Chemical constituents from the leaves of Sindora siamensis var. maritima and their antimicrobial and α-glucosidase inhibitory activities.

Two new glycosides, sindosides A-B (1-2), along with 11 previously identified metabolites (3-13), were isolated from an ethanolic extract of the leaves of Sindora siamensis var. maritima. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (IR, NMR, and HRMS). The absolute configuration of compound 1 was established by experimental and calculated ECD spectra. The antimicrobial results revealed that compound 8 selectively inhibited C. albicans fungal with a MIC value of 64 µg/mL, whereas 11 presented a weak inhibition toward E. faecalis, S. aureus, and B. cereus bacterial strains with the same MIC value of 128 µg/mL. Interestingly, compounds 1, 2, 8, 9, and 11 showed α-glucosidase inhibitory activity with IC50 values ranging from 14.42 ± 0.21 to 30.62 ± 0.18 µM, which were more active than the positive control (acarbose, with an IC50 value of 46.78 ± 1.37 µM). Enzyme kinetic analysis revealed that compounds 1, 2, and 11 behaved as uncompetitive inhibitors with Ki values of 8.60 ± 1.04, 5.16 ± 0.73, and 7.17 ± 0.98 µM, respectively.

Glycoside constituents from Miliusa sinensis leaves and their anti-inflammatory and acetylcholine protective effects.

Repeated column chromatography resulted in the isolation of two new glycosides, miliusides A-B (1 and 7), along with six known metabolites (2-6, and 8) from the leaves of Miliusa sinensis Finet and Gagnep. The structures of the purified phytochemicals were elucidated by interpreting their spectroscopic data (NMR, HRMS), as well as comparison with the previous literature. The biological evaluation of acetylcholinesterase (AChE) inhibitory effects and anti-inflammatory activity by measuring nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophage cells, were also conducted. Among them, compounds 5 and 7 exhibited significant AChE inhibitory activities (IC50 = 53.36 ± 4.20 and 88.50 ± 8.79 µM, respectively), compared with the positive control (Galanthamine, IC50 = 1.65 ± 0.15 µM). Only the MeOH extract showed suppression effects on NO production in LPS-induced RAW264.7 cells (IC50 = 38.18 ± 3.25 µg/mL) comparable to that of the positive control, l-NMMA (IC50 = 2.21 ± 0.56 µg/mL).

Chemical constituents of Vietnamese mangrove Hibiscus tiliaceus with antioxidant and alpha-glucosidase inhibitory activity.

Using various chromatographic techniques, a total of 15 compounds, including one novel megastigmane named tiliaceic acid A (1) and 14 known compounds, were isolated from the traditional medicinal Vietnamese mangrove Hibiscus tiliaceus. Their structures were confirmed based on spectroscopic experiments including, UV, 1 D- and 2 D-NMR, HR-ESI-MS, and ECD analysis. The antioxidant and α-glucosidase inhibitory activities of the isolated compounds from H. tiliaceus were evaluated for the first time. Compound 2 showed strong α-glucosidase inhibitory activity with an IC50 of 77.78 ± 1.00 µM compared with the positive control acarbose at 105.71 ± 2.29 µM.

Protective Effects of Compounds from Cimicifuga dahurica against Amyloid Beta Production in Vitro and Scopolamine-Induced Memory Impairment in Vivo.

Cimicifuga dahurica has traditionally been used as an antipyretic, analgesic, and anti-inflammatory agent and as a treatment for uterine and anal prolapse. This study has investigated the potential beneficial effects of this medicinal plant and its components on Alzheimer's disease (AD) with a focus on amyloid beta (Aß) production and scopolamine-induced memory impairment in mice. An ethanol extract from C. dahurica roots decreased Aß production in APP-CHO cells [Chinese hamster ovarian (CHO) cells stably expressing amyloid precursor protein (APP)], as determined by an enzyme-linked immunosorbent assay and Western blot analysis. Then, the compounds isolated from C. dahurica were tested for their antiamyloidogenic activities. Four compounds (1-4) efficiently interrupted Aß generation by suppressing the level of ß-secretase in APP-CHO cells. Moreover, the in vivo experimental results demonstrated that compound 4 improved the cognitive performances of mice with scopolamine-induced disruption on behavioral tests and the expression of memory-related proteins. Taken together, these results suggest that C. dahurica and its constituents are potential agents for preventing or alleviating the symptoms of AD.

Acylated flavonoid glycosides from Barringtonia racemosa.

Using various chromatographic separations, three new acylated flavonoid glycosides, namely barringosides G-I (1-3), were isolated from the water-soluble extract of Barringtonia racemosa branches and leaves. The structure elucidation was performed by extensive analysis of the 1D and 2D NMR and HR-QTOF-MS data. Of the isolated compounds, barringoside I (3) showed moderate inhibitory effects on LPS-induced NO production in RAW264.7 cells with an IC50 of 52.48 ± 1.04 µM.

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.

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.

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.

Two new simple iridoids from the ant-plant Myrmecodia tuberosa and their antimicrobial effects.

Six iridoid derivatives (1-6), including two new compounds myrmecodoides A and B (1 and 2), were isolated from the ant-plant Myrmecodia tuberosa. Their structures were determined on the basis of spectroscopic data ((1)H and (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, NOESY and HR-ESI-MS) and by comparison with the literature values. Among isolates, 3 and 4 exhibit weak antibacterial effect against Staphylococcus aureus subsp. aureus with MIC value of 100.0 µg/mL.

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.

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.

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.

Two novel iridoids from Morinda longifolia.

Six secondary metabolites, including two novel iridoids, longifolides A (1) and B (2), were isolated by various chromatographic methods from a methanol extract of branches and leaves of Morinda longifolia Craib. The structures of the compounds were determined on the basis of NMR spectroscopic (1H and 13C NMR, HSQC, HMBC, 1H-1H COSY, NOESY) and FTICR-MS data, as well as by comparison of them with literature values.