Madecassic Acid

Madecassic Acid at a Glance

Madecassic acid is a pentacyclic triterpene acid and one of the four characteristic triterpenes of gotu kola (Centella asiatica), alongside asiatic acid, asiaticoside and madecassoside. Structurally it is the aglycone (the sugar-free core) of madecassoside, and a 6-hydroxy analogue of asiatic acid — the two aglycones differ only by an extra hydroxyl group ^{9Reference 9Sun B et al. · 2020ReviewTherapeutic potential of Centella asiatica and its triterpenes: a reviewView study →}.

Its clearest laboratory signal is anti-inflammatory: in a head-to-head macrophage study it was the more potent of the gotu-kola triterpenes at shutting down NF-κB-driven inflammatory mediators ^{1Reference 1Won JH et al. · 2010Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cellsView study →}. That mechanism reappears in mouse models of colitis, diabetes and cancer. All of this evidence is preclinical — cell and rodent work on the isolate, or the whole standardised extract — with no human trials of madecassic acid itself.

Aglycone vs. Glycoside — And vs. Asiatic Acid

Gotu kola’s triterpenes come in glycoside/aglycone pairs, and keeping them straight is central to reading this molecule:

• Madecassoside is the abundant, water-soluble glycoside (a triterpene carrying sugar chains). It is the most plentiful of the four markers in the herb but is poorly absorbed intact.
• Madecassic acid is its aglycone — the same triterpene core after the sugars are cleaved. In people, the gut hydrolyses the glycoside and it is largely this aglycone that actually reaches the bloodstream ^{8Reference 8Wright KM et al. · 2022RCTPharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trialView study →}.

So madecassic acid is best understood as the circulating active form of dietary madecassoside, in the same way asiatic acid is the circulating form of asiaticoside.

Madecassic acid and asiatic acid are near-twins: both are ursane-type pentacyclic acids, and madecassic acid is simply asiatic acid with one extra hydroxyl group at position 6 (hence its other name, 6β-hydroxyasiatic acid) ^{9Reference 9Sun B et al. · 2020ReviewTherapeutic potential of Centella asiatica and its triterpenes: a reviewView study →}. That difference is why the two are often studied side by side and why claims made for one should not be assumed for the other without direct data.

What It's Used For

The evidence is entirely preclinical and splits between the isolated aglycone (the cell and rodent studies below) and the whole standardised extract that carries gotu kola’s clinical reputation. Read every row as in-vitro or animal data.

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. There is no human isolate data, so every score stays modest by design.

01Anti-Inflammatory & Anti-Colitis (IBD)Promising52%NF-κB suppression in macrophages + two in-vivo DSS colitis mouse models (PPARγ) ^{1,2,3Reference 1Won JH et al. · 2010Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cellsView study →Reference 2Xu X et al. · 2017Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathwayView study →Reference 3Yun X et al. · 2020Inhibition of the activation of γδT17 cells through the PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acidView study →}

02Metabolic / Anti-DiabeticShaky34%One 6-week streptozotocin diabetic-mouse dietary study ^{4Reference 4Hsu YM et al. · 2015Anti-diabetic effects of madecassic acid and rotundic acidView study →}

03Anticancer (Immunomodulatory)Shaky28%One CT26 mouse colon-cancer model + apoptosis in vitro ^{6Reference 6Zhang H et al. · 2014AnimalMadecassic acid inhibits the mouse colon cancer growth by inducing apoptosis and immunomodulationView study →}

04Chondroprotective (Osteoarthritis)Shaky26%IL-1β chondrocytes + one ACLT rat model ^{5Reference 5Fu X et al. · 2022In vitroMadecassic acid ameliorates the progression of osteoarthritis: an in vitro and in vivo studyView study →}

Mechanisms

The unifying thread is NF-κB suppression; the PPARγ activation seen in the colitis work is the most specific molecular target reported for this triterpene.

Pharmacokinetics

Like other triterpene acids, madecassic acid has poor oral bioavailability — the Centella triterpenes are absorbed rapidly but reach less than ~1% systemic availability, and are largely metabolised and excreted via the gut ^{8Reference 8Wright KM et al. · 2022RCTPharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trialView study →}. Its pharmacokinetics are best understood through the glycoside→aglycone conversion: in a Phase 1 human trial of a standardised Centella asiatica product, the parent glycoside madecassoside was essentially undetectable in plasma despite being abundant in the dose, whereas the aglycone madecassic acid was detected in plasma (≈36–68 ng/mL) — consistent with gut hydrolysis of the sugar moiety releasing the absorbable aglycone ^{8Reference 8Wright KM et al. · 2022RCTPharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trialView study →}. In rats the aglycones are barely detectable in plasma, a species difference worth noting when reading rodent efficacy data ^{8Reference 8Wright KM et al. · 2022RCTPharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trialView study →}. No dedicated half-life or absolute-bioavailability figure for the pure isolate is established.

Clinical Trials

There are no clinical trials of isolated madecassic acid. Human evidence for gotu kola comes from standardised whole extracts (TTFCA/TECA, ECa 233), in which madecassic acid is one of several triterpenes and cannot be credited alone.

Last checked: July 2026.

Isolate vs. Plant Studies

The mechanistic studies above (macrophages, DSS colitis, diabetic mice, CT26 tumours, chondrocytes) use the isolated molecule, which is a genuine strength for attributing the NF-κB/PPARγ pharmacology to madecassic acid specifically ^{1,2,3Reference 1Won JH et al. · 2010Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cellsView study →Reference 2Xu X et al. · 2017Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathwayView study →Reference 3Yun X et al. · 2020Inhibition of the activation of γδT17 cells through the PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acidView study →}. But the human evidence is all whole-extract: gotu kola’s clinical record for wound healing, venous insufficiency and cognition rests on standardised triterpene fractions (TTFCA/TECA/ECa 233), where madecassic acid is a minor component beside the more abundant madecassoside and asiaticoside ^{8Reference 8Wright KM et al. · 2022RCTPharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trialView study →}. Because the isolate is never dosed in people and its oral bioavailability is low, the preclinical potency does not transfer cleanly to a predicted human effect.

Prevalence in Nature

Madecassic acid is essentially a gotu kola (Centella asiatica) marker. It occurs as one of the four principal centellosides — the two aglycone acids (asiatic acid and madecassic acid) and their glycosides (asiaticoside and madecassoside) ^{9Reference 9Sun B et al. · 2020ReviewTherapeutic potential of Centella asiatica and its triterpenes: a reviewView study →}. In the raw herb it is a minor constituent, reported at roughly 0.02–0.72% of dry weight across accessions, with one methanolic-extract analysis putting madecassic acid at ~0.54% ^{9Reference 9Sun B et al. · 2020ReviewTherapeutic potential of Centella asiatica and its triterpenes: a reviewView study →}. Content varies enormously with accession, growing conditions, plant part and season, and commercial extracts are standardised far higher (often 40–100% total triterpenes) than the raw plant. It is generally the second-most-abundant of the aglycones, above asiatic acid but well below the glycoside madecassoside.

Discovery & Synthesis

Gotu kola’s triterpene chemistry was worked out through the mid-twentieth century: asiaticoside was characterised in the 1940s (famous for early anti-leprosy interest) and, on hydrolysis, yielded the aglycone asiatic acid. Madecassic acid and its glycoside madecassoside were isolated somewhat later, by French researchers in the early-to-mid 1960s (Rahandraha and co-workers; Pinhas) ^{9Reference 9Sun B et al. · 2020ReviewTherapeutic potential of Centella asiatica and its triterpenes: a reviewView study →}. The name reflects madecassoside (from Madecassol, the Centella extract product), and the molecule is also called 6β-hydroxyasiatic acid — a direct nod to its structural relationship to asiatic acid — and brahmic acid in the older literature.

Manufacture today is by extraction from Centella asiatica (often via hydrolysis of the more abundant glycoside madecassoside to the aglycone) rather than by total synthesis; no efficient commercial de-novo synthesis dominates, and medicinal-chemistry work centres on semi-synthetic derivatives of the natural acid rather than the parent itself.

Patents: not yet researched.

Toxicity & Safety

Madecassic acid carries a low flag. It is a natural constituent of gotu kola, a plant with a long record of food and medicinal use; it circulates at low levels even after extract dosing (poor bioavailability), and no isolate-specific toxicity signal has emerged from the preclinical literature. The practical cautions belong to the whole herb, not the isolated triterpene.

Safety at a Glance

✅ Low / no toxicity

• Constituent of a long-used edible/medicinal herb. Present at low levels in gotu kola and its standardised extracts, which have an established tolerability record.
• Low systemic exposure. Poor oral bioavailability keeps circulating levels of the isolate low.
• Whole-herb cautions apply, not isolate-specific ones. Topical Centella preparations can occasionally cause contact dermatitis, and rare hepatotoxicity has been reported with oral gotu-kola products — these are herb-level, not madecassic-acid-specific.
• No dedicated isolate safety dataset. No formal genotoxicity, repeat-dose or reproductive-toxicity package exists for the pure compound; interactions have not been systematically assessed.

Reproductive note (prose only). No dedicated reproductive- or developmental-toxicity dataset exists for isolated madecassic acid. Pregnancy and lactation decisions belong to the gotu-kola herb page and any specific product, where intake is actually decided, not to this molecule page.

Dosage

There is no established human dose for isolated madecassic acid — it has never been dosed as a stand-alone in people. The figures in the literature are research concentrations: micromolar in cell assays, and 0.05–0.1% of the diet in the six-week mouse studies ^{4Reference 4Hsu YM et al. · 2015Anti-diabetic effects of madecassic acid and rotundic acidView study →}. Real-world exposure is indirect, as one of several triterpenes in standardised gotu-kola extracts (TTFCA/TECA/ECa 233), which are dosed as the whole fraction rather than by madecassic-acid content. These are research figures, not a personal recommendation.

References

1. Won JH, Shin JS, Park HJ, Jung HJ, Koh DJ, Jo BG, Lee JY, Yun K, Lee KT (2010). Anti-inflammatory effects of madecassic acid via the suppression of NF-κB pathway in LPS-induced RAW 264.7 macrophage cells. Planta Medica. https://pubmed.ncbi.nlm.nih.gov/19774506/
2. Xu X, Wang Y, Wei Z, Wei W, Zhao P, Tong B, Xia Y, Dai Y (2017). Madecassic acid, the contributor to the anti-colitis effect of madecassoside, enhances the shift of Th17 toward Treg cells via the PPARγ/AMPK/ACC1 pathway. Cell Death & Disease. https://pubmed.ncbi.nlm.nih.gov/28358365/
3. Yun X, Fang Y, Lv C, Qiao S, Tao Y, Dai Y, Xia Y (2020). Inhibition of the activation of γδT17 cells through the PPARγ–PTEN/Akt/GSK3β/NFAT pathway contributes to the anti-colitis effect of madecassic acid. Cell Death & Disease. https://pubmed.ncbi.nlm.nih.gov/32929062/
4. Hsu YM, Hung YC, Hu L, Lee YJ, Yin MC (2015). Anti-diabetic effects of madecassic acid and rotundic acid. Nutrients. https://pubmed.ncbi.nlm.nih.gov/26633490/
5. Fu X, He S, Wang L, Xue Y, Qiao S, An J, Xia T (2022). Madecassic acid ameliorates the progression of osteoarthritis: an in vitro and in vivo study. Drug Design, Development and Therapy. https://pubmed.ncbi.nlm.nih.gov/36345305/
6. Zhang H, Zhang M, Tao Y, Wang G, Xia B (2014). Madecassic acid inhibits the mouse colon cancer growth by inducing apoptosis and immunomodulation. Journal of BUON. https://pubmed.ncbi.nlm.nih.gov/24965394/
7. Yang B, Xu Y, Hu Y, Luo Y, Lu X, Tsui CK, Lu L, Liang X (2016). Madecassic acid protects against hypoxia-induced oxidative stress in retinal microvascular endothelial cells via ROS-mediated endoplasmic reticulum stress. Biomedicine & Pharmacotherapy. https://pubmed.ncbi.nlm.nih.gov/27728894/
8. Wright KM, Bollen M, David J, Speers AB, Brandes MS, Gray NE, Alcázar Magaña A, McClure C, Stevens JF, Maier CS, Quinn JF, Soumyanath A (2022). Pharmacokinetics and pharmacodynamics of key components of a standardized Centella asiatica product in cognitively impaired older adults: a Phase 1, double-blind, randomized clinical trial. Antioxidants (Basel). https://pubmed.ncbi.nlm.nih.gov/35204098/
9. Sun B, Wu L, Wu Y, Zhang C, Qin L, Hayashi M, Kudo M, Gao M, Liu T (2020). Therapeutic potential of Centella asiatica and its triterpenes: a review. Frontiers in Pharmacology. https://doi.org/10.3389/fphar.2020.568032

View all 9 references▾