Icariside E4

Inhibitory Effects of Roseoside and Icariside E4 Isolated from a Natural Product Mixture (No-ap) on the Expression of Angiotensin II Receptor 1 and Oxidative Stress in Angiotensin II-Stimulated H9C2 Cells.[Pubmed:30678135]

Molecules. 2019 Jan 23;24(3). pii: molecules24030414.

Hypertension is a major risk factor for the development of cardiovascular diseases. This study aimed to elucidate whether the natural product mixture No-ap (NA) containing Pine densiflora, Annona muricate, and Monordica charantia, or its single components have inhibitory effects on hypertension-related molecules in Angiotensin II (Ang II)-stimulated H9C2 cells. Individual functional components were isolated and purified from NA using various columns and solvents, and then their structures were analyzed using ESI(-)MS, (1)H-NMR, and (13)H-NMR spectra. H9C2 cells were stimulated with 300 nM Ang II for 7 h. NA, telmisartan, ginsenoside, roseoside (Roseo), Icariside E4 (IE4), or a combination of two components (Roseo and IE4) were administered to the cells 1 h before Ang II stimulation. The expression and activity of hypertension-related molecules or oxidative molecules were determined using RT-PCR, western blot, and ELISA. Ang II stimulation increased the expression of Ang II receptor 1 (AT1), tumor necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1), tumor growth factor-beta (TGF-beta) mRNA, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and the levels of hydrogen peroxide (H(2)O(2)) and superoxide anion (*O(2)(-)) and reduced anti-oxidant enzyme activity. NA significantly improved the expression or activities of all hypertension-related molecules altered in Ang II-stimulated cells. Roseo or IE4 pretreatment either decreased or increased the expression or activities of all hypertension-related molecules similar to NA, but to a lesser extent. The pretreatment with a combination of Roseo and IE4 (1:1) either decreased or increased the expression of all hypertension-related molecules, compared to each single component, revealing a synergistic action of the two compounds. Thus, the combination of single components could exert promising anti-hypertensive effects similar to NA, which should be examined in future animal and clinical studies.

Characterization of Vasorelaxant Principles from the Needles of Pinus morrisonicola Hayata.[Pubmed:29301239]

Molecules. 2017 Dec 31;23(1). pii: molecules23010086.

Pinus morrisonicola Hayata, usually called Taiwan five-leaf pine (5LP), is an endemic species in Taiwan and is traditionally used to relieve hypertension symptoms and improve cardiovascular function. In this study, the needle extract of 5LP was fractionated and analyzed by LC/MS/MS to search for possible antihypertensive candidates. In addition, bioassay-guided purification of the bioactive components was performed by Ca(2+) fluorescent signal (Fluo 4-AM) assays. Two dihydrobenzofuran lignans, pinumorrisonide A (1) and Icariside E4 (2), and one acylated flavonoid glycoside, kaempferol 3-O-alpha-(6'''-p-coumaroylglucosyl-beta-1,4-rhamnoside) (3) were characterized from the active fractions. The structure of a new compound 1 was established on the basis of 2D NMR spectroscopic and mass spectrometric analyses, and the known compounds 2 and 3 were identified by comparison of their physical and spectroscopic data with those reported in the literature. The purified compounds 1-3 exhibited significant inhibition of Ca(2+) fluorescence with IC50 values of 0.71, 0.36, and 0.20 mM, respectively. A mechanism study showed that these compounds showed vasorelaxant effects by blocking the voltage-operated Ca(2+) channel (VOCC) and inhibiting Ca(2+) influx to the cytoplasmic. These results suggested that 5LP and the three characterized components could be promising antihypertensive candidates for the use as VOCC blockers.

LC/ESI-MS/MS profiling of Ulmus parvifolia extracts and evaluation of its anti-inflammatory, cytotoxic, and antioxidant activities.[Pubmed:27197132]

Z Naturforsch C J Biosci. 2016 Nov 1;71(11-12):415-421.

In this study, a comparative liquid chromatography/mass spectroscopy (LC/ESI-MS/MS) profiling of different fractions of Ulmus parvifolia leaves and stems was performed. Identification of compounds was based on comparing the mass spectrometric information obtained including m/z values and individual compound fragmentation pattern to tandem mass spectral library search and literature data. Eleven compounds were tentatively identified in the different analyzed fractions. One of the major constituents of this plant was isolated and identified as Icariside E4 [dihydro-dehydro-diconiferyl alcohol-4-O-alpha-L-rhamnopyranoside] (5). The evaluation of anti-inflammatory activity of the total methanolic extract using nitric oxide inhibition on LPS-stimulated RAW 264.7 cells model strong anti-inflammatory activity with 17.5% inhibition of nitric oxide production versus 10% inhibition for dexamethasone. The cytotoxic activity of the methanolic extract and Icariside E4 was evaluated against four types of human cell lines using MTT assay. Icariside E4 showed cytotoxic effect against Hep-G2, MCF-7, and CACO-2 cell lines compared to a negligible activity for the total extract. The same extract showed a moderate antioxidant activity with SC50=362.5 mug/mL.

Heteromeles Arbutifolia, a Traditional Treatment for Alzheimer's Disease, Phytochemistry and Safety.[Pubmed:28930127]

Medicines (Basel). 2016 Jul 7;3(3). pii: medicines3030017.

Background: This study examined the chemistry and safety of Heteromeles arbutifolia, also called toyon or California holly, which is a traditional California Indian food and treatment for Alzheimer's disease. Methods: Plant extracts were examined by HPLC/MS, NMR and other techniques to identify compounds. Volunteers were recruited to examine the acute safety of the plant medicine using a standard short-term memory test. Results: The plant was found to contain Icariside E4, dihydroxyoleanenoic acid, maslinic acid, betulin, trihydroxyoxo-seco-ursdienoic acid, catechin, vicenin-2, farrerol, kaempferide and tetrahydroxyoleanenoic acid. These compounds are anti-inflammatory agents that may protect the blood-brain barrier and prevent inflammatory cell infiltration into the brain. The dried berries were ingested by six volunteers to demonstrate the safety of the medicine. Conclusion: The plant medicine was found to contain several compounds that may be of interest in the treatment of Alzheimer's disease. The plant medicine was found to be safe.

Inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells by stem bark of Ulmus pumila L.[Pubmed:25313277]

Saudi J Biol Sci. 2014 Nov;21(5):427-35.

This study was designed to isolate and identify a potent inhibitory compound against nitric oxide (NO) production from the stem bark of Ulmus pumila L. Ethyl acetate fraction of hot water extract registered a higher level of total phenolics (756.93 mg GAE/g) and also showed strong DPPH (IC50 at 5.6 mug/mL) and ABTS (TEAC value 0.9703) radical scavenging activities than other fractions. Crude extract and its fractions significantly decreased nitrite accumulation in LPS-stimulated RAW 264.7 cells indicating that they potentially inhibited the NO production in a concentration dependent manner. Based on higher inhibitory activity, the ethyl acetate fraction was subjected to Sephadex LH-20 column chromatography and yielded seven fractions and all these fractions registered appreciable levels of inhibitory activity on NO production. The most effective fraction F1 was further purified and subjected to (1)H, (13)C-NMR and mass spectrometry analysis and the compound was identified as Icariside E4. The results suggest that the U. pumila extract and the isolated compound Icariside E4 effectively inhibited the NO production and may be useful in preventing inflammatory diseases mediated by excessive production of NO.

Isolation of a dihydrobenzofuran lignan, icariside E4, with an antinociceptive effect from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark.[Pubmed:25138119]

Arch Pharm Res. 2015 Jun;38(6):950-6.

The antinociceptive activity of Icariside E4, a dihydrobenzofuran-type lignan isolated from Tabebuia roseo-alba (Ridley) Sandwith (Bignoniaceae) bark, was evaluated in mice by using chemical and thermal models of nociception. Intraperitoneal (i.p.) administration of crude T. roseo-alba bark extract and its methanol fraction inhibited acetic acid-induced abdominal constriction in mice. Furthermore, i.p. administration of 0.1, 1, and 10 mg/kg of Icariside E4 reduced the number of writhes evoked by acetic acid injection by 46.9, 82.3, and 66.6%, respectively. Icariside E4 administration had no effect in the first phase of the formalin test, but it reduced nociceptive behavior in the second phase as indicated by a reduction in the licking time. Icariside E4 did not modify thermal nociception in the hot-plate test model, suggesting that it had a peripheral antinociceptive action. The antinociceptive effect of Icariside E4 in the writhing test was reversed by pre-administration of glibenclamide, but not of naloxone, atropine, yohimbine, or haloperidol. Together, these results indicated that the antinociceptive activity of Icariside E4 from T. roseo-alba in models of chemical pain occurred through ATP-sensitive K(+) channel-dependent mechanisms.

Lignans and neolignans from the stems of Vibrunum erosum and their neuroprotective and anti-inflammatory activity.[Pubmed:24676553]

Arch Pharm Res. 2015 Jan;38(1):26-34.

A new lignan, (7'S,8S,8'S)-3,5'-dimethoxy-3',4,9'-trihydroxy-7',9-epoxy-8,8'-lignan, named vibruresinol (1), was isolated from the stems of Viburnum erosum by silica gel, ODS, and Sephadex LH-20 column chromatography. In addition, four other known lignans, (7'R,8S,8'S)-3,5'-dimethoxy-3',4,8',9'-tetrahydroxy-7',9-epoxy-8,8'-lignan (2), (+)-syringaresinol (3), (+)-pinoresinol (4), and (+)-pinoresinol-4-O-beta-D-glucopyranoside (5), and five known neolignans, herpetol (6), vibsanol (7), (-)-dehydrodiconiferyl alcohol (8), Icariside E4 (9), and dihydrodehydrodiconiferyl alcohol (10), were isolated in the same manner. The chemical structures of the compounds were determined based on spectroscopic data including NMR, MS, and IR. All of the compounds described above were isolated from V. erosum for the first time. The isolated compounds 3, 4, and 6 were evaluated for neuroprotective activity on glutamate-induced cell death in HT22 cells and had EC50 values of 6.33 +/- 1.22, 6.96 +/- 0.65, and 9.15 +/- 0.36 muM, respectively. Likewise, the same compounds had inhibitory activity on NO production in LPS-induced RAW 264.7 cells with IC50 values of 8.30 +/- 1.56, 7.89 +/- 1.22, and 9.32 +/- 0.36 muM, respectively.

A new lignan glycoside from Juniperus rigida.[Pubmed:22210029]

Arch Pharm Res. 2011 Dec;34(12):2043-9.

A new lignan glycoside, named juniperigiside (1) was isolated from the CHCl(3) soluble fraction of the MeOH extract of stems and leaves of Juniperus rigida S.et Z. Compound 1 was identified by 1D- and 2D-NMR spectroscopy as well as CD analysis as (2R,3S)-2,3-dihydro-7-methoxy-2-(4'-hydroxy-3'-methoxyphenyl)-3-hydroxymethyl-5-b enzofuranpropanol 4'-O-(3-O-methyl)-alpha-L-rhamnopyranoside. Five known lignans, Icariside E4 (2), desoxypodophyllotoxin (3), savinin (4), thujastandin (5), and (-)-nortrachelogenin (6) in addition to five known labdane diterpenes including trans-communic acid (7), 13-epi-torulosal (8), 13-epi-cupressic acid (9), imbricatoric acid (10), and isocupressic acid (11) were also isolated and their structures were characterized by comparing their spectroscopic data with those in the literature. All compounds were isolated for the first time from this plant, and 5 and 6 were first reported from the genus Juniperus. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using a Sulforhodamin B bioassay. Compounds 3, 4, 7, and 8 showed considerable cytotoxicity against four human cancer cell lines in vitro.

Further investigation into maple syrup yields 3 new lignans, a new phenylpropanoid, and 26 other phytochemicals.[Pubmed:21675726]

J Agric Food Chem. 2011 Jul 27;59(14):7708-16.

Maple syrup is made by boiling the sap collected from certain maple ( Acer ) species. During this process, phytochemicals naturally present in tree sap are concentrated in maple syrup. Twenty-three phytochemicals from a butanol extract of Canadian maple syrup (MS-BuOH) had previously been reported; this paper reports the isolation and identification of 30 additional compounds (1-30) from its ethyl acetate extract (MS-EtOAc) not previously reported from MS-BuOH. Of these, 4 compounds are new (1-3, 18) and 20 compounds (4-7, 10-12, 14-17, 19, 20, 22-24, 26, and 28-30) are being reported from maple syrup for the first time. The new compounds include 3 lignans and 1 phenylpropanoid: 5-(3'',4''-dimethoxyphenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-(hydroxym ethyl)dihydrofuran-2-one (1), (erythro,erythro)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl) ethoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (2), (erythro,threo)-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)et hoxy]-3,5-dimethoxyphenyl]-1,2,3-propanetriol (3), and 2,3-dihydroxy-1-(3,4- dihydroxyphenyl)-1-propanone (18), respectively. In addition, 25 other phenolic compounds were isolated including (threo,erythro)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)e thoxy]-3-methoxyphenyl]-1,2,3-propanetriol (4), (threo,threo)-1-[4-[(2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl)eth oxy]-3-methoxyphenyl]-1,2,3-propanetriol (5), threo-guaiacylglycerol-beta-O-4'-dihydroconiferyl alcohol (6), erythro-1-(4-hydroxy-3-methoxyphenyl)-2-[4-(3-hydroxypropyl)-2,6-dimethoxyphenoxy ]-1,3-propanediol (7), 2-[4-[2,3-dihydro-3-(hydroxymethyl)-5-(3-hydroxypropyl)-7-methoxy-2-benzofuranyl] -2,6-dimethoxyphenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-propanediol (8), acernikol (9), leptolepisol D (10), buddlenol E (11), (1S,2R)-2-[2,6-dimethoxy-4-[(1S,3aR,4S,6aR)-tetrahydro-4-(4-hydroxy-3,5-dimethoxy phenyl)-1H,3H-furo[3,4-c]furan-1-yl]phenoxy]-1-(4-hydroxy-3-methoxyphenyl)-1,3-pr opanediol (12), syringaresinol (13), isolariciresinol (14), Icariside E4 (15), sakuraresinol (16), 1,2-diguaiacyl-1,3-propanediol (17), 2,3-dihydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone (19), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)propan-1-one (20), dihydroconiferyl alcohol (21), 4-acetylcatechol (22), 3',4',5'-trihydroxyacetophenone (23), 3,4-dihydroxy-2-methylbenzaldehyde (24), protocatechuic acid (25), 4-(dimethoxymethyl)pyrocatechol (26), tyrosol (27), isofraxidin (28), and 4-hydroxycatechol (29). One sesquiterpene, phaseic acid (30), which is a known metabolite of the phytohormone abscisic acid, was also isolated from MS-EtOAc. The antioxidant activities of MS-EtOAc (IC(50) = 75.5 mug/mL) and the pure isolates (IC(50) ca. 68-3000 muM) were comparable to that of vitamin C (IC(50) = 40 muM) and the synthetic commercial antioxidant butylated hydroxytoluene (IC(50) = 3000 muM), in the diphenylpicrylhydrazyl radical scavenging assay. The current study advances scientific knowledge of maple syrup constituents and suggests that these diverse phytochemicals may impart potential health benefits to this natural sweetener.