A new triterpenoid from the stems of Kadsura coccinea with antiproliferative activity.

A series of schiartane C29 nortriterpenoids with 5/5/7/6/5 membered consecutive rings (1‒5) with an unique schinortriterpenoid skeleton including a new, kadcoccilactone V (1), together with four known ones (2‒5) and three known triterpenoids (6‒8) were identified from stems of Kadsura coccinea (Lem.) A. C. Smith. The structures of 1 and known compounds were elucidated by interpretation of 1D and 2D NMR, and HR-ESI-MS data as well as comparing those data in the literature. All the isolated compounds were examined for cytotoxic effects against six human cancer cell lines [(HCT-15 (colon), NUGC-3 (stomach), NCI-H23 (lung), ACHN (renal), PC-3 (prostate), and MDA-MB-231 (breast)]. Among them, compound 6 showed potent cytotoxicity against NCI-H23 (GI50 1.28 µM) and NUGC-3 (GI50 1.28 µM), and significantly inhibited on PC-3, MDA-MB-231, ACHN, HCT-15 with GI50 values around 2.33 to 2.67 µM.

Dendrodoristerol, a cytotoxic C20 steroid from the Vietnamese nudibranch mollusk Dendrodoris fumata.

Using various chromatographic separations, four steroids including one new C20 steroid namely dendrodoristerol (1), were isolated from the Vietnamese nudibranch mollusk Dendrodoris fumata. The structure elucidation was confirmed by combination of spectroscopic experiments including 1D and 2D NMR, HR QTOF MS, and CD. Compound 1 was found to exhibit significant in vitro cytotoxic activity against six human cancer cell lines as HL-60, KB, LU-1, MCF-7, LNCaP, and HepG2. In addition, 1 induced HL-60 cancer cell death by apoptosis and necrosis.

A new [7.7]paracyclophane from Vietnamese marine snail Planaxis sulcatus (Born, 1780).

A new [7.7]paracyclophane (1), together with eight known compounds (2-9), were isolated from a MeOH extract of the sea snail Planaxis sulcatus (Born, 1780). Their structures were elucidated by HR-ESI-MS and NMR techniques as well as comparison with those reported in literatures. The absolute configuration of metabolite 1 was determined using ECD spectroscopy. Among nine compounds, 1 exhibited significant cytotoxicity toward all eight cancer cells tested with IC50 values between 1.81 and 3.80 µg/mL.[Figure: see text].

Wedtrilosides A and B, two new diterpenoid glycosides from the leaves of Wedelia trilobata (L.) Hitchc. with α-amylase and α-glucosidase inhibitory activities.

In the ongoing research to find new diabetes constituents from the genus Wedelia, the chemical constituent of Wedelia trilobata leaves, a Vietnamese medicinal plant species used to treat type 2 diabetes mellitus, was selected for detailed investigation. From a methanolic extract, two new ent-kaurane diterpenoids, wedtrilosides A and B (1 and 2), along with five known metabolites (3-7), were isolated from W. trilobata. The chemical structures of (1-7) were assigned via spectroscopic techniques (IR, 1D, 2D NMR and HR-QTOF-MS data) and chemical methods. The isolates were evaluated for α-amylase and α-glucosidase inhibitory activities compared to the clinical drug acarbose. Among them, compounds 4, 6, and 7 showed the most potent against α-glucosidase enzyme with IC50 values of 27.54 ±â€¯1.12, 173.78 ±â€¯2.37, and 190.40 ±â€¯2.01 µg/mL. While moderate inhibitory effect against α-amylase was observed with compounds 6 and 7 (with IC50 = 181.97 ±â€¯2.62 and 52.08 ±â€¯0.56 µg/mL, respectively). The results suggested that the antidiabetic properties from the leaves of W. trilobata are not simply a result of each isolated compound, but are due to other factors such as the accessibility of polyphenolic groups to α-amylase and α-glucosidase activities.

α-Amylase and α-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves.

As part of an ongoing search for new natural products from medicinal plants to treat type 2 diabetes, two new compounds, a megastigmane sesquiterpenoid sulfonic acid (1) and a new cyclohexylethanoid derivative (2), and seven related known compounds (3-9) were isolated from the leaves of Wedelia chinensis (Osbeck.) Merr. The structures of the compounds were conducted via interpretation of their spectroscopic data (1D and 2D NMR, IR, and MS), and the absolute configurations of compound 1 were determined by the modified Mosher's method. The MeOH extract of W. chinensis was found to inhibit α-amylase and α-glucosidase inhibitory activities as well as by the compounds isolated from this extract. Furthermore, compound 7 showed the strongest effect with IC50 values of 112.8 ± 15.1 µg/mL (against α-amylase) and 785.9 ± 12.7 µg/mL (against α-glucosidase). Compounds 1, 8, and 9 showed moderate α-amylase and α-glucosidase inhibitory effects. Other compounds showed weak or did not show any effect on both enzymes. The results suggested that the antidiabetic properties from the leaves of W. chinensis are not simply a result of each isolated compound but are due to other components such as the accessibility of polyphenolic groups to α-amylase and α-glucosidase activities.

A new saponin from Acanthopanax koreanum with anti-inflammatory activity.

Twelve saponins were isolated from the leaves of Acanthopanax koreanum, including one new lupane-type triterpene glycoside, named acankoreoside R (1), together with 11 known triterpenoid saponins (2-12). Their structures were elucidated by 1D and 2D nuclear magnetic resonance (NMR), mass spectroscopic data (MS). All of the fractions and isolated saponins were evaluated for anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) by ELISA. Among them, compounds 1-5, 7, 10, and 12 showed strong inhibitions towards interleukin-12 (IL-12) production with IC50 values ranging from 1.59 to 5.46 µM. Other compounds were weak or inactive toward IL-12 p40 production.

In vitro anti-inflammatory components isolated from the carnivorous plant Nepenthes mirabilis (Lour.) Rafarin.

CONTEXT: Nepenthes mirabilis (Lour.) Rafarin (Nepenthaceae) is a carnivorous plant used as a folk medicine in the treatment of jaundice, hepatitis, gastric ulcers, ureteral stones, diarrhea, diabetes, and high blood pressure. Neither the phytochemical content nor biological activities of N. mirabilis have been reported. OBJECTIVE: The anti-inflammatory activity from the N. mirabilis methanolic extract led to the isolation of compounds (1-26). MATERIALS AND METHODS: Chromatographic methods were used to isolate compounds from the methanol extract of N. mirabilis branches and leaves. The anti-inflammatory activity of these isolated compounds was investigated in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) using ELISA. Primary BMDCs were used to examine the production of pro-inflammatory cytokines (IL-12 p40, IL-6, and TNF-α, at concentrations of 0.1, 0.2, and 1.0 µM) as compared with a positive control, SB203580 (1.0 µM). MTT assays showed that isolated compounds (1-26) did not exhibit significant cytotoxicity at concentrations up to 20.0 µM. RESULTS: Compound 9 showed potent inhibition of IL-12 p40, IL-6, and TNF-α production (IC50 = 0.17 ± 0.02, 0.46 ± 0.01, and 8.28 ± 0.21 µM, respectively). Compound 4 showed potent inhibition of IL-12 p40 and IL-6 production (IC50 = 1.17 ± 0.01 and 2.15 ± 0.04 µM). In addition, IL-12 p40 inhibition by naphthalene derivatives (1-7, 9, and 10), phenolic compounds (11-15), lupeone (18), and flavonoids (22, 25, and 26) was more potent than with the positive control. The isolated compounds exhibited little and/or no inhibitory effects on TNF-α production in LPS-stimulated BMDCs. DISCUSSION AND CONCLUSION: Taken together, these data suggest that the isolated components have significant inhibitory effects on pro-inflammatory cytokine production and warrant further study concerning their potential medicinal use.

Role of Ethylene and Its Cross Talk with Other Signaling Molecules in Plant Responses to Heavy Metal Stress.

Excessive heavy metals (HMs) in agricultural lands cause toxicities to plants, resulting in declines in crop productivity. Recent advances in ethylene biology research have established that ethylene is not only responsible for many important physiological activities in plants but also plays a pivotal role in HM stress tolerance. The manipulation of ethylene in plants to cope with HM stress through various approaches targeting either ethylene biosynthesis or the ethylene signaling pathway has brought promising outcomes. This review covers ethylene production and signal transduction in plant responses to HM stress, cross talk between ethylene and other signaling molecules under adverse HM stress conditions, and approaches to modify ethylene action to improve HM tolerance. From our current understanding about ethylene and its regulatory activities, it is believed that the optimization of endogenous ethylene levels in plants under HM stress would pave the way for developing transgenic crops with improved HM tolerance.

Cytotoxic Biscembranoids from the Soft Coral Sarcophyton pauciplicatum.

Ten biscembranoids (1-10), including the two new compounds sarcophytolides M and N (1 and 2), were isolated from the methanol extract of the Vietnamese soft coral Sarcophyton pauciplicatum. Their structures were elucidated by spectroscopic methods including one dimensional (1D)- and 2D-NMR, high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and circular dichroism (CD). The in vitro cytotoxic activity of all isolated compounds against a panel of eight human cancer cell lines including HepG2 (hepatoma cancer), HL-60 (acute leukemia), KB (epidermoid carcinoma), LNCaP (prostate cancer), LU-1 (lung cancer), MCF7 (breast cancer), SK-Mel2 (melanoma), and SW480 (colon adenocarcinoma) was evaluated using the sulforhodamine B colorimetric assay. Among the isolated biscembranoids, 1, 3, 4, 7, 9, and 10 exhibited significant cytotoxic effects and may be selected for further studies of their anticancer activity.

Anti-inflammatory tirucallane saponins from Paramignya scandens.

Five new tirucallane saponins, paramignyosides A-E (1-5), were isolated from the water fraction of the Paramignya scandens stem and leaves. Their structures were elucidated on the basis of spectroscopic evidence including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and one dimensional (1D)- and 2D-NMR. The effects of isolated compounds on pro-inflammatory cytokines were evaluated by measuring the production of interleukin (IL)-12 p40, IL-6, and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs). Paramignyoside C (3) exhibited selective and potent inhibitory effect (IC50=5.03±0.19 µM) on the production of IL-12 p40 comparable to that of the positive control, SB203580 (IC50=5.00±0.16 µM). Further studies are required to confirm efficacy in vivo and the mechanism of anti-inflammatory effects.

Cytotoxic triterpene saponins from Cercodemas anceps.

Seven holostane-type triterpene saponins (1-7), including five new compounds namely cercodemasoides A-E (2-6), were isolated from the sea cucumber Cercodemas anceps. Their structures were elucidated on the basis of spectroscopic evidence including HR ESI MS, ESI MS/MS, 1D and 2D NMR. The cytotoxic effects of isolated compounds were evaluated by SRB method on five human cancer cell lines including Hep-G2 (hepatoma cancer), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma). Compounds 1-7 showed potent cytotoxicity on five tested cancer cell lines with IC50 values ranging from 0.03 ± 0.01 to 7.36 ± 0.46 µM. With respect to the potent cytotoxicity of the isolated saponins, further studies are required to confirm efficacy in vivo and the mechanism of cytotoxic effects.

Asterosaponins and glycosylated polyhydroxysteroids from the starfish Culcita novaeguineae and their cytotoxic activities.

Using combined chromatographic methods, two asterosaponins (compounds 1 and 2), including a new compound novaeguinoside E (compound 1), and six glycosylated polyhydroxysteroids (compounds 3-8) were isolated from a methanol extract of the starfish Culcita novaeguineae. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, ROESY, and HRESI-MS) and by comparison with the literature values. The new compound 1 represents the third example of asterosaponins containing the 5α-cholesta-9(1l)-en-3ß,6α,20,22-tetraol aglycone. Among isolated compounds, 4-7 exhibited moderate to weak cytotoxic activities against five human cancer cell lines such as Hep-G2 (hepatoma), KB (epidermoid carcinoma), LNCaP (prostate cancer), MCF7 (breast cancer), and SK-Mel2 (melanoma).

Two new naphthalene glucosides and other bioactive compounds from the carnivorous plant Nepenthes mirabilis.

Two new naphthalene diglucosides named nepenthosides A (1) and B (2), together with eleven known compounds (3-13), were isolated from the carnivorous plant Nepenthes mirabilis. The structures of these compounds were elucidated based on extensive spectroscopic analysis, including 1D- and 2D-NMR, and MS. The antioxidant activities of compounds 1-13 were evaluated in terms of their peroxyl radical-scavenging (trolox equivalent, TE) and reducing capacities. All isolates showed peroxyl radical-scavenging and reducing activities at concentrations of 1.0 and 10.0 µM. Anti-osteoporotic activities were investigated using murine osteoclastic RAW 264.7 cells. Compounds 1-7 and 9-12 significantly suppressed tartrate-resistant acid phosphatase activity down to 91.13 ± 1.18 to 42.39 ± 1.11%, relative to the control (100%) in nuclear factor-κB ligand (RANκL)-induced osteoclastic RAW 264.7 macrophage cells.

Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus.

BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S) 5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S) 5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.

Chemical constituents from Kandelia candel with their inhibitory effects on pro-inflammatory cytokines production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs).

Chemical investigation of Kandelia candel resulted in the isolation of 19 compounds (1-19), including one new sesquiterpene glycoside, kandelside (1), three megastigman glycoside compounds (7-9), 16 known phenolic compounds (2-6 and 10-19). Structures of the isolated compounds were elucidated based on spectral data comparison with reported values. Isolated compounds were also evaluated for their inhibitory effects on the production of pro-inflammatory cytokines interleukin (IL)-12 p40, IL-6, and tumor necrosis factor α (TNF-α) in lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells. Among these compounds, compound 9 exhibited strong inhibitory activity against IL-6 production (IC50=0.07 ± 0.05 µM) and moderate inhibitory activity against TNF-α production (IC50=49.86 ± 1.02 µM), but exhibited no activity on IL-12 p40 production. Compounds 5 and 6 significantly inhibited IL-12 p40, IL-6, and TNF-α production with IC50 values of 11.68 ± 0.38, 44.52 ± 1.08, and 28.73 ± 0.96 µM, respectively.

The anti-osteoporosis and antioxidant activities of chemical constituents from Chrysanthemum indicum flowers.

Two new compounds, chrysinoneside A (1) and (-)-trans-chrysanthenol-6-O-ß-D-glucopyranoside (2), along with 17 known compounds (3-19) were isolated from Chrysanthemum indicum flowers. The total phenolic and flavonoid contents of various fractions were determined. The EtOAC fraction had the highest total phenolic content (525.84 ± 23.51 mg GAE/g DR) and the total flavonoid content (63.49 ± 3.32 mg QE/g DR). The EtOAc and water fractions showed the greatest peroxyl radical-scavenging capacity and the ability to reduce Cu(I) ions, with ORAC and CUPRAC values ranging from 24.00 ± 0.44 to 28.06 ± 1.35 and 16.90 ± 0.51 to 49.77 ± 0.97 µM, respectively. Compounds 5-11, 18, and 19 displayed strong effects in both peroxyl radical-scavenging and reducing capacity assays at a concentration of 10 µM. The anti-osteoporosis activity of these compounds was also evaluated. Compounds 10, 13, and 19 exhibited the most potent tartrate-resistant acid phosphatase activity in receptor activator of nuclear factor-κB ligand-induced osteoclastic RAW 264.7 cells with values of 105.95 ± 1.18, 110.32 ± 3.95, and 112.58 ± 6.42%, respectively.

Peroxisome proliferator-activated receptor transactivational effects in HepG2 cells of cembranoids from the soft coral Lobophytum crassum Von Marenzeller.

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of multiple genes involved in metabolic, anti-inflammatory, and developmental processes. This study evaluated the PPARs transactivational effects of thirteen cembranoid diterpenoids 1-13 from the soft coral Lobophytum crassum, using PPAR-responsive elements-luciferase reporter and GAL4-PPAR chimera assays. All isolated compounds activated the transcription of PPARs in a dose-dependent manner, with EC50 values ranging from 2.07 ± 1.73 to 130.20 ± 1.85 µM. Moreover, compounds 6-9 affected the transactivation of all three PPAR types, PPARα, γ, ß(δ), in a dose-dependent manner, with EC50 values in a ranging from 11.92 ± 1.23 to 122.50 ± 2.12 µM. These results provide a scientific rationale for further studies on the soft coral L. crassum and its diterpenoid constituents to develop medicinal products against inflammatory and metabolic diseases.

Steroidal constituents from the edible sea urchin Diadema savignyi Michelin induce apoptosis in human cancer cells.

Bioassay-directed fractionation and purification were used to isolate 12 steroids (1-12) from a CH(2)Cl(2) extract of the edible Vietnamese sea urchin Diadema savignyi Michelin. The cytotoxic activity of the CH(2)Cl(2) extract and 12 steroids was evaluated in three human cancer cell lines (HL-60, PC-3, and SNU-C5). Relative to the effects of the positive control, mitoxantrone, the CH(2)Cl(2) extract (with an inhibitory concentration of 50% [IC(50)] values ranging from 1.37±0.15 to 3.11±0.15 µg/mL) and compounds 2 (with IC(50) values ranging from 5.29±0.11 to 6.80±0.67 µM) and 11 (with IC(50) values ranging from 4.95±0.07 to 6.99±0.28 µM) exhibited potent cytotoxic effects against all three tested human cancer cell lines. In addition, the CH(2)Cl(2) extract and compounds 2 and 11 were found to induce apoptosis. The induction of apoptosis was accompanied by alterations of the apoptosis-related protein expression, inactivation of ERK1/2 mitogen-activated protein kinase signaling, and decreased c-Myc expression. These data suggest that compounds 2 and 11 from the edible sea urchin D. savignyi may have potential for the treatment of colon cancer, leukemia, and prostate cancer as complementary cancer remedies.

Anti-inflammatory components of Chrysanthemum indicum flowers.

One new octulosonic acid derivative, chrysannol A (1), along with 17 known compounds (2-18), were isolated from Chrysanthemum indicum flowers. Their structures were determined from 1D NMR, 2D NMR, HR-ESI-MS spectral data, and comparisons with previous reports. The effects of these compounds on lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) production by RAW 264.7 cells were investigated. Compound 8 showed the highest inhibition of NO production of 46.09% at a concentration of 10.0µM. Compounds 7, 10, 11, and 16 inhibited TNF-α secretion at all concentration tested (0.4, 2.0, and 10.0µM), with inhibition values ranging from 22.27% to 33.13%. In addition, compound 8 and 9 decrease COX-2 and iNOS protein on Western blot analysis in dose dependent manner.

Anti-inflammatory components of the Vietnamese starfish Protoreaster nodosus

BACKGROUND: In the present study, we examined the inhibitory effects of a methanolic extract, dichloromethane fraction, water layer, and polyhydroxylated sterols (1-4) isolated from the Vietnamese starfish Protoreaster nodosus on pro-inflammatory cytokine (IL-12 p40, IL-6, and TNF-α) production in LPS-stimulated bone marrow-derived dendritic cells (BMDCs) using enzyme-linked immunosorbent assays (ELISA). RESULTS: The methanolic extract and dichloromethane fraction exerted potent inhibitory effects on the production of all three pro-inflammatory cytokines, with IC50 values ranging from 0.60 ± 0.01 to 26.19 ± 0.64 µg/mL. Four highly pure steroid derivatives (1-4) were isolated from the dichloromethane fraction and water layer of P. nodosus. Potent inhibitory activities were also observed for (25S)5α-cholestane-3ß,4ß,6α,7α,8ß,15α,16ß,26-octol (3) on the production of IL-12 p40 and IL-6 (IC50s = 3.11 ± 0.08 and 1.35 ± 0.03 µM), and for (25S) 5α-cholestane-3ß,6α,8ß,15α,16ß,26-hexol (1) and (25S)5α-cholestane-3ß,6α,7α,8ß,15α,16ß,26-heptol (2) on the production of IL-12 p40 (IC50s = 0.01 ± 0.00 and and 1.02 ± 0.01 µM). Moreover, nodososide (4) exhibited moderate inhibitory effects on IL-12 p40 and IL-6 production. CONCLUSION: This is the first report of the anti-inflammatory activity from the starfish P. nodosus. The main finding of this study is the identification oxygenated steroid derivatives from P. nodosus with potent anti-inflammatory activities that may be developed as therapeutic agents for inflammatory diseases.