Sakuranetin

Pharmacology & Research

Sakuranetin is the 7-O-methyl ether of naringenin — and its honest identity is botanical: it is the principal inducible flavonoid phytoalexin of rice, biosynthesised from naringenin by naringenin 7-O-methyltransferase on demand after UV, jasmonate or blast-fungus (Magnaporthe oryzae) attack ^{4Reference 4Rakwal R et al. · 2000Naringenin 7-O-methyltransferase involved in the biosynthesis of the flavanone phytoalexin sakuranetin from riceView study →}. That antifungal role is plant self-defense, not human therapeutics. Its most developed therapeutic literature is a preclinical anti-asthma/airway-remodeling story in mice; its antimicrobial, antiparasitic and antiviral activities are all in vitro. There are no human trials of the isolate.

1. Anti-inflammatory / anti-asthma

Sakuranetin’s most developed therapeutic literature. In ovalbumin-sensitised mice, intranasal/systemic sakuranetin (~20 mg/kg) reduced airway hyperresponsiveness, eosinophilic/neutrophilic infiltration, Th2/Th17 cytokines, serum IgE and mucus, and reversed airway/peribronchial remodeling (collagen, elastic fibres) ^{1Reference 1Toledo AC et al. · 2013AnimalFlavanone treatment reverses airway inflammation and remodeling in an asthma murine modelView study →}, via NF-κB suppression plus inhibition of MAPK (ERK1/2, JNK, p38) and STAT3–SOCS3 signalling ^{2Reference 2Santana FPR et al. · 2019AnimalInhibition of MAPK and STAT3–SOCS3 by sakuranetin attenuated chronic allergic airway inflammation in miceView study →}.

Gap: a single lab lineage, rodent-only, with no inhaled/oral human PK bridge and no clinical data ^{1,2Reference 1Toledo AC et al. · 2013AnimalFlavanone treatment reverses airway inflammation and remodeling in an asthma murine modelView study →Reference 2Santana FPR et al. · 2019AnimalInhibition of MAPK and STAT3–SOCS3 by sakuranetin attenuated chronic allergic airway inflammation in miceView study →}.

2. Antimicrobial / antiviral

As a phytoalexin, sakuranetin is directly antifungal against rice blast ^{3Reference 3Hasegawa M et al. · 2014Analysis of the blast-fungus-responsive characters of the flavonoid phytoalexin sakuranetinView study →}; from Baccharis retusa it showed antileishmanial and antitrypanosomal activity ^{5Reference 5Grecco SS et al. · 2012In-vitro antileishmanial and antitrypanosomal activities of flavanones from Baccharis retusaView study →}, and in cell culture it inhibited human rhinovirus 3 ^{6Reference 6Choi HJ · 2017In-vitro antiviral activity of sakuranetin against human rhinovirus 3View study →} and influenza B (acting at attachment/entry/post-entry) ^{7Reference 72018Suppression of influenza B virus replication by sakuranetin and the mode of its actionView study →}.

Gap: all in-vitro, at weak-to-moderate µg/mL potencies, with no in-vivo infection efficacy or mammalian selectivity data — and the antifungal biology is rice self-defense, not a human antifungal claim ^{3,6Reference 3Hasegawa M et al. · 2014Analysis of the blast-fungus-responsive characters of the flavonoid phytoalexin sakuranetinView study →Reference 6Choi HJ · 2017In-vitro antiviral activity of sakuranetin against human rhinovirus 3View study →}.

3. Antioxidant

Sakuranetin’s antioxidant activity is a mechanistic contributor to its anti-inflammatory effect (oxidative-stress reduction in airway models) rather than a standalone indication ^{1,9Reference 1Toledo AC et al. · 2013AnimalFlavanone treatment reverses airway inflammation and remodeling in an asthma murine modelView study →Reference 9Stompor-Gorący M et al. · 2020ReviewA review on sources and pharmacological aspects of sakuranetinView study →}.

Gap: no isolate outcome studies — typical flavanone radical scavenging, not distinctive ^{9Reference 9Stompor-Gorący M et al. · 2020ReviewA review on sources and pharmacological aspects of sakuranetinView study →}.

4. Anticancer / chemopreventive

Sakuranetin is a member of the yerba-santa cancer-chemopreventive fraction identified in a 1992 screen ^{11Reference 11Liu YL et al. · 1992Isolation of potential cancer-chemopreventive agents from Eriodictyon californicumView study →}.

Gap: a fraction-level/association claim with no dedicated in-vivo tumour efficacy for the isolate ^{11Reference 11Liu YL et al. · 1992Isolation of potential cancer-chemopreventive agents from Eriodictyon californicumView study →}.

Mechanisms

Target / pathway	Effect	Relevant to
NF-κB	↓ activation (in-vivo airway)	anti-inflammatory / asthma
MAPK (ERK1/2, JNK, p38); STAT3–SOCS3	↓ phosphorylation; ↓ IL-17	Th17-driven airway inflammation
Th2/Th17 cytokines, IgE, eosinophils, mucus	reduced	allergic-asthma phenotype
Fungal / parasite / viral targets	direct growth/replication inhibition (entry/post-entry for influenza B)	antimicrobial breadth
CYP450s / UGTs (esp. UGT1A3)	substrate + modulator	pharmacokinetics / interaction signal

Pharmacokinetics

Sakuranetin is a flavanone aglycone with poor oral bioavailability typical of the class — presystemic elimination in gut and liver. It undergoes rapid phase-II glucuronidation (UGT1A3 responsible for >80%) in mouse/rat/dog microsomes but is comparatively stable in human liver microsomes — a notable species difference — and is also 7-O-demethylated back to naringenin ^{8Reference 82018Hepatic metabolism of sakuranetin and its modulating effects on cytochrome P450s and UDP-glucuronosyltransferasesView study →}. Because it modulates CYP450s and UGTs, a theoretical drug-metabolism-interaction signal exists (in vitro only), and no human oral pharmacokinetic parameters are reported for the isolate.

Clinical trials

There are no human clinical trials of isolated sakuranetin for any indication; all efficacy evidence is in-vitro or rodent.

Last checked: July 2026.

Toxicity & Safety

Sakuranetin has low apparent toxicity in the available data — no cytotoxicity at antiviral test concentrations (≤100 µg/mL in HeLa) ^{6Reference 6Choi HJ · 2017In-vitro antiviral activity of sakuranetin against human rhinovirus 3View study →} and good tolerability at efficacious doses in mouse asthma models ^{1,2Reference 1Toledo AC et al. · 2013AnimalFlavanone treatment reverses airway inflammation and remodeling in an asthma murine modelView study →Reference 2Santana FPR et al. · 2019AnimalInhibition of MAPK and STAT3–SOCS3 by sakuranetin attenuated chronic allergic airway inflammation in miceView study →}. No dedicated repeat-dose, genotoxicity or reproductive-toxicity studies exist, and the main theoretical caution is CYP/UGT modulation with herb–drug-interaction potential ^{8Reference 82018Hepatic metabolism of sakuranetin and its modulating effects on cytochrome P450s and UDP-glucuronosyltransferasesView study →}. As a bitter-receptor (hTAS2R31) antagonist in a cell assay ^{10Reference 10Reichelt KV et al. · 2011In-vitro evaluation of flavonoids from Eriodictyon californicum for antagonist activity against the bitterness receptor hTAS2R31View study →}, it shares yerba santa’s taste-modifying biology — a flavour finding, not a therapeutic mechanism.

Pregnancy & lactation

Dietary trace fine; avoid therapeutic/supplemental doses. Dietary trace exposure (rice, cherry) is not a concern, but there are no reproductive-safety data, so concentrated isolate use should be avoided in pregnancy and lactation.

Dosage

There is no established human dose — no isolate is sold or dosed clinically. Rodent efficacy used ~20 mg/kg in asthma models, which is not translatable to a human dose, so the honest answer is that no dose is established.

References