Compound Monograph
Spinosin
Spinosin is a flavone C-glycoside (2''-O-β-glucopyranosyl swertisin, a 6-C-glucosyl apigenin derivative) and one of the two official quality markers of sour jujube seed (Ziziphus jujuba var. spinosa, suan zao ren). Its moderate preclinical profile is anchored by a distinctive serotonergic sedative mechanism — it potentiates pentobarbital-induced sleep via post-synaptic 5-HT1A receptors, setting it apart from the herb's GABAergic saponins — with a genuine second signal in cognition (anti-amnesic, anti-amyloid). There are no human trials of the isolate; the herb's insomnia use belongs to the whole seed and Suanzaoren decoction. Oral bioavailability is low.
Sources · 4
Where Does It Come From?
Spinosin is a naturally occurring flavonoid (flavone c-glycoside), found in Sour Jujube seed and 3 other sources. It is well tolerated orally (low toxicity).
Source Passion Fruit Passiflora edulis Herb monograph → 
Source Zizyphus Ziziphus spinosa Herb monograph → 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.
Spinosin at a Glance
Spinosin is a flavone C-glycoside of sour jujube seed and, with jujuboside A, one of the two official quality markers of suan zao ren.
The C-glycoside linkage matters: unlike the O-glycosides that dominate plant flavonoids, a carbon–carbon sugar bond cannot be hydrolysed by gut enzymes or bacteria, so spinosin is absorbed and circulates intact rather than releasing an aglycone.
Its moderate preclinical record covers sedative and anxiolytic activity.
What It's Used For
Spinosin is a flavone C-glycoside (2”-O-β-glucopyranosyl swertisin — a 6-C-glucosyl apigenin derivative) and one of the two official quality markers of sour jujube seed (Ziziphus jujuba var. spinosa, suan zao ren), the other being jujuboside A. Its distinctive place among the seed’s actives is chemical and mechanistic: where the triterpenoid saponins jujuboside A and jujuboside B and the cyclopeptide alkaloid sanjoinine A are GABAergic, spinosin is the serotonergic outlier — its sedative effect runs through post-synaptic 5-HT1A receptors. The load-bearing discipline is the usual one: the herb’s human insomnia use is the whole seed and Suanzaoren decoction, in which spinosin is a marker and one contributor, not a separately-trialled drug.
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, so scores stay modest by design.
Spinosin’s marquee signal and the clean chemical differentiator from the herb’s GABAergic saponins/alkaloid. Three convergent rodent studies show it potentiates pentobarbital-induced sleep (↑ duration, ↓ latency) via the serotonergic system, specifically post-synaptic 5-HT1A receptors 1,
A 2025 EEG/EMG study found spinosin raises NREM/slow-wave sleep and shifts c-Fos in sleep-wake nuclei 5Reference 5AnimalSpinosin enhances non-rapid-eye-movement sleep and alters c-Fos expression in sleep-wake regulatory brain regions in miceView study →.
Gap: all rodent, and mostly hypnotic potentiation (co-administered barbiturate) rather than standalone sleep induction; human insomnia efficacy belongs to the whole seed / Suanzaoren decoction, in which spinosin is one of two markers, not a validated standalone hypnotic 1,
A genuine second signal, distinct from the sedative saponins. Spinosin reversed scopolamine-induced memory impairment in mice (cholinergic/anti-amnesic) 6Reference 6AnimalAmeliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in miceView study → and improved learning/memory with anti-amyloid and neuroprotective effects in an Alzheimer’s-model mouse 7Reference 7AnimalNeuroprotective effects of spinosin on the recovery of learning and memory in a mouse model of Alzheimer’s diseaseView study →.
Gap: two separate models with no independent replication of the AD-model result, no human cognition data, and no established translation to oral dosing 6,
Spinosin produced anxiolytic-like behavior in mice, with both GABA-A and 5-HT (5-HT1A) systems implicated — consistent with the serotonergic sedative story 4Reference 4AnimalGABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in miceView study →.
Gap: a single behavioral study with a hedged dual mechanism and no dose-response translation or human data 4Reference 4AnimalGABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in miceView study →.
Mechanisms
| Target / pathway | Effect | Relevant to |
|---|---|---|
| Post-synaptic 5-HT1A receptors (serotonergic) | agonist-like potentiation → prolonged pentobarbital sleep (the replicated, distinctive mechanism) | sedative / hypnotic (differentiator from the GABAergic saponins) |
| Presynaptic 5-HT1A receptor | involved in augmentation of pentobarbital loss-of-righting-reflex | sedative / hypnotic |
| GABA-A / GABAergic transmission | co-implicated (with 5-HT) in anxiolytic-like behavior | anxiolytic |
| NREM / slow-wave sleep; c-Fos in sleep-wake nuclei | ↑ NREM/SWS; altered c-Fos in sleep-regulatory regions (EEG/EMG) | sleep architecture |
| Cholinergic signaling (scopolamine reversal) | anti-amnesic; restores scopolamine-impaired memory | cognition |
| Amyloid-β / neuroprotection (AD model) | ↓ Aβ burden, improved learning/memory | cognition / neuroprotective |
The 5-HT1A serotonergic route is the load-bearing, replicated finding and the clean distinction from jujuboside A/B and sanjoinine A (all GABAergic). A single study also reports cardioprotection against ischemia-reperfusion 8Reference 8AnimalSpinosin and 6‴-feruloylspinosin protect the heart against acute myocardial ischaemia and reperfusion in ratsView study →, off the neuro-axis and not promoted here.
Pharmacokinetics
Spinosin is a flavone C-glycoside: the sugar is attached by a C–C bond, so — unlike O-glycosides — it resists acid/enzymatic hydrolysis and is not readily cleaved to an aglycone in the gut. Despite that stability, oral bioavailability is low, and this is the principal translational limit for the isolate 9Reference 9ReviewThe pharmacology, pharmacokinetics and toxicity of spinosin: a mini reviewView study →. Central exposure is the mechanistically relevant question (the activity is central), and rodent work reports central effects after systemic dosing, but robust human ADME — Cmax, half-life, absolute oral bioavailability, BBB quantification — is not established. Net: a metabolically stable but poorly-absorbed C-glycoside whose rodent CNS activity outruns its documented oral pharmacokinetics.
Clinical trials
There are no human trials of isolated spinosin. Human insomnia/anxiety evidence belongs to the whole seed (suan zao ren) and the multi-herb Suanzaoren decoction, within which spinosin is one of the two official quality-control markers (with jujuboside A) — not a separately-trialled drug 9,
| Completed | Planned | Terminated | Preclinical |
|---|---|---|---|
| —(none, isolate) | — | — | Moderate(multi-lab rodent 5-HT1A sedative + separate cognition thread) |
Last checked: July 2026.
Toxicity & Safety
Spinosin looks benign — a marker constituent of a food-and-medicine seed with a long decoction history — but the concrete caution is additive sedation, and no proper toxicology package exists for the pure compound.
- A food-and-medicine seed constituent. Long dietary and decoction history, with no acute toxicity signal at the doses used in rodent studies.
- Avoid the isolate in pregnancy and lactation.
- Additive CNS depression. Alcohol, benzodiazepines, barbiturates, Z-drugs and other sedatives compound its effect.
- No comprehensive isolate toxicology. No definitive LD50, genotoxicity or repeat-dose organ-toxicity package for the pure compound.
Full Safety & Interactions Detail
Spinosin carries a low flag. It is a natural flavone C-glycoside of a food-and-medicine seed (suan zao ren) with a long dietary/decoction history, and rodent efficacy studies report no acute toxicity signal at the doses used; the dedicated mini-review characterizes its toxicity profile as low 9Reference 9ReviewThe pharmacology, pharmacokinetics and toxicity of spinosin: a mini reviewView study →.
The caveats: there is no comprehensive isolate toxicology (no definitive LD50, genotoxicity or repeat-dose organ-toxicity package for the pure compound), and — as a centrally-active sedative — it implies additive CNS depression with alcohol, benzodiazepines, barbiturates, Z-drugs and other sedatives. Poor oral bioavailability further limits real-world isolate exposure.
Dosage
There is no established or recommended human dose for isolated spinosin. Cited figures in the literature are preclinical rodent research doses only (low mg/kg i.p./oral in the pentobarbital-sleep and cognition studies), not recommendations. Human exposure occurs via the whole seed — traditionally 9–18 g of dry-fried suan zao ren in decoction — within which spinosin occurs at roughly 0.34–1.84 mg/g of dried seed (an official marker; content varies with germplasm, harvest timing and dry-frying/roasting) alongside the co-marker jujuboside A.
References
- Wang LE, et al. (2008). Spinosin, a C-glycoside flavonoid from Semen Zizyphi Spinosae, potentiated pentobarbital-induced sleep via the serotonergic system. Pharmacology, Biochemistry, and Behavior. https://pubmed.ncbi.nlm.nih.gov/18466960/
- Wang LE, et al. (2010). The potentiating effect of spinosin on pentobarbital-induced sleep may be related to postsynaptic 5-HT1A receptors. Phytomedicine. https://pubmed.ncbi.nlm.nih.gov/20171860/
- Wang LE, Zhang XQ, Yin YQ, et al. (2012). Augmentative effect of spinosin on pentobarbital-induced loss of righting reflex in mice associated with presynaptic 5-HT1A receptors. Journal of Pharmacy and Pharmacology. https://pubmed.ncbi.nlm.nih.gov/22221104/
- Liu J, et al. (2015). GABA and 5-HT systems are implicated in the anxiolytic-like effect of spinosin in mice. Pharmacology, Biochemistry, and Behavior. https://pubmed.ncbi.nlm.nih.gov/25449359/
- Zhao W, Zhang H, Li L, et al. (2025). Spinosin enhances non-rapid-eye-movement sleep and alters c-Fos expression in sleep-wake regulatory brain regions in mice. Sleep & Breathing. https://pubmed.ncbi.nlm.nih.gov/39934412/
- Jung IH, Lee HE, Park SJ, et al. (2014). Ameliorating effect of spinosin, a C-glycoside flavonoid, on scopolamine-induced memory impairment in mice. Pharmacology, Biochemistry, and Behavior. https://pubmed.ncbi.nlm.nih.gov/24582850/
- He B, et al. (2019). Neuroprotective effects of spinosin on the recovery of learning and memory in a mouse model of Alzheimer’s disease. Biomolecules & Therapeutics. https://pubmed.ncbi.nlm.nih.gov/29925225/
- Gu M, et al. (2019). Spinosin and 6‴-feruloylspinosin protect the heart against acute myocardial ischaemia and reperfusion in rats. Molecular Medicine Reports. https://pubmed.ncbi.nlm.nih.gov/31545438/
- Kuang G, et al. (2022). The pharmacology, pharmacokinetics and toxicity of spinosin: a mini review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/36193419/
- He SR, Zhao CB, Zhang JX, et al. (2020). Botanical, traditional, phytochemical, pharmacological, pharmacokinetic and toxicological characteristics of Ziziphi Spinosae Semen: a review. Evidence-Based Complementary and Alternative Medicine. https://pubmed.ncbi.nlm.nih.gov/32695210/
- Liu Y, et al. (2024). Phytochemical, pharmacological, pharmacokinetic and toxicological characteristics of Ziziphi Spinosae Semen: a review. Frontiers in Pharmacology. https://pubmed.ncbi.nlm.nih.gov/39679366/
