Chemical constituents of Desmodium triflorum and their antifungal activity against various phytopathogenic fungi.

In the course of finding new antifungal natural compounds against plant pathogens, the methanol extract of Desmodium triflorum was investigated phytochemically. From n-butanol-soluble fraction, seven compounds (1-7) were isolated and structurally elucidated. Of which, six compounds belong to flavone 6- or 8-C-glycoside class (1-6). Three major compounds (1-3) exhibited moderate in vitro antifungal activity against Sclerotium rolfsii, Fusarium oxysporum f. sp. cubense, and Phytophthora palmivora. Compound 1 (IC50 = 162.1 µg/mL) was most active against S. rolfsii in a dose-dependent manner. At 300 µg/mL, compounds 1 and 2 significantly inhibited P. palmivora, whereas compound 3 lacked effectiveness. In addition, the nanoemulsion of the methanol extract with a droplet size of 12.2 nm displayed an excellent inhibition against S. rolfsii and P. palmivora compared with the normal extract. The presence of 1 (0.846%) and 2 (0.759%) in the methanol extract may attribute to the antifungal activity of D. triflorum. These results proved the potential of D. triflorum and its C-glycoside flavonoids against phytopathogenic fungi for the first time. Besides, an enhancement in the effectiveness of nanoemulsion containing D. triflorum extract against the fungi was confirmed. The structural characteristics of 1 and 2 could be considered to develop new fungicidal substances in the future.

Procyanidin trimer C1 derived from Theobroma cacao reactivates latent human immunodeficiency virus type 1 provirus.

Despite remarkable advances in combination antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) infection remains incurable due to the incomplete elimination of the replication-competent virus, which persists in latent reservoirs. Strategies for targeting HIV reservoirs for eradication that involves reactivation of latent proviruses while protecting uninfected cells by cART are urgently needed for cure of HIV infection. We screened medicinal plant extracts for compounds that could reactivate the latent HIV-1 provirus and identified a procyanidin trimer C1 derived from Theobroma cacao as a potent activator of the provirus in human T cells latently infected with HIV-1. This reactivation largely depends on the NF-κB and MAPK signaling pathways because either overexpression of a super-repressor form of IκBα or pretreatment with a MEK inhibitor U0126 diminished provirus reactivation by C1. A pan-PKC inhibitor significantly blocked the phorbol ester-induced but not the C1-induced HIV-1 reactivation. Although C1-induced viral gene expression persisted for as long as 48 h post-stimulation, NF-κB-dependent transcription peaked at 12 h post-stimulation and then quickly declined, suggesting Tat-mediated self-sustainment of HIV-1 expression. These results suggest that procyanidin C1 trimer is a potential compound for reactivation of latent HIV-1 reservoirs.

Inhibition of TNF-alpha-Mediated NF-kappaB Transcriptional Activity by Dammarane-Type Ginsenosides from Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells

Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-kappaB and the expression of tumor necrosis factor-alpha (TNF-alpha)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides Rk3 and Rs4 exerted the strongest activity, inhibiting NF-kappaB in a dose-dependent manner. SF and Rg6 also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-alpha-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-alpha-mediated diseases such as chronic hepatic inflammation.

Inhibition of TNF-alpha-Mediated NF-kappaB Transcriptional Activity by Dammarane-Type Ginsenosides from Steamed Flower Buds of Panax ginseng in HepG2 and SK-Hep1 Cells

Panax ginseng is a medicinal herb that is used worldwide. Its medicinal effects are primarily attributable to ginsenosides located in the root, leaf, seed, and flower. The flower buds of Panax ginseng (FBPG) are rich in various bioactive ginsenosides, which exert immunomodulatory and anti-inflammatory activities. The aim of the present study was to assess the effect of 18 ginsenosides isolated from steamed FBPG on the transcriptional activity of NF-kappaB and the expression of tumor necrosis factor-alpha (TNF-alpha)-stimulated target genes in liver-derived cell lines. Noticeably, the ginsenosides Rk3 and Rs4 exerted the strongest activity, inhibiting NF-kappaB in a dose-dependent manner. SF and Rg6 also showed moderately inhibitory effects. Furthermore, these four compounds inhibited the TNF-alpha-induced expression of IL8, CXCL1, iNOS, and ICAM1 genes. Consequently, ginsenosides purified from steamed FBPG have therapeutic potential in TNF-alpha-mediated diseases such as chronic hepatic inflammation.

Oleanolic triterpene saponins from the roots of Panax bipinnatifidus.

Ten oleanane-type saponins (1-10), including three new compounds, namely bifinosides A-C (1-3), were isolated from the roots of Panax bipinnatifidus SEEM. Their structures were elucidated on the basis of chemical and spectroscopic methods.

Oleanane-type triterpenoids from Panax stipuleanatus and their anticancer activities.

One newly (1) and 10 known oleanane-type triterpenoids (2-11) were isolated from the methanol extract of Panax stipuleanatus rhizomes. Based on their spectroscopic data, these compounds were identified as spinasaponin A methyl ester (1), pesudoginsenoside RP(1) methyl ester (2), spinasaponin A 28-O-glucoside (3), pseudoginsenoside RT(1) methyl ester (4), pseudoginsenoside RT(1) (5), stipuleanoside R(2) methyl ester (6), stipuleanoside R(2) (7), araloside A methyl ester (8), 3-O-ß-D-glucopyranosyl (1→3)-ß-D-glucuronopyranoside-28-O-ß-D-glucopyranosyl oleanolic acid methyl ester (9), 3-O-ß-D-xylopyranosyl (1→2)-ß-D-glucopyranosyl-28-O-ß-D-glucopyranosyl oleanolic acid (10), and chikusetsusaponin IVa (11). When the cytotoxic activities of the isolated compounds were evaluated, compound 1 exhibited significant cytotoxic activity with IC(50) values of 4.44 and 0.63 µM against HL-60 (leukemia) and HCT-116 (colon cancer) cell lines, respectively. Compound 2 showed potent cytotoxicity with an IC(50) of 6.50 µM against HCT-116, whereas it was less cytotoxic against HL-60 (IC(50)=41.45 µM). After HL-60 and HCT-116 were treated with compounds 1 and 2, increased production of apoptotic bodies was observed. Furthermore, compounds 1 and 2 in HCT-116 cells activated intrinsic and extrinsic apoptosis pathways by upregulating DR-5 and Bax, downregulating Bcl-2, activating caspase-9, and cleaving poly-ADP-ribose polymerase (PARP). We also observed the activation of ERK1/2 MAPK by both compounds in the HCT-116 cells. Together, compounds 1 and 2 might induce intrinsic and extrinsic apoptosis pathways through the activation of the ERK1/2 MAPK pathway in HCT-116 colon cancer cells. Structure-activity relationship analysis indicated that a carboxyl group at position-28 is potentially responsible for the cytotoxic effects.

Lupane-type triterpene glycosides from the leaves of Acanthopanax koreanum and their in vitro cytotoxicity.

Three new lupane triterpene glycosides, acankoreosides J-L ( 1- 3), were isolated from the leaves of Acanthopanax koreanum. Based on the spectroscopic data, the chemical structures were determined as 3 alpha-hydroxy-20-oxo-30-norlupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 1); 3 alpha,20,29-trihydroxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 2); and (20S)-3 alpha-hydroxy-29,29-dimethoxylupane-23,28-dioic 28- O- alpha- L-rhamnopyranosyl-(1 --> 4)- beta- D-glucopyranosyl-(1 --> 6)- beta- D-glucopyranosyl ester ( 3). Compounds 1- 3 were evaluated for their cytotoxicity and showed moderate activity against four cell lines, A549 (lung), HL-60 (leukemia), MCF-7 (breast), and U937 (leukemia), with IC (50) values of 23.4, 36.5, 22.6, and 18.5 microM for 1; 6.8, 18.6, 23.1, and > 100 microM for 2; and 28.9, 21.8, 11.0, and 27.5 microM for 3, respectively.

Dammarane-type saponins from the flower buds of Panax ginseng and their effects on human leukemia cells.

Six dammarane-type saponins, including three new compounds, floralginsenosides Ta-Tc (1-3), and three known, floralginsenoside Td (4), ginsenoside F(1) (5), and ginsenoside F(5) (6), were isolated from the flower buds of Panax ginseng. Floralginsenoside Td (4) was first isolated from natural plant sources. Their structures were elucidated on the basis of extensive chemical and spectroscopic methods. Compounds 1, 5, and 6 showed cytotoxic activities towards the HL-60 human leukemia cell line with respective IC(50) values of 36.3, 23.2, and 62.4microM. In addition, after the HL-60 cells were treated with these compounds, several apoptosis events, including chromatin condensation and increase in the population of sub-G1 hypodiploid cells, were observed.

Rhusonoside A, a new megastigmane glycoside from Rhus sylvestris, increases the function of osteoblastic MC3T3-E1 cells.

Chemical investigation of the stems and leaves of Rhus Sylvestris afforded a new megastigmane glycoside named rhusonoside A ( 1), along with four other known compounds: dihydroquercetin ( 2), astragalin ( 3), hyperin ( 4), and kaempferol-3- O-rutinoside ( 5). Their structures were determined by a combination of spectroscopic analysis and application of the modified Mosher's method. The effect of compounds 1 - 5 on the function of osteoblastic MC3T3-E1 cells was examined by determining cell viability, alkaline phosphatase (ALP) activity, collagen synthesis, and mineralization. Rhusonoside A ( 1) significantly increased the function of osteoblastic MC3T3-E1 cells. Cell viability, ALP activity, and collagen synthesis were increased dose dependently, up to 155.39 %, 171.27 %, and 134.25 %, respectively, of the basal value at 10 muM ( P < 0.05). In addition, 0.1 muM of compound 1 significantly increased mineralization of MC3T3-E1 cells to 142.78 % ( P < 0.05) of the basal value.