Asperulosidic Acid

Asperulosidic Acid at a Glance

Asperulosidic acid is a bitter iridoid glycoside — a monoterpene glucoside carrying a free carboxylic acid — and one of the marker iridoids of the madder family (Rubiaceae). It recurs in cleavers (Galium aparine) aerial parts, in the Chinese medicinal herb Hedyotis diffusa (the source of most of its pharmacology), and in the fruit of noni (Morinda citrifolia).

Chemically it sits in the middle of a small, easily-confused family: asperuloside is its lactone/ester form, and deacetylasperulosidic acid is the same molecule minus an acetyl group. The three differ only by acetylation and by whether the acid is free or esterified, and they are routinely reported together as the bitter, cooling principles of Rubiaceae herbs.

Its evidence is entirely preclinical but internally consistent: a coherent anti-inflammatory and anti-fibrotic signal built on suppression of the NF-κB and MAPK pathways, seen across isolate cell and rodent models ^{7Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →}. There are no human trials of the isolate, much of the supporting data comes from a single research lineage working with Hedyotis diffusa, and — importantly — the pharmacokinetics that are actually measured belong mostly to its congeners rather than to asperulosidic acid itself.

Asperulosidic Acid Among the Rubiaceae Iridoids

The single most useful framing for this molecule is its place in a tight family of Rubiaceae iridoids that are constantly reported side by side and are trivial to mix up:

Compound	How it differs	Typical framing
Asperuloside	The lactone / esterified form — the acid ring is closed	The classic Rubiaceae marker; named from sweet woodruff (Asperula odorata)
Asperulosidic acid	The free carboxylic-acid congener (this molecule)	A bitter iridoid of cleavers, Hedyotis and noni
Deacetylasperulosidic acid (DAA)	Asperulosidic acid minus the C10 acetyl group	The usual quantified quality-control marker of noni products 10Reference 10Bittová M et al. · 2015Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) productsView study →
10-Desacetylasperulosidic acid	Deacetylated at position 10	Co-reported bitter iridoid of Galium

Because these congeners interconvert conceptually by a single acetylation or esterification step, the literature often treats them as a set — and quantitative work (content figures, pharmacokinetics) tends to land on asperuloside or DAA rather than on asperulosidic acid specifically. That is a recurring honesty point here: where a number is quoted for a relative rather than for the acid, it is flagged.

Two genuine isolate signals stand out. First, asperulosidic acid is one of the bitter iridoids of cleavers (with monotropein and 10-desacetylasperulosidic acid) credited with the aerial-part extract’s immunostimulant (lymphocyte blast-transformation) activity — though that was whole-extract work, not an isolate assay ^{1Reference 1Ilina T et al. · 2019In vitroPhytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine LView study →}. Second, and more solidly, when asperuloside and asperulosidic acid were tested head-to-head as isolates in inflamed macrophages, both suppressed inflammatory mediators, giving the molecule a defined anti-inflammatory mechanism of its own ^{7Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →}.

What It's Used For

Asperulosidic acid’s dossier is preclinical but coherent: one anti-inflammatory core (NF-κB/MAPK suppression) that surfaces as organ protection in kidney, placenta, eye and tumour models. The load-bearing caveats are the compound-page disciplines — no human data, much of the work from one Hedyotis diffusa research lineage, and isolate pharmacokinetics that are essentially uncharacterised for the acid itself.

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. No human isolate data exists, so scores stay modest by design.

01Anti-Inflammatory (NF-κB / MAPK)Shaky42%Head-to-head isolate macrophage study + rodent uveitis ^{5,7Reference 5Du Y et al. · 2024Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitisView study →Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →}

02Anti-Fibrotic / RenoprotectiveShaky34%Two UUO rodent models (TGF-β/Smad; indoxyl-sulfate/OAT) ^{2,3Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →Reference 3Wang J et al. · 2023AnimalAsperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice modelView study →}

03Metabolic (Gestational Diabetes)Shaky26%One GDM mouse model, placental oxidative stress ^{4Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →}

04Antitumour (Hepatocellular)Shaky22%One cell + xenograft study (MEKK1/NF-κB) ^{6Reference 6Li L · 2024Asperulosidic acid restrains hepatocellular carcinoma development and enhances chemosensitivity through inactivating the MEKK1/NF-κB pathwayView study →}

Mechanisms

The load-bearing, repeated node is NF-κB (with MAPK and PI3K/Akt feeding into it); the organ-specific labels — kidney, placenta, eye, liver tumour — are largely single- or double-study extensions of that same anti-inflammatory core.

Pharmacokinetics

This is the honest hole in the file. No dedicated pharmacokinetic study of asperulosidic acid as an isolate was located — its oral bioavailability, half-life and metabolism are essentially uncharacterised. What exists is measured on its congeners: pharmacokinetic and tissue-distribution work after Morinda officinalis extract dosing quantifies monotropein and deacetylasperulosidic acid (the deacetyl relative), not the acetylated acid ^{9Reference 9Shen Y et al. · 2018AnimalPharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in ratsView study →}. Reasoning from the class, asperulosidic acid is a polar iridoid glucoside and would be expected to share the family’s poor oral absorption — which is why several efficacy studies dose it intraperitoneally ^{2Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →} and why in-vitro/high-dose potency likely overreads what an oral intake delivers. Any bioavailability, active-metabolite or half-life figure quoted for “the iridoid” in Rubiaceae PK papers should be checked to confirm it refers to this molecule and not to asperuloside or DAA.

Clinical Trials

There are no clinical trials of isolated asperulosidic acid, and none in progress that were located. Human exposure is incidental, through whole Rubiaceae herbs and noni products in which the acid is one bitter iridoid among several ^{1,10Reference 1Ilina T et al. · 2019In vitroPhytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine LView study →Reference 10Bittová M et al. · 2015Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) productsView study →}. The entire evidence base below is preclinical.

Last checked: July 2026.

Isolate vs. Plant Studies

The split is unusually clean. The anti-inflammatory / organ-protection literature — the macrophage screen ^{7Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →}, the UUO renal-fibrosis models ^{2,3Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →Reference 3Wang J et al. · 2023AnimalAsperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice modelView study →}, the gestational-diabetes placenta ^{4Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →}, the uveitis model ^{5Reference 5Du Y et al. · 2024Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitisView study →} and the HCC study ^{6Reference 6Li L · 2024Asperulosidic acid restrains hepatocellular carcinoma development and enhances chemosensitivity through inactivating the MEKK1/NF-κB pathwayView study →} — is almost all done with the isolated compound in rodents and cell lines. That is a genuine strength: those are asperulosidic acid’s own measured effects, not a plant extract’s, and the head-to-head macrophage comparison with asperuloside ^{7Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →} is exactly the kind of isolate evidence a compound page wants. The weaknesses are translational rather than attributional — no human data, much of it from one Hedyotis diffusa lineage, and the poor-absorption chemistry of polar iridoid glucosides.

The whole-herb context is the counterweight: in cleavers, asperulosidic acid is one of several bitter iridoids credited with the aerial-part extract’s immunostimulant activity, but that was a whole-extract assay in which the acid was never isolated or dose-attributed ^{1Reference 1Ilina T et al. · 2019In vitroPhytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine LView study →}; and in noni, it is the deacetyl congener (DAA), not asperulosidic acid, that serves as the quantified quality-control marker ^{10Reference 10Bittová M et al. · 2015Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) productsView study →}. Read asperulosidic acid’s own dossier as the NF-κB/MAPK anti-inflammatory story; its appearance in cleavers or noni analyses says little about the isolate.

Prevalence in Nature

Asperulosidic acid is a Rubiaceae iridoid, distributed across the madder family’s aerial parts and fruit rather than being concentrated in any one flagship source. It is reported in cleavers (Galium aparine) aerial parts — where it co-occurs with monotropein, asperuloside and 10-desacetylasperulosidic acid as the bitter cooling principles ^{1Reference 1Ilina T et al. · 2019In vitroPhytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine LView study →} — in the Chinese medicinal herb Hedyotis diffusa (Oldenlandia diffusa), which supplies most of its pharmacology ^{7Reference 7He J et al. · 2018Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophagesView study →}, in the fruit of noni (Morinda citrifolia), and in Paederia (“Ji shi teng”), whose congener deacetylasperulosidic acid methyl ester carries an analgesic signal ^{8Reference 8Chen YF et al. · 2012AnimalThe analgesic activity and possible mechanisms of deacetyl asperulosidic acid methyl ester from Ji shi teng in miceView study →}, and Morinda officinalis root, where its deacetyl and monotropein congeners are the quantified markers ^{9,10Reference 9Shen Y et al. · 2018AnimalPharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in ratsView study →Reference 10Bittová M et al. · 2015Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) productsView study →}.

Biosynthetically it belongs to the iridoid pathway (geraniol → 8-oxogeranial → iridodial via iridoid synthase, then oxidation, esterification/acetylation and glucosylation), sharing a scaffold with aucubin, harpagide and the other bitter iridoid glucosides. Its absolute content is rarely quantified as % dry weight; it is usually catalogued qualitatively alongside its relatives, so no reliable cross-source concentration ranking exists — a gap tracked for a later pass rather than asserted here.

Discovery & Synthesis

Asperulosidic acid does not have a cleanly documented discrete first isolation. It belongs to the broad nineteenth- and twentieth-century effort to characterise the bitter iridoid glucosides of the Rubiaceae — a chemistry whose namesake, asperuloside, was named after sweet woodruff (Asperula odorata), the fragrant Rubiaceae herb from which the parent compound was obtained. Asperulosidic acid is best understood as the free-acid congener in that series, sitting between asperuloside (its lactone/ester) and deacetylasperulosidic acid (its deacetylated form).

Manufacture today is by extraction from iridoid-rich Rubiaceae — Hedyotis diffusa and Morinda species are the usual research sources — rather than by total synthesis: the molecule is available enough from plant material, and its polar, multiply-oxygenated glucoside structure makes isolation more practical than synthesis for the milligram quantities preclinical work requires. No dominant commercial or total-synthesis route is documented for it as an isolate.

Patents: not yet researched.

Toxicity & Safety

Asperulosidic acid reads as a low-toxicity, food-and-medicine-adjacent iridoid — it occurs in the edible fruit of noni and in long-used Rubiaceae herbs, and rodent efficacy studies at 10–40 mg/kg report no acute toxicity signal ^{2,4Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →}. Two honest caveats keep the rating off “none,” and no isolate toxicology package exists.

Safety at a Glance

✅ Low / no toxicity

• A widespread dietary/medicinal-plant iridoid. Present in noni fruit and in long-used Rubiaceae herbs, with no acute toxicity signal at the doses used in rodent studies ^{2,4Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →}.
• No comprehensive isolate toxicology. No definitive LD50, genotoxicity or repeat-dose organ-toxicity package for the pure compound; reproductive safety of the isolate is not established.
• Interactions not assessed. No CYP/transporter interaction data for asperulosidic acid; note that it up-regulates renal OAT1/OAT3 in one model ^{3Reference 3Wang J et al. · 2023AnimalAsperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice modelView study →}, a transporter-level effect whose drug-interaction relevance is unstudied.

Full Safety & Interactions Detail

Asperulosidic acid carries a low flag. It is a natural iridoid glycoside of foods (noni fruit) and long-used medicinal herbs, and rodent efficacy studies — including an oral gestational-diabetes model dosed from conception ^{4Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →} and 14-day renal-fibrosis models ^{2,3Reference 2Lu Xianyuan et al. · 2019AnimalAnti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstructionView study →Reference 3Wang J et al. · 2023AnimalAsperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice modelView study →} — report therapeutic effects without a described acute-toxicity signal. The caveats are evidentiary rather than observed harms. First, there is no comprehensive isolate toxicology: no definitive LD50, genotoxicity or repeat-dose package, and no dedicated reproductive-safety dataset for the pure compound. Second, the molecule’s drug-interaction profile is unstudied — there is no CYP or transporter-inhibition data, and while one model shows it inducing renal organic-anion transporters (OAT1/OAT3) ^{3Reference 3Wang J et al. · 2023AnimalAsperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice modelView study →}, the clinical significance of that for co-administered OAT-substrate drugs is unknown.

Reproductive note (prose only). One study reports oral asperulosidic acid improving outcomes in a gestational-diabetes mouse model, with effects examined in placental tissue ^{4Reference 4Wu Q et al. · 2022Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathwaysView study →} — this is a preclinical efficacy finding, not a safety clearance, and no reproductive-toxicity dataset exists for the isolate. Pregnancy and lactation decisions belong to the source herb or product (cleavers, noni) where intake is decided, not to this molecule-level page. Poor expected oral absorption of the polar glucoside further limits real-world isolate exposure.

Dosage

There is no established or recommended human dose for isolated asperulosidic acid — it has never been given to people as an isolate for therapy. Cited figures are preclinical research doses, not recommendations, and they do not translate:

Several studies dose intraperitoneally precisely to bypass the poor oral absorption expected of a polar iridoid glucoside, so even these rodent figures overstate what an oral intake would deliver. Human exposure occurs only incidentally through whole Rubiaceae herbs and noni products, where the acid is one bitter iridoid among several ^{1,10Reference 1Ilina T et al. · 2019In vitroPhytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine LView study →Reference 10Bittová M et al. · 2015Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) productsView study →}. These are doses studied in research and are not a personal recommendation.

References

1. Ilina T, Kashpur N, Granica S, Bazylko A, Shinkovenko I, Kovalyova A, Goryacha O, Koshovyi O. (2019). Phytochemical profiles and in vitro immunomodulatory activity of ethanolic extracts from Galium aparine L. Plants (Basel). https://pubmed.ncbi.nlm.nih.gov/31775336/
2. Lu Xianyuan, Zou Wei, Dong Yaqian, et al. (2019). Anti-renal fibrosis effect of asperulosidic acid via TGF-β1/smad2/smad3 and NF-κB signaling pathways in a rat model of unilateral ureteral obstruction. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/30668407/
3. Wang J, Shi B, Pan Y, Yang Z, Zou W, Liu M. (2023). Asperulosidic acid ameliorates renal interstitial fibrosis via removing indoxyl sulfate by up-regulating organic anion transporters in a unilateral ureteral obstruction mice model. Molecules. https://pubmed.ncbi.nlm.nih.gov/38067420/
4. Wu Q, Gai S, Zhang H. (2022). Asperulosidic acid, a bioactive iridoid, alleviates placental oxidative stress and inflammatory responses in gestational diabetes mellitus by suppressing NF-κB and MAPK signaling pathways. Pharmacology. https://pubmed.ncbi.nlm.nih.gov/35008094/
5. Du Y, Lu J, Feng L, Zhao L, Wu P, He Y, Zhou L, Wang X, Peng H. (2024). Asperulosidic acid inhibits the PI3K/Akt/NF-κB pathway to suppress endotoxin-induced uveitis. Frontiers in Medicine. https://pubmed.ncbi.nlm.nih.gov/39839649/
6. Li L, Qiu H. (2024). Asperulosidic acid restrains hepatocellular carcinoma development and enhances chemosensitivity through inactivating the MEKK1/NF-κB pathway. Applied Biochemistry and Biotechnology. https://pubmed.ncbi.nlm.nih.gov/37097403/
7. He J, Lu X, Wei T, Dong Y, Cai Z, Tang L, Liu M. (2018). Asperuloside and asperulosidic acid exert an anti-inflammatory effect via suppression of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages. International Journal of Molecular Sciences. https://pubmed.ncbi.nlm.nih.gov/30002289/
8. Chen YF, Zhang JY, Zhao MH, Yan M, Zhao QC, Wu Q, Jin H, Shi GB. (2012). The analgesic activity and possible mechanisms of deacetyl asperulosidic acid methyl ester from Ji shi teng in mice. Pharmacology, Biochemistry, and Behavior. https://pubmed.ncbi.nlm.nih.gov/22841536/
9. Shen Y, Zhang Q, Wu YB, He YQ, Han T, Zhang JH, Zhao L, Hsu HY, Song HT, Lin B, Xin HL, Qi YP, Zhang QY. (2018). Pharmacokinetics and tissue distribution of monotropein and deacetyl asperulosidic acid after oral administration of extracts from Morinda officinalis root in rats. BMC Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/30355303/
10. Bittová M, Hladůkova D, Roblová V, Krácmar S, Kubán P, Kubán V. (2015). Analysis of organic acids, deacetyl asperulosidic acid and polyphenolic compounds as a potential tool for characterization of noni (Morinda citrifolia) products. Natural Product Communications. https://pubmed.ncbi.nlm.nih.gov/26749805/

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