Inhibitory Activities of Dimeric Ellagitannins Isolated from on Benign Prostatic Hypertrophy.

Benign prostatic hypertrophy (BPH) is an intractable chronic inflammatory disease. We studied the efficacy of two ellagitannins, namely camptothin B () and cornusiin A () that were isolated from (CA) for the treatment of BPH, which is a common health issue in older men. The ellagitannins ( and ) were evaluated on its inhibitory activities of the enzyme 5α-reductase and tumor necrosis factor (TNF)-α, its interleukin (IL)-1β, IL-6, and IL-8 production, and its anti-proliferation and apoptosis induction in prostate cells that show hypertrophy (RWPE-1 cell).

Papuamine Inhibits Viability of Non-small Cell Lung Cancer Cells by Inducing Mitochondrial Dysfunction.

Background/aim: Despite the Warburg effect, mitochondria play an essential role in the survival and maintenance of cancer cells. Thus, mitochondria have been considered a target for anticancer agents. Here, we identified a mitochondria-targeting anticancer agent from natural products.

The natural compound gracillin exerts potent antitumor activity by targeting mitochondrial complex II.

Mitochondria play a pivotal role in cancer bioenergetics and are considered a potential target for anticancer therapy. Considering the limited efficacy and toxicity of currently available mitochondria-targeting agents, it is necessary to develop effective mitochondria-targeting anticancer drugs. By screening a large chemical library consisting of natural products with diverse chemical entities, we identified gracillin, a steroidal saponin, as a mitochondria-targeting antitumor drug.

Erybraedin A is a potential Src inhibitor that blocks the adhesion and viability of non-small-cell lung cancer cells.

The adhesion of cancer cells to the extracellular matrix (ECM) is crucial for cell proliferation, survival, and metastasis. Thus, it is necessary to inhibit cell-ECM adhesion by blocking the activation of the associated signaling to control cancer. Here, we identify erybraedin A (EBA) as a potential Src inhibitor that blocks cell adhesion and viability in non-small-cell lung cancer (NSCLC).

Antioxidative and Anti-Inflammatory Activities of Galloyl Derivatives and Antidiabetic Activities of .

Chromatographic isolation of the 80% MeOH extract of (AG) yielded seven galloyl derivatives: gallic acid (), ginnalin B (), acertannin (), maplexin D (), maplexin E (), quercetin-3--(2''-galloyl)--L-rhamnopyranoside (), and kaempferol-3--(2''-galloyl)--L-rhamnopyranoside (). This is the first study to report the isolation of compounds and from AG. Galloyl derivatives - exhibited potent radical scavenging activities, with and showing particularly strong inhibitory activities against nitric oxide production in lipopolysaccharides- (LPS-) stimulated RAW264.

Essential Role of DNA Methyltransferase 1-mediated Transcription of Insulin-like Growth Factor 2 in Resistance to Histone Deacetylase Inhibitors.

Histone deacetylase inhibitors (HDI) are promising anticancer therapies; however, drug resistance limits their efficacy. Here, we investigated the molecular mechanisms underlying HDI resistance, focusing on the mechanism of HDI-mediated induction of insulin-like growth factor 2 (IGF2) based on our previous study. The methylation status of CCCTC-binding factor (CTCF)-binding sites in the imprinting control region (ICR) were determined by methylation-specific PCR and bisulfite sequencing.

Antiproliferative Effects of New Dimeric Ellagitannin from Cornus alba in Prostate Cancer Cells Including Apoptosis-Related S-Phase Arrest.

Activity-guided isolation of 80% acetone extract of Cornus alba, which is traditionally used as an anti-inflammatory, hemostatic and diuretic in Korea, yielded one novel compound, tentatively designated cornusiin H (13), together with 12 known compounds. The known compounds included four flavonoids (catechin (1), quercetin-3-O-β-D-glucuronide (2), quercetin-3-O-β-D-glucopyranoside (3), kaempferol-3-O-β-D-glucopyranoside (4)) and eight hydrolysable tannins (gallic acid (5), 2,6-di-O-galloyl-hamamelofuranoside (6), 2-galloyl-4-caffeoyl-L-threonic acid (7) 2,3-di-O-galloyl-4-caffeoyl-L-threonic acid (8), 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranoside (9), cornusiin B (10), cornusiin A (11) and camptothin B (12)). All compounds exhibited potent 1,1-diphenyl-2-picrylhydrazyl (DPPH)-free radical scavenging activity.

Deguelin Analogue SH-1242 Inhibits Hsp90 Activity and Exerts Potent Anticancer Efficacy with Limited Neurotoxicity.

The Hsp90 facilitates proper folding of signaling proteins associated with cancer progression, gaining attention as a target for therapeutic intervention. The natural rotenoid deguelin was identified as an Hsp90 inhibitor, but concerns about neurotoxicity have limited prospects for clinical development. In this study, we report progress on deguelin analogues that address this limitation, focusing on the novel analogue SH-1242 as a candidate to broadly target human lung cancer cells, including those that are chemoresistant or harboring KRAS mutations.

Two new phenolic compounds from the leaves of Alnus sibirica Fisch. ex Turcz.

Two new phenolic compounds, 4-O-glucopyranosyl-5-O-caffeoylshikimic acid (1) and 2,3-digalloyl oregonin (2), were isolated along with eight known phenolic compounds (3-10) from an 80% acetone extract of Alnus sibirica leaves. The chemical structures of these compounds were elucidated using 1D/2D nuclear magnetic resonance and high resolution-MS. The anti-oxidative activities of these compounds were determined by assaying their 1,1-diphenyl-2-picrylhydrazyl radical and nitroblue tetrazolium superoxide anion scavenging activity.

Activation of insulin-like growth factor receptor signaling mediates resistance to histone deacetylase inhibitors.

Histone deacetylases (HDACs) are considered promising targets in the treatment of hematologic malignancies and several types of solid tumors, including non-small cell lung cancer (NSCLC). However, the efficacy of HDAC inhibitors in solid tumors is marginal, and the mechanisms underlying resistance to HDAC inhibitors are largely unknown. Here, we demonstrate the involvement of type 1 insulin-like growth factor receptor (IGF-1R) signaling in resistance to HDAC inhibitors in NSCLC.

Effect of topical application of quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside on atopic dermatitis in NC/Nga mice.

Background: Quercetin-3-O-(2″-gallate)-α-l-rhamnopyranoside (QGR) is a new quercetin derivative which is isolated from the leaves of Acer ginnala Maxim, a native plant of Korea. Quercetin has several biological effects including antioxidative, anti-inflammatory, and anti-allergic effects. However, the topical effect of QGR on atopic dermatitis (AD) like skin lesion in NC/Nga mice has not been studied.

Topical application of Rosa multiflora root extract improves atopic dermatitis-like skin lesions induced by mite antigen in NC/Nga mice.

The roots of Rosa multiflora THUNB. (RM) has been used in oriental traditional medicines as remedies for scabies, rheumatic arthralgia and stomatitis which were practicably related with today's inflammatory and allergic diseases. In the present study, we evaluated whether RM root extract (RME) and its major constituent, 2-(3,4-dihydroxyphenyl)-6-(4-hydroxyphenyl)-8-(2,4-dihydroxyphenyl)-2,3-trans-6,7-cis-7,8-trans-3,4,7,8-tetrahydro-2H,6H-pyrano[2,3-f] chromene-3,7,9-triol (RM-3) belongs to condensed tannins, improve atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by mite antigen.

Anti-oxidative and anti-inflammatory activities of caffeoyl hemiterpene glycosides from Spiraea prunifolia.

Activity guided isolation of a Spiraea prunifolia extract yielded five caffeoyl hemiterpene glycosides: 4'-(6-O-caffeoyl-β-D-glucopyranosyl)-2'-methyl butyric acid, 1-O-caffeoyl-6-O-(4'-hydroxy-2'-methylene-butyroyl)-β-D-glucopyranoside, 1,2-O-dicaffeoyl-6-O-(4'-hydroxy-2'-methylene-butyroyl)-β-D-glucopyranoside, 1-O-caffeoyl-6-O-(4'-caffeoyl-2'-methylene-butyroyl)-β-D-glucopyranoside, and 1-O-caffeoyl-6-O-(4'-caffeoyl-3'-hydroxy-2'-methylene-butyroyl)-β-D-glucopyranoside, and nine known compounds. Structures were elucidated by analysis of 1D and 2D NMR spectra and FAB-MS. To evaluate the anti-oxidative and anti-inflammatory properties of all fourteen compounds, DPPH radical scavenging, NBT superoxide scavenging, and inhibition of nitric oxide production in LPS-stimulated RAW264.

Quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside prevents TRAIL-induced apoptosis in human keratinocytes by suppressing the caspase-8- and Bid-pathways and the mitochondrial pathway.

Quercetin and its derivatives have antioxidant and anti-inflammatory effects. Nevertheless, in human keratinocytes, compared to the reports on other toxic insults, researches on the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis that may be involved in skin diseases are rare. Furthermore, the effect of quercetin-3-O-(2"-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on TRAIL-induced apoptosis in keratinocytes has not been studied.

Quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside inhibits TNF-α-activated NF-κB-induced inflammatory mediator production by suppressing ERK activation.

Quercetin and its derivatives have anti-inflammatory and anti-oxidant effects. However, the effect of quercetin-3-O-(2″-galloyl)-α-l-rhamnopyranoside (QGR), a new quercetin derivative, on the tumor necrosis factor (TNF)-α-stimulated production of inflammatory mediators in keratinocytes is unclear. In addition, the effect of QGR on the ERK and NF-κB-mediated inflammatory process has not been studied.

Three new orcinol-conjugated hydrolysable tannins from the leaves of Cleyera japonica.

Three new orcinol (3-hydroxy-5-methylphenol)-conjugated hydrolysable tannins, together with two known compounds were isolated from the leaves of Cleyera japonica (CJ), and have been tentatively named cleyeratannin A (1), cleyeratannin B (2) and cleyeratannin C (3). The chemical structures of these compounds were elucidated using 1 dimensional (1D)/2D NMR and high resolution FAB-MS, and the absolute configuration was confirmed by circular dichroism (CD). To evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH)/free radical scavenging activity and nitroblue tetrazolium (NBT)/superoxide anion scavenging activity were determined.

Two new hemiterpene glycosides from the leaves of Ilex rotunda. Thunb.

Chromatographic separation of the 80% MeOH extract of the leaves of Ilex rotunda (IR) led to isolation of two new hemiterpene glycosides, tentatively named as rotundarpenoside A (1) and rotundarpenoside B (2), along with five known caffeoyl derivatives (3-7). The chemical structures of these compounds were elucidated using 1D/2D NMR, HR-MS, and the absolute configuration was confirmed by Mosher's method. In order to evaluate their anti-oxidative activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity and xanthine oxidase superoxide scavenging activities (NBT) were determined.

The antioxidant and anti-inflammatory effects of phenolic compounds isolated from the root of Rhodiola sachalinensis A. BOR.

Isolation of compounds from the root of Rhodiola sachalinensis (RRS) yielded tyrosol (1), salidroside (2), multiflorin B (3), kaempferol-3,4'-di-O-β-D-glucopyranoside (4), afzelin (5), kaempferol (6), rhodionin (7), and rhodiosin (8). Quantification of these compounds was performed by high-performance liquid chromatography (HPLC). To investigate the antioxidant and anti-inflammatory effects of the compounds, DPPH radical scavenging, NBT superoxide scavenging and nitric oxide production inhibitory activities were examined in LPS-stimulated Raw 264.

Anti-oxidative, anti-inflammatory and whitening effects of phenolic compounds from Bambusae Caulis in Liquamen.

Bambusae Caulis in Liquamen (BCL) is the distilled product of the condensation from the burning of Phyllostachys nigra var. henosis (Gramineae). The activity-guided isolation of BCL yielded four phenolic compounds: 2,6-dimethoxyphenol (1), 1,2-dihydroxybenzene (2), 1,3-dihydroxybenzene (3) and 1,2-dibenzenecarboxylic acid (4).

Antioxidative and anti-inflammatory effects of phenolic compounds from the roots of Ulmus macrocarpa.

The roots of Ulmus macrocarpa Hance (Ulmaceae) have been used as an oriental traditional medicine for the treatment of inflammation, ulcers, cancers, and parasites. Activity guided isolation from the roots of U. macrocarpa yielded three flavonoids [catechin 7-O-β-D-apiofuranoside (1), (+)-catechin (2), taxifolin 6-C-glucopyranoside (3)], and one coumarin [fraxin (4)].

Topical application of two condensed tannins from the root of Rosa multiflora Thunberg for the treatment of atopic dermatitis (AD) in NC/Nga mice.

Recently, the isolation of several condensed tannins from the roots of Rosa multiflora Thunberg, a traditional herbal therapy in oriental medicine for rheumatoid arthritis and scabies, was described. Two of the major condensed tannins - procyanidin B-3 (ProB3) and ent-guibourtinidol-(4β → 6)-catechin (RM-1) - were then applied topically to atopic dermatitis-like skin lesions on NC/Nga mice in order to assess their immunomodulatory properties. Both ProB3 and RM-1 significantly reduced the serum levels of eosinophils, IgE and certain Th2 cytokines (IL-4, 5 and 13) (p < 0.

Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by phenolic compounds from roots of Rhododendron mucronulatum.

The roots of Rhododendron mucronulatum Turzaninov have been used in Oriental traditional medicine for the treatment of dysuria, fever, increase of digestive activity and tonics in China and Korea. Activity guided isolation of the roots of Rhododendron mucronulatum Turzaninov has led to the isolation of three flavonoids, one flavan 3-ol and one proanthocyanidin. Chemical investigation of the 80% Me2 CO extract from the roots of Rhododendron mucronulatum led to the isolation and identification of five compounds: taxifolin (1), taxifolin 3-O-β-D-glucopyranoside (2), quercetin 3-O-α-L-arabinofuranoside (3), (-)-epicatechin (4), procyanidin B-3 (5).

Atopic dermatitis-like skin lesions reduced by topical application and intraperitoneal injection of Hirsutenone in NC/Nga mice.

Atopic dermatitis (AD) is a common inflammatory skin disease. The increasing prevalence and severity of AD have prompted the developments of safer, more effective drugs. Although topical corticosteroids have been used as first line therapy for AD, their potential side effects limit their clinical applications.

Inhibitory effects of phenolic compounds from needles of Pinus densiflora on nitric oxide and PGE2 production.

The needles of Pinus densiflora Siebold et Zuccarini, a representative Pinus species that grows in Korea, have been used in oriental traditional medicine as remedies for rheumatitis, hemorrhage, cancer, etc. Phytochemical examination of the needles of Pinus densiflora Siebold et Zuccarini led to the isolation of four lignans, one flavan-3-ol, two flavonols and one organic acid. They were identified as icariside E(4) (1), cupressoside A (2), schizandriside (3), (+)-isolariciresinol (4), (+)-catechin (5), quercetin 3-O-β-D-glucopyranoside (6), 5,7,8,4'-tetrahydroxy-3-methoxy-6-methylflavone 8-O-β-D-glucopyranoside (7) and (-)-shikimic acid (8).

Effect of Alnus japonica extract on a model of atopic dermatitis in NC/Nga mice.

Aim Of The Study: The bark of Alnus species has long been used in traditional oriental medicine in the treatment of many pathological conditions, including fever, hemorrhage, diarrhea, alcoholism, various skin diseases (e.g. chronic herpes, eczema and prurigo), and inflammation.