Tae Su Jang

Two new secoiridoid glycosides from the rhizomes of Gentiana scabra Bunge

Two new secoiridoid glycosides, 4‴-O-β-D-glucopyranosyltrifloroside 1 and 4‴-O-β-D-glucopyranosylscabraside 2, along with three known secoiridoids were isolated from the rhizomes of Gentiana scabra (Gentianaceae) in our recent phytochemical study. Their chemical structures were determined by spectroscopic data including 1D and 2D NMR spectra. The chemotaxonomic significance of the secoiridoid glycosides is briefly discussed.

Steroidal Alkaloids from Veratrum nigrum Enhance Glucose Uptake in Skeletal Muscle Cells

Veratrum nigrum is recognized as a medicinal plant used for the treatment of hypertension, stroke, and excessive phlegm. Chemical investigation of the roots and rhizomes led to the isolation of five new steroidal alkaloids, jervine-3-yl formate (1), veramarine-3-yl formate (2), jerv-5,11-diene-3β,13β-diol (3), (1β,3β,5β)-1,3-dihydroxyjervanin-12(13)-en-11-one (4), and veratramine-3-yl acetate (5). Compounds 1 and 5 exhibited potent inhibitory activity (11.3 and 4.7 μM, respectively) against protein tyrosine phosphatase 1B (PTP1B), which has emerged as a viable target for treatment of type 2 diabetes mellitus. On the basis of their PTP1B inhibitory activity, the compounds were evaluated for their potential to enhance glucose uptake in C2C12 skeletal muscle cells. The insulin-stimulated glucose uptake was enhanced upon treatment with compounds 1 and 5 (10 μM) by 49.9 ± 6.5% and 56.0 ± 9.7%, respectively, in a more potent manner than that with the positive control rosiglitazone (47.3 ± 3.4% at 30 μM). These results suggest that steroidal alkaloids serve as practical antidiabetes mellitus leads capable of enhancing glucose uptake.

Protective effect of lanostane triterpenoids from the sclerotia of Poria cocos Wolf against cisplatin-induced apoptosis in LLC-PK1 cells

Cisplatin-induced nephrotoxicity is a serious adverse effect that limits the use of cisplatin in cancer patients. In the present study, we investigated the protective effect of lanostane triterpenoids (1-10) isolated from the ethanolic extract of Poria cocos Wolf against cisplatin-induced cell death in LLC-PK1 kidney tubular epithelial cells. Treatment of cisplatin induced significant cell death, which was suppressed by treatment with dehydroeburicoic acid monoacetate (1) and 3β-acetoxylanosta-7,9(11),24-trien-21-oic acid (9). Compound 1 exhibited the highest efficacy among the tested compounds and was thus subjected to further mechanistic studies. The increase in the percentage of apoptotic cells induced by cisplatin reduced by 4.3% after co-treatment of cells with compound 1 (50 and 100μM). Furthermore, phosphorylation of the mitogen-activated protein kinases JNK, ERK, and p38, and caspase-3, which characterize oxidative stress-mediated apoptosis, increased significantly after treatment with cisplatin, and decreased after treatment with compound 1. These results indicate that the renoprotective effects of compound 1 may be mediated by its anti-apoptotic activity.

Caffeoyl glucosides from Nandina domestica inhibit LPS-induced endothelial inflammatory responses.

Endothelial dysfunction is a key pathological feature of many inflammatory diseases, including sepsis. In the present study, a new caffeoyl glucoside (1) and two known caffeoylated compounds (2 and 3) were isolated from the fruits of Nandina domestica Thunb. (Berberidaceae). The compounds were investigated for their effects against lipopolysaccharide (LPS)-mediated endothelial inflammatory responses. At 20 μM, 1 and 2 inhibited LPS-induced hyperpermeability, adhesion, and migration of leukocytes across a human endothelial cell monolayer in a dose-dependent manner suggesting that 1 and 2 may serve as potential scaffolds for the development of therapeutic agents to treat vascular inflammatory disorders.

Chemical constituents from the rare mushroom Calvatia nipponica inhibit the promotion of angiogenesis in HUVECs

Calvatia species, also known as puffball mushrooms, are common sources of food worldwide. Calvatia nipponica (Agaricaceae) is one of the most rare species in the Calvatia genus. It was first validated in 2008. Due to its scarcity, C. nipponica has never been chemically investigated. Its recent discovery in Korea allowed to conduct this study, and using bioactivity-guided fractionation for antiangiogenic activity, chemical investigation of the MeOH extract of the fruiting bodies of C. nipponica led to the isolation of five alkaloids (1-5) and two phenolic compounds (6-7). This is the first study to report the chemical investigation of C. nipponica, and compound 1 was previously reported as chemically synthesized only until our report of its isolation and identification from natural sources. The structure of 1 was determined by spectroscopic analysis by 1D and 2D NMR spectra and HR-MS. All compounds (1-7) were tested for inhibition of angiogenesis using human umbilical vein endothelial cells (HUVECs). Compounds 2, 4 and 5 significantly inhibited the promotion of angiogenesis in HUVECs. Compound 5 showed the most potent inhibition via downregulation of VEGF, p38 and ERK signaling pathways. These results suggested that the rare mushroom C. nipponica might be beneficial in antiangiogenesis therapy for cancer treatment.

Cytotoxic effect of sanguiin H-6 on MCF-7 and MDA-MB-231 human breast carcinoma cells

Sanguiin H-6 is a dimer of casuarictin linked by a bond between the gallic acid residue and one of the hexahydroxydiphenic acid units. It is an effective compound extracted from Rubus coreanus. It has an anticancer effect against several human cancer cells; however, its effect on breast cancer cells has not been clearly demonstrated. Thus, we aimed to investigate the anticancer effect and mechanism of action of sanguiin H-6 against two human breast carcinoma cell lines (MCF-7 and MDA-MB-231). We found that sanguiin H-6 significantly reduced cell viability in a concentration-dependent manner. It also increased the rates at which MCF-7 and MDA-MB-231 cells underwent apoptosis. Furthermore, sanguiin H-6 induced the cleavage of caspase-8, caspase-3, and poly(ADP-ribose) polymerase, which resulted in apoptosis. However, cleavage of caspase-9 was only detectable in MCF-7 cells. In addition, sanguiin H-6 increased the ratio of Bax to Bcl-2 in both MCF-7 and MDA-MB-231 cells. These findings suggest that sanguiin H-6 is a potent therapeutic agent against breast cancer cells. In addition, it exerts its anticancer effect in an estrogen-receptor-independent manner.

Antigastritis effects of Armillariella tabescens (Scop.) Sing. and the identification of its anti-inflammatory metabolites

This study demonstrates the biological and chemical analysis of the mushroom Armillariella tabescens (Scop.) Sing. (Tricholomataceae).

Curcuzedoalide contributes to the cytotoxicity of Curcuma zedoaria rhizomes against human gastric cancer AGS cells through induction of apoptosis

ETHNOPHARMACOLOGICAL RELEVANCE Curcuma zedoaria Roscoe (Zingiberaceae), also known as white turmeric or zedoaria, has been used in Ayurveda and traditional Chinese medicine to treat various cancers, and it possesses several sesquiterpenoid compounds. OBJECTIVE This study aimed to evaluate the therapeutic effects of a methanolic (MeOH) extract of C. zedoaria rhizomes, as well as its active constituents, against gastric cancer, which is a frequently diagnosed cancer in South Korea. MATERIALS AND METHODS Repeated column chromatography, together with semi-preparative HPLC purification, was used to separate the bioactive constituents from the C. zedoaria MeOH extract. The cytotoxic effects of the C. zedoaria MeOH extract and its active compounds were measured in human gastric cancer AGS cells. Expression of proteins related to apoptosis was evaluated using Western blotting analysis. RESULTS The MeOH extract of C. zedoaria rhizomes exerted a cytotoxic effect on AGS cells (IC50: 96.60 ± 4.87μg/mL). Based on the bioactivity-guided fractionation for antiproliferative activity, a chemical investigation of the MeOH extract led to the isolation of five sesquiterpenes including isoprocurcumenol (1), germacrone (2), curzerenone (3), curcumenol (4), and curcuzedoalide (5). Among these, curcuzedoalide demonstrated the strongest effect in suppressing gastric cancer cell proliferation in a dose-dependent manner with an IC50 value of 125.11±2.77μM. Western blotting analysis showed that curcuzedoalide inhibited AGS human gastric cancer cell viability by activating caspase-8, caspase-9, caspase-3, and PARP, which contributed to apoptotic cell death in AGS human gastric cancer cells. CONCLUSION These data indicate that curcuzedoalide contributed to the cytotoxicity of C. zedoaria by activating the cleavage of caspases and PARP, which are representative markers for apoptosis. Therefore, curcuzedoalide is a positive candidate for the development of novel chemotherapeutics.

Chemical characterization of cytotoxic indole acetic acid derivative from mulberry fruit (Morus alba L.) against human cervical cancer

The fruit of the white mulberry tree (Morus alba L.) is a multiple fruit with a sweet flavor commonly consumed around the world. Chemical investigation of the fruits led to the isolation of two indole acetic acid derivatives (1 -2) including a new compound, which turned out to be an isolation artifact, 3S-(β-D-glucopyranosyloxy)-2,3-dihydro-2-oxo-1H-indole-3-acetic acid butyl ester (1), along with five known compounds (3 -7). Compounds 2 and 7 were newly identified from mulberry fruit. The new isolation artifact (1) exhibited cytotoxic effect on human cervical cancer Hela cells in a dose-dependent manner. Compound 1 activated caspase-8, caspase-9, and caspase-3, followed by cleavage of PARP, a substrate of caspase-3, in a dose-dependent manner. Simultaneous alterations in protein expression of mitochondrial factors Bax, BID and Bcl-2 were also observed. A comparison between compounds 1 and 2 led to a structure-activity relationship analysis of the cytotoxic effect. These results suggest that compound 1 could be beneficial in human cervical cancer treatment, and provide a theoretical basis for further application of compound 1.

In vitro assessment of selected Korean plants for antioxidant and antiacetylcholinesterase activities

Abstract Context: Antiacetylcholinesterase (AChE) drugs have been a main therapeutic treatment for Alzheimer’s disease because increased AChE levels play a key role in reducing neurotransmission. Objectives: Extracts from 35 Korean plants were selected and screened for antioxidant and anti-cholinesterase activity to explore new sources derived from Korean natural resources that could be used as AD therapeutic agents. Materials and methods: The antioxidant effect of extracts from 35 selected Korean plants was determined using two most common free radical scavenging assays using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS). Additionally, the effect of extracts, identified as antioxidants, on acetylcholinesterase inhibition was assessed by an acetylcholinesterase assay kit. Results: Out of 36 extracts of 35 plants tested, Oenothera biennis L. (9.09 μg/mL), Saururus chinensis (Lour.) Baill. (9.52 μg/mL) and Betula platyphylla var. japonica (9.85 μg/mL) showed strong DPPH scavenging activity. Twelve other extracts also exerted moderate free radical scavenging activities with IC50 values ranging from 10 to 50 μg/mL. Antioxidant capacity detected by ABTS assay was only significant in O. biennis (23.40 μg/mL), while the other extracts were weak or unable to reduce the production of ABTS. Based on the antioxidant activities of these plant extracts, 19 extracts with IC50 values less than 100 μg/mL in DPPH assay were selected for further AChE inhibition assay. Among the extracts tested, the IC50 value for Prunella vulgaris var. lilacina NAKAI (18.83 μg/mL) in AChE inhibitory activity was the lowest, followed by O. biennis (20.09 μg/mL) and Pharbitis nil Chosy (22.79 μg/mL). Conclusions: Considering complex multifactorial etiology of AD, the extracts of P. vulgaris var. lilacina (aerial part), O. biennis (seed) and P. nil (seed) may be safe and ideal candidates for future AD modifying therapies.