In vitro biological evaluation and in silico studies of linear diarylheptanoids from Curcuma aromatica Salisb. as urease inhibitors.

Plants of the Zingiberaceae family, specifically those belonging to the Curcuma species, are commonly under consideration as potential therapeutic agents for the management of gastrointestinal diseases. In this study, we carried out a phytochemical study on Curcuma aromatica Salisb. (or so-called "Nghe trang" in Vietnamese) grown in Vietnam, which yields three newly discovered 3,5-diacetoxy diarylheptanoids (1-3) and six known 3,5-dihydroxyl diarylheptanoids (4-9). The bioactivity assessment shows that all isolated compounds, except compounds 3, 7, and 8, could inhibit urease. Compounds 4 and 9 significantly inhibit urease, with an IC50 value of 9.6 and 21.4 µM, respectively, more substantial than the positive control, hydroxyurea (IC50 = 77.4 µM). The structure-activity relationship (SAR) of linear diarylheptanoids was also established, suggesting that the hydroxyl groups at any position of skeleton diarylheptanoids are essential for exerting anti-urease action. Through a comparative analysis of the binding sites of hydroxyurea and diarylheptanoid compounds via our constructed in silico model, the mechanism of action of diarylheptanoid compounds is predicted to bind to the dynamic region close to the dinickel active center, resulting in a loss of catalytic activity. Such insights certainly help design and/or find diarylheptanoid-based compounds for treating gastric ulcers through inhibiting urease.

A novel diphenylbutenoid-type compound from the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr. (Zingiberaceae).

From the EtOAc-soluble extract of the rhizomes of Zingiber montanum (J.Koenig) Link ex A.Dietr., a novel diphenylbutenoid, montadinin A (1) and a previously unreported phenylbutenoid compound, 1-(3,4-dimethoxyphenyl)but-3-en-2-ol (7), in natural source were isolated. Additionally, seven known phenylbutenoids were also identified. The structures of all compounds were elucidated through NMR spectroscopic interpretation. Compounds cis-3-(3,4-dimethoxyphenyl)-4-[(E)-3,4-dimethoxystyryl]cyclohex-1-ene (2), cis-4-[(E)-3,4-dimethoxystyryl]-3-(2,4,5-trimethoxyphenyl)cyclohex-1-ene (3), trans-3-(3,4,-dimethoxyphenyl)-4-[(E)-2,4,5-trimethoxystyryl]cyclohex-1-ene (5), and cis-3-(3,4-dimethoxyphenyl)-4-[(Z)-2,4,5-trimethoxylstyryl]cyclohex-1-ene (6) showed weak cytotoxicity against HepG2 cells with IC50 values of 122.9, 127.3, 257.5, and 168.5 µM, respectively.

Taxotrophises A and B, two new polyphenols from the stems of Taxotrophis ilicifolius.

From the EtOAc extract of the wood of the stems of Taxotrophis ilicifolius (Moraceae), two new secondary metabolites, named taxotrophises A (1) and B (2), were isolated, together with five known compounds (3-7). Their chemical structures have been elucidated by extensive NMR spectroscopic analysis. All isolated compounds have been evaluated for α-glucosidase inhibitory activity. In the present work, compounds 1 and 4 showed the strongest α-glucosidase inhibitory activity with IC50 values of 6.5 and 1.5 µM, respectively, and stronger than that of a positive control, acarbose (IC50; 214.5 µM).

A New abeo-Icetexane-Type Diterpenoid from the Stem Barks of Taxus wallichiana.

From a CH2 Cl2 -soluble fraction of the stem barks of Taxus wallichiana, one new abeo-icetexane-type diterpenoid, taxamairin I (1), was isolated. Its absolute configuration was elucidated based on spectroscopic interpretation and time-dependent density functional theory (TD-DFT) calculation of optical rotation. In addition, the plausible biosynthesis pathway for the formation of the new abeo-icetexane-type diterpenoid was proposed. Taxamairin I (1), at a concentration of 100 µM, did not show cytotoxicity against Hep3B human liver cancer cell lines.

Paratrimerin Z, an undescribed chromene derivative from the roots of Paramignya trimera.

From an EtOAc-soluble fraction of the roots of Paramignya trimera, one undescribed chromene derivative, paratrimerin Z (1), was isolated. Its structure was elucidated on the basis of NMR spectroscopic interpretation. The absolute configuration of 1 was determined by the specific rotation analysis of its acid-catalyzed hydrolysis product. Paratrimerin Z (1), at a concentration of 100 µM, did not show cytotoxicity against Hep3B human liver cancer cell line.

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 flavanone derivative from the rhizomes of Boesenbergia pandurata.

From the methanolic extract of the rhizomes of Boesenbergia pandurata, a new flavanone derivative named (2R,7″S)-8-(1-phenyl-2-carboxyethyl)pinocembrin (1) and four known flavonoids (2-5) were isolated. Its absolute configuration was concluded by NMR and MS spectroscopic analysis, together with comparison between experimental and calculated ECD data. In turn, compound 1 exhibited strong cytotoxicity against the PANC-1 human pancreatic cancer cell line with a PC50 value of 6.4 µM under nutrient-deprived conditions, comparable with that of arctigenin (PC50, 0.83 µM).

Strebluses E-H, four new stilbene-like derivatives from the stems of Streblus ilicifolius.

Following bioactivity-guided isolation, four new stilbene-like derivatives, named Strebluses E-H, were isolated from the EtOAc-soluble fraction of the stems of Streblus ilicifolius (Moraceae). Their chemical structures were elucidated based on NMR spectroscopic data interpretation and optical rotation calculation. Streblus E possesses potent tyrosinase inhibitory activity with an IC50 value of 0.1 µM. Oxy-tyrosinase has two bound Cu2+ ions and a peroxide group in the binding site, which has a role in the catalytic oxidation. Thus, a docking study of Streblus E with oxy-tyrosinase was performed to analyze the ligand-protein interactions. With in silico modelling, the S value and the ligand-protein interactions suggested that Streblus E showed lower binding affinity for oxy-tyrosinase than that of Streblus C.

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 phenylheptanoid from the leaves of Gnetum gnemon L.

Phytochemical study on the EtOAC-soluble extract of the leaves of Gnetum gnemon furnished the isolation of a new phenylheptanoid, gnetumal (1), along with five known compounds (2-6). Their isolation was carried out by using the column chromatography and their structures were elucidated based on the basis of the spectral interpretation. Bioactivity assay of these compounds indicated that gnetumal (1) and p-coumaric acid (5) possessed more potent tyrosinase inhibitory activity, with IC50 values of 31.6 and 2.3 µM, respectively, than that of a positive control kojic acid (IC50; 44.6 µM).

Decumbic anhydride from the stem barks of Swintonia floribunda (Anacardiaceae).

From an EtOAc-soluble fraction of the stem barks of Swintonia floribunda (Anacardiaceae), decumbic anhydride (1) and four known compounds 2-5 were isolated. Their chemical structures were elucidated based on the spectroscopic data interpretation. The GIAO-DFT calculation of 13C NMR chemical shifts was carried out to clarify the structure of 1. The absolute configuration of 1 was assigned based on the Cotton effects in its ECD spectrum. Compound 1 showed potent tyrosinase inhibitory activity with an IC50 value of 52.2 µM.

Paratrimerin I, cytotoxic acridone alkaloid from the roots of Paramignya trimera.

Bioactivity-guided fractionation of the CHCl3-soluble extract of the roots of Paramignya trimera was carried out to obtain a new acridone alkaloid, paratrimerin I. Its structure was elucidated based on NMR spectroscopic data interpretation. Paratrimerin I showed noteworthy cytotoxicity against the HepG2 human hepatocellular and MCF-7 human breast carcinoma cell lines, with the submicromolar IC50 values of 0.43 and 0.26 µM, respectively. The N-methyl, C-4 methoxy, and C-5 hydroxy groups in the acridone skeleton can be proposed as a structural feature for good cytotoxicity.

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.

α-Glucosidase Inhibitory and Cytotoxic Taxane Diterpenoids from the Stem Bark of Taxus wallichiana.

From a CH2Cl2 extract of the bark of Taxus wallichiana, six new taxoids, wallitaxanes A-F (1-6), were isolated, together with 29 known compounds. The structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. Wallitaxane D (4) was identified as an opened oxetane-type taxoid having the first naturally occurring C(H)-20 acetal group, while wallitaxanes E (5) and F (6) are representative of the rare abeo-taxoid class. The isolated compounds were evaluated for their α-glucosidase inhibitory activity and for cytotoxicity against the HeLa human cervical cancer cell line. In the present work, taxanes were found to exhibit α-glucosidase inhibitory activity for the first time, and wallitaxane A (1) showed the most potent effect, with an IC50 value of 3.6 µM. In turn, 7-epi-taxol (16) and 7-epi-10-deacetyltaxol (17) showed IC50 values of 0.05 and 0.085 nM, respectively, against HeLa cells.