trans-Hinokiresinol

Stereochemistry of cis- and trans-hinokiresinol and their estrogen-like activity.[Pubmed:10726863]

Chem Pharm Bull (Tokyo). 2000 Mar;48(3):389-92.

Naturally occurring phenylpropanoids, hinokiresinol (trans-Hinokiresinol) and nyasol (cis-hinokiresinol) were found to possess appreciable estrogen receptor binding activity. Strong differences in activity were observed between the geometrical isomers and enantiomers. Among these, (3S)-cis-hinokiresinol displayed the highest activity, one order of magnitude greater than the activity of genistein. Furthermore, cis- and trans-Hinokiresinol stimulated the proliferation of estrogen-dependent T47D breast cancer cells, and their stimulatory effects were blocked by an estrogen antagonist, indicating that the compounds are estrogen agonists. In addition, the absolute configuration of C-3 in (+)-cis-hinokiresinol has been assigned as S by comparison with the circular dichroism spectra of the hydrogenated products prepared from cis and trans ((3S)-trans-Hinokiresinol: previously assigned) isomers. These results incidentally provide us with an unambiguous answer to contradictory reports regarding the assignment of the full stereochemisry of cis- and trans-Hinokiresinol that have existed in the literature for more than two decades.

Effects of Chamaecyparis formosensis Matasumura extractives on lipopolysaccharide-induced release of nitric oxide.[Pubmed:17291735]

Phytomedicine. 2007 Oct;14(10):675-80.

Chamaecyparis formaosensis, commonly known as Taiwan red cypress, is native to Taiwan and grows at elevations of 1500-2150 m in Taiwan's central mountains. Many compounds have been identified from different pasts of C. formosensis, but up until now, little research has been done on the link between the constituents of C. formosensis and its bioactivities. In this study, we found that an ethyl acetate fraction (EA) of methonal extract of C. formosecsis, strongly inhibited LPS-mediated nitric oxide (NO) production in Raw 264.7 cells. The EA was further divided into 25 subfractions (EA1-EA25) by column chromatography. EA12 possessed the strongest NO production inhibition activity (IC(50) was 4.1 microg/mL). At a dosage of 20 microg/mL, EA12 completely inhibited NO production and the mRNA expression of inducible nitric oxide synthase (iNOS) in LPS-stimulated macrophage RAW264.7 cells. Bioactivity-guided chromatographic fractionation and metabolite profiling coupled with spectroscopic analyses, including (1)H-NMR, (13)C-NMR analyses, identified six compounds: vanillin (1), 4-hydroxybenzaldehyde (2), trans-Hinokiresinol (3), taiwanin E (4), 4alpha-hydroxyeudesm- 11-en-12-al (5), savinin (6). All of these six compounds were the first identified and reported from this tree species. Compounds (1), (3) and (5) demonstrated significant NO inhibition effect through reduction of NO production in activated RAW 264.7 cells due to the suppression of iNOS gene expression: compounds that can selectively inhibit undesirable expression of iNOS are important as they may serve as potential cancer chemopreventatives. This study suggests that C. formosensis may have potential for use as a natural resource for human health care.

Differential anti-ischemic efficacy and therapeutic time window of trans- and cis-hinokiresinols: stereo-specific antioxidant and anti-inflammatory activities.[Pubmed:23287539]

Neuropharmacology. 2013 Apr;67:465-75.

During cerebral ischemia, neurons are injured by various mechanisms including excitotoxicity, oxidative stress, and inflammatory responses. Thus, pharmacological manipulation of multiple cytotoxic pathways has been pursued for the treatment of ischemic injury. Cis-hinokiresinol, a naturally occurring phenylpropanoid, was previously reported to possess anti-oxidant, anti-inflammatory and estrogen-like activities. In the present study, we investigated anti-ischemic effects of trans- and cis-hinokiresinols using in vitro as well as in vivo experimental models. The ORAC and DPPH assays showed that two isomers had similar free radical scavenging activities. However, only trans-Hinokiresinol significantly decreased neuronal injury in cultured cortical neurons exposed to oxygen-glucose deprivation (75 min) followed by re-oxygenation (9 h). The differential neuroprotective effect could be due to the stereo-specific augmentation of Cu/Zn-SOD activity by trans-Hinokiresinol, when compared with cis-hinokiresinol. Similarly, in rats subjected to transient middle cerebral artery occlusion (1.5 h) followed by 24-h reperfusion, pre-ischemic treatment with trans-Hinokiresinol, but not with cis-isomer, reduced cerebral infarct volume. Interestingly, however, post-ischemic treatment with both hinokiresinols (2 and 7 h after onset of ischemia) significantly reduced cerebral infarct. When administered after onset of ischemia, trans-Hinokiresinol, but not its cis-isomer reduced nitrotyrosine immunoreactivity in ischemic regions. In contrast, both hinokiresinols suppressed neutrophil infiltration and IL-1beta release to a similar extent. The observed differential anti-oxidant, but comparable anti-inflammatory, activities may explain the stereo-specific anti-ischemic activities and different therapeutic time windows of the hinokiresinols examined. More detailed delineation of the anti-ischemic mechanism(s) of hinokiresinols may provide a better strategy for development of efficacious regimens for cerebral ischemic stroke.

Hinokiresinol inhibits IgE-induced mouse passive cutaneous anaphylaxis reaction.[Pubmed:17051467]

Planta Med. 2006 Nov;72(14):1328-30.

The antiallergic effect of hinokiresinol isolated from the whole plant of TRAPA Pseudoincisa S. at. Z. was measured in vitro and in vivo. Hinokiresinol not only potently inhibited beta-hexosaminidase release from RBL-2H3 cells induced by IgE, with an IC50 value of 98 microM, but also inhibited the proinflammatory cytokines IL-6, IL-4 and TNF-alpha in RBL-2H3 cells stimulated by IgE. Orally and intraperitoneally administered hinokiresinol potently inhibited the passive anaphylaxis reaction in mice induced by IgE.

Hinokiresinol is not a precursor of agatharesinol in the norlignan biosynthetic pathway in Japanese cedar.[Pubmed:16884819]

J Plant Physiol. 2006 Dec;163(12):1221-8.

The biosynthetic relationship between the two norlignans agatharesinol and trans-Hinokiresinol was investigated. Fresh sapwood sticks of Cryptomeria japonica were fed with stable isotope-labeled compounds, namely p-coumaryl alcohol-[9,9-(2)H], p-coumaryl alcohol-[9-(18)O] and trans-Hinokiresinol-[1-(2)H], and then incubated under high-humidity for approximately 20 days, during which the two norlignans were produced simultaneously. While trans-Hinokiresinol was strongly deuterium-labeled after feeding with p-coumaryl alcohol-[9,9-(2)H], agatharesinol was only lightly labeled after feeding with either p-coumaryl alcohol-[9,9-(2)H] or -[9-(18)O]. These results suggest that p-coumaryl alcohol, which is a precursor of hinokiresinol, is not involved in the biosynthesis of agatharesinol. Therefore, the norlignan carbon skeleton of agatharesinol must be framed from different types of phenylpropanoid monomers compared to those utilized by the trans-Hinokiresinol pathway. The biosynthesis of these two norlignans seems to branch at an early stage, i.e., before the framing of the norlignan carbon skeleton. Furthermore, agatharesinol was not labeled with deuterium after feeding with (2)H-labeled trans-Hinokiresinol, which has the simplest norlignan structure. This result strongly supports the suggestion that the conversion of trans-Hinokiresinol to agatharesinol is not part of the biosynthesis of norlignans and that early branching occurs instead.