(-)-Maackiain

Experientia. 1986 May 15;42(5):568-70.

The effect of the phytoalexins, lubimin, (-)-maackiain, pinosylvin, and the related compounds dehydroloroglossol and hordatine M on human lymphoblastoid cell lines.[Pubmed: 3709764]

METHODS AND RESULTS:
We have tested the effect of the phytoalexins lubimin, (-)-Maackiain and pinosylvin and the related compounds dehydroloroglossol and hordatine M on the growth of the human lymphoblastoid cell lines Molt and Raji. (-)-Maackiain, pinosylvin and dehydroloroglossol showed significant growth inhibitory action on the cells. Suppression of [3H] thymidine and [3H] leucine uptake was tested and noted in pinosylvin and dehydroloroglossol.
CONCLUSIONS:
The phytoalexins and related compounds are widespread in plants and provide a potential source of antineoplastic substances.

Xenobiotica. 2015 Jun 11:1-13.

Pharmacokinetic properties of trifolirhizin, (-)-maackiain, (-)-sophoranone and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran after intravenous and oral administration of Sophora tonkinensis extract in rats.[Pubmed: 26068519]

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-Maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea.
METHODS AND RESULTS:
This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed.
CONCLUSIONS:
6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

J. Biol. Chem.,2015, 290(45):27393-402.

Disruption of Heat Shock Protein 90 (Hsp90)-Protein Kinase Cδ (PKCδ) Interaction by (−)-Maackiain Suppresses Histamine H1 Receptor Gene Transcription in HeLa Cells*[Pubmed: 26391399]

The histamine H1 receptor (H1R) gene is an allergic disease sensitive gene, and its expression level is strongly correlated with the severity of allergic symptoms. (-)-Maackiain was identified as a Kujin-derived anti-allergic compound that suppresses the up-regulation of the H1R gene. However, the underlying mechanism of H1R gene suppression remains unknown.
METHODS AND RESULTS:
Here, we sought to identify a target protein of (-)-Maackiain and investigate its mechanism of action. A fluorescence quenching assay and immunoblot analysis identified heat shock protein 90 (Hsp90) as a target protein of (-)-Maackiain. A pull-down assay revealed that (-)-Maackiain disrupted the interaction of Hsp90 with PKCδ, resulting in the suppression of phorbol 12-myristate 13-acetate (PMA)-induced up-regulation of H1R gene expression in HeLa cells. Additional Hsp90 inhibitors, including 17-(allylamino)-17-demethoxygeldanamycin, celastrol, and novobiocin also suppressed PMA-induced H1R gene up-regulation. 17-(Allylamino)-17-demethoxygeldanamycin inhibited PKCδ translocation to the Golgi and phosphorylation of Tyr(311) on PKCδ.
CONCLUSIONS:
These data suggest that (-)-Maackiain is a novel Hsp90 pathway inhibitor. The underlying mechanism of the suppression of PMA-induced up-regulation of H1R gene expression by (-)-Maackiain and Hsp90 inhibitors is the inhibition of PKCδ activation through the disruption of Hsp90-PKCδ interaction. Involvement of Hsp90 in H1R gene up-regulation suggests that suppression of the Hsp90 pathway could be a novel therapeutic strategy for allergic rhinitis.

Plant Physiol.,1987 Feb;83(2):365-70.

Role of oxygenases in pisatin biosynthesis and in the fungal degradation of maackiain.[Pubmed: 16665251 ]

METHODS AND RESULTS:
Some isolates of the plant pathogen Nectria haematococca detoxify the isoflavonoid phytoalexin (-)-Maackiain by hydroxylation at carbon 6a. Precursor feeding studies strongly suggest that the penultimate step in (+)pisatin biosynthesis by Pisum sativum is 6a-hydroxylation of (+)maackiain. We have used (18)O labeling to test the involvement of oxygenases in these two reactions. When fungal metabolism of maackiain took place under (18)O(2), the product was labeled with 99% efficiency; no label was incorporated by metabolism in H(2) (18)O. Pisatin synthesized by pea pods in the presence of (18)O(2) or H(2) (18)O was a mixture of molecules containing up to three labeled oxygen atoms. Primary mass spectra of such mixtures were complex but were greatly simplified by tandem MS. This analysis indicated that the 6a oxygen of pisatin was derived from H(2)O and not from O(2). Labeling patterns for the other five oxygen atoms were consistent with the proposed pathway for biosynthesis of pisatin and related isoflavonoids.
CONCLUSIONS:
We conclude that the fungal hydroxylation of maackiain is catalyzed by an oxygenase, but the biosynthetic route to the 6a hydroxyl of pisatin is unknown.