Compound Monograph
Obovatol
Obovatol is a diphenyl-ether bisphenol neolignan from the bark and leaves of Japanese bigleaf magnolia (Magnolia obovata) and houpo (M. officinalis) — a close chemical relative of magnolol and honokiol with a genuine but entirely preclinical profile: neuroprotection and anti-neuroinflammation with an anti-amyloid/memory signal, NF-κB and inflammasome-directed anti-inflammatory activity, pro-apoptotic anticancer effects across several cell lines, antiplatelet/antithrombotic action, and rodent anxiolytic effects. No human trials.
Sources · 4
Where Does It Come From?
Obovatol is a naturally occurring neolignan (diphenyl-ether bisphenol), found in Japanese bigleaf magnolia, Houpo / magnolia bark and 2 other sources. It is well tolerated orally (low toxicity).
Concentration
Content by Source
Concentrations not reported. No percent-dry-weight or mg/g figures have been published for this compound in its source plants.
Obovatol at a Glance
Obovatol is a neolignan from the bark and leaves of Japanese bigleaf magnolia (Magnolia obovata) and houpo (Magnolia officinalis) — the same plants that supply the far better-known magnolol and honokiol. Structurally it belongs to the same bisphenol neolignan family, but its two allyl-phenol units are joined by a diphenyl-ether (C–O–C) bridge rather than the direct carbon–carbon biaryl bond of magnolol and honokiol.
Its research profile is real but entirely preclinical. The most developed line of work is neurological: obovatol reduces microglial neuroinflammation, promotes neurotrophic signalling, and improves memory in rodent Alzheimer’s-type models with an accompanying anti-amyloid signal 1,
There are no human trials of obovatol, and almost every study uses the isolated molecule rather than whole magnolia bark — so the honest posture is a promising but early preclinical candidate, not an established therapeutic. Its measured toxicity is low in animals, but it is a potent inhibitor of the drug-metabolising enzyme CYP2C19 in vitro, which is the most concrete safety flag on the molecule 18Reference 18In vitroIn vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomesView study →.
Obovatol vs. Magnolol & Honokiol
The magnolia neolignans are usually discussed as a trio, but obovatol is chemically distinct from its two famous siblings in a way worth holding onto.
- Magnolol and honokiol are biaryls — two phenol rings joined directly by a carbon–carbon bond (they are positional isomers of each other).
- Obovatol is a diphenyl ether — the two allyl-phenol rings are joined through an oxygen bridge instead, making it a distinct bisphenol scaffold rather than a magnolol isomer.
Functionally the three overlap heavily — all are lipophilic bisphenols that scavenge radicals, suppress NF-κB-driven inflammation, and show pro-apoptotic and neuroactive effects — which is why obovatol keeps appearing in the same anti-Alzheimer’s and anti-inflammatory reviews as the biaryls 1Reference 1Systematic reviewNeolignans in Magnolia officinalis as natural anti-Alzheimer’s disease agents: a systematic reviewView study →. But obovatol is by far the least-studied and least-abundant of the three: magnolol and honokiol are the standardisation markers of commercial magnolia bark, while obovatol is a minor constituent whose data are thinner and human-untested. Findings for magnolol or honokiol should not be assumed to transfer to obovatol, and vice versa.
What It's Used For
Obovatol’s pharmacology is broad on paper but shallow in evidence tier: many mechanisms, several animal models, no human data, and — apart from a handful of magnolia-bark neuroinflammation studies — the isolated molecule rather than the whole plant. The evidence is best read mechanism-by-mechanism.
Support is an experimental score — weighted by study type (human > animal > in vitro) and volume. A beta, not a validated metric. Every row here is preclinical (no human trials), so the scores rank animal-vs-in-vitro depth, not clinical proof.
The molecule’s best-developed application, and always the isolated compound in rodent models. Obovatol attenuates microglia-mediated neuroinflammation: in LPS-stimulated BV-2 microglia it inhibits nitric oxide, pro-inflammatory cytokines and iNOS by suppressing NF-κB, STAT1 and MAPK signalling, with peroxiredoxin-2 identified as a molecular target whose ROS-scavenging activity it enhances 5Reference 5Obovatol attenuates microglia-mediated neuroinflammation by modulating redox regulationView study →.
It also acts as a neurotrophic agent, increasing NGF and BDNF release and neurite outgrowth in embryonic rat neurons through ERK activation 6Reference 6AnimalNeurotrophic activity of obovatol on cultured embryonic rat neuronal cells by increase of neurotrophin release through activation of ERK pathwayView study →.
In memory models it improves performance after β-amyloid (Aβ1-42) infusion and in transgenic Tg2576 mice (1 mg/kg/day for 3 months), suppressing astroglial activation, BACE1 expression and NF-κB, and — distinctively — inhibiting Aβ fibrillation in vitro 2Reference 2AnimalObovatol improves cognitive functions in animal models for Alzheimer’s diseaseView study →; parallel work shows it blunts LPS- and scopolamine-induced memory deficits with reduced β-/γ-secretase activity and amyloid load 3,
Related magnolia neolignans isolated from Magnoliae Cortex are likewise neuroprotective against glutamate toxicity in HT22 cells 21Reference 21Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate-induced apoptotic stimuli in HT22 cellsView study →.
Gap: every result is preclinical (rodent or cultured cell); there is no human cognitive data, no head-to-head against magnolol/honokiol, and the anti-amyloid claim rests on model systems rather than clinical Alzheimer’s endpoints 1Reference 1Systematic reviewNeolignans in Magnolia officinalis as natural anti-Alzheimer’s disease agents: a systematic reviewView study →.
Obovatol’s anti-inflammatory action runs through two arms. The first is NF-κB suppression, the shared throughline of its neuro-, anti-amyloid and anticancer effects 3,
The second, more specific, is inflammasome inhibition: in macrophages obovatol blocked NLRP3, AIM2 and non-canonical inflammasome activation, reducing IL-1β, IL-18 and caspase-1 by disrupting ASC pyroptosome formation, lowering mitochondrial ROS, and interfering with the priming step; in mice it attenuated the serum IL-1β rise to monosodium-urate crystals 7Reference 7Obovatol inhibits NLRP3, AIM2, and non-canonical inflammasome activationView study →.
This is the isolate tested in cell and mouse systems, consistent with magnolia bark’s traditional use for inflammatory complaints.
Gap: in-vitro and short-term mouse models only; no dose-ranging chronic-inflammation or human data, and the whole-bark contribution of obovatol (a minor constituent) to magnolia’s overall anti-inflammatory effect is not quantified 1,
Obovatol induces mitochondrial (intrinsic) apoptosis across a range of isolated tumour cell lines — shifting the Bax/Bcl-2 balance and activating caspase-3/-9, usually alongside NF-κB inhibition or MAPK (JNK/ERK/p38) activation. Reported models include acute myeloid leukaemia (MM6) 12Reference 12Induction of apoptosis by obovatol as a novel therapeutic strategy for acute myeloid leukemiaView study →, docetaxel-sensitised prostate and colon lines where 5 µM obovatol synergised with chemotherapy through NF-κB inactivation 11Reference 11Obovatol enhances docetaxel-induced prostate and colon cancer cell death through inactivation of nuclear transcription factor-kappaBView study →, non-small-cell lung cancer via CHOP/ER-stress 16Reference 16Obovatol induces apoptosis in non-small cell lung cancer cells via C/EBP homologous protein activationView study →, tongue squamous-cell carcinoma via EGF-mediated JAK-STAT 15Reference 15Obovatol inhibits the growth and aggressiveness of tongue squamous cell carcinoma through regulation of the EGF-mediated JAK-STAT signaling pathwayView study →, hepatocellular carcinoma via JAK/STAT3/PD-L1 (with an immune-escape angle) 14Reference 14Obovatol inhibits proliferation, invasion and immune escape of hepatocellular carcinoma cells through modulating the JAK/STAT3/PD-L1 axisView study →, and triple-negative breast lines (MDA-MB-231/-468, IC50 ~48–51 µM) with tumour-growth suppression and “considerable biological safety” in nude-mouse xenografts 13Reference 13Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathwayView study →.
It also inhibited uterine fibroid (leiomyoma) cells in vitro 20Reference 20Inhibitory and protective effect of obovatol against uterine fibroid (leiomyoma) cellsView study →.
Gap: almost all in-vitro, with only scattered xenograft support; cytotoxic potency is in the tens of µM, well above the sub-µM concentrations obovatol reaches in metabolism/enzyme studies, and no clinical oncology data exist 13,
A coherent cardiovascular signal from one research group. Oral obovatol prevented carotid arterial thrombosis in rats and inhibited collagen-induced platelet aggregation without changing coagulation times (aPTT/PT) — i.e. the effect is antiplatelet, not anticoagulant — with in-vitro IC50 values of 2.4–4.8 µM against collagen- and arachidonic-acid-induced rabbit platelet aggregation, working through blockade of PLC-γ2 phosphorylation, calcium mobilisation, arachidonate liberation and serotonin secretion 9Reference 9AnimalAntiplatelet activity of obovatol, a biphenolic component of Magnolia obovata, in rat arterial thrombosis and rabbit platelet aggregationView study →.
A diacetylated derivative extended this by inhibiting cyclooxygenase and lipoxygenase activities 10Reference 10Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activitiesView study →, and obovatol also inhibited vascular-smooth-muscle-cell proliferation and intimal hyperplasia by inducing p21Cip1 17Reference 17Obovatol from Magnolia obovata inhibits vascular smooth muscle cell proliferation and intimal hyperplasia by inducing p21Cip1View study →.
Gap: single-lab, rodent/rabbit and in-vitro; no human antiplatelet data — and this same activity is the basis of the bleeding-additive caution in Safety 9,
In mice, oral obovatol (0.2–1.0 mg/kg) increased open-arm entries and time on the elevated plus-maze and head-dipping on the hole-board, comparable to diazepam (1 mg/kg); both effects were reversed by flumazenil, and obovatol competitively displaced [³H]flunitrazepam and increased chloride influx blocked by flumazenil — implicating the GABA-A/benzodiazepine receptor complex and selective upregulation of the GABA-A α1 subunit in the amygdala 8Reference 8Anxiolytic-like effects of obovatol isolated from Magnolia obovata: involvement of GABA/benzodiazepine receptors complexView study →. It was mildly muscle-relaxant and reduced locomotion, but less so than diazepam.
Gap: one study from a single laboratory, rodent only, isolated compound; no replication and no human anxiety data 8Reference 8Anxiolytic-like effects of obovatol isolated from Magnolia obovata: involvement of GABA/benzodiazepine receptors complexView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| NF-κB | suppression of NF-κB DNA-binding and transcription | anti-inflammatoryanticanceranti-amyloid |
| NLRP3 / AIM2 / non-canonical inflammasomes | blocks ASC pyroptosome, lowers mitochondrial ROS → ↓ IL-1β/IL-18/caspase-1 | anti-inflammatory |
| Peroxiredoxin-2 (Prx2) | enhances Prx2 ROS-scavenging → dampened microglial pro-inflammatory signalling | neuroinflammation |
| ERK / neurotrophins (NGF, BDNF) | ↑ neurotrophin release and neurite outgrowth via ERK | neuroprotection |
| BACE1 / β- & γ-secretase; Aβ fibrillation | ↓ amyloidogenic processing; direct anti-fibrillar effect on Aβ | anti-amyloid / memory |
| Bax/Bcl-2, caspase-3/-9; MAPK (JNK/ERK/p38) | intrinsic (mitochondrial) apoptosis in tumour cells | anticancer |
| JAK/STAT (STAT1, STAT3/PD-L1) | STAT-pathway inhibition; reduced tumour immune escape | anticancer / anti-inflammatory |
| PLC-γ2 / arachidonate cascade / COX & LOX | ↓ platelet aggregation, calcium mobilisation, thromboxane pathway | antiplatelet |
| GABA-A / benzodiazepine receptor (α1 subunit) | flumazenil-reversible Cl⁻ influx → anxiolysis | anxiolytic |
| CYP2C19 | potent inhibition (IC50 0.8 µM) — drug-interaction liability | pharmacokinetics / safety |
The unifying thread is a lipophilic bisphenol that both scavenges/regulates ROS and suppresses NF-κB — the same chemistry that ties it to magnolol and honokiol. The GABAergic anxiolytic action and CYP2C19 inhibition are the two mechanisms most specific to the molecule’s own data.
Pharmacokinetics
Human PK is uncharacterised — there are no clinical pharmacokinetic data. The best information comes from human liver microsomes, where obovatol is oxidised to two hydroxy-obovatol metabolites (M1/M2) and then conjugated to mono- and di-glucuronides (M3–M6), i.e. it undergoes both CYP-mediated hydroxylation and glucuronidation 18Reference 18In vitroIn vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomesView study →. The same study found obovatol potently inhibits CYP2C19 (IC50 0.8 µM) — the one hard, reproducible number on the molecule and the basis of its interaction caution 18Reference 18In vitroIn vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomesView study →. As a lipophilic bisphenol it is presumed to be reasonably membrane-permeant (the neuro-effects imply brain penetration), but oral bioavailability, plasma levels and half-life are unmeasured, which matters because the anticancer effects require tens-of-µM concentrations that may not be reachable systemically from oral dosing.
Clinical Trials
There are no clinical trials of obovatol — the entire evidence base is in-vitro and animal, and human magnolia data belong to whole-bark or magnolol/honokiol-standardised products, not to obovatol as an isolate.
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| — | — | — | Neuroprotection/anti-amyloid, anti-inflammatory (NF-κB/inflammasome), anticancer, antiplatelet, anxiolytic |
Last checked: July 2026.
Isolate vs. Plant Studies
Obovatol’s evidence is almost entirely for the isolated molecule, not for magnolia bark as consumed. The memory, anxiolytic, antiplatelet and anticancer studies all dose purified obovatol into rodents or cells 2,
Prevalence in Nature
Obovatol occurs in the bark and leaves of Magnolia obovata (Japanese bigleaf magnolia, hō-no-ki) and the closely related houpo, Magnolia officinalis 2,
Discovery & Synthesis
Obovatol was isolated from Magnolia obovata, the Japanese bigleaf magnolia whose bark (kōboku/hō-no-ki) has a long history in East Asian traditional medicine for inflammatory and digestive complaints — the species also gives the molecule its name. That traditional anti-infective use has a modern echo: obovatol shows antibacterial activity, including disruption of the Salmonella type III secretion system 19Reference 19Inhibitory effect of obovatol from Magnolia obovata on the Salmonella type III secretion systemView study →. It sits in the same phytochemical family as magnolol and honokiol but was characterised later and studied far less; the precise first-isolation date is not well documented in the accessible literature.
Because obovatol is a comparatively simple diphenyl-ether bisphenol, it is amenable to total synthesis, and synthetic and semi-synthetic chemistry — rather than plant extraction — has driven much of its later research. Total synthesis of obovatol and neolignan analogues has been reported in the context of screening for α-glucosidase / α-amylase inhibitors 22Reference 22Synthesis of obovatol and related neolignan analogues as α-glucosidase and α-amylase inhibitorsView study →, and several derivatives (diacetylated obovatol, Mannich bases, and designated leads such as JJK694, JY0691 and OD 78) have been made to sharpen its antiplatelet, anti-proliferative and anticancer activities 10Reference 10Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activitiesView study →. This synthetic accessibility, plus its low natural abundance, means research-grade obovatol is typically made or semi-synthesised rather than extracted at scale.
Patents: not yet researched.
Toxicity & Safety
Obovatol carries a low toxicity flag — a preclinical, not a human, judgement. Rodents tolerated oral dosing at low mg/kg for up to three months in memory studies without reported overt toxicity 2Reference 2AnimalObovatol improves cognitive functions in animal models for Alzheimer’s diseaseView study →, and a breast-cancer xenograft study explicitly noted “considerable biological safety” in mice 13Reference 13Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathwayView study →. There is, however, no human safety data, and two mechanism-based cautions are concrete rather than theoretical.
- Low toxicity in animal studies. Oral rodent dosing (≤1 mg/kg/day for up to 3 months) and mouse xenograft work reported no overt toxicity 2,
13Reference 2AnimalObovatol improves cognitive functions in animal models for Alzheimer’s diseaseView study →Reference 13Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathwayView study → . - CYP2C19 inhibition (drug interactions). Obovatol potently inhibits CYP2C19 in vitro (IC50 0.8 µM), so it could raise levels of CYP2C19 substrates (e.g. clopidogrel activation, some PPIs, certain antidepressants) — the clearest interaction liability 18Reference 18In vitroIn vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomesView study →.
- Antiplatelet / additive bleeding risk. Its documented antithrombotic and platelet-inhibiting activity could add to anticoagulant or antiplatelet drugs and other magnolia neolignans 9,
10Reference 9AnimalAntiplatelet activity of obovatol, a biphenolic component of Magnolia obovata, in rat arterial thrombosis and rabbit platelet aggregationView study →Reference 10Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activitiesView study → . - No human data. All safety inference is preclinical; oral bioavailability, chronic-exposure and reproductive toxicology for the isolate are uncharacterised.
Reproductive note (prose only). No dedicated reproductive- or developmental-toxicity dataset exists for isolated obovatol. Pregnancy and lactation decisions belong to the herb or product page where intake is actually decided, not to this molecule-level page; the finding here is simply that the data do not exist.
Dosage
There is no established human dose — obovatol has never been tested in people. The figures below are preclinical research doses, included for context only:
| Setting | Model | Dose / concentration |
|---|---|---|
| Anxiolytic | mouse, oral | 0.2–1.0 mg/kg |
| Anti-neuroinflammation / memory | mouse, oral | 0.2–1.0 mg/kg/day (up to 1 mg/kg/day × 3 months, Tg2576) |
| Antiplatelet | rabbit platelets, in vitro | IC50 2.4–4.8 µM |
| Anticancer (chemo-sensitisation) | prostate/colon cells | ~5 µM (with docetaxel) |
| Anticancer (single agent) | breast cells | IC50 ~48–51 µM |
Note the gap between the low-µM concentrations active on platelets and the tens-of-µM needed for direct cytotoxicity — and that none of these have known human-achievable equivalents, since obovatol’s oral bioavailability is unmeasured. These are doses studied in research and are not a personal recommendation.
References
- Li N, Liang Y, Zhang L, Xu C, Wang L (2024). Neolignans in Magnolia officinalis as natural anti-Alzheimer’s disease agents: a systematic review. Ageing Research Reviews. https://pubmed.ncbi.nlm.nih.gov/38955265/
- Choi DY, Lee JW, Peng J, et al. (2012). Obovatol improves cognitive functions in animal models for Alzheimer’s disease. Journal of Neurochemistry. https://pubmed.ncbi.nlm.nih.gov/22212065/
- Choi DY, Lee JW, Lin G, et al. (2012). Obovatol attenuates LPS-induced memory impairments in mice via inhibition of NF-κB signaling pathway. Neurochemistry International. https://pubmed.ncbi.nlm.nih.gov/22107706/
- Choi DY, et al. (2012). Attenuation of scopolamine-induced cognitive dysfunction by obovatol. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/22864751/
- Ock J, Han HS, Hong SH, et al. (2010). Obovatol attenuates microglia-mediated neuroinflammation by modulating redox regulation. British Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/20397299/
- Lee YK, Song JK, Choi IS, et al. (2010). Neurotrophic activity of obovatol on cultured embryonic rat neuronal cells by increase of neurotrophin release through activation of ERK pathway. European Journal of Pharmacology. https://pubmed.ncbi.nlm.nih.gov/20868677/
- Kim J, Ahn H, Han BC, et al. (2019). Obovatol inhibits NLRP3, AIM2, and non-canonical inflammasome activation. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/31302317/
- Seo JJ, Lee SH, Lee YS, et al. (2007). Anxiolytic-like effects of obovatol isolated from Magnolia obovata: involvement of GABA/benzodiazepine receptors complex. Progress in Neuro-Psychopharmacology & Biological Psychiatry. https://pubmed.ncbi.nlm.nih.gov/17698274/
- Park ES, Lim Y, Lee SH, et al. (2011). Antiplatelet activity of obovatol, a biphenolic component of Magnolia obovata, in rat arterial thrombosis and rabbit platelet aggregation. Journal of Atherosclerosis and Thrombosis. https://pubmed.ncbi.nlm.nih.gov/21512279/
- Yu JY, Lee JJ, Jung JK, et al. (2012). Anti-platelet activity of diacetylated obovatol through regulating cyclooxygenase and lipoxygenase activities. Archives of Pharmacal Research. https://pubmed.ncbi.nlm.nih.gov/23263814/
- Lee SY, Cho JS, Yuk DY, et al. (2009). Obovatol enhances docetaxel-induced prostate and colon cancer cell death through inactivation of nuclear transcription factor-kappaB. Journal of Pharmacological Sciences. https://pubmed.ncbi.nlm.nih.gov/19834284/
- Kim HS, Lim GY, Hwang J, et al. (2014). Induction of apoptosis by obovatol as a novel therapeutic strategy for acute myeloid leukemia. International Journal of Molecular Medicine. https://pubmed.ncbi.nlm.nih.gov/25319672/
- Zhang L, Wei C, Yang X, et al. (2026). Obovatol induces apoptosis in breast cancer by downregulating the PI3K/Akt pathway. Translational Cancer Research. https://pubmed.ncbi.nlm.nih.gov/41969497/
- Liao C, et al. (2024). Obovatol inhibits proliferation, invasion and immune escape of hepatocellular carcinoma cells through modulating the JAK/STAT3/PD-L1 axis. International Immunopharmacology. https://pubmed.ncbi.nlm.nih.gov/39146776/
- Duan M, et al. (2018). Obovatol inhibits the growth and aggressiveness of tongue squamous cell carcinoma through regulation of the EGF-mediated JAK-STAT signaling pathway. Molecular Medicine Reports. https://pubmed.ncbi.nlm.nih.gov/29845251/
- Kim H, et al. (2016). Obovatol induces apoptosis in non-small cell lung cancer cells via C/EBP homologous protein activation. Phytotherapy Research. https://pubmed.ncbi.nlm.nih.gov/27489231/
- Lim Y, et al. (2010). Obovatol from Magnolia obovata inhibits vascular smooth muscle cell proliferation and intimal hyperplasia by inducing p21Cip1. Atherosclerosis. https://pubmed.ncbi.nlm.nih.gov/20022323/
- Joo J, Lee D, Wu Z, et al. (2013). In vitro metabolism of obovatol and its effect on cytochrome P450 enzyme activities in human liver microsomes. Biopharmaceutics & Drug Disposition. https://pubmed.ncbi.nlm.nih.gov/23446989/
- Choi WS, et al. (2017). Inhibitory effect of obovatol from Magnolia obovata on the Salmonella type III secretion system. The Journal of Antibiotics. https://pubmed.ncbi.nlm.nih.gov/28874849/
- Chen L, et al. (2020). Inhibitory and protective effect of obovatol against uterine fibroid (leiomyoma) cells. Pakistan Journal of Pharmaceutical Sciences. https://pubmed.ncbi.nlm.nih.gov/32122859/
- Yang EJ, et al. (2013). Neuroprotective effects of neolignans isolated from Magnoliae Cortex against glutamate-induced apoptotic stimuli in HT22 cells. Food and Chemical Toxicology. https://pubmed.ncbi.nlm.nih.gov/23454146/
- Sciacca C, et al. (2024). Synthesis of obovatol and related neolignan analogues as α-glucosidase and α-amylase inhibitors. Bioorganic Chemistry. https://pubmed.ncbi.nlm.nih.gov/38723423/
