Yasuaki Hirai

The chemical constituents of fresh Gentian Root

We isolated and characterized 23 compounds, including a new iridoid named gentiolutelin and its dimethyl acetal, and a new lignan named gentioluteol from fresh roots (including small amounts of rhizome) of Gentiana lutea cultivated in Japan (Hokkaido). The structures of gentiolutelin and gentioluteol were determined as (1S,2R,3S,5R)-3-hydroxy-2-methyl-5-(2-oxoethyl)-cyclopentanecarboxylic acid methyl ester and (7R,8S,8′S)-4,4′,8,9-tetrahydroxy-3,3′,5-trimethoxy-7,9′-epoxylignan, respectively, on the basis of chemical and spectroscopic evidence. It was noteworthy that gentiopicroside, known to be a major secoiridoid glycoside in Gentian root, was not detected from the fresh roots of 3-year-old G. lutea.

Pharmacognostic studies on ginger and related drugs—part 1: five sulfonated compounds from Zingiberis rhizome (Shokyo)

Five sulfonated compounds, namely 4-gingesulfonic acid and shogasulfonic acids A, B, C and D, were isolated together with seven known compounds including 6-gingesulfonic acid from Zingiberis rhizome (Japanese name: Shokyo) made out of ginger. Their structures were characterized by means of spectroscopic analysis.

Two novel oleanolic acid saponins having a sialyl Lewis X mimetic structure from Achyranthes fauriei root

Two novel triterpene glycosides, achyranthosides E and F, were isolated as methyl esters from the root of Achyranthes fauriei, an antiinflammatory medicinal plant. Their structures were characterized as oleanolic acid glucuronides having unique substituents composed of C6H9O5 and C9H15O7, respectively, at the C-3 position of glucuronic acid. These compounds are active components which can inhibit the excess recruiting of neutrophiles to injured tissues 1,000 times more potently than sialyl Lewis X.

Lupane triterpenoid glycosyl esters from leaves of Acanthopanax divaricatus

Abstract Further investigation of the leaves of Acanthopanax divaricatus gave two analogues of chiisanoside, which is a lupane triterpenoid oligoglycosyl ester. The structures were established as 28- O -α- l -rhamnopyranosyl(1 → 4)-β- d -glucopyranosyl(1 → 6)β- d -glucopyranosyl esters of 1β,11α-dihydroxy-3-oxo-lup-20(29)-en-28-oic acid and 1( R ),11α,22α-trihydroxy-3,4-seco-lupa-4(23),20(29)-diene-3,28-dioic acid 3,11α-lactone based on chemical and spectroscopic evidence. in biosynthetic terms, one is the precursor of chiisanoside and the other is an oxygenated derivative chiisanoside.

Novel phenolic glycosides, adenophorasides A–E, from Adenophora roots

Five novel phenolic glycosides, adenophorasides A (1), B (2), C (3), D (4), and E (5), were isolated from commercial Adenophora roots, together with vanilloloside (6), 3,4-dimethoxybenzyl alcohol 7-O-β-d-glucopyranoside (7), and lobetyolin (8). The structures of the new compounds (1–5) were characterized as 4-hydroxy-3-methoxyphenylacetonitrile 4-O-β-d-glucopyranoside (1), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (2), 4-hydroxy-3-methoxyphenylacetonitrile 4-O-α-l-rhamnopyranosyl-(1→6)-β-d-glucopyranoside (3), 4-hydroxyphenylacetonitrile 4-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (4), and 4-hydroxy-3-methoxybenzyl alcohol 4-O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranoside (5), respectively, by means of spectroscopic and chemical analyses.

Eight new oleanane-type triterpenoid saponins from platycodon root

Eight new triterpenoid saponins, platyconic acids B (1), C (2), D (3), E (4), platycodins J (5), K (6), L (7) and platycosaponin A (8), were isolated from Platycodon Root, together with twelve known compounds, and they were characterized on the basis of their spectroscopic and chemical data.

Mansonone E from Mansonia gagei Inhibited α-MSH-Induced Melanogenesis in B16 Cells by Inhibiting CREB Expression and Phosphorylation in the PI3K/Akt Pathway

Many natural products that inhibit melanogenesis, freckles, and hyperpigmentation have been selectively used in cosmetics because melanogenesis is linked to the multiple biogenesis cascades of melanin synthesis. However, some of these compounds have side effects that may result in their restriction in the future. We report here the isolation and structural elucidation of compounds extracted from Mansonia gagei and evaluate their activity on melanogenesis inhibition. We isolated five known compounds from M. gagei and identified them as mansonone E (1), mansorin I (2), populene F (3), mansonone G (4), and mansorin B (5). After evaluating the five compounds for cytotoxicity against B16 cells and inhibitory activity on α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis, we determined that the cytotoxicity and melanogenesis-inhibitory effect of 1 were relatively low and high, respectively. Next, the effect of 1 on the expression of melanogenesis-related proteins was assessed; it was confirmed that 1 dose-dependently inhibited the expression levels of tyrosinase, tyrosinase-related protein 1 (TRP-1), TRP-2, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) which were increased after stimulation by α-MSH. Furthermore, the effects of 1 on the phosphorylation levels of intracellular signaling pathway-related proteins were evaluated, and it was found that 1 dose-dependently rescued the phosphorylation of Akt and p38 mitogen-activated protein kinases (MAPK), which were up- or down-regulated after stimulation by α-MSH. In contrast, treatment with the phosphoinositide 3-kinase (PI3K)/Akt inhibitor wortmannin enhanced melanogenesis inhibition by mansonone E. Cumulatively, the data suggest that 1 suppresses α-MSH-induced melanogenesis in B16 cells by inhibiting both phosphorylation in the PI3K/Akt pathway and the expression of melanogenesis-related proteins.

Dihydrochalcone designed from methylophiopogonanone B strongly inhibits hypoxia-inducible factor (HIF)-1α activity

Inhibition of hypoxia-inducible factor (HIF)-1α activity of methylophiopogonanone B (1) and its derivatives were investigated. As the modification of the structure of 1, dihydrochalcone (11) was leaded and showed one order higher activity (IC 50 : 0.2 μg/mL) than methylophiopogonanone B (1) (IC 50 : 2.2 μg/mL).

First synthesis of racemic methylophiopogonanone B and its inhibitory activity of hypoxia-inducible factor-1α

- Methylophiopogonanone B, a constituent of Ophiopogonis tuber, found to be a potent inhibitor of hypoxia induced factor-1α (HIF-1α) activity, was synthesized from 2,4,6-trihydroxy-3,5-dimethylacetophenone in 57% yield. The synthetic methylophiopogonanone B inhibited the reporter activity at 3 to 10 μg/mL.

Requirement of the glycosyl parts in platycodin D to stimulate pancreatic exocrine secretion.

The whole structure of platycodin D is found to be essential to stimulate the volumetric increase in the pancreatic exocrine secretion, while the prosapogenins prepared from platycodin D increased only protein output of pancreatic juice.