Anti-inflammatory secondary metabolites from the stems of Millettia dielsiana Harms ex Diels.

A phytochemical investigation for the constituents of the stems of Millettia dielsiana Harms ex Diels resulted in the isolation of a new isoflavone glycoside, mildiside A (1), and 14 known compounds (2-15). Their chemical structures were determined using a combination of IR, NMR, MS, and optical rotation analysis, as well as comparison with the literature data. The ethanolic (EtOH) extract and several isolated compounds exert the inflammatory effect of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophage cells.

Chemical Constituents from Cimicifuga dahurica and Their Anti-Proliferative Effects on MCF-7 Breast Cancer Cells.

This study was designed to search for novel anti-cancer compounds from natural plants. The 70% ethanolic extract from the rizhomes of Cimicifuga dahurica (Turcz.) Maxim. (Ranunculaceae) was found to possess significant in vitro anti-proliferative effects on MCF-7 breast cancer cells. A phytochemical investigation using assay-guided fractionation of the ethanolic extract of C. dahurica resulted in the isolation of one new phenolic amide glycoside 3, two new lignan glycosides 4 and 7, one new 9,19-cycloartane triterpenoid glycoside 6, and thirteen known constituents 1, 2, 5, and 8⁻17. The structures of 3, 4, 6, and 7 were established using contemporary NMR methods and from their HRESIMS data. The anti-proliferative effects of isolated compounds were evaluated using the BrdU-proliferation kit. Five among the 17 isolated compounds showed significant anti-proliferative effects (p ≤ 0.05), wherein compound 7 showed the most significant anti-proliferative and cell cycle arresting effect (p ≤ 0.05) which followed a dose dependent manner. Western blot protein expression analysis showed a down expression of c-Myc and cyclin D1 which further elucidated the anti-proliferation mechanism of compound 7 while apoptotic effects were found in association with Bcl-2 family protein expression variations. Conclusively this study reports the isolation and identification of 17 compounds from C. dahurica, including four novel molecules, in addition to the fact that compound 7 possesses significant anti-proliferative and apoptotic effects in vitro that may require further exploration.

Rat intestinal sucrase inhibited by minor constituents from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen.

In the search for plants, containing compounds with α-glucosidase inhibitory activity, we found that a methanolic extract from the leaves and twigs of Archidendron clypearia (Jack.) Nielsen significantly inhibited rat intestinal sucrase in vitro. A phytochemical investigation of the aqueous layer of an A. clypearia extract led to the isolation of 14 compounds (1-14). Their structures were established through extensive 1D and 2D NMR, CD data, and MS analysis. The methanolic extract, as well as the water layer at a concentration of 3.0mg/mL, showed potent sucrase inhibitory activity, with 67.78±2.53% and 95.33±2.15% inhibition, respectively. In addition, compounds 6, 7, and 10 (1.0mM) showed potent sucrase inhibition (88.36±1.15%, 81.57±1.07%, and 66.32±4.73% inhibition, respectively), which was comparable to that of the positive control, acarbose, which exhibited 89.54±0.91% inhibition. Other compounds showed moderate or weak inhibitory activity at the same concentration. The sucrase inhibitory activity of the extracts and purified compounds may provide a novel opportunity to develop a new class of antidiabetic agents.

Anti-inflammatory Flavonoid C-Glycosides from Piper aduncum Leaves.

Four new compounds, acacetin 8-C-[ß-D-apiofuranosyl-(1 → 2)-ß-D-glucopyranoside] (1), 7-methoxyacacetin 8-C-[ß-D-apiofuranosyl-(1 → 3)-ß-D-glucopyranoside] (2), 7-methoxyacacetin 8-C-[ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranoside] (3), and 4‴-O-acetylacacetin 8-C-[α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranoside] (4), along with ten known compounds (5-14), were isolated from Piper aduncum leaves. The effects of these compounds on lipopolysaccharide-induced expression of the proinflammatory cytokines IL-12 p40, IL-6, and TNF-α in bone marrow-derived dendritic cells were evaluated. Compounds 2, 3, 6, 8, 9, and 11-13 inhibited the production of both IL-12 p40 and IL-6, with IC50 values ranging from 0.35 ± 0.01 to 1.40 ± 0.04 µM and 1.22 ± 0.02 to 3.79 ± 0.10 µM, respectively. Compounds 5 and 10 only showed strong inhibition effects on the production of IL-12 p40, with IC50 values of 2.76 ± 0.08 and 0.39 ± 0.05 µM, respectively. However, all compounds showed weak activity or no activity on TNF-α production at the tested concentrations.

Identification of six new lupane-type triterpenoids from Acanthopanax koreanum leaves and their tyrosinase inhibitory activities.

Chemical investigation of Acanthopanax koreanum leaves resulted in the isolation of 13 compounds (1-13), including six new (20,29)-dehydrolupane-type triterpenoids: 3α,11α,30-trihydroxylup-20(29)-en-23,28-dioic acid (1), 3α,11α,30-trihydroxylup-20(29)-en-28-oic acid (2), 3α,11α,30-trihydroxylup-23-al-20(29)-en-28-oic acid (3), 3α, 11α-dihydroxy-20-oxo-30-norlupane-23,28-dioic acid (5), (20S)-3α-hydroxy-30 oxolupane-23,28-dioic acid (8), (20S)-3ß,7ß,29-trihydroxy-lupane-23-al-28-oic acid (10), and one novel compound isolated for the first time, named 3α,20α,29-trihydroxylupane-23,28-dioic acid (9), together with six known compounds (4, 6, 7, and 11-13). Chemical structures of the isolated compounds were evaluated by analyzing and comparing spectroscopic data with those reported in the literature. These compounds were also evaluated for their tyrosinase inhibitory effects. Among them, compounds 3, 7, 9, and 12 showed significant inhibitory effects, with inhibitory concentrations of 50% (IC50) values ranging from 8.61 to 63.5 µM.

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.

Chemical constituents of Miliusa balansae leaves and inhibition of nitric oxide production in lipopolysaccharide-induced RAW 264.7 cells.

Methanolic extract of Miliusa balansae Finet et Gagnep exerts an anti-inflammatory effect via inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Three new megastigmane glycosides, milbasides A-C (1-3), together with fifteen known compounds (4-18), were isolated from the active fraction. Their chemical structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR, HR ESI MS, and CD analysis, as well as comparison with previously reported data. Compounds 1-3, 11 and 14 (20.0 µM) showed potent inhibitory activities with inhibition values of 98.5 ± 1.6%, 90.9 ± 7.8%, 84.8 ± 3.5%, 91.5 ± 8.7%, and 91.8 ± 2.7%, respectively. Our results suggest that megastigmane glycosides from M. balansae leaves may be used to treat 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.

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.

A new phenolic component from Triticum aestivum sprouts and its effects on LPS-stimulated production of nitric oxide and TNF-α in RAW 264.7 cells.

An unusual new phenolic component, triticumoside (1), and eight known compounds, isoorientin (2), isoscoparin (3), (2R)-2-O-ß-D-glucopyranosyloxy-4,7-dimethoxy-2H-1,4-benzoxazin-3(4H)-one (4), adenosine (5), ß-sitosterol (6), daucosterol (7), 6'-O-linolenoyl daucosterol (8), α-tocopherol (9), were isolated fromTriticum aestivum sprouts. The hybrid structure of 1, which is a hybrid between a flavone and a polyoxygenated benzene, is rarely found in natural sources. In addition, the effects of these compounds on LPS-induced NO and TNF-α production in RAW 264.7 cells were evaluated. At a concentration of 2.0 µM, compounds 2-4 significantly inhibited the production of both NO and TNF-α. Compound 1 exhibited inhibitory activity on the secretion of TNF-α at concentrations as low as 2.0 µM, but it did not reduce NO levels at any of the tested concentrations.

Triterpene saponins from the sea cucumber Stichopus chloronotus.

Sea cucumbers have been used as a dietary delicacy and important ingredient in Asian traditional medicine and functional foods over many centuries. Using combined chromatographic methods, six triterpene saponins (1-6), including a new compound, stichloroside F (1), were isolated from a methanol extract of the sea cucumber Stichopus chloronotus Brandt. Their structures were determined on the basis of spectroscopic (1H and 13C NMR, HSQC, HMBC, 1H-1lH COSY, ROESY) and FTICR-MS data and by comparison with literature values.

Anti-inflammatory components of Euphorbia humifusa Willd.

Two new compounds, euphorbinoside (1) and dehydropicrorhiza acid methyl diester (2), along with 24 known compounds (3-26) were isolated from Euphorbia humifusa Willd. The effects of these compounds on soluble epoxide hydrolase (sEH) inhibitory activity were evaluated. Flavonoid compounds (10-21) exhibited high sEH inhibitory activity. Among them, compounds 12, 13, and 19 greatly inhibited sEH enzymatic activity, with IC50 values as low as 18.05±1.17, 18.64±1.83, and 17.23±0.84 µM, respectively. In addition, 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. Compounds 3-6, 8, 18, 20-23, and 25-26 inhibited the production of both NO and TNF-α, with IC50 values ranging from 11.1±0.9 to 45.3±1.6 µM and 14.4±0.5 to 44.5±1.2 µM, respectively.

Triterpenoid saponins from the roots of Rosa rugosa Thunb. as rat intestinal sucrase inhibitors.

Medicinal plants constitute an important source of potential therapeutic agents for diabetes. The purpose of present study is to investigate the effect of root extract of Rosa rugosa Thunb. on inhibition of sucrase related to diabetes mellitus (DM). Bioassay-guided fractionation of the methanol extract led to the identification of 13 triterpenoid saponins (1-13). Their structures were elucidated on the basis of extensive spectroscopic analysis, including 1D, 2D NMR, and MS. The n-butanol fraction showed potent rat intestinal sucrase inhibitory activity with value of 87.62 ± 5.84 % inhibition compared to the positive control acarbose (50.96 ± 2.97 % inhibition at 0.02 mM). Subsequently, compounds 11-13 (1.0 mM) exhibited significant sucrase inhibitory activity, with inhibition percentage values of 41.17 ± 3.52, 46.80 ± 4.00, and 39.39 ± 4.19 %, respectively. Whereas, compounds 2-6, 8, and 10 showed moderate sucrase inhibitory activity (ranging from 13.26 ± 7.00 to 32.08 ± 6.04 % inhibition) at a same concentration. The data provide a starting point for creating new sucrase inhibitors, which may be useful for the development of effective therapies for the treatment of DM.

Anti-inflammatory and PPAR transactivational properties of flavonoids from the roots of Sophora flavescens.

Anti-inflammatory and peroxisome proliferator-activated receptors (PPARs) transactivational effects of nine compounds (1 - 9) from the roots of Sophora flavescens were evaluated using NF-κB-luciferase, reverse transcriptase polymerase chain reaction, peroxisome proliferator response element (PPRE)-luciferase, and GAL-4-PPAR chimera assays. Compounds 4 and 8 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values of 4.0 and 4.4 µM, respectively. Furthermore, the transcriptional inhibitory function of these compounds was confirmed by a decrease in cyclooxgenase 2 and inducible nitric oxide synthase gene expression levels in HepG2 cells. Compounds 1, 3, 5, 6, 8, and 9 significantly activated the transcription of PPARs in a dose-dependent manner, with EC50 values ranging from 1.1 to 13.0 µM. Compounds 1, 3, 5, 6, 8, and 9 exhibited dose-dependent PPARα transactivational activity, with EC50 values in a range of 0.9 - 16.0 µM. Compounds 1, 3, 8, and 9 also significantly upregulated PPARγ activity in a dose-dependent manner, with EC50 values of 10.5, 6.6, 15.7, and 1.6 µM, whereas compounds 1, 8, and 9 demonstrated transactivational PPARß(δ) effects with EC50 values of 11.4, 10.3, and 1.5 µM, respectively. These results provide a scientific rationale for the use of the roots of S. flavescens and warrant further studies to develop new agents for the prevention and treatment of inflammatory and metabolic diseases.

Plantagiolides I and J, two new withanolide glucosides from Tacca plantaginea with nuclear factor-kappaB inhibitory and peroxisome proliferator-activated receptor transactivational activities.

A novel withanolide glucoside, plantagiolide I (1), a new withanolide glucoside, plantagiolide J (2), and six known compounds (3-8) were isolated from the whole plant of Tacca plantaginea. Their structures were determined by spectroscopic and chemical methods. Compound 3 significantly inhibited tumor necrosis factor alpha (TNFα)-induced nuclear factor-kappaB (NF-κB) transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values of 9.0 µM. Compounds 1-8 enhanced the transcriptional activity of peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner, with EC(50) values ranging from 1.6 to 49.7 µM. In addition, the transactivational effects of compounds 1-8 on three individual PPAR subtypes, including PPARα, ß(δ), and γ were evaluated. Compounds 1-8 significantly activated the transcriptional activity of PPARß(δ), with EC(50) values in a ranging from 4.1 to 29.6 µM. These results provide scientific support for the use of T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.

Diarylheptanoid glycosides from Tacca plantaginea and their effects on NF-κB activation and PPAR transcriptional activity.

In the screening search for NF-κB inhibitory and PPAR transactivational agents from medicinal plants, a methanol extract of the whole plant of Tacca plantaginea and its aqueous fraction showed the significant activities. Bioassay-guided fractionation combined with repeated chromatographic separation of the aqueous fraction of the methanol extract of T. plantaginea resulted in the isolation of two new diarylheptanoid glycosides, plantagineosides A (1) and B (2), an unusual new cyclic diarylheptanoid glycoside, plantagineoside C (3), and three known compounds (4-6). Their structures were determined by extensive spectroscopic and chemical methods. Compounds 3-6 significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC(50) values ranging from 0.9 to 9.4 µM. Compounds 1-6 significantly activated the transcriptional activity of PPARs in a dose-dependent manner, with EC(50) values ranging from 0.30 to 10.4 µM. In addition, the transactivational effects of compounds 1-6 were evaluated on three individual PPAR subtypes, including PPARα, γ, and ß(δ). Compounds 1-6 significantly enhanced the transcriptional activity of PPARß(δ), with EC(50) values in a range of 11.0-30.1 µM. These data provide the rationale for using T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.