A new lignan from the stems of Buchanania lucida Blume (Anacardiaceae).

From the EtOAc-soluble extract of the stems of Buchanania lucida, one new lignan, (+)-(8S,8'S)-5'-methoxy-4,4'-di-O-methylsecoisolariciresinol (1), together with five known compounds (2-6) were isolated. Their structures were elucidated on the basis of NMR spectroscopic interpretation. The absolute configuration of 1 was determined based on the Cotton effects in the ECD spectrum. In the tyrosinase inhibitory activity test, p-hydroxybenzoic acid (6) showed the strong effect, with an IC50 value of 9.35 µM.

A new 8,3'-neolignan from Solanum procumbens Lour.

The phytochemical investigation of the EtOAc-soluble fraction of the aerial parts of Solanum procumbens Lour. has been carried out to obtain seven compounds, including a new 8,3'-neolignan named solacanin A (1). Their chemical structures were elucidated based on the spectroscopic data interpretation. All isolated compounds were tested for their α-glucosidase inhibitory activity. Compounds 1 and 3-6 showed inhibitory activity with IC50 values of 221.5, 18.9, 6.0, 104.1, and 219.7 µM, respectively.[Formula: see text].

Two new derivatives of 8-prenyl-5,7-dihydroxycoumarin from the stems of Streblus ilicifolius (S.Vidal) Corn.

From the EtOAc-soluble extract of the stems of Streblus ilicifolius (Moraceae), two new secondary metabolites named strebluses A (1) and B (2) were isolated. Their chemical structures have been concluded based on the chemical derivatisation and the spectroscopic interpretation. All compounds have been tested for their tyrosinase inhibitory activity. They showed weaker inhibitory activity than that of kojic acid (IC50, 44.6 µM).[Formula: see text].

δ-Tocopherol derivatives from the leaves of Muntingia calabura L.

From an ethyl acetate-soluble fraction of the leaves of Muntingia calabura, one new trimeric δ-tocopherol derivative named as tocomuntin A (1), together with three known δ-tocopherol derivatives (2-4) were isolated. Their structures were elucidated based on the interpretation of NMR and MS spectroscopic data. In this work, δ-tocopherol (3) was found to have α-glucosidase inhibitory activity for the first time (IC50, 47.3 µM).

A new diphenylheptanoid from the rhizomes of Curcuma zedoaria.

A phytochemical investigation of the rhizomes of Curcuma zedoaria was carried out, leading to the isolation of a new diphenylheptanoid, zedoaroxane A (1), together with four known compounds (2-5). Their structures were elucidated based on NMR spectroscopic data. All isolated compounds possessed α-glucosidase inhibitory activity, with the IC50 values ranging from 35.2 to 89.0 µM, more potent than that of the positive control acarbose (IC50, 214.5 µM).

A new phenolic acid from the wood of Mangifera gedebe.

From the methanol extract of the wood of Mangifera gedebe (Anacardiaceae), we had isolated a new secondary metabolite named gedebic acid (1) and six known compounds (2-7). Their chemical structures were determined by spectroscopic methods as well as comparing with data in the literature. All compounds were tested for α-glucosidase inhibitory activity. Compounds 4-7 showed more potent inhibitory activity, with IC50 values ranging from 45.3 to 142.6 µM, than that of a positive control acarbose (IC50, 214.5 µM).

4-Hydroxypanduratin A and Isopanduratin A Inhibit Tumor Necrosis Factor α-Stimulated Gene Expression and the Nuclear Factor κB-Dependent Signaling Pathway in Human Lung Adenocarcinoma A549 Cells.

Tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine, regulates inflammatory and immune responses by up-regulating gene expression in a manner that is dependent on the transcription factor nuclear factor κB (NF-κB). In the present study, we found that 4-hydroxypanduratin A and isopanduratin A, constituents of the rhizomes of Boesenbergia pandurata, inhibited the TNF-α-stimulated up-regulation of intercellular adhesion molecule-1 (ICAM-1) in human lung adenocarcinoma A549 cells. 4-Hydroxypanduratin A and isopanduratin A also reduced ICAM-1 mRNA expression and NF-κB-responsive luciferase activity in TNF-α-stimulated A549 cells. Moreover, 4-hydroxypanduratin A and isopanduratin A prevented the TNF-α-stimulated translocation of the NF-κB subunit p65 to the nucleus and the phosphorylation and proteasomal degradation of the inhibitor of the NF-κB α protein. The present results revealed that 4-hydroxypanduratin A and isopanduratin A inhibit TNF-α-stimulated gene expression and the NF-κB-dependent signaling pathway in A549 cells.

Willughbeia cochinchinensis prevents scopolamine-induced deficits in memory, spatial learning, and object recognition in rodents.

ETHNOPHARMACOLOGICAL RELEVANCE: Willughbeia cochinchinensis (WC) has been used in Vietnamese traditional medicine for the treatment of dementia as well as diarrhea, heartburn, and cutaneous abscess and as a diuretic. AIM: Alzheimer's disease (AD) is one of the most prevalent diseases in elderly individuals. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors have been widely used to treat patients with AD. In the present study, we investigated anti-AChE and anti-BChE activities of a natural product, WC, for its potential applications in therapies to prevent/treat dementia. MATERIALS AND METHODS: First, compounds extracted from WC were tested for their AChE and BChE inhibitory activities in vitro. Second, in vivo behavioral experiments were performed to investigate the effects of WC at doses of 100, 150, and 200mg/kg on scopolamine (1.5mg/kg)-induced memory and cognitive deficits in mice. The behavior of mice treated with and without WC and/or scopolamine was tested using the Y-maze, Morris water maze, and novel object recognition task. RESULTS: The results of the in vitro assay demonstrated anti-AChE and anti-BChE activities of the compounds extracted from WC. The results of behavioral experiments showed that the administration of WC prevented 1) scopolamine-induced decrease in spontaneous alternation (%) behavior in the Y-maze, 2) scopolamine-induced deficits in spatial learning and memory in the Morris water maze, and 3) scopolamine-induced deficits in novel object recognition. These results indicate that WC prevents cognitive and memory deficits induced by scopolamine injection. CONCLUSIONS: Our findings suggest that WC may represent a novel candidate for the treatment of memory and cognitive deficits in humans with dementia.

Constituents of the Rhizomes of Boesenbergia pandurata and Their Antiausterity Activities against the PANC-1 Human Pancreatic Cancer Line.

Human pancreatic cancer cell lines have a remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions represents a novel antiausterity strategy in anticancer drug discovery. In this investigation, a methanol extract of the rhizomes of Boesenbergia pandurata showed potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions, with a PC50 value of 6.6 µg/mL. Phytochemical investigation of this extract led to the isolation of 15 compounds, including eight new cyclohexene chalcones (1-8). The structures of the new compounds were elucidated by NMR spectroscopic data analysis. Among the isolated compounds obtained, isopanduratin A1 (14) and nicolaioidesin C (15) exhibited potent preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrition-deprived conditions, with PC50 values of 1.0 and 0.84 µM, respectively.

Anti-cholinesterases and memory improving effects of Vietnamese Xylia xylocarpa.

BACKGROUND: Alzheimer's disease (AD) is the most common cause of dementia among the elderly and is characterized by loss of memory and other cognitive functions. An increase in AChE (a key enzyme in the cholinergic nervous system) levels around ß-amyloid plaques and neurofibrillary tangles is a common feature of AD neuropathology. Amnesic effects of scopolamine (acetylcholine receptor antagonist) can be investigated in various behavioral tests such as Morris water maze, object recognition, Y-maze, and passive avoidance. In the scope of this paper, we report the anti-AChE, anti-BChE properties of the isolated compound and the in vivo effects of the methanolic extract of Xylia xylocarpa (MEXX) on scopolamine-induced memory deficit. RESULTS: In further phytochemistry study, a new hopan-type triterpenoid, (3ß)-hopan-3-ol-28,22-olide (1), together with twenty known compounds were isolated (2-21). Compound 1, 2, 4, 5, 7-9, and 11-13 exhibited potent acetylcholinesterase (AChE) inhibitory activity in a concentration-dependent manner with IC50 values ranging from 54.4 to 94.6 µM. Compound 13 was also shown anti-butyrylcholinesterase (BChE) activity with an IC50 value of 42.7 µM. The Morris water Y-maze, Y-maze, and object recognition test were also carried out. CONCLUSIONS: It is noteworthy that MEXX is effective when administered orally to mice, experimental results are consistent with the traditional use of this medicinal plant species.

A New Cassane-type Diterpene from the Seed of Caesalpinia sappan.

Phytochemical investigation of the CH2Cl2 extract of the Vietnamese medicinal plant Caesalpinia sappan Linn resulted in the isolation of a new cassane-type diterpene named tomocin I (1). Its chemical structure was determined by NMR spectroscopic and mass spectrometric analysis.

α-Glucosidase inhibitors from the leaves of Embelia ribes.

A novel and rare 1,4-dehydrated ceramide, embelamide (1), and a new C-glycoalkaloid which is based on a ß-carboline ring system, 1-(2'-deoxy-α-d-ribopyranosyl)-ß-carboline (4), were isolated from the CHCl3 soluble fraction of the leaves of Embelia ribes (Myrsinaceae), together with thirteen known compounds (2-3, 5-15). Their structures were elucidated on the basis of spectroscopic data. Compounds 1, and 5-12 possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, and showed more potent inhibitory activity, with IC50 values ranging from 1.3 to 155.0 µM, than that of a positive control acarbose (IC50, 214.5 µM).

α-Glucosidase inhibitors from the stems of Embelia ribes.

From the ethyl acetate extract of the stems of Embelia ribes (Myrsinaceae), a new alkenylresorcinol, embeliphenol A (1), together with 11 known compounds have been isolated. Their structures were elucidated on the basis of spectroscopic data. All compounds possessed significant α-glucosidase inhibitory activity in a concentration-dependent manner, except for 2 and 9. Compounds 1, 3-6, 8, and 12 showed more potent inhibitory activity, with IC50 values ranging from 10.4 to 116.7 µM, than that of a positive control acarbose (IC50 , 214.5 µM).

Geranyl dihydrochalcones from Artocarpus altilis and their antiausteric activity.

Human pancreatic cancer cell lines have remarkable tolerance to nutrition starvation, which enables them to survive under a tumor microenvironment. The search for agents that preferentially inhibit the survival of cancer cells under low nutrient conditions is a novel antiausterity strategy in anticancer drug discovery. In this study, the methanolic extract of the leaves of Artocarpus altilis showed 100 % preferential cytotoxicity against PANC-1 human pancreatic cancer cells under nutrient-deprived conditions at a concentration of 50 µg/mL. Further investigation of this extract led to the isolation of eight new geranylated dihydrochalcones named sakenins A-H (1-8) together with four known compounds (9-12). Among them, sakenins F (6) and H (8) were identified as potent preferentially cytotoxic candidates with PC50 values of 8.0 µM and 11.1 µM, respectively.

Cleistanthane diterpenes from the seed of Caesalpinia sappan and their antiausterity activity against PANC-1 human pancreatic cancer cell line.

Three new cleistanthane diterpenes named tomocinon (1), tomocinol A (2), and tomocinol B (3), were isolated from the EtOAc extract of the seed of Caesalpinia sappan. Their structures were determined by extensive NMR spectroscopic analysis. The absolute stereochemistry of tomocinon (1) has been established by CD spectroscopic analysis. Cleistanthane diterpenes (1-3) represents the novel class of antiausterity agents having preferential cytotoxicity against PANC-1 human pancreatic cancer cell line under nutrient deprived condition with PC50 value of 34.7 µM, 42.4 µM and 39.4 µM, respectively.

Xanthine oxidase inhibitors from Vietnamese Blumea balsamifera L.

From the MeOH extract of the aerial part of Blumea balsamifera L., a new dihydroflavonol, (2R,3S)-(-)-4'-O-methyldihydroquercetin (1), together with seven known compounds has been isolated. Their structures were elucidated on the basis of spectroscopic data. Compounds 1-4 and 6-8 displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compounds 1, 6 and 8 showed more potent inhibitory activity, with IC50 values ranging from 0.23 to 1.91 µM, than that of a positive control allopurinol (IC50 2.50 µM).

Phenolic constituents from the heartwood of Artocapus altilis and their tyrosinase inhibitory activity.

From the MeOH extract of the heartwood of Artocapus altilis, thirteen phenolic compounds have been isolated, namely curcumin (1), desmethoxycurcumin (2), retrodihydrochalcone (3), apigenin (4), tangeretin (5), nobiletin (6), O-methyldehydrodieugenol (7), dehydrodieugenol (8), beta-hydroxypropiovanillone (9), p-coumaric acid (10), p-hydroxybenzaldehyde (11), vanillin (12), and vanillic acid (13). This is the first report on the presence of these compounds in the heartwood of A. altilis. Compounds 1, 2, and 10 showed more potent tyrosinase inhibitory activities, with IC50 values ranging from 2.3 to 42.0 microM, than the positive control kojic acid (IC50, 44.6 microM). The most active compound, p-coumaric acid (10) (IC50, 2.3 microM), was 22 times more active in tyrosinase inhibitory activity than kojic acid.

Secoisolariciresinol and isotaxiresinol inhibit tumor necrosis factor-alpha-dependent hepatic apoptosis in mice.

The effects of secoisolariciresinol (1) and isotaxiresinol (2), two major lignans isolated from the wood of Taxus yunnanensis, on tumor necrosis factor-alpha (TNF-alpha)-dependent hepatic apoptosis induced by D-galactosamine (d-GalN)/lipopolysaccharide (LPS) were investigated in mice. Co-administration of d-GalN (700 mg/kg) and LPS (10 microg/kg) resulted in a typical hepatic apoptosis characterized by DNA fragmentation and the formation of apoptotic bodies. Serum glutamic pyruvic transaminase (sGPT) and glutamic oxaloacetic transaminase (sGOT) levels were also raised at 8 h after d-GalN/LPS intoxication due to a severe necrosis of hepatocytes. Pre-administration of 1 or 2 (50, 10 mg/kg, i.p.) 12 and 1 h before d-GalN/LPS significantly reduced DNA fragmentation and prevented chromatin condensation, apoptotic body formation and hepatitis. Pro-inflammatory cytokines such as TNF-alpha and interferon-gamma (IFN-gamma) secreted from LPS-activated macrophages are important mediators of hepatocyte apoptosis in this model. Pre-treatment with 1 or 2 significantly inhibited the elevation of serum TNF-alpha and IFN-gamma levels. In a separate experiment, both lignans had a significant dose-dependent protective effect on d-GalN/TNF-alpha-induced cell death in primary cultured mouse hepatocytes and TNF-alpha-mediated cell death in murine L929 fibrosarcoma cells. These results indicated that 1 and 2 prevent d-GalN/LPS-induced hepatic injury by inhibiting hepatocyte apoptosis through the blocking of TNF-alpha and IFN-gamma production by activated macrophages and direct inhibition of the apoptosis induced by TNF-alpha.

Hepatoprotective effect of taxiresinol and (7'R)-7'-hydroxylariciresinol on D-galactosamine and lipopolysaccharide-induced liver injury in mice.

The hepatoprotective effect of taxiresinol ( 1) and (7' R)-7'-hydroxylariciresinol ( 2), two tetrahydrofuran-type lignans isolated from the wood of Taxus yunnanensis, were investigated on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced hepatic liver injury in mice. Pre-administration of 1 or 2 at doses of 50 and 10 mg/kg ( i. p.) at 12 and 1 h before D-GalN/LPS injection significantly inhibited hepatocyte DNA fragmentation and apoptotic body formation. Pre-treatment of these two lignans further suppressed hepatic necrosis which occur at later stage of D-GalN/LPS intoxication as demonstrated by the significant and dose-dependent reduction in serum glutamic pyruvic transaminase (sGPT) and serum glutamic oxaloacetic transaminase (sGOT) at 8 h after intoxication. The elevation of serum tumor necrosis factor-alpha (TNF- alpha) level by D-GalN/LPS toxication was significantly inhibited by 1 or 2 at doses of 50 and 10 mg/kg. Moreover, both of these lignans significantly protected hepatocytes from D-GalN/TNF- alpha-induced cell death in primary cultured mouse hepatocytes. These results suggested that 1 and 2 had protected the hepatocytes from apoptosis via an inhibition of TNF- alpha production by activated macrophages and a direct inhibition of apoptosis induced by TNF- alpha in D-GalN/LPS-treated mice.

DPPH radical scavenging and nitric oxide inhibitory activities of the constituents from the wood of Taxus yunnanensis.

The H2O, H2O/MeOH (1 : 1) and MeOH extracts of the wood of Taxus yunnanensis possessed significant DPPH radical scavenging and nitric oxide (NO) inhibitory activities. Chemical investigation of these extracts led us to isolation of nineteen compounds, i. e., five lignans, two simple phenolics, and twelve taxane-type diterpenes. Isotaxiresinol and seco-isolariciresinol, two major lignans of the wood, possessed potent DPPH radical scavenging activities with IC 50 values of 21.7 and 28.9 microM, respectively. Similarly, coniferyl aldehyde, taxusin, 10-deacetyltaxuyunnanine C, hongdoushan A, and 2alpha,5alpha,10beta-triacetoxy-14beta-[( S)-2-methylbutyryloxy]-4(20),11-taxadiene showed potent NO inhibitory activity with IC 50 values of 18.0, 22.1, 28.5, 15.0 and 26.4 microM, respectively, which were either equal or lower than the positive control NG-monomethyl- L-arginine ( L -NMMA) with an IC 50 value of 28.5 microM.