Hyoung Ja Kim

Neuroprotective effects of antioxidative flavonoids, quercetin, (+)-dihydroquercetin and quercetin 3-methyl ether, isolated from Opuntia ficus-indica var. saboten.

The flavonoids quercetin, (+)-dihydroquercetin, and quercetin 3-methyl ether were isolated from the ethyl acetate fractions of the fruits and stems of Opuntia ficus-indica var. saboten. In the present study, we evaluated their protective effects against oxidative neuronal injuries induced in primary cultured rat cortical cells and their antioxidant activities by using three different cell-free bioassays. Quercetin was found to inhibit H(2)O(2)- or xanthine (X)/xanthine oxidase (XO)-induced oxidative neuronal cell injury, with an estimated IC(50) of 4-5 micro g/ml. However, it was no more protective at concentrations of 30 micro g/ml and above. (+)-Dihydroquercetin concentration-dependently inhibited oxidative neuronal injuries, but it was less potent than quercetin. On the other hand, quercetin 3-methyl ether potently and dramatically inhibited H(2)O(2)- and X/XO-induced neuronal injuries, with IC(50) values of 0.6 and 0.7 micro g/ml, respectively. All three principles markedly inhibited lipid peroxidation and scavenged 1,1-diphenyl-2-picrylhydrazyl free radicals. In addition, quercetin and quercetin 3-methyl ether were shown to inhibit XO activity in vitro, with respective IC(50) values of 10.67 and 42.01 micro g/ml. These results indicate that quercetin, (+)-dihydroquercetin, and quercetin 3-methyl ether are the active antioxidant principles in the fruits and stems of Opuntia ficus-indica var. saboten exhibiting neuroprotective actions against the oxidative injuries induced in cortical cell cultures. Furthermore, quercetin 3-methyl ether appears to be the most potent neuroprotectant of the three flavonoids isolated from this plant.

Constituents of the stems and fruits of Opuntia ficus-indica var. saboten

From the stems and fruits ofOpuntia ficus-indica var.saboten, eight flavonoids, kaempferol (1), quercetin (2), kaempferol 3-methyl ether (3), quercetin 3-methyl ether (4), narcissin (5), (+)-dihydrokaempferol (aromadendrin,6), (+)-dihydroquercetin (taxifolin,7), eriodictyol (8), and two terpenoids, (6S,9S)-3-oxo-α-ionol-|β-D-glucopyranoside (9) and corchoionoside C (10) were isolated and identified by means of chemical and spectroscopic. Among these isolates, compounds3–5 and8–10 were reported for the first time from the stems and fruits of O.ficusindica var.saboten.

Angiotensin converting enzyme inhibitory phenylpropanoid glycosides from Clerodendron trichotomum.

The stems of Clerodendron trichotomum have been traditionally used for treatment of hypertension in far East Asia including China, Korea, and Japan. Bioassay-guided fractionation and purification of the EtOAc-soluble extract of Clerodendron trichotomum afforded acteoside (1), leucosceptoside A (2), martynoside (3), acteoside isomer (4), and isomartynoside (5). The angiotensin converting enzyme (ACE) activities were significantly inhibited by the addition of these phenylpropanoid glycosides (1-5) in a dose-dependent manner of which IC(50) values were 373+/-9.3 microg/ml, 423+/-18.8 microg/ml, 524+/-28.1 microg/ml, 376+/-15.6 microg/ml, 505+/-26.7 microg/ml, respectively. These results suggest that the antihypertensive effect of Clerodendron trichotomum may be, at least in part, due to ACE inhibitory effect of phenylpropanoid glycosides.

HIV-1 integrase inhibitory phenylpropanoid glycosides from Clerodendron trichotomum.

Seven phenylpropanoid glycosides named acteoside (1), acteoside isomer (2), leucosceptoside A (3), plantainoside C (4), jionoside D (5), martynoside (6), and isomartynoside (7) were isolated from Clerodendron trichotomum. Compounds 1 and 2 showed potent inhibitory activities against HIV-1 integrase with IC50 values of 7.8 +/- 3.6 and 13.7 +/- 6.0 microM, respectively.

A Prenylated Flavonol, Sophoflavescenol: A Potent and Selective Inhibitor of cGMP Phosphodiesterase 5

During the search for naturally occurring cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5) inhibitors, it was found that the extracts from Sophora flavescens exhibit potent inhibitory activity against cGMP PDE5 prepared from rat diaphragm. Therefore, the inhibitory activities of five flavonoids, kushenol H (1), kushenol K (2), kurarinol (3), sophoflavescenol (4) and kuraridine (5), isolated from S. flavescens were measured against cGMP PDE5 to identify potent cGMP PDE5 inhibitory constituents. Among tested compounds, sophoflavescenol (4), a C-8 prenylated flavonol, showed the most potent inhibitory activity (IC(50)=0.013 microM) against cGMP PDE5 with 31.5- and 196.2-fold selectivity over PDE3 and PDE4, respectively. Kinetic analysis revealed that sophoflavescenol was a mixed inhibitor of PDE5 with a K(i) value of 0.005 microM.

Synthesis of tyrosinase inhibitory (4-oxo-4H-pyran-2-yl)acrylic acid ester derivatives

Melanogenesis is a physiological process that results in the production of melanin pigment. However, excessive accumulations of epidermal pigmentation can cause various hyperpigmentary disorders such as, melasma and age spots. Kojic acid and hydroxylated cinnamic acid derivatives are known to inhibit tyrosinase, a key component of melanin biosynthesis. Pyronyl-acrylic acid esters 3a-i, which share structural features of kojic acid and hydroxylated cinnamic acid, were prepared and their abilities to inhibit tyrosinase and melanin production were evaluated. Of the esters synthesized, 3e and 3h, which derived from diethylene glycol moieties were found to inhibit melanin production by ca. 20% at 20 microg/ml, whereas kojic acid at 200 microg/ml inhibited melanin production by 15.8%.

Antioxidant caffeic acid derivatives from leaves ofparthenocissus tricuspidata

Five caffeic acid derivatives; methyl ester of caffeoylglycolic acid (1), dimethyl ester of caffeoyltartaric acid (2), dimethyl ester of caffeoyltartronic acid (3), monomethyl ester of caffeoyltartronic acid (4), methyl ester of caffeic acid (5), and some other secondary metabolites including; quercetin, quercetin 3-O-β-D-glucuronide methyl ester, kaempferol, 3,5,7,4′-O-tetramethylkaempferol, β-sitosterol glucoside, 2α-hydroxyursolic acid and 2,24-dihydroxyursolic acid, have been isolated and characterized. All the isolated compounds were characterized with the help of NMR spectroscopy and mass spectrometry. Structure of compound3 was also confirmed by a single X-ray crystallographic technique. Isolates were evaluated for antioxidant activities and most of the tested compounds were found to be potent in DPPH free radical scavenging (IC50 = 4.56–14.17 μg/mL) and superoxide anion scavenging (IC50= 0.58–7.39 μg/mL) assays.

A new epicatechin gallate and calpain inhibitory activity from Orostachys japonicus

Calpains are calcium-dependent proteases that cleave a variety of intracellular substrates. The overactivation of mu-calpain is associated with a wide range of disease conditions. To search for calpain inhibitors from natural products, the phytochemical constituents of the ethyl acetate fraction of the whole plant of Orostachys japonicus (Crassulaceae) were studied. The various chromatographic separation of this fraction led to the isolation of a new tannin, (-)-epicatechin 5-gallate (1) along with 9 known compounds. Their structures were elucidated by spectroscopic and chemical analyses. Among them, (-)-epicatechin 5-gallate (1) and kaempferol (9) exhibited moderate inhibitory activity against mu-calpain with IC(50) values of 18.0+/-2.9 and 15.4+/-2.0 microg/ml, respectively.

A new pterocarpan, (-)-maackiain sulfate, from the roots of Sophora subprostrata.

A new pterocarpan, (-)-maackiain 3-sulfate (1) was isolated from the methanol extract of roots of Sophora subprostarata together with (-)-maackiain (2), trifolirhizin (3), lupeol (4), ononin (5), 7,4′-dihydroxyflavone (6), and (+)-syringaresinol (7). The structure of1 was determined by analyses of 2D NMR and HRFABMS. Compounds5–7 were isolated from this plant for the first time.

Anti-herpetic activity of various medicinal plant extracts.

In order to find antiviral compounds againstHerpes simplex virus type I (HSV-1) and II (HSV-2) from natural products, a convenient virus-induced cytopathic effect (CPE) inhibition assay was introduced. More than 300 fractions were prepared by solvent fractionation from sixty collected plants or purchased herbal medicines, and their anti-herpetic activities were evaluated. Among them, several medicinal plants showed potent anti-herpetic activity. Selective indexes (SI) of the EtOAc extract of Caraganae Radix (Caragana sinica) against HSV-1 and HSV-2 were more than 8.06 and 24.79, SI of the MeOH extract ofAcer okamotoanum leaves were 3.92 and 3.51, SI of the CH2Cl2 extract of Veratri Rhizoma et Radix (Veratrum patulum) were 5.49 and 1.31 and SI of the MeOH extract of aerial part of Osmundae Rhizoma (Osmunda japonica) were more than 3.45 and 1.25, respectively.