evidence is for the standardised whole-herb extract (titrated to andrographolide, often in combination products), not for isolated neoandrographolide. As a large, poorly-absorbed glucoside, its oral bioavailability is low, which further separates its in-vitro potency from what a person swallowing andrographis actually receives.

A Major Andrographis Diterpenoid Glycoside

Andrographis owes most of its reputation to a small family of ent-labdane diterpenoids. Comprehensive phytochemical reviews count more than fifty such diterpenoids in the plant, but three dominate the pharmacology and the commercial standardisation conversation ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}:

• Andrographolide — the marker diterpene lactone, the compound extracts are standardised to and the one carrying most of the mechanistic and clinical attention.
• 14-Deoxy-11,12-didehydroandrographolide — a co-occurring diterpene lactone of the same series.
• Neoandrographolide — this one, and the odd one out structurally.

What makes neoandrographolide distinctive is the glucose. Where andrographolide and its dehydro relative are free diterpene lactones, neoandrographolide is the C-19 glucoside — biosynthetically it is formed when a glucosyltransferase (ApUGT) attaches a glucose to the C-19 hydroxyl of the aglycone andrograpanin ^{7Reference 7Li Y et al. · 2018A glucosyltransferase capable of catalyzing the last step in neoandrographolide biosynthesisView study →}. That sugar changes its behaviour on two fronts that recur throughout: it appears to give the molecule antioxidant strength the free aglycone lacks (relevant to the liver findings below), and it makes the molecule larger and more polar, which works against oral absorption.

Practically, all three diterpenoids are used together as standardisation co-markers — analytical methods routinely quantify neoandrographolide as one of the “major active diterpenoids” of a batch of andrographis ^{10,12Reference 10Pholphana N et al. · 2016Andrographis paniculata: dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteersView study →Reference 12Songvut P et al. · 2023Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participantsView study →}. That is its most established real-world role: a chemical fingerprint of a quality extract, rather than a stand-alone drug.

Anti-Inflammatory & Hepatoprotective Research

Neoandrographolide’s own literature is narrow but coherent: a cluster of anti-inflammatory studies centred on the activated macrophage, and a smaller set of hepatoprotective studies where — unusually — the glucoside beat the more famous andrographolide. Everything here is isolate work in cells or rodents; where a human trial exists, it tested the whole plant.

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 cell/rodent data; there is no human trial of neoandrographolide itself, so read each row as preclinical.

01Anti-inflammatory (macrophage / NO / iNOS)Promising46%Consistent in-vitro macrophage suppression (NO, PGE2, TNF-α) + rodent oedema models ^{1,2,3Reference 1Batkhuu J et al. · 2002In vitroSuppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculataView study →Reference 2Liu J et al. · 2007AnimalInhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophageView study →Reference 3Liu J et al. · 2007In vitroIn vivo and in vitro anti-inflammatory activities of neoandrographolideView study →}

02HepatoprotectiveShaky40%Mouse liver-injury models; matched silymarin, restored GSH — but isolate-only, no human data ^{4Reference 4Kapil A et al. · 1993Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculataView study →}

03Other Preclinical SignalsShaky26%Scattered single studies: cardioprotective, anti-osteoclast, anticancer, FXR/gallstone (a derivative) ^{5,6,8,9,14Reference 5Liu Y et al. · 2021Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activitiesView study →Reference 6Tang K et al. · 2025Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosisView study →Reference 8Zhang J et al. · 2020Structure-based discovery of neoandrographolide as a novel inhibitor of Rab5 to suppress cancer growthView study →Reference 9Sharma R et al. · 2023Dealkenylation of neoandrographolide, a phytochemical from Andrographis paniculata, stimulates FXR (farnesoid X receptor) and enhances gallstone dissolutionView study →Reference 14Sharma V et al. · 2019Carbohydrate modifications of neoandrographolide for improved reactive-oxygen-species-mediated apoptosis through the mitochondrial pathway in colon cancerView study →}

Mechanisms

The macrophage axis (p38 MAPK → iNOS/COX-2/TNF-α) is the consistent thread; the hepatoprotective GSH effect is the one place the molecule’s defining glucoside is explicitly credited for activity ^{4Reference 4Kapil A et al. · 1993Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculataView study →}. The FXR and anticancer entries rest on modified derivatives or single studies and should be read as leads, not established pharmacology.

Pharmacokinetics

The dominant PK fact is poor oral bioavailability, and it follows directly from the chemistry: neoandrographolide is a large, polar glucoside, so gut absorption of the intact molecule is limited. In human studies it is measured only as one of several diterpenoids in a whole-herb extract, never dosed as a pure compound — after oral Andrographis paniculata it appears in plasma at low concentrations with a Tmax around 1–1.5 h, and it is extensively conjugated to glucuronide and sulfate metabolites that reach higher concentrations and persist longer than the parent ^{10,12,13Reference 10Pholphana N et al. · 2016Andrographis paniculata: dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteersView study →Reference 12Songvut P et al. · 2023Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participantsView study →Reference 13Tee KB et al. · 2026Clinical pharmacokinetics and pharmacometabolomics of Andrographis paniculata capsules: bridging drug disposition and metabolic response to precision medicineView study →}. In other words, most circulating “neoandrographolide-derived” material is conjugate, not the active parent. This low, heavily-metabolised systemic exposure is the central caveat over every in-vitro result above: micromolar potency in a macrophage dish does not imply that a person taking andrographis reaches those tissue levels of the free molecule.

Clinical Trials

There are no clinical trials of isolated neoandrographolide. All human evidence sits at the whole-herb level — standardised Andrographis paniculata extracts (titrated to andrographolide, frequently as combination products such as the andrographis–Eleutherococcus product used for upper-respiratory symptoms), within which neoandrographolide is a minor constituent and a standardisation co-marker rather than the tested agent ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}.

Last checked: July 2026.

Isolate vs. Plant Studies

Neoandrographolide is a clean example of the isolate-vs-plant gap. Its own pharmacology is entirely isolate work — purified molecule in murine macrophages and mouse injury models ^{1,2,3,4Reference 1Batkhuu J et al. · 2002In vitroSuppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculataView study →Reference 2Liu J et al. · 2007AnimalInhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophageView study →Reference 3Liu J et al. · 2007In vitroIn vivo and in vitro anti-inflammatory activities of neoandrographolideView study →Reference 4Kapil A et al. · 1993Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculataView study →} — which is a strength for mechanistic clarity (we know what this molecule does to iNOS and GSH) but a weakness for translation. The human evidence, by contrast, is entirely whole-plant: the well-known andrographis trials use standardised extracts titrated to andrographolide, often in fixed combinations, and none isolates the contribution of neoandrographolide ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}. Because the compound is poorly absorbed and heavily conjugated ^{10,12,13Reference 10Pholphana N et al. · 2016Andrographis paniculata: dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteersView study →Reference 12Songvut P et al. · 2023Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participantsView study →Reference 13Tee KB et al. · 2026Clinical pharmacokinetics and pharmacometabolomics of Andrographis paniculata capsules: bridging drug disposition and metabolic response to precision medicineView study →}, the amount of free neoandrographolide a person receives from a standardised extract is small — so its in-vitro potency cannot simply be read across to the herb’s clinical effects. Where it genuinely earns its place in human use today is analytical: as one of the diterpenoid markers that define a quality-controlled andrographis extract.

Prevalence in Nature

Neoandrographolide is essentially an andrographis molecule. It occurs in the aerial parts (stem and leaf) of Andrographis paniculata, where — with andrographolide and 14-deoxy-11,12-didehydroandrographolide — it is one of the three principal diterpenoids of a plant that carries more than fifty ent-labdane diterpenoids in total ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}. Diterpenoid content in andrographis peaks in the leaves and at flowering, which is when medicinal aerial-part material is traditionally harvested; the flavonoids of the plant, by contrast, concentrate in the root, which is largely not the part used ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}.

Beyond A. paniculata itself, neoandrographolide has been reported in the related species Andrographis alata, proposed as an alternative botanical source, with the full-length biosynthetic genes identified by transcriptome analysis ^{15Reference 15Tanuja · 2023Whole transcriptome analysis identifies full-length genes for neoandrographolide biosynthesis from Andrographis alata, an alternate source for antiviral compoundsView study →}. A firm percent-dry-weight figure for neoandrographolide specifically is not well established in the sources reviewed here — it is quantified analytically batch-by-batch rather than reported as a fixed abundance, and closing that number is tracked in this molecule’s gaps note.

Discovery & Synthesis

The andrographis diterpenoid story opens with R.A. Gorter, who in 1911 isolated the crystalline parent lactone andrographolide from the plant and characterised it as a diterpene lactone — the anchor from which the rest of the series, including neoandrographolide, was later distinguished ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}. Neoandrographolide was subsequently identified as the glucoside member of the group: structurally it is the C-19 β-glucoside of the aglycone andrograpanin.

Its biosynthesis was pinned down more recently. In 2018, Li and colleagues characterised ApUGT, a diterpene glucosyltransferase from Andrographis paniculata that catalyses the final step — transferring a glucose onto the C-19 hydroxyl of andrograpanin to form neoandrographolide ^{7Reference 7Li Y et al. · 2018A glucosyltransferase capable of catalyzing the last step in neoandrographolide biosynthesisView study →}; the same broadly-active enzyme could glycosylate a range of substrates, illuminating how the plant decorates its ent-labdane diterpenes with sugars. Manufacture today is by extraction from andrographis aerial parts (it is isolated during the same diterpenoid work-up that yields andrographolide); there is no commercial total synthesis, though medicinal-chemistry groups have prepared carbohydrate-modified semi-synthetic analogues of neoandrographolide to probe and improve its activity ^{14Reference 14Sharma V et al. · 2019Carbohydrate modifications of neoandrographolide for improved reactive-oxygen-species-mediated apoptosis through the mitochondrial pathway in colon cancerView study →}.

Patents: not yet researched.

Toxicity & Safety

Neoandrographolide carries a low flag. No notable toxicity signal has surfaced for the isolated molecule: it was non-cytotoxic to macrophages across the 30–150 µM range used in the anti-inflammatory assays ^{3Reference 3Liu J et al. · 2007In vitroIn vivo and in vitro anti-inflammatory activities of neoandrographolideView study →}, and oral doses of 100–150 mg/kg in mice were tolerated in the efficacy studies above ^{3,4Reference 3Liu J et al. · 2007In vitroIn vivo and in vitro anti-inflammatory activities of neoandrographolideView study →Reference 4Kapil A et al. · 1993Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculataView study →}. Its poor oral absorption further limits systemic exposure to the intact compound. The low badge, though, is as much a reflection of how little dedicated isolate safety data exist as of demonstrated safety — there is no repeat-dose, genotoxicity or human safety package specific to this molecule, so absence of reported harm should not be read as a clean bill of health.

Two scope points matter. First, interactions and organ toxicity have not been formally characterised for isolated neoandrographolide; what safety information exists for “andrographis” belongs to the whole herb, where the cautions cluster around andrographolide and, notably, around injectable andrographolide derivatives (which account for most reported adverse reactions) rather than the oral herb. Second, reproductive and pregnancy questions are handled at the herb level, not here (prose only): andrographis has a traditional reputation for antifertility/abortifacient activity — attributed to the plant and to andrographolide, and studied mostly in animals — so pregnancy and lactation decisions belong on the andrographis herb page, where intake is actually decided, not on this single-molecule page. No dedicated reproductive-toxicity dataset exists for isolated neoandrographolide.

Safety at a Glance

✅ Low / no toxicity

• No specific toxicity signal for the isolate. Non-cytotoxic in the macrophage assays and tolerated at rodent efficacy doses; as a poorly-absorbed glucoside, systemic exposure to the free molecule is low.
• Safety data are thin, not reassuring by evidence. There is no repeat-dose, genotoxicity, interaction or human safety package for isolated neoandrographolide — the low badge partly reflects a data gap.
• Pregnancy/fertility is a whole-herb question. Andrographis carries a traditional antifertility/abortifacient caution (linked to the plant and andrographolide); those decisions belong on the herb page, not this molecule page.

Dosage

There is no established human dose for isolated neoandrographolide, and it is not sold or used as a stand-alone agent. The only figures available are preclinical:

Real human exposure is indirect: neoandrographolide is one of several diterpenoids in standardised Andrographis paniculata extracts, which are titrated to andrographolide (research products commonly deliver ~60 mg andrographolide/day, up to ~360 mg/day short-term), not to neoandrographolide ^{11Reference 11Hossain MS et al. · 2014ReviewAndrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacologyView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Batkhuu J, Hattori K, Takano F, Fushiya S, Oshiman K, Fujimiya Y (2002). Suppression of NO production in activated macrophages in vitro and ex vivo by neoandrographolide isolated from Andrographis paniculata. Biological & Pharmaceutical Bulletin. https://pubmed.ncbi.nlm.nih.gov/12230111/
2. Liu J, Wang ZT, Ji LL, Ge BX (2007). Inhibitory effects of neoandrographolide on nitric oxide and prostaglandin E2 production in LPS-stimulated murine macrophage. Molecular and Cellular Biochemistry. https://pubmed.ncbi.nlm.nih.gov/17109078/
3. Liu J, Wang ZT, Ji LL (2007). In vivo and in vitro anti-inflammatory activities of neoandrographolide. The American Journal of Chinese Medicine. https://pubmed.ncbi.nlm.nih.gov/17436371/
4. Kapil A, Koul IB, Banerjee SK, Gupta BD (1993). Antihepatotoxic effects of major diterpenoid constituents of Andrographis paniculata. Biochemical Pharmacology. https://pubmed.ncbi.nlm.nih.gov/8347130/
5. Liu Y, Liu Y, Zhang HL, et al. (2021). Amelioratory effect of neoandrographolide on myocardial ischemic-reperfusion injury by its anti-inflammatory and anti-apoptotic activities. Environmental Toxicology. https://pubmed.ncbi.nlm.nih.gov/34397165/
6. Tang K, Deng W, Huang Z, et al. (2025). Neoandrographolide inhibits mature osteoclast differentiation to alleviate bone loss and treat osteoporosis. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/40008134/
7. Li Y, Lin HX, Wang J, et al. (2018). A glucosyltransferase capable of catalyzing the last step in neoandrographolide biosynthesis. Organic Letters. https://pubmed.ncbi.nlm.nih.gov/30234309/
8. Zhang J, Sun Y, Zhong LY, et al. (2020). Structure-based discovery of neoandrographolide as a novel inhibitor of Rab5 to suppress cancer growth. Computational and Structural Biotechnology Journal. https://pubmed.ncbi.nlm.nih.gov/33335690/
9. Sharma R, Kumar K, Tanvi K, et al. (2023). Dealkenylation of neoandrographolide, a phytochemical from Andrographis paniculata, stimulates FXR (farnesoid X receptor) and enhances gallstone dissolution. Journal of Biomolecular Structure & Dynamics. https://pubmed.ncbi.nlm.nih.gov/35253613/
10. Pholphana N, Panomvana D, Rangkadilok N, et al. (2016). Andrographis paniculata: dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers. Journal of Ethnopharmacology. https://pubmed.ncbi.nlm.nih.gov/27702690/
11. Hossain MS, Urbi Z, Sule A, Rahman KMH (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/
12. Songvut P, Rangkadilok N, Pholphana N, et al. (2023). Comparative pharmacokinetics and safety evaluation of high dosage regimens of Andrographis paniculata aqueous extract after single and multiple oral administration in healthy participants. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/37663270/
13. Tee KB, Mohamad Haron DE, Jamil IN, et al. (2026). Clinical pharmacokinetics and pharmacometabolomics of Andrographis paniculata capsules: bridging drug disposition and metabolic response to precision medicine. Naunyn-Schmiedeberg’s Archives of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/41039060/
14. Sharma V, Qayum A, Kaul S, et al. (2019). Carbohydrate modifications of neoandrographolide for improved reactive-oxygen-species-mediated apoptosis through the mitochondrial pathway in colon cancer. ACS Omega. https://pubmed.ncbi.nlm.nih.gov/31858026/
15. Tanuja, Parani M (2023). Whole transcriptome analysis identifies full-length genes for neoandrographolide biosynthesis from Andrographis alata, an alternate source for antiviral compounds. Gene. https://pubmed.ncbi.nlm.nih.gov/36270458/
16. Pfisterer PH, Rollinger JM, Schyschka L, et al. (2010). Neoandrographolide from Andrographis paniculata as a potential natural chemosensitizer. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/20446243/

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