Symplosaponins A-D: New acylated oleanane-type triterpene saponins from Symplocos cochinchinensis and their hepatoprotective effect.

Four new acylated oleanane-type triterpene saponins, symplosaponins A-D (1-4) were successfully isolated from the leaves of Symplocos cochinchinensis (Lour.) S. Moore, alongside with five known compounds (5-9), 2-methoxy-4-prop-1-enylphenyl-1-O-ß-D-apiofuranosyl-(1 → 6)-ß-D-glucopyranoside (5), and 1-[O-ß-d-xylopyranosyl-(1 → 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6), 6-O-p-coumaroylsucrose (7), arillatose B (8), and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9). The structures of these compounds were elucidated through spectroscopic methods, comparison with existing data, and chemical methods. Furthermore, all compounds were assessed for their impact on hepatocellular viability using the Resazurin reduction assay. These investigations aimed to explore the potential hepatoprotective properties of isolated compounds. As a result, 1-[O-ß-d-xylopyranosyl-(1 → 6)-O-ß-d-glucopyranosyl]-2,6-dimethoxy-4-propenyl-phenol (6) and (-)-secoisolariciresinol-O-ß-D-glucopyranoside (9) demonstrated statistically significant hepatoprotective activity in a concentration-dependent manner.

Four Unidentified Compounds Isolated from the Stem Barks of Aphanamixis polystachya and Their NO Production Inhibition in LPS Activated RAW 264.7 Cells.

Phytochemical study on the methanol extract of the stem barks of Aphanamixis polystachya led to the isolation of four previously undescribed ( 1-4) and ten known compounds (5-14). Their chemical structures were elucidated to be 11-methoxysawaranospiroride C (1), 6α,9S,10,13-tetrahydroxymegastigmane-3-one (2), 11-hydroxyaphanamixin B (3), (2Z,6E,13E)-2,6,13-triene-11,15-dihydroxyphytanic acid (4), cinnacasside D (5), cinnacasside E (6), vilsonol F (7), (3S,5R,6S,7E,9R)-3,5,6,9-tetrahydroxy-7-en-megastigmane (8), (3S,5R,6R,7E,9R)-3,6,9,10-tetrahydroxy-7-en-megastigmane (9), citroside A (10), threo-1-(3,4,5-trimethoxyphenyl)-1,2,3-propanetriol (11), 3,4,5-trimethoxyphenyl-1-O-ß-D-glucopyranoside (12), p-coumaric acid (13), ferulic acid (14) by HR-ESI-MS, ECD, 1D-, and 2D-NMR spectra. Compounds 1, 3, 4, and 9 showed NO production inhibitory activity in LPS activated RAW 264.7 cells with IC50 values of 42.0, 67.9, 20.5, and 78.6 µM, respectively, while the remaining compounds were inactive with IC50 values over 100 µM.

Discovery of a novel natural compound, vitekwangin B, with ANO1 protein reduction properties and anticancer potential.

Background: Prostate cancer and non-small cell lung cancer (NSCLC) present significant challenges in the development of effective therapeutic strategies. Hormone therapies for prostate cancer target androgen receptors and prostate-specific antigen markers. However, treatment options for prostatic small-cell neuroendocrine carcinoma are limited. NSCLC, on the other hand, is primarily treated with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors but exhibits resistance. This study explored a novel therapeutic approach by investigating the potential anticancer properties of vitekwangin B, a natural compound derived from Vitex trifolia. Methods: Vitekwangin B was chromatographically isolated from the fruits of V. trifolia. ANO1 protein levels in prostate cancer and NSCLC cells were verified and evaluated again after vitekwangin B treatment. Results: Vitekwangin B did not inhibit anoctamin1 (ANO1) channel function but significantly reduced ANO1 protein levels. These results demonstrate that vitekwangin B effectively inhibited cancer cell viability and induced apoptosis in prostate cancer and NSCLC cells. Moreover, it exhibited minimal toxicity to liver cells and did not affect hERG channel activity, making it a promising candidate for further development as an anticancer drug. Conclusion: Vitekwangin B may offer a new direction for cancer therapy by targeting ANO1 protein, potentially improving treatment outcomes in patients with prostate cancer and NSCLC. Further research is needed to explore its full potential and overcome existing drug resistance challenges.

Oleanane-Type Triterpene Glycosides from Camellia phanii and Their α-Glucosidase Inhibitory Activity.

Three new oleanane-type triterpene saponins, named camphanosides A-C (1-3), along with five known compounds, chikusetsusaponin IVa (4), spinasaponin A 28-O-glucoside (5), (-)-epicatechin (6), (-)-epicatechin 3-O-gallate (7), and (-)-epigallocatechin 3-O-gallate (8) were isolated from the leaves Camellia phanii Hakoda & Ninh. Their structures were established by 1D and 2D-NMR and mass spectral analysis and chemical methods. Moreover, compounds 1-5 were also evaluated for α-glucosidase inhibitory activity. Compounds 1-3 exhibited moderate α-glucosidase inhibitory activity with IC50 values of 230.7±18.0, 251.4±22.7, and 421.4±25.6 µM, respectively.

Cryptobuchanosides A-G: seven previously undescribed triterpene glycosides from Cryptolepis buchananii R.Br. ex Roem. and Schult. with nitric oxide production inhibition activity.

In this study, nine triterpene glycosides including seven previously undescribed compounds (1-7), were isolated from leaves of Cryptolepis buchananii R.Br. ex Roem. and Schult. using various chromatographic methods. The chemical structures of the compounds were elucidated to be 3-O-ß-D-glucopyranosyl-(1 → 6)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (1), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (2), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosyluncargenin C 28-O-ß-D-glucopyranosyl-(1 → 4)-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (3), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß-D-glucopyranosylhederagenin 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (4), 3-O-ß-D-glucopyranosylarjunolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (5), 3-O-ß-D-glucopyranosyl-(1 → 2)-ß- D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (6), 3-O-ß-D-glucopyranosyl-6ß,23-dihydroxyursolic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (7), asiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (8), and 3-O-ß-D-glucopyranosylasiatic acid 28-O-α-L-rhamnopyranosyl-(1 → 2)-ß-D-glucopyranosyl ester (9), through infrared, high-resolution electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance spectral analyses. The isolates inhibited nitric oxide production in lipopolysaccharide-activated RAW 264.7 cells, with half-maximal inhibitory concentration (IC50) values of 18.8-58.5 µM, compared to the positive control compound, dexamethasone, which exhibited an IC50 of 14.1 µM.

Undescribed (2-7')-neolignans and polyoxygenated cyclohexene glycosides from the aerial parts of Piper mutabile C. DC. and their inhibitory effects on nitric oxide production.

A phytochemical study of the aerial parts of Piper mutabile C. DC. revealed seven undescribed compounds [two (2-7')-neolignans and five polyoxygenated cyclohexene glycosides] and six known propenylcatechol derivatives. The chemical structures of the isolated compounds were elucidated by extensive HR-ESI-MS and NMR analyses, as well as comparison with the literature. The absolute configurations of the (2-7')-neolignans were confirmed by GIAO 13C NMR calculations with a sorted training set strategy and TD-DFT calculation ECD spectra. The (2-7')-neolignans and polyoxygenated cyclohexene glycosides are unusual in natural sources. Undescribed neolignans 1 and 2 inhibited NO production in RAW 264.7 cells, with respective IC50 values of 14.4 and 9.5 µM.

Undescribed sesquiterpene-diterpene heterodimers from the fruits of Aphanamixis polystachya selectively modulate inflammatory markers in RAW 264.7 cells.

Aphanapolystachones A-C (1-3), three undescribed sesquiterpene-diterpene heterodimers, were obtained from the fruits of Aphanamixis polystachya. Their structures and absolute configurations were identified by extensive analysis of HR-ESI-MS, NMR, experimental and TD-DFT calculated ECD spectra. The biosynthetic pathway of them was also proposed, which is produced by key intermolecular Diels-Alder [4 + 2]-cycloaddition reaction between a guaiane sesquiterpene and an acyclic diterpene. Compounds 1-3 inhibited NO production in LPS activated RAW 264.7 cells with the IC50 values of 1.7 ± 0.2, 3.0 ± 0.3, 5.3 ± 0.3 µM, respectively, lower than that of the positive control L-NMMA (31.5 ± 2.6 µM). In addition, compounds 1-3 significantly reduced IL-6 secretion at diluted concentration of 0.4 µM.

Alkaloids and Lignans from the Aerial Parts of Rauvolfia tetraphylla Inhibit NO Production in LPS-activated RAW 264.7 Cells.

Three previously undescribed compounds named rauvolphyllas A-C (1-3), along with thirteen known compounds, 18ß-hydroxy-3-epi-α-yohimbine (4), yohimbine (5), α-yohimbine (6), 17-epi-α-yohimbine (7), (E)-vallesiachotamine (8), (Z)-vallesiachotamine (9), 16S-E-isositsirikine (10), Nb -methylisoajimaline (11), Nb -methylajimaline (12), ajimaline (13), (+)-lyoniresinol 3α-O-ß-D-glucopyranoside (14), (+)-isolarisiresinol 3α-O-ß-D-glucopyranoside (15), and (-)-lyoniresinol 3α-O-ß-D-glucopyranoside (16) were isolated from the aerial parts of Rauvolfia tetraphylla L. Their chemical structures were elucidated based on the extensive spectroscopic interpretation of HR-ESI-MS, 1D and 2D NMR spectra. The absolute configurations of 2 and 3 were determined by experimental ECD spectra. Compounds 5, 6, 7, and 11-13 exhibited nitric oxide production inhibition activity in LPS-activated RAW 264.7 cells with the IC50 values of 79.10, 44.34, 51.28, 33.54, 37.67, and 28.56 µM, respectively, compared to that of the positive control, dexamethasone, which showed IC50 value of 13.66 µM. The other isolates were inactive with IC50 values over 100 µM.

Labdane-type diterpenoids and sesquiterpenes from Curcuma aromatica and their nitric oxide inhibitory activity in lipopolysaccharide-stimulated RAW264.7 macrophages.

One new labdane-type diterpenoid, 3ß,15-dihydroxylabda-8(17),12E-dien-16,15-olide (1) named curcumatin and twelve known compounds, coronarin D (2), isocoronarin D (3), (E)-labda-8(17),12-diene-15,16-dial (4), zerumin A (5), (E)-labda-8(17),12-dien-15,16-dioic acid (6), furanodiene (7), linderazulene (8), zedoarol (9), zedoarondiol (10), germacrone-1,10-epoxide (11), germacrone-4,5-epoxide (12), and zingiberenol (13) were isolated from the ethanol extract of the roots of Curcuma aromatica Salisb. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, and comparing with the NMR data reported in the literature. Compounds 2, 5, and 13 significantly inhibited the nitric oxide production effect in LPS-stimulated RAW 264.7 macrophages with IC50 values of 8.8 ± 1.7, 4.0 ± 0.9, and 6.2 ± 0.4 µM, respectively.

Chemical constituents from the heterotrophic marine microalgae Aurantiochytrium sp. SC145 and their antimicrobial activities.

One new indol, N-methoxymethyltryptophol (1), one new phenolic, (2 R)-2-(4-hydroxyphenyl)ethyl 2-hydroxy-3-phenylpropanoate (2) and fifteen known compounds (3-17) were isolated from the methanol extract of the fermentation of marine microalgae Aurantiochytrium sp. SC145. Their structures were elucidated by 1D-, 2D-NMR spectroscopic analysis, HR-ESI-MS, quantum chemical calculation methods and by comparing their NMR data with those reported in the literature. All compounds were evaluated for their antimicrobial activities against microorganisms. Compounds 2, 3 and 11 significantly exhibited antimicrobial activities on all tested Gram-(+), Gram-(-) bacteria and the yeast C. albicans with MIC values ranging from 32 to 256 µg/mL.

Four Steroidal Saponins from the Trunks of Dracaena cambodiana with Inhibition of NO Production in LPS Activated RAW264.7 Cells.

Dracaena cambodiana Pierre ex Gagnep. is well known as a medicinal plant and widely distributed in Vietnam. Phytochemical investigation on the trunks of D. cambodiana lead to the isolation of four undescribed compounds (1-4) together with seven known ones (5-11). Their structures were determined to be pennogenin-24-yl-O-ß-D-glucopyranoside (1), 17α-hydroxycambodianoside C (2), (25R)-27-hydroxypenogenin 3-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (3), (3ß,25R)-17α,22α-dihydroxy-furost-5-en-3-yl-O-α-L-rhamnopyranosyl-(1→3)-[α-L-rhamnopyranosyl-(1→2)]-ß-D-glucopyranoside (4), dracagenin A (5), 1-O-ß-D-glucopyranosyl-2-hydroxy-4-allylbenzene (6), 1-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-2-hydroxy-allylbenzene (7), 2-O-α-L-rhamnopyranosyl-(1→6)-ß-D-glucopyranosyl-1-hydroxy-allylbenzene (8), cinnamrutinoside A (9), icariside D1 (10), and seco-isolariciresinol 9-O-ß-glucopyranoside (11) by extensive spectroscopic investigation, HR-ESI-MS, 1D and 2D NMR spectra. The anti-inflammatory activity of the isolated compounds was evaluated on macrophages. Compounds 1-6 significantly inhibited nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Among them, compound 1 showed the best inhibitory activity with an IC50 value of 8.90±0.56 µM.

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).

Desmodinosides A-E: New Flavonoid C-glycosides from Desmodium heterocarpon var. stigosum with hepatoprotective and antifungal activity.

Five new flavonoid C-glycosides named desmodinosides A-E (1-5) and one known compound, apigenin 6-C-ß-d-xylopyranosyl-2''-O-ß-D-glucopyranoside (6) have been isolated from the methanol extract of the aerial parts of Desmodium heterocarpon var. stigosum. These compounds were determined by 1D and 2D-NMR and HR-MS spectroscopies. The methanol extract of this plant, in particular, demonstrated hepatoprotection and antifungal inhibition. This extract has a remarkable hepatoprotection and activity-dose response with an EC50 of 43.07 µg/mL. The hepatoprotective effect on human liver hepatoma cells (HepG2) of the isolated flavonoid C-glycosides 1-6 was observed. Desmodinosides A-C (1-3) were found to exhibit moderate hepatoprotective activity on HepG2 cells. Of these, compound 2 showed the best hepatoprotective activity with an EC50 value of 74.12 µg/mL. While compounds 1 and 3 displayed EC50 values of 271.21 and 211.99 µg/mL, respectively. Quercetin, a positive control, also caused an EC50 value of 36.42 µg/mL. In addition to having hepatoprotective effect, the methanol extract had an inhibitory effect on the growth of oomycete; it inhibited Phytophthora infestans with IC50 of 13.3 µg/mL and IC90 of 78.7 µg/mL. The oomycete inhibition was directly attributed to compounds 5 and 6, which significantly inhibited P. infestans with IC50 values of 27.4 and 24.7 µg/mL, respectively. Both 5 and 6 and methanol extract were active against P. infestanse in a dose-dependent manner. Our study demonstrated for the first time the new flavonoid C-glycosides from D. heterocarpon var. stigosum and their novel pharmacological properties. The study findings also suggest the plant extract and its metabolites could be used as a new botanical source of bioactive compounds.

Four new lignans obtained from the leaves of Schisandra cauliflora and their effect on skeletal muscle cell proliferation.

Plants of the Schisandra genus are commonly used in folk medicinal remedies. Some Schisandra species and their lignans have been reported to improve muscle strength. In the present study, four new lignans, named schisacaulins A-D, together with three previously described compounds ananonin B, alismoxide, and pregomisin were isolated from the leaves of S. cauliflora. Their chemical structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. Schisacaulin D and alismoxide significantly stimulated skeletal muscle cell proliferation by increasing the number of fused myotubes and expression of myosin heavy chain (MyHC) which may be good candidates for the treatment of sarcopenia.

New nitric oxide production inhibitors from Syzygium bullockii.

Three undescribed triterpene glycosides syzybullosides A-C (1-3) along with fourteen known compounds were isolated from the leaves of Syzygium bullockii (Hance) Merr.& L.M. Perry, including six triterpene glycosides (1-6), four phenolics (7-9, 17), four megastigmanes (10-13), and three flavonoids (14-16). The structures of 1-17 were elucidated by extensive spectroscopic analysis, including IR, HR-ESI-MS, 1D and 2D NMR spectra. Compounds 1-10 and 12-17 inhibited nitric oxide (NO) production in lipopolysaccharide activated RAW264.7 cells with IC50 values ranging from 1.30 to 13.70 µM, lower than that of the positive control compound, L-NMMA (IC50 = 33.8 µM).

ANO1-downregulation induced by schisandrathera D: a novel therapeutic target for the treatment of prostate and oral cancers.

Anoctamin 1 (ANO1), a drug target for various cancers, including prostate and oral cancers, is an intracellular calcium-activated chloride ion channel that plays various physiopathological roles, especially in the induction of cancer growth and metastasis. In this study, we tested a novel compound isolated from Schisandra sphenanthera, known as schisandrathera D, for its inhibitory effect on ANO1. Schisandrathera D dose-dependently suppressed the ANO1 activation-mediated decrease in fluorescence of yellow fluorescent protein; however, it did not affect the adenosine triphosphate-induced increase in the intracellular calcium concentration or forskolin-induced cystic fibrosis transmembrane conductance regulator activity. Specifically, schisandrathera D gradually decreased the levels of ANO1 protein and significantly reduced the cell viability in ANO1-expressing cells when compared to those in ANO1-knockout cells. These effects could be attributed to the fact that schisandrathera D displayed better binding capacity to ANO1 protein than the previously known ANO1 inhibitor, Ani9. Finally, schisandrathera D increased the levels of caspase-3 and cleaved poly (ADP-ribose) polymerase 1, thereby indicating that its anticancer effect is mediated through apoptosis. Thus, this study highlights that schisandrathera D, which reduces ANO1 protein levels, has apoptosis-mediated anticancer effects in prostate and oral cancers, and thus, can be further developed into an anticancer agent.

Two new lignan glycosides from Acanthus ilicifoliusL. with their NO inhibition and cytotoxic activity.

A phytochemical investigation of the methanolic extract of aerial parts of the Acanthus ilicifolius led to the isolation of two new lignan glycosides, acaniliciosides A and B (1 and 2), together with ten known compounds (3-12). The structures of isolated compounds were elucidated based on HR-ESI-MS, 1D and 2D NMR spectroscopic data. The absolute configurations of two new compounds were established by CD spectra. With the exception of compound 12, other compounds inhibited NO production in LPS activated RAW264.7 cells with IC50 values of 2.14-28.18 µM, as potent as that of the positive control of NG-monomethyl-L-arginine acetate (L-NMMA, IC50 of 32.50 µM). In addition, compounds 5-8 showed cytotoxic effects against SK-LU-1 and HepG2 cell lines with the IC50 values ranging from 16.48 to 76.40 µM compared to the positive control (ellipticine) with the IC50 values ranging from 1.23 to 1.46 µM.

Dimethylbutyrylated Dibenzocyclooctadiene Lignans from the Fruits of Schisandra cauliflora Inhibit NO Production in LPS-Activated RAW264.7 Cells.

From the fruits of Schisandra cauliflora, five new dimethylbutyrylated dibenzocyclooctadiene lignans, named schisandracaurins A-E, were isolated using separation and chromatographic techniques. Their structures were determined by extensive analyses of HR-ESI-MS, NMR, and ECD spectra. The schisandracaurins A-E potentially inhibited NO production in LPS-activated RAW264.7 cells with their IC50 values from 21.4 to 30.3 µM.