Four Undescribed compounds Isolated from the Aerial Parts of Phyllanthus cochinchinensis with Antimicrobial Activity and NO Production Inhibitory Activity in LPS Activated RAW 264.7 Cells.

Four previously undescribed compounds named phyllancosides A and B (1 and 2), and phyllancochines A and B (3 and 4) together with ten known compounds (5-14) were isolated from the aerial parts of Phyllanthus cochinchinensis Spreng. Their chemical structures were elucidated on the basis of comprehensive analysis of IR, HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) spectra. Compounds 3, 4, and 10 showed antimicrobial activity against E. faecalis, S. aureus, and B. cereus with the MIC values in range of 32-256 µg/mL. Compound 11 inhibited E. faecalis and B. cereus, and 7 inhibited S. aureus with the MIC values in range of 64-128 µg/mL. In addition, compounds 1, 3, 4, 8, and 9 showed significantly NO production inhibitory activity in LPS activated RAW 264.7 cells with IC50 values ranging from 36.57 to 56.34 µM.

Undescribed Triterpenes from the Leaves of Syzygium myrsinifolium with Their α-Glucosidase and α-Amylase Inhibition Activity.

Two undescribed triterpenes, syzyfolium A (1) and syzyfolium B (2), together with twelve known compounds, terminolic acid (3), actinidic acid (4), piscidinol A (5), threo-dihydroxydehydrodiconiferyl alcohol (6), lariciresinol-4-O-ß-D-glucoside (7), icariol A2 (8), 14ß,15ß-dihydroxyklaineanone (9), garcimangosone D (10), (+)-catechin (11), myricetin-3-O-α-L-rhamnopyranoside (12), quercitrin (13), and 3, 4, 5-trimethoxyphenyl-(6'-O-galloyl)-O-ß-D-glucopyranoside (14) were isolated from the leaves of Syzygium myrsinifolium. Their chemical structures were determined by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 3 and 4 inhibited significantly α-glucosidase with IC50 values of 23.99 and 36.84, respectively, and compounds 1 and 2 inhibited significantly α-amylase with IC50 values of 35.48 and 43.65 µM, respectively.

Four New Steroidal Saponins from the Roots of Dracaena cambodiana with NO Production Inhibition Activity in LPS Activated RAW 264.7 Cells.

Seven steroidal saponins including three new 16,23-cyclocholestanes (1-3) and one new pregane (4) were isolated from the roots of Dracaena cambodiana Pierre ex Gagnep. Their chemical structures were elucidated to be (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17(20)-dien-22-one-3ß,16α,26-triol-3-O-α-L-rhamnopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucopyranoside (1), (23R,25R)-26-O-ß-D-glucopyranosyl-16,23-cyclocholesta-5,17,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (2), (23R,25R)-16,23-cyclocholesta-5,16,20(22)-trien-3ß,22,26-triol-3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucopyranoside (3), 3ß-[(O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-gluco-pyranosyl)oxy]-pregna-5,17(20)-diene-16-one-20-carboxylic acid 4''''-O-ß-D-glucopyranosylisopentyl ester (4), cambodianoside A (5), diosbulbiside C (6), and diosbulbiside D (7), by IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1 and 4-7 inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW 264.7 cells with IC50 values ranging from 19.03±1.84 to 67.92±3.81 µM, whereas compounds 2 and 3 were inactive with IC50 values over 100 µM.

Three Undescribed Iridoid Derivatives Isolated from the Fruits of Vitex trifolia with Their Cytotoxic and Antimicrobial Activities.

Vitex trifolia L. is a medicinal plant and widely distributed in the northern mountainous areas of Vietnam. Phytochemical study on the fruits of this plant led to the isolation of nine iridoid derivatives (1-9) including three undescribed compounds (1-3). Their structures were elucidated to be 3''-hydroxyscrophuloside A1 (1), 3''-hydroxycallicoside D (2), 2'-p-hydroxybenzoylaucubin (3), 6'-p-hydroxybenzoylmussaenosidic acid (4), nishindaside (5), agnuside (6), 10-O-vanilloylaucubin (7), 6'-O-p-hydroxybenzoyl-gardoside (8), and buddlejoside B (9) based on extensive analyses of HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1, 2, 4, and 8 significantly posessed anti-barterial activity against Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa strains with MIC values in range of 16-64 µg/mL. At concentration of 20 µM, compounds 1-9 did not show cytotoxic effects against human lung cancer cells (PC9).

One new furostane saponin from Allium ramosum and lipid accumulation inhibitory activity.

A new furostane saponin, ramosaponin (1), and four known furostane saponins, protodioscin (2), dehydrotomatoside (3), (25 R)-26-O-(ß-D-glucopyranosyl)-furost-5-ene-3ß,22α,26-triol 3-O-ß-D-glucopyranosyl-(1→4)-ß-D-galactopyranoside (4), and anguivioside A (5) were isolated from the methanol extract of Allium ramosum seeds. Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for reduction of lipid accumulation in HepG2 cell line. As a result, compound 1 showed significant lipid accumulation inhibitory activity with an IC50 value of 64.32 ± 3.87 µM.

Three new chromanes and one new flavone C-glycoside from Mallotus apelta.

Three new chromanes, malloapeltas J-L (1-3), and one new flavone C-glycoside, malloflavoside (4), together with four known compounds, apigenin 6-C-ß-D-xylopyranosyl-8-C-α-L-arabinopyranoside (5), apigenin 6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (6), apigenin 7-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (7), and acantrifoside E (8) were isolated from the methanol extract of the leaves of Mallotus apelta. Their chemical structures were determined using spectroscopic methods, including 1D, 2D NMR, and HR-ESI-MS methods. All the isolated compounds were evaluated their cytotoxic activity against human prostate cancer (PC-3) and human breast cancer (MCF-7) cells, but none of them showed cytotoxicities on both human cancer cell lines.

Furostane Saponins from the Seeds of Allium ramosum and Their Lipid Accumulation Inhibitory Activity.

Three new furostane saponins, ramofurosides A-C (1-3), and two known saponins, fistulosaponin B (4) and (25R)-26-O-ß-D-glucopyranosyl-1ß,3ß,26-trihydroxyfurosta-5,20(22)-diene-1-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside (5) were isolated from the methanol extract of Allium ramosum seeds. Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for reduction of lipid accumulation in HepG2 cell lines. As a result, compounds 1 and 3 showed a significant reduction in total lipid content by 27.93±3.05 and 27.54±1.68 %, respectively, at a concentration of 100 µM.

Four new sucrose diesters of substituted truxinic acids from Trigonostemon honbaensis with their anoctamin-1 inhibitory activity.

Truxinic acid sucrose diesters analogs possess interesting chemical structure by the presence of cyclobutane-ring and macrocyclic sucrose diesters moieties which are rarely found from natural sources. This paper describes the isolation and structural elucidation of four new sucrose diesters of substituted truxinic acids, trigohonbanosides A-D (1-4), from the leaves of Trigonostemon honbaensis. Their chemical structures were elucidated by HR-ESI-MS, NMR, and CD spectroscopic methods. At a concentration of 30 µM, compounds 1-4 moderately inhibited ANO-1 activity with inhibitory percentages of 27.7 ± 1.10%, 35.6 ± 0.92%, 43.7 ± 1.61%, and 40.8 ± 1.25%, respectively.

Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.

Mallotusapelta(Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M.apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovariancancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 µM and IC50 values ranging from 1.62 to 10.42 µM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.

Novel ANO1 Inhibitor from Mallotus apelta Extract Exerts Anticancer Activity through Downregulation of ANO1.

Anoctamin1 (ANO1), a calcium-activated chloride channel, is frequently overexpressed in several cancers, including human prostate cancer and oral squamous cell carcinomas. ANO1 plays a critical role in tumor growth and maintenance of these cancers. In this study, we have isolated two new compounds (1 and 2) and four known compounds (3-6) from Mallotus apelta. These compounds were evaluated for their inhibitory effects on ANO1 channel activity and their cytotoxic effects on PC-3 prostate cancer cells. Interestingly, compounds 1 and 2 significantly reduced both ANO1 channel activity and cell viability. Electrophysiological study revealed that compound 2 (Ani-D2) is a potent and selective ANO1 inhibitor, with an IC50 value of 2.64 µM. Ani-D2 had minimal effect on cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel activity and intracellular calcium signaling. Notably, Ani-D2 significantly reduced ANO1 protein expression levels and cell viability in an ANO1-dependent manner in PC-3 and oral squamous cell carcinoma CAL-27 cells. In addition, Ani-D2 strongly reduced cell migration and induced activation of caspase-3 and cleavage of PARP in PC-3 and CAL-27 cells. This study revealed that a novel ANO1 inhibitor, Ani-D2, has therapeutic potential for the treatment of several cancers that overexpress ANO1, such as prostate cancer and oral squamous cell carcinoma.

Five New Pregnane Glycosides from Gymnema sylvestre and Their α-Glucosidase and α-Amylase Inhibitory Activities.

Gymnema sylvestre, a medicinal plant, has been used in Indian ayurvedic traditional medicine for the treatment of diabetes. Phytochemical investigation of Gymnema sylvestre led to the isolation of five new pregnane glycosides, gymsylosides A-E (1-5) and four known oleanane saponins, 3ß-O-ß-D-glucopyranosyl (1→6)-ß-D-glucopyranosyl oleanolic acid 28-O-ß-D-glucopyranosyl ester (6), gymnemoside-W1 (7), 3ß-O-ß-D-xylopyranosyl-(1→6)-ß-D- glucopyranosyl-(1→6)-ß-D-glucopyranosyl oleanolic acid 28-O-ß-D-glucopyranosyl ester (8), and alternoside XIX (9). Their structures were identified based on spectroscopic evidence and comparison with those reported in the literature. All compounds were evaluated for their α-glucosidase and α-amylase inhibitory activities. Compounds 2-4 showed significant α-amylase inhibitory activity, with IC50 values ranging from 113.0 to 176.2 µM.

Chemical constituents of the Annona glabra fruit and their cytotoxic activity.

CONTEXT: Traditional Chinese medicines have attracted increasing interest as potential sources of novel drugs with a wide range of biological and pharmacological activities. Annona glabra Linn (Annonaceae) is used in traditional medicine as an anticancer drug. Phytochemical investigation of this plant led to the isolation of acetogenins, ent-kauranes, peptides, and alkaloids. In addition, compounds exhibited anticancer, anti-HIV-reserve, and antimalaria. OBJECTIVE: Isolation, structure determination, and cytotoxic activity evaluation of compounds from the methanol extract from A. glabra fruits. MATERIALS AND METHODS: Using chromatographic methods to isolate compounds from the A. glabra methanol extract. The cytotoxic activity of compounds was evaluated by a 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. In addition, compounds which showed significant cytotoxic activity were chosen for further study apoptosis characteristics. RESULTS: One new, (2E,4E,1'R,3'S,5'R,6'S)-dihydrophaseic acid 1,3'-di-O-ß-d-glucopyranoside, and eight known compounds, (2E,4E,1'R,3'S,5'R,6'S)-dihydrophaseic acid 3'-O-ß-d-glucopyranoside (2), icariside D2 (3), icariside D2 6'-O-ß-d-xylopyranoside (4), 3,4-dimethoxyphenyl O-ß-d-glucopyranoside (5), 3,4-dihydroxybenzoic acid (6), blumenol A (7), cucumegastigmane I (8), and icariside B1 (9), were isolated from the fruits of A. glabra. Icariside D2 (3) was found to show significant cytotoxic activity on the HL-60 cell line with the IC50 value of 9.0 ± 1.0 µM and did not show cytotoxic activity on the Hel-299 normal cell line. The further test indicated that compound 3 induced apoptosis via alteration of expression of apoptosis-related proteins and decreased phosphorylation of AKT in HL-60 cells. DISCUSSION AND CONCLUSION: The results suggested that the constituents from A. glabra may contain effective compounds which can be used as anticancer agents.

Glycoside constituents of Camellia amplexicaulis and their α-glucosidase inhibitory activity.

Four new glycosides, named amplexicosides A-D (1-4), and five known compounds: benzyl 2-[ß-D-glucopyranosyl-(1→6)-ß-D-glucopyranosyloxy]-benzoate (5), benzyl 2-neohesperidosyloxy-6-hydroxybenzoate (6), chrysandroside A (7), chrysandroside B (8) and camelliquercetiside C (9) were isolated from the branches and leaves of Camellia amplexicaulis (Pit.) Cohen-Stuart. Their structures were elucidated using HR-ESI-MS and 1D- and 2D-NMR spectra and compared to reported NMR data. All of the isolated compounds were screened in an α-glucosidase assay. Compounds 4, 8, and 9 significantly inhibited α-glucosidase with respective IC50 values of 254.9 ± 4.2, 304.8 ± 11.9 and 228.1 ± 16.4 µM.

Achyranbidens A-C: three new compounds from Achyranthes bidentata Blume.

Phytochemical study on the roots of Achyranthes bidentata Blume led to the isolation of sixteen compounds including three new ones (1-3). Their chemical structures were determined as oleanolic acid 28-O-ß-D-glucopyranoside-3-O-[ß-D-glucopyranosyl-(1→3)-ß-D-galactopyranoside) (1), methyl (8Z,11Z)-5,6,7-trihydroxytetradeca-8,11-dienoate (2), methyl (6E,11Z)-5,8,9-trihydroxytetradeca-6,11-dienoate (3), fulgidic acid (4), (9E,11E)-13-oxooctadeca-9,11-dienoic acid (5), (9Z,11E,15Z)-13-hydroxyoctadeca-9,11,15-trienoic acid (6), oleanolic acid 28-O-ß-D-glucopyranoside-3-O-α-L-rhamnopyranosyl-(1→4)-ß-D-glucuronopyranoside (7), oleanolic acid 28-O-ß-D-glucopyranoside-3-O-ß-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucuronopyranoside (8), oleanolic acid 3-O-ß-D-glucopyranosyl-(1→2)-[α-L-rhamnopyranosyl-(1→3)]-ß-D-glucuronopyranoside (9), oleanolic acid 3-O-α-L-rhamnopyranosyl-(1→3)-ß-D-glucuronopyranoside (10), blumenol C glucoside (11), citroside A (12), 6S,9S-roseoside (13), ginsenoside Rg1 (14), 20-hydroxyecdysone (15), and benzyl α-L-rhamnopyranosyl-(1→6)]-ß-D-glucopyranoside (16) by spectroscopic analysis. Compounds 1, 7 and 11-16 inhibited NO production in LPS-activated RAW264.7 cells with IC50 values in the range from 28.03 to 54.23 µM (positive control, L-NMMA: IC50 = 35.52 µM). Compounds 14 and 15 showed anti α-glucosidase activity with IC50 values of 176.24 and 156.92 µM, respectively, compared with the positive control, acarbose, IC50 = 160.99 µM.

Phytochemical constituents from Elsholtzia ciliata (Thunb.) Hyl. and their nitric oxide production inhibitory activities.

A new megastigmane glycoside, (3S,4R,7E)-megastigma-5,7-diene-9-one-3,4-diol 3-O-ß-D-apiofuranosyl-(1→2)-ß-D-glucopyranoside (1) and a new cyanogenic glycosyl derivative, (S)-2-(6'-O-R-rosmarinoyl-ß-D-glucopyranosyloxy)-phenylacetonitrile (2) were isolated from the methanol extract of the Elsholtzia ciliata together with twelve known compounds, 1-O-ß-D-glucopyranosyl-2-hydroxy-4-allylbenzene (3), citrusin C (4), 1,2-di-O-ß-D-glucopyranosyl-4-allylbenzene (5), manglieside B (6), 4-allyl-2-hydroxyphenyl 1-O-ß-D-apiofuranosyl-(1→6)-ß-D-glucopyranoside (7), (-)-isolariciresinol 3α-ß-D-glucopyranoside (8), 7R,8R-threo-4,7,9-trihydroxy-3,3'-dimethoxy-8-O-4'-neolignan-9'-O-ß-D-glucopyranoside (9), 7R,8R-threo-4,7,9,9'-tetrahydroxy-3-methoxy-8-O-4'-neolignan-9'-O-ß-D-glucopyranoside (10), cedrusin-4-O-ß-D-glucopyranoside (11), icariside E3 (12), everlastoside L (13) and rosmarinic acid (14). Their chemical structures were elucidated on the basic of extensive 1D and 2D-NMR experiments, as well as their mass spectroscopic data. The absolute configurations of the compounds 1 and 2 were successfully indicated by both theoretical and calculated CD spectra. Compounds 3-7, 9 and 10 potential inhibited NO production in LPS-activated RAW264.7 cells with IC50 values of 6.71, 8.97, 12.38, 14.27, 16.13, 13.54, 16.27 µM, respectively, compared to that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA), IC50 = 32.51 µM.

Two new triterpenoid glycosides from Bacopa monnieri and their cytotoxic activity.

Using combined chromatographic methods, two new triterpenoid glycosides, bacopasaponin K (1) and bacopasaponin L (2), along with eight known compounds, bacopaside IV (3), bacopaside VII (4), bacopasaponin E (5), bacoside A3 (6), bacopasaponin F (7), bacopasaponin C (8), bacopaside I (9), and bacopaside II (10) were isolated from the methanol extract of the Bacopa monnieri. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS and comparing with the NMR data reported in the literature. All these compounds were evaluated for their cytotoxic activity using the cell counting kit-8 (CCK-8) assay. Compounds 4, 6, 8, and 10 exhibited potential cytotoxic effects against human lung cancer cells (PC9) and human colon cancer cells (SW620).

Dihydrostilbene glycosides from Camellia sinensis var. assamica and their cytotoxic activity.

Three undescribed dihydrostilbene glycosides, 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(4'''-hydroxylbenzoyl)]-ß-D-glucopyranoside (1), 3,5-dihydroxyldihydrostilbene 4'-O-(6''-O-galloyl)-ß-D-glucopyranoside (2), and 3,5-dihydroxyldihydrostilbene 4'-O-[6''-O-(3''',4'''-dimethoxyl)galloyl]-ß-D-glucopyranoside (3), and seven known compounds, kaempferol 3-O-ß-D-glucopyranoside (4), isoquercitrin (5), kaempferol 3-O-α-L-rhamnoside (6), quercitrin (7), (6S,9R)-roseoside (8), (-)-epicatechin 3-O-gallate (9), and (-)-epigallocatechin 3-O-gallate (10) have been isolated from the methanol extract of the leaves of Camellia sinensis var. assamica (J.W.Mast.) Kitam. (synnonym of Camellia assamica (Mast.) H.T.Chang) (Theaceae). Their structures were elucidated by spectroscopic methods (1 D-, 2 D-NMR) and mass spectra. All compounds were evaluated for cytotoxic activity against human oral cancer (CAL27) and human breast cancer (MDAMB231) cell lines. Compound 10 showed significant cytotoxic activity against CAL27 and MDAMB231 cell lines with IC50 values of 9.78 ± 0.25 and 3.27 ± 0.18 µM, respectively, compared to those of positive control, capecitabine (IC50 values of 8.20 ± 0.75 and 5.20 ± 0.89 µM).

Dihydrostilbene glycosides from Camellia sasanqua and their α-glucosidase and α-amylase inhibitory activities.

Using chromatographic methods, three new dihydrostilbene glycosides, sasastilbosides A-C (1-3) and four known compounds, catechin (4), rutin (5), nicotiflorin (6), and rehmaionoside A (7) have been isolated from Camellia sasanqua Thunb. Their chemical structures were elucidated by spectroscopic methods (1 D-, 2 D-NMR) and mass spectra. Compounds 1-7 were evaluated for α-glucosidase and α-amylase inhibitory effects. Compounds 3 and 4 showed α-glucosidase inhibitory activity with IC50 values of 77.6 ± 1.6 and 72.4 ± 1.3 µM, respectively. Compound 1 showed α-amylase inhibitory activity with IC50 value of 53.7 ± 1.6 µM.

Pregnane glycosides from Gymnema inodorum and their α-glucosidase inhibitory activity.

Two new pregnane glycosides, gyminosides A and B (1 and 2) and three known, tinctoroside B (3), tinctoroside C (4), and gymnepregoside F (5) were isolated from the leaves of Gymnema inodorum (Lour.) Decne. Their structures were elucidated by physical and chemical methods and comparing with those reported in the literature. All these compounds were evaluated for α-glucosidase assay. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 63.7 ± 3.9% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 40.0 to 52.1%.

Four new pregnane glycosides from Gymnema latifolium and their α-glucosidase and α-amylase inhibitory activities.

Four new pregnane glycosides, gymlatifosides A - D (1 - 4) and one known pregnane glycoside, verticilloside J (5) were isolated from the leaves of Gymnema latifolium Wall. ex Wight. Their chemical structures were elucidated on the basis of extensive spectroscopic methods, including 1D, 2D NMR, HR-ESI-MS, and in comparison with the reported data. All these compounds were tested for α-glucosidase and α-amylase inhibitory activities. Compound 5 exhibited the most anti α-glucosidase activity with inhibitory percentage of 37.8 ± 1.5% at the concentration of 200 µM. Compounds 1-4 showed moderate anti α-glucosidase activity with inhibitory percentage ranging from 7.0 to 30.1%. In addition, all compounds 1-5 showed moderate/weak anti α-amylase activity in the investigated test.