Yeon-Hee Seong

Effects of ginseng total saponin on cocaine-induced hyperactivity and conditioned place preference in mice

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.

Blockade by ginseng total saponin of the development of cocaine induced reverse tolerance and dopamine receptor supersensitivity in mice

Daily repeated administration of cocaine (15 mg/kg, over a 7-day period) developed reverse tolerance to the ambulation-accelerating effect of cocaine. Intraperitoneal administration of ginseng total saponin (GTS, 100 and 200 mg/kg of body weight) prior to and during chronic administration of cocaine inhibited the development of reverse tolerance. Dopamine receptor supersensitivity was also developed in reverse tolerant mice that had received the same cocaine. The development of dopamine receptor supersensitivity was evidenced by the enhanced hypothermic response to apomorphine (1 mg/kg) and the enhanced ambulatory activity of apomorphine (4 mg/kg). GTS also prevented the development of dopamine receptor supersensitivity induced by the chronic administration of cocaine. These results provide that GTS may be useful for the prevention and therapy of the adverse action of cocaine. It is concluded that the development of reverse tolerance to the ambulation-accelerating effect of cocaine may be associated with the enhanced dopamine receptor sensitivity because both phenomena were blocked by GTS.

Cytotoxic constituents from angelicae sinensis radix.

Cytotoxic bioassay-guided fractionation of methanol extract of Angelicae Sinensis Radix led to the isolation of a new dimericZ-ligustilide, named neodiligustilide (1), together with three known compounds,Z-ligustilide (2), 11(S),16(R)-dihydroxy-octadeca-9Z, 17-dien-12, 14-diyn-1-yl acetate (3), and 3(R), 8(S)-falcarindiol (4). Among them, 2 showed the strongest cytotoxicity against L1210 and K562 cell lines with IC50 values of 2.27 ± 0.10 and 4.78 ± 0.18 μM, respectively, while 1 showed moderate cytotoxicity with IC50 values of 5.45 ±0.19 and 9.87 ±0.14 μM. Two polyacetylenes, 3 and 4, showed cytotoxicity only against L1210 cell line with IC50 values of 2.60 ± 0.90 and 2.87 ± 0.49 μM, respectively.

Inhibitory effect on TNF-α-induced IL-8 production in the HT29 cell of constituents from the leaf and stem ofWeigela subsessilis

Twelve compounds were isolated from the MeOH extract of the leaf and stem of the Korean endemic plantWeigela subsessilis L. H. Bailey. Their chemical structures were elucidated on the basis of physicochemical and spectroscopic data and by comparison with those of published literatures. These compounds were identified as three sterols, β-sitosterol acetate (2), β-sitosterol (3), daucosterol (11), eight triterpenoids, squalene (1), ursolic acid (4), ilekudinol A (5), corosolic acid (6), ilekudinol B (7), esculentic acid (8), pomolic acid (9), asiatic acid (10), and one iridoid glycoside, alboside I (12). This is the first report pertaining to the isolation of these compounds fromWeigela subsessilis L. H. Bailey. In addition, three compounds7, 9, and12 were found to display a strong inhibitory effect on the production of IL-8 in the HT29 cells stimulated by TNF-α.

β-Secretase (BACE1) inhibitors from Sanguisorbae Radix

In the course of screening anti-dementia agents from natural products, two β-secretase (BACE1) inhibitors were isolated from the ethyl acetate soluble fraction of Sanguisorbae Radix by the activity-guided purification using silica gel, Sephadex LH-20, and RP-HPLC. They were identified as 1,2,3-trigalloyl-4,6-hexahydroxydiphenoyl-β-d-glucopyranoside (Tellimagrandin II,1) and 1,2,3,4,6-pentagalloyl-β-d-glucopyranoside (2) and were shown to non-competitively inhibit β-secretase (BACE1) with the IC50 values of 3.10×10−6 M and 3.76×10−6 M, respectively. TheKi values of1 and2 were 6.84×10−6 M and 5.13×10−6 M. They were less inhibitory to α-secretase (TACE) and other serine proteases such as chymotrypsin, trypsin, and elastase, suggesting that they were relatively specific inhibitors of BACE1.

Effects of ginseng total saponin on morphine-induced hyperactivity and conditioned place preference in mice

A single or repeated administration of morphine in mice produced hyperactivity, conditioned place preference (CPP) and postsynaptic dopamine (DA) receptor supersensitivity. The hyperactivity induced by morphine was evidenced by measuring the enhanced ambulatory activity using a tilting-type ambulometer. CPP effects were evaluated assessing the increased time spent by the mice to morphine and the inhibition of CPP by the decreased time spent by the mice in the white compartment. Postsynaptic DA receptor supersensitivity in mice displaying a morphine-induced CPP was evidenced by the enhanced response in ambulatory activity to the DA agonist, apomorphine (2 mg/kg, s.c.). The intraperitoneal injection of ginseng total saponin (GTS) from the root of Panax ginseng C.A. Meyer (Araliaceae), prior to and during the morphine treatment in mice inhibited morphine-induced hyperactivity and CPP. GTS inhibited the development of postsynaptic DA receptor supersensitivity. A single dose administration of GTS also inhibited apomorphine-induced climbing behavior, showing the antidopaminergic action of GTS at the postsynaptic DA receptor. These results suggest that the development of morphine-induced CPP may be associated with the enhanced DA receptor sensitivity and that GTS inhibition of the morphine-induced hyperactivity and CPP may be closely related with the inhibition of dopaminergic activation induced by morphine.

Syringin from stem bark of Fraxinus rhynchophylla protects Aβ(25–35)-induced toxicity in neuronal cells

The medicinal herb Jinpi, derived from the dried stem barks of Fraxinus rhynchophylla belonging to Oleaceae is widely used as a variety of Korean folk remedies for anti-inflammatory, febricide, antidiarrhea, and antileukorrhea diseases. In the course of screening antidementia agents from natural products, F. rhynchophylla showed significant inhibitory activity toward Aβ(25–35)-induced neuronal cell death. An active principle was isolated and identified as syringin. When the neuroblastoma cells were exposed to 50 μM Aβ(25–35), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction rate (survival rate) decreased to 60.21 ± 2.16% over control while syringin treated ones recovered cell viability up to 79.12 ± 1.39% at 20 μM. In addition, 20 μM syringin almost completely removed Aβ(25–35)-induced reactive oxygen species. The neuroprotective effect of syringin seemed to be originated from the reduction of apoptosis since decrease in caspase-3 activity and expression, reduction in cleaved PARP, and DNA fragmentation were observed. These results suggest that F. rhynchophylla and syringin are expected to be useful for preventing Aβ(25–35)-induced neuronal cell damage.

Effects of ginseng total saponins on the antinociception and the tolerance development of U-50,488H

These studies were performed to investigate the acting sites of ginseng total saponins (GTS) on the U-50,488H-induced antinociception. And the possible mechanisms of the antagonistic effect on the U-50,488H-induced antinociception and the inhibitory effect of the development of tolerance to U-50,488H-induced antinociception by GTS were studied. The U-50,488H-induced antinociception was antagonized in mice pretreated with GTS intraperitoneally, intracerebrally and intrathecally. These antagonisms were reversed by the pretreatment with a serotonin precursor, 5-hydroxytryptophan (5-HTP), but not with a noradrenaline precursor, L-dihydroxyphenylalanine (L-DOPA). However, the intraplantar administration of GTS did not alter the intraplantar U-50,488H-induced antinociception. These findings suggest that U-50,488H-induced antinociception are mediated via the spinal and supraspinal sites. On the other hand, GTS inhibited the development of tolerance to U-50,488H-induced antinociception. The inhibitory effect of GTS on the development of tolerance to U-50,488H-induced antinociception was reversed by pretreatment with 5-HTP, but not with L-DOPA. Therefore, the antagonism of U-50,488H-induced antinociception and the inhibition of the development of tolerance to U-50,488H-induced antinociception by GTS are dependent on serotonergic mechanisms.