Falcarindiol and dichloromethane fraction are bioactive components in Oplopanax elatus: Colorectal cancer chemoprevention via induction of apoptosis and G2/M cell cycle arrest mediated by cyclin A upregulation.

Oplopanax elatus (Nakai) Nakai has a long history of use as an ethnomedicine by the people living in eastern Asia. However, its bioactive constituents and cancer chemopreventive mechanisms are largely unknown. The aim of this study was to prepare O. elatus extracts, fractions, and single compounds and to investigate the herb's antiproliferative effects on colon cancer cells and the involved mechanisms of action. Two polyyne compounds were isolated from O. elatus, falcarindiol and oplopandiol. Based on our HPLC analysis, falcarindiol and oplopandiol are major constituents in the dichloromethane (CH2Cl2) fraction. For the HCT-116 cell line, the dichloromethane fraction showed significant effects. Furthermore, the IC50 for falcarindiol and oplopandiol was 1.7 µM and 15.5 µM, respectively. In the mechanistic study, after treatment with 5 µg/ml for 48 h, dichloromethane fraction induced cancer cell apoptosis by 36.5% (p < 0.01% vs. control of 3.9%). Under the same treatment condition, dichloromethane fraction caused cell cycle arrest at the G2/M phase by 32.6% (p < 0.01% vs. control of 23.4%), supported by upregulation of key cell cycle regulator cyclin A to 21.6% (p < 0.01% vs. control of 8.6%). Similar trends were observed by using cell line HT-29. Data from this study filled the gap between phytochemical components and the cancer chemoprevention of O. elatus. The dichloromethane fraction is a bioactive fraction, and falcarindiol is identified as an active constituent. The mechanisms involved in cancer chemoprevention by O. elatus were apoptosis induction and G2/M cell cycle arrest mediated by a key cell cycle regulator cyclin A.

Inhibitory Mechanisms of Water Extract of Oplopanax elatus on Lipopolysaccharide-Induced Inflammatory Responses in RAW 264.7 Murine Macrophage Cells.

OBJECTIVE: To study the anti-inflammatory action and cellular mechanism of Oplopanax elatus. METHODS: A hot water extract of OE (WOE) was prepared and a major constituent, syringin, was successfully isolated. Its content in WOE was found to be 214.0 µg/g dried plant (w/w). Their anti-inflammatory activities were examined using RAW 264.7 macrophages and a mouse model of croton oil-induced ear edema. RESULTS: In lipopolysaccharide (LPS)-treated RAW 264.7 cells, a mouse macrophage cell line, WOE was found to significantly and strongly inhibit cyclooxygenase-2 (COX-2)-induced prostaglandin E2 (PGE2) production [half maximal inhibitory concentration (IC50)=135.2 µg/mL] and inducible nitric oxide synthase (iNOS)-induced NO production (IC50=242.9 µg/mL). In the same condition, WOE was revealed to inhibit NO production by down-regulating iNOS expression, mainly by interrupting mitogen activated protein kinases (MAPKs)/activator protein-1 (AP-1) pathway. The activation of all three major MAPKs, p38 MAPK, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase, was inhibited by WOE (50-300 µg/mL). On the other hand, WOE reduced PGE2 production by inhibiting COX-2 enzyme activity, but did not affect COX-2 expression levels. In addition, WOE inhibited the production of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. In croton oil-induced ear edema in mice, oral administration of WOE (50-300 mg/kg) dose-dependently inhibited edematic inflammation. CONCLUSION: Water extract of OE exhibited multiple anti-inflammatory action mechanisms and may have potential for treating inflammatory disorders.

Adventitious root cultures of Oplopanax elatus inhibit LPS-induced inflammation via suppressing MAPK and NF-κB signaling pathways.

Bioreactor-cultured adventitious roots (ARs) of the endangered medicinal plant Oplopanax elatus Nakai is a novel alternative plant material. To utilize ARs in the product production, the present study investigated the anti-inflammatory effect of O. elatus ARs. In the in vivo experiment, lipopolysaccharide (LPS)-induced acute lung injury disease model was established and several inflammatory indexes were determined. For the LPS-stimulated mice, after pretreatment of AR crude extract (200 mg/kg), cell infiltration in lungs was decreased, the production of proinflammatory mediators, including nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin (IL)-6, and 1ß in the bronchoalveolar lavage fluid was evidently reduced, which indicated that O. elatus ARs had an anti-inflammatory effect. In the in vitro experiment, ethyl acetate (EtOAc) fractions (12.5, 25, and 50 µg/mL) were used to treat LPS-induced peritoneal macrophages (PMs) of mice. The production of NO, prostaglandin E2, TNF-α, IL-6, and IL-1ß in LPS-stimulated PMs was obviously inhibited (p < 0.05) after pretreatment with EtOAc fractions, and the expression of the inducible nitric oxide synthase and cyclooxygenase were also suppressed. To clarify the anti-inflammatory mechanism, effects of EtOAc fraction on changes of proteins related to the pathways of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) were investigated. The phosphorylation of extracellular regulated protein kinases, c-jun n-terminal kinase, and p38 MAPK in LPS-induced PMs was inhibited after pretreatment of EtOAc fractions. In addition, EtOAc fractions enhanced inhibitor of nuclear factor-kappa B-α expression and decreased nuclear translocation of p65 NF-κB. Thus, EtOAc from O. elatus ARs is involved in regulating MAKP and NF-κB signaling pathways to inhibit LPS-induced inflammation.

Chemo-Preventive Potential of Falcarindiol-Enriched Fraction from Oplopanax elatus on Colorectal Cancer Interfered by Human Gut Microbiota.

Oplopanax elatus (Nakai) Nakai is an oriental herb, the polyyne-enriched fraction of which (PEFO) showed anticolorectal cancer (anti-CRC) effects. Other concomitant components, which are inevitably bio-transformed by gut microbiota after oral administration, might be interfere with the pharmacodynamics of polyynes. However, the influence of human gut microbiota on molecules from O. elatus possessing anticancer activity are yet unknown. In this study, the compounds in PEFO and PEFO incubated with human gut microbiota were analyzed and tentatively identified by HPLC-DAD-QTOF-MS. Two main polyynes ((3S,8S)-falcarindiol and oplopandiol) were not significantly decomposed, but some new unknown molecules were discovered during incubation. However, the antiproliferative effects of PEFO incubated with human gut microbiota for 72 h (PEFO I) were much lower than that of PEFO on HCT-116, SW-480, and HT-29 cells. Furthermore, PEFO possessed better anti-CRC activity in vivo, and significantly induced apoptosis of the CRC cells, which was associated with activation of caspase-3 according to the Western-blot results (P<0.05). These results suggest anticolorectal cancer activity of polyynes might be antagonized by some bio-converted metabolites after incubation with human gut microbiota. Therefore, it might be better for CRC prevention if the polyynes could be orally administrated as purified compounds.

Devil's Club Falcarinol-Type Polyacetylenes Inhibit Pancreatic Cancer Cell Proliferation.

Natural falcarinol-type (FC-type) polyacetylenes are known to show anticancer activities. We studied the bioactivity of synthetic FC, 1,2-dihydrofalcarinol (FCH) and 3-acetoxyfalcarinol (FCA) and compared them with the natural bioactive polyacetylene [9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate] (DCA) isolated from Devil's club (DC) Oplopanax horridus. Antiproliferation activity of these polyacetylenes, along with DC inner stem bark 70% ethanol and water extracts, was tested on human pancreatic ductal adenocarcinoma cell lines PANC-1 and BxPC-3. Chemically synthesized FC and FCA showed consistent IC50 (50% inhibition concentration) and higher potency than DCA. FC and DCA's mechanism of action investigated by antibody array on apoptosis-associated genes, and cellular features confirmed by microscopy demonstrated that both compounds modulated genes related to pro-apoptosis, antiapoptosis, apoptosis, cell cycle, stress related, and death receptors. FC-type polyacetylenes with a terminal double bond (FC, FCA, and DCA) are potent inhibitors of pancreatic cancer cell proliferation compared to FCH with a terminal single bond. Liquid chromatography mass spectrometry confirmed the presence of FC and FCH in the inner stem bark of DC. For potential applications of FC-type polyacetylenes as anticancer agents, preparing them by chemical synthesis may provide an advantage over the labor intensive extraction process from raw plant material.

Synergetic Inhibition of Human Colorectal Cancer Cells by Combining Polyyne-Enriched Fraction from Oplopanax elatus and Irinotecan.

Although irinotecan is an important anticancer drug for treating colorectal cancer, its dose-dependent side effects limited its clinical application. Thus, it's important to develop low-toxic candidates to enhance the efficacy of irinotecan. Polyynes from genus Oplopanax were reported to possess potential anticancer effects on colorectal cancer. Hereby, we evaluated the synergetic inhibition of human colorectal cancer cells by combining polyyne-enriched fraction from Oplopanax elatus (the dichloromethane fraction of Oplopanax elatus, OED) and irinotecan. The results showed that 5 µg/ml of OED combined with 40 µM of irinotecan possessed significant synergetic inhibition on SW-480 cells with a combination index (CI) of 0.56. Besides, the percentage of apoptotic cells was significantly increased from 69.57% (40 µM of irinotecan) or 72.7% (5 µg/ml of OED) to 95.6% after treatment of OED combined with irinotecan (OCI), suggesting OED and irinotecan possess the synergistic apoptotic effect (P < 0.01). Furthermore, Caspase-3 was significantly activated in OCI group (P < 0.05). Besides, the percentage of apoptotic cells of OED or/and irinotecan significantly decreased after inhibition of caspase-3. These data indicated that OED could enhance antiproliferative effects of irinotecan on colorectal cancer cells, which was related with induction of apoptosis and regulations of activity of caspase-3.

Polyyne-Enriched Extract from Oplopanax elatus Significantly Ameliorates the Progression of Colon Carcinogenesis in ApcMin/+ Mice.

Colorectal cancer (CRC) is the third most common cancer in the world. Oplopanax elatus is widely used in traditional medicine. However, little is known about its pharmacological effects and bioactive compounds. We evaluated the effects of the polyyne-enriched extract from O. elatus (PEO) on the progression of colon carcinogenesis in ApcMin/+ mice. In addition, these effects were also investigated in HCT116 and SW480 cells. After PEO oral administration (0.2% diet) for 12 weeks, PEO significantly improved body weight changes and reduced the tumor burden and tumor multiplicity compared with the untreated mice. Meanwhile, western blot and immunohistochemistry results showed PEO significantly reduced the expression of ß-catenin and cyclinD1 in both small intestine and the colon tissues compared with the untreated mice. In addition, PEO treatment significant decreased the cell viability in both HCT116 and SW480 cell lines. It also decreased the levels of ß-catenin, cyclinD1, c-myc and p-GSK-3ß in HCT116 and SW480 cells at 25 µM. These results indicate that PEO may have potential value in prevention of colon cancer by down-regulating Wnt-related protein.

Pharmacokinetic profiles of falcarindiol and oplopandiol in rats after oral administration of polyynes extract of Oplopanax elatus.

Polyynes, such as facarindiol (FAD) and oplopandiol (OPD), are responsible for anticancer activities of Oplopanax elatus (O. elatus). A novel approach to pharmacokinetics determination of the two natural polyynes in rats was developed and validated using a liquid chromatography-electrospray ionization-mass spectrometry (LC-MS) method. Biosamples were prepared by liquid-liquid extraction using ethyl acetate/n-hexane (V : V = 9 : 1) and the analytes were eluted on an Agilent ZORBAX Eclipse Plus C18 threaded column (4.6 mm × 50 mm, 1.8 µm) with the mobile phase of acetonitrile-0.1% aqueous formic acid at a flow-rate of 0.5 mL·min(-1) within a total run time of 11 min. All analytes were simultaneously monitored in a single-quadrupole mass spectrometer in the selected ion monitoring (SIM) mode using electrospray source in positive mode. The method was demonstrated to be rapid, sensitive, and reliable, and it was successfully applied to the pharmacokinetic studies of the two polyynes in rat plasma after oral administration of polyynes extract of O. elatus.

Screening and identifying antioxidants from Oplopanax elatus using 2,2'-diphenyl-1-picrylhydrazyl with off-line two-dimensional HPLC coupled with diode array detection and tandem time-of-flight mass spectrometry.

The root of Oplopanax elatus (Nakai) Nakai has a well-known history of use for the treatment of diseases such as neurasthenia, cardiovascular disorders, and cancer by the native people in northeast China. It is important to screen and identify the bioactive molecules from its root rapidly. Hereby, an off-line two-dimensional high performance liquid chromatography coupled with diode array detection and tandem time-of-flight mass spectrometry together with 2,2'-diphenyl-1-picrylhydrazyl was established to screen antioxidants from the root of O. elatus. A Waters cyanogen column (150 × 3.9 mm, id, 4 µm) was used for the first dimensional liquid chromatography, while a Hypersil BDS-C18 column (250 × 4.6 mm, id, 5 µm) was installed for the second dimension liquid chromatographic analysis. Twenty-eight compounds had been tentatively identified from the methanol extract of the air-dried root of O. elatus including six polyynes and eight phenolic derivatives were screened with antioxidant activity. The developed method could be expedient for screening and identifying antioxidants from O. elatus.

Inhibition of Human Pancreatic Cancer Cell Proliferation by Devil's Club Oplopanax horridus and Its Polyacetylene Bioactive Compound.

Devil's club Oplopanax horridus (DC) is a close relative of ginseng; its inner root and stem bark extract showed antiproliferation activity on human leukemia, ovarian, breast and colon cancer cells. We study here the effects of DC 70% ethanol extract alone, or in combination with cisplatin, gemcitabine, and paclitaxel on pancreatic endocrine HP62 and pancreatic ductal carcinoma PANC-1 and BxPC-3 cells. Antiproliferation activity assay, cell cycle analysis by flow cytometry, apoptosis-related markers by antibody array, and RT-PCR assay were used for this study. DC extract inhibited proliferation of HP62 with IC50 (50% inhibition concentration) at 0.037±0.002% (v/v), PANC-1 at 0.0058 ± 0.0004% and BxPC-3 at 0.021 ± 0.003%. DC at 0.0033% combined with 1 nM of paclitaxel showed inhibition synergy on PANC-1 cells with a combination index of 0.44. Apoptosis focused antibody array profile indicated upregulation of cytochrome C, claspin, cIAP-2 and HTRA2/Omi apoptosis-related markers in DC-treated HP62 and PANC-1. Our data suggest that DC acts through targeting the intrinsic mitochondrial apoptosis pathway in the pancreatic cancer cells. The high antiproliferation potency of DC on PANC-1 is potentially useful as an adjunct therapy for treating pancreatic cancer, which is known for developing resistance to conventional chemotherapeutics.

Unstable simple volatiles and gas chromatography-tandem mass spectrometry analysis of essential oil from the roots bark of Oplopanax horridus extracted by supercritical fluid extraction.

Volatile oil from the root bark of Oplopanax horridus is regarded to be responsible for the clinical uses of the title plant as a respiratory stimulant and expectorant. Therefore, a supercritical fluid extraction method was first employed to extract the volatile oil from the roots bark of O. horridus, which was subsequently analyzed by GC/MS. Forty-eight volatile compounds were identified by GC/MS analysis, including (S,E)-nerolidol (52.5%), τ-cadinol (21.6%) and S-falcarinol (3.6%). Accordingly, the volatile oil (100 g) was subjected to chromatographic separation and purification. As a result, the three compounds, (E)-nerolidol (2 g), τ-cadinol (62 mg) and S-falcarinol (21 mg), were isolated and purified from the volatile oil, the structures of which were unambiguously elucidated by detailed spectroscopic analysis including 1D- and 2D-NMR techniques.

Extracts of Devil's club (Oplopanax horridus) exert therapeutic efficacy in experimental models of acute myeloid leukemia.

Acute myeloid leukemia (AML) is a group of hematological malignancies defined by expanded clonal populations of immature progenitors (blasts) of myeloid phenotype in blood and bone marrow. Given a typical poor prognostic outlook, there is great need for novel agents with anti-AML activity. Devil's club (Oplopanax horridus) is one of the most significant medicinal plants used among the indigenous people of Southeast Alaska and the coastal Pacific Northwest, with different linguistic groups utilizing various parts of the plant to treat many different conditions including cancer. Studies identifying medically relevant components in Devil's club are limited. For this research study, samples were extracted in 70% ethanol before in vitro analysis, to assess effects on AML cell line viability as well as to study regulation of tyrosine phosphorylation and cysteine oxidation. The root extract displayed better in vitro anti-AML efficacy in addition to a noted anti-tyrosine kinase activity independent of an antioxidant effect. In vivo therapeutic studies using an immunocompetent murine model of AML further demonstrated that Devil's club root extract improved the murine survival while decreasing immunosuppressive regulatory T cells and improving CD8+ T-cell functionality. This study defines for the first time an anti-AML efficacy for extracts of Devil's club.

Chemopreventive effects of oplopantriol A, a novel compound isolated from Oplopanax horridus, on colorectal cancer.

Oplopanax horridus is a North American botanical that has received limited investigations. We previously isolated over a dozen of the constituents from O. horridus, and among them oplopantriol A (OPT A) is a novel compound. In this study, we firstly evaluated the in vivo chemoprevention activities of OPT A using the xenograft colon cancer mouse model. Our data showed that this compound significantly suppressed tumor growth with dose-related effects (p < 0.01). Next, we characterized the compound's growth inhibitory effects in human colorectal cancer cell lines HCT-116 and SW-480. With OPT A treatment, these malignant cells were significantly inhibited in both a concentration- and time-dependent manner (both p < 0.01). The IC50 was approximately 5 µM for HCT-116 and 7 µM for SW-480 cells. OPT A significantly induced apoptosis and arrested the cell cycle at the G2/M phase. From further mechanism explorations, our data showed that OPT A significantly upregulated the expression of a cluster of genes, especially the tumor necrosis factor receptor family and caspase family, suggesting that the tumor necrosis factor-related apoptotic pathway plays a key role in OPT A induced apoptosis.

Human ovarian cancer multicellular spheroids: a model for testing antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents.

This study was conducted to employ an ovarian cancer Ovcar 10 three-dimensional model to assess the antiproliferation activity of the medicinal plant Devil's club, Oplopanax horridus, and its active compound, alone and in combination, with chemotherapeutic agents compared to Ovcar 10 two-dimensional cells grown as monolayer cells. Ovcar 10 three-dimensional spheroids were prepared with a rotary cell culture system. Cell counting kit-8 assessed the antiproliferation activity. Apoptosis-related gene expression in three-dimensional spheroids and two- dimensional cells was analyzed with an apoptosis antibody array. Flow cytometry was used to analyze the cell cycle. Ovcar 10 cells formed compact three-dimensional spheroids after 5 days of culture in a rotary culture system. Ovcar 10 three-dimensional spheroids were significantly more resistant to killing by Devil's club extract, its active compound alone, gemcitabine, and paclitaxel, but not cisplatin compared to two-dimensional cells, with IC50 levels closer to that observed in vivo. Devil's club extract and its active compound alone significantly enhanced the antiproliferation activity of cisplatin and gemcitabine at some concentrations, but did not affect the activity of paclitaxel. A number of apoptosis-related genes were differentially expressed in three-dimensional spheroids, two-dimensional cells, and cells treated with Devil's club extract compared to untreated controls. In three-dimensional spheroids, the proportion of cells in the G2/M phase was slightly increased and the S phase was slightly decreased compared to two-dimensional cells. Ovcar 10 cells in three-dimensional spheroids altered the expression of multiple apoptosis-related genes, which may have contributed to the increased resistance of the cells to some drugs.

Anticancer activities of polyynes from the root bark of Oplopanax horridus and their acetylated derivatives.

Six polyynes OH-1~6, some of which are occur naturally in acetylated form, had been isolated and identified from the root bark of Oplopanax horridus (Devil's Club), a natural dietary supplement and medicinal plant in North America. During the evaluation of the polyynes' potential anticancer activities, sixteen more acetylated derivatives OHR-1~16 have synthesized and their anti-proliferation activity on MCF-7, MDA-MB-231, A549, HepG2 and LO2 cells assayed to elucidate their structure-activity relationships. The results showed that OH-1 ((3S, 8S)-falcarindiol) had the most potent anticancer activity, with IC50 values of 15.3, 23.5, 7.7 and 4.7 µM on MCF-7, A549, HepG2 and MDA-MB-231 cells, respectively. For the primary structure-activity relationship, the anticancer activities of polyynes become weaker if their hydroxyl groups are acetylated, the terminal double bonds transformed into single bonds or they contain one more methylene group in the main skeleton chain.

Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids.

Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73±0.04 and 3.15±0.16µM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds.

Identification of potential anticancer compounds from Oplopanax horridus.

Oplopanax horridus is a plant native to North America. Previous reports have demonstrated that this herb has antiproliferative effects on cancer cells but study mostly focused on its extract or fractions. Because there has been limited phytochemical study on this herb, its bioactive compounds are largely unknown. We recently isolated and identified 13 compounds, including six polyynes, three sesquiterpenes, two steroids, and two phenolic acids, of which five are novel compounds. In this study, we systemically evaluated the anticancer effects of compounds isolated from O. horridus. Their antiproliferative effects on a panel of human colorectal and breast cancer cells were determined using the MTS assay. Cell cycle distribution and apoptotic effects were analyzed by flow cytometry. The in vivo antitumor effect was examined using a xenograft tumor model. Among the 13 compounds, strong antiproliferative effects were observed from falcarindiol and a novel compound oplopantriol A. Falcarindiol showed the most potent antiproliferative effects, significantly inducing pro-apoptosis and cell cycle arrest in the S and G2/M phases. The anticancer potential of falcarindiol was further verified in vivo, significantly inhibiting HCT-116 tumor growth in an athymic nude mouse model at 15 mg/kg. We also analyzed the relationship between polyyne structures and their pharmacological activities. We observed that both the terminal hydroxyl group and double bond obviously affected their anticancer potential. Results from this study supplied valuable information for future semi-synthesis of polyyne derivatives to develop novel cancer chemopreventive agents.

Chemical and pharmacological studies of Oplopanax horridus, a North American botanical.

Oplopanax horridus (OH), or Devil's club, is an ethnobotanical used by the indigenous people native to the Pacific Northwest of North America. There are three species in the genus Oplopanax, and OH is the only species that is distributed in North America. Compared with the extensive research on OH's "cousin," American ginseng, there is comparatively little reported about the chemical makeup and pharmacological effects of OH. Nevertheless, there has been some research over the past few years that shows promise for the future usage perspectives of OH. To date, 17 compounds were isolated and elucidated, including polyynes, glycosides, lignans, and polyenes, with most of the attention being paid to the polyynes. Gas chromatography (GC) and high-performance liquid chromatography (HPLC) were used to determine the contents of volatile compounds and polyynes in the essential oil and extracts of OH. For the pharmacological studies, antibacterial and antidiabetes effects of polyynes were reported. Our recent study has focused more on the anticancer effects of OH and the involved mechanisms of action. In this review, we will summarize the research status in the botany, phytochemistry, and pharmacology of OH.

Oplopanphesides A-C, three new phenolic glycosides from the root barks of Oplopanax horridus.

Three new phenolic glycosides, named oplopanphesides A-C (1-3), have been isolated from the root barks of Oplopanax horridus. Their structures were elucidated by a combination of spectroscopic analyses, including 1D- and 2D-NMR techniques. These phenolic glycosides possess a novel feature in their sugar moieties that a 3-hydroxy-3-methylglutaryl moiety was connected with C-6 of the ß-D-glucopyranosyl group. Those compounds showed no cytotoxic effects against human cancer cell lines (MDA-231 and MCF-7) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method.