Alpha-Glucosidase Inhibitory Activity of Saponins Isolated from Vernonia gratiosa Hance.

Species belonging to the Vernonia (Asteraceae), the largest genus in the tribe Vernonieae (consisting of about 1,000 species), are widely used in food and medicine. These plants are rich sources of bioactive sesquiterpene lactones and steroid saponins, likely including many as yet undiscovered chemical components. A phytochemical investigation resulted in the separation of three new stigmastane-type steroidal saponins (1 - 3), designated as vernogratiosides A-C, from whole plants of V. gratiosa. Their structures were elucidated based on infrared spectroscopy (IR), one-dimensional (1D) and two-dimensional nuclear magnetic resonance (2D NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism analyses (ECD), as well as chemical reactivity. Molecular docking analysis of representative saponins with α-glucosidase inhibitory activity was performed. Additionally, the intended substances were tested for their ability to inhibit α-glucosidase activity in a laboratory setting. The results suggested that stigmastane-type steroidal saponins from V. gratiosa are promising candidate antidiabetic agents.

Isolation, structural elucidation and molecular docking studies against SARS-CoV-2 main protease of new stigmastane-type steroidal glucosides isolated from the whole plants of Vernonia gratiosa.

Phytochemical investigation of the whole plants of Vernonia gratiosa Hance. led in the isolation and identification of two new stigmastane-type steroidal glucosides (1-2), namely vernogratiosides A (1), and B (2). Their chemical structures were fully elucidated based on 1 D/2D NMR spectroscopic, HR-ESI-MS data analyses, and by producing derivatives by chemical reactions. The binding potential of the isolated compounds to replicase protein - main protease of SARS-CoV-2 were examined using the molecular docking simulations. Our results show that the isolated steroidal glucosides (1-2) bind to the substrate-binding site of SARS-CoV-2 main protease with binding affinities of -7.2 and -7.6 kcal/mol, respectively, as well as binding abilities equivalent to N3 inhibitor that has already been reported (-7.5 kcal/mol).

SARS-CoV-2 main protease and papain-like protease inhibition by abietane-type diterpenes isolated from the branches of Glyptostrobus pensilis using molecular docking studies.

Using various chromatographic methods, five abietane-type diterpenes were isolated from the branches of Glyptostrobus pensilis for the first time. The chemical structures of the isolates were identified by modern spectroscopic techniques, including 1H and 13C nuclear magnetic resonance spectroscopy and by comparison with the literature. In addition, the binding potential of the isolated compounds to replicase protein, SARS-CoV-2 main protease and papain-like protease, were examined using molecular docking studies. In silico results suggested that G. pensilis as well as abietane-types diterpenes are potential candidates for the prevention and treatment of SARS-CoV-2.

A new steroidal saponin from the aerial parts of Solanum torvum.

A new steroidal saponin, torvoside R (1), was isolated along with torvoside Q (2) and macaoside (3) from dichloromethane soluble-portion of the aerial parts of Solanum torvum. Their chemical structures were elucidated using HRESIMS, 1 D- and 2 D-NMR as well as comparison with those reported in the literature. All isolated compounds (1 - 3) exhibited cytotoxicity against SK-LU-1, HepG2, MCF-7, and T24 cancer cell lines with IC50 values ranging from 14.18 to 89.31 µg/mL.

Pharmacological Properties, Volatile Organic Compounds, and Genome Sequences of Bacterial Endophytes from the Mangrove Plant Rhizophora apiculata Blume.

Mangrove plant endophytic bacteria are prolific sources of bioactive secondary metabolites. In the present study, twenty-three endophytic bacteria were isolated from the fresh roots of the mangrove plant Rhizophora apiculata. The identification of isolates by 16S rRNA gene sequences revealed that the isolated endophytic bacteria belonged to nine genera, including Streptomyces, Bacillus, Pseudovibrio, Microbacterium, Brevibacterium, Microbulbifer, Micrococcus, Rossellomorea, and Paracoccus. The ethyl acetate extracts of the endophytic bacteria's pharmacological properties were evaluated in vitro, including antimicrobial, antioxidant, α-amylase and α-glucosidase inhibitory, xanthine oxidase inhibitory, and cytotoxic activities. Gas chromatography-mass spectrometry (GC-MS) analyses of three high bioactive strains Bacillus sp. RAR_GA_16, Rossellomorea vietnamensis RAR_WA_32, and Bacillus sp. RAR_M1_44 identified major volatile organic compounds (VOCs) in their ethyl acetate extracts. Genome analyses identified biosynthesis gene clusters (BGCs) of secondary metabolites of the bacterial endophytes. The obtained results reveal that the endophytic bacteria from R. apiculata may be a potential source of pharmacological secondary metabolites, and further investigations of the high bioactive strains-such as fermentation and isolation of pure bioactive compounds, and heterologous expression of novel BGCs in appropriate expression hosts-may allow exploring and exploiting the promising bioactive compounds for future drug development.

Inhibitory Effects of Cucurbitane-Type Triterpenoids from Momordica charantia Fruit on Lipopolysaccharide-Stimulated Pro-Inflammatory Cytokine Production in Bone Marrow-Derived Dendritic Cells.

The bitter melon, Momordica charantia L., was once an important food and medicinal herb. Various studies have focused on the potential treatment of stomach disease with M. charantia and on its anti-diabetic properties. However, very little is known about the specific compounds responsible for its anti-inflammatory activities. In addition, the in vitro inhibitory effect of M. charantia on pro-inflammatory cytokine production by lipopolysaccharide (LPS)-stimulated bone marrow-derived dendritic cells (BMDCs) has not been reported. Phytochemical investigation of M. charantia fruit led to the isolation of 15 compounds (1-15). Their chemical structures were elucidated spectroscopically (one- and two-dimensional nuclear magnetic resonance) and with electrospray ionization mass spectrometry. The anti-inflammatory effects of the isolated compounds were evaluated by measuring the production of the pro-inflammatory cytokines interleukin IL-6, IL-12 p40, and tumor necrosis factor α (TNF-α) in LPS-stimulated BMDCs. The cucurbitanes were potent inhibitors of the cytokines TNF-α, IL-6, and IL-12 p40, indicating promising anti-inflammatory effects. Based on these studies and in silico simulations, we determined that the ligand likely docked in the receptors. These results suggest that cucurbitanes from M. charantia are potential candidates for treating inflammatory diseases.

In vitro study on α-amylase and α-glucosidase inhibitory activities of a new stigmastane-type steroid saponin from the leaves of Vernonia amygdalina.

Using various chromatographic separations, four compounds, including one new steroid saponin named vernoamyoside E (1), were isolated from the leaves of the Vietnamese medicinal plant Vernonia amygdalina Delile (Asteraceae). Their structures were established by spectroscopic methods such as 1D- and 2D-NMR, HR-ESI-MS, and HPLC analysis. The inhibitory activities against α-glucosidase and α-amylase of the isolated compounds from V. amygdalina were reported for the first time. The results indicated that compound 1 significantly inhibited both against α-amylase and α-glucosidase activity.

Enhancement of an In Vivo Anti-Inflammatory Activity of Oleanolic Acid through Glycosylation Occurring Naturally in Stauntonia hexaphylla.

Stauntonia hexaphylla (Lardizabalaceae) has been used as a traditional herbal medicine in Korea and China for its anti-inflammatory and analgesic properties. As part of a bioprospecting program aimed at the discovery of new bioactive compounds from Korean medicinal plants, a phytochemical study of S. hexaphylla leaves was carried out leading to isolation of two oleanane-type triterpene saponins, 3-O-[ß-d-glucopyranosyl (1→2)-α-l-arabinopyranosyl] oleanolic acid-28-O-[ß-d-glucopyranosyl (1→6)-ß-d-glucopyranosyl] ester (1) and 3-O-α-l-arabinopyranosyl oleanolic acid-28-O-[ß-d-glucopyranosyl (1→6)-ß-d-glucopyranosyl] ester (2). Their structures were established unambiguously by spectroscopic methods such as one- and two-dimensional nuclear magnetic resonance and infrared spectroscopies, high-resolution electrospray ionization mass spectrometry and chemical reactions. Their anti-inflammatory activities were examined for the first time with an animal model for the macrophage-mediated inflammatory response as well as a cell-based assay using an established macrophage cell line (RAW 264.7) in vitro. Together, it was concluded that the saponin constituents, when they were orally administered, exerted much more potent activities in vivo than their sapogenin core even though both the saponins and the sapogenin molecule inhibited the RAW 264.7 cell activation comparably well in vitro. These results imply that saponins from S. hexaphylla leaves have a definite advantage in the development of oral medications for the control of inflammatory responses.

Coral and Coral-Associated Microorganisms: A Prolific Source of Potential Bioactive Natural Products.

Marine invertebrates and their associated microorganisms are rich sources of bioactive compounds. Among them, coral and its associated microorganisms are promising providers of marine bioactive compounds. The present review provides an overview of bioactive compounds that are produced by corals and coral-associated microorganisms, covering the literature from 2010 to March 2019. Accordingly, 245 natural products that possess a wide range of potent bioactivities, such as anti-inflammatory, cytotoxic, antimicrobial, antivirus, and antifouling activities, among others, are described in this review.

Naphtoquinones and Sesquiterpene Cyclopentenones from the Sponge Smenospongia cerebriformis with Their Cytotoxic Activity.

Two new naphtoquinones (smenocerones A and B, 1 and 2) and four known sesquiterpene cyclopentenones (dactylospongenones A-D, 3-6) were isolated from sponge Smenospongia cerebriformis living in the Eastern Sea of Vietnam. Their chemical structures were determined by high resolution electrospray ionization (HR-ESI)-MS, NMR spectroscopic analysis, and in comparison with the reported data. The chiroptical properties of compounds 3-6 were examined by experiment and theoretical calculation of circular dichroism (CD) spectra to prove their absolute configurations. Compound 2 significantly exhibited cytotoxic activity towards lung carcinoma (LU-1), hepatocellular carcinoma (HepG-2), promyelocytic leukemia (HL-60), breast carcinoma (MCF-7), and melanoma (SK-Mel-2) human cancer cells with IC50 values of 5.5±0.8, 3.2±0.2, 4.0±0.7, 4.1±0.8, and 5.7±1.1 µg/mL, respectively.

Sesquiterpene derivatives from marine sponge Smenospongia cerebriformis and their anti-inflammatory activity.

Using various chromatographic methods, five new sesquiterpene derivatives named smenohaimiens A-E (1-5) and five known, 19-hydroxy-polyfibrospongol B (6), ilimaquinone (7), dictyoceratin C (8), polyfibrospongol A (9), and polyfibrospongol B (10) were isolated from the marine sponge Smenospongia cerebriformis Duchassaing & Michelotti, 1864. Their structures were assigned by 1D, 2D NMR spectroscopic analysis, HR ESI MS, and calculations of the electron circular dichroism spectra. All compounds were evaluated for the inhibitory activity against NO production in lipopolysaccharide-stimulated in BV2 microglia cells. As the results, compound 7 significantly inhibited NO production with the IC50 value of 10.40±1.28µM. The remaining compounds showed moderate inhibitory NO production activities with IC50 values ranging from 24.37 to 30.43µM.

Oleanane-type Saponins from Glochidion hirsutum and Their Cytotoxic Activities.

Five new oleanane-type saponins, hirsutosides A - E, were isolated from the leaves of Glochidion hirsutum (Roxb.) Voigt. Their structures were elucidated as 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranoside (1), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-ß-d-glucopyranoside (2), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-6-acetyl-[ß-d-glucopyranosyl-(1 â†’ 3)]-ß-d-glucopyranoside (3), 21ß-benzoyloxy-3ß,16ß,23,28-tetrahydroxyolean-12-ene 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-〈-l-arabinopyranoside (4), and 21ß-benzoyloxy-3ß,16ß,23-trihydroxyolean-12-ene-28-al 3-O-ß-d-glucopyranosyl-(1 â†’ 3)-α-l-arabinopyranoside (5). All isolated compounds were evaluated for cytotoxic activities on four human cancer cell lines, HepG-2, A-549, MCF-7, and SW-626 using the SRB assay. Compounds 1, 2, 4, and 5 showed significant cytotoxic activities against all human cancer cell lines with IC50 values ranging from 3.4 to 10.2 µm. Compound 3 containing acetyl group at glc C(6″) exhibited weak cytotoxic activity with IC50 values ranging from 47.0 to 54.4 µm.

Steroidal saponins from Datura metel.

Datura metel L. (Solanaceae) is an annual herb that has been widely used in the traditional medicine for the treatment of coughs, bronchial asthma, and rheumatism. Chemical investigation of an acidic methanol extract of the whole plants of D. metel resulted in the isolation of five new steroidal saponins (1-3, 5, and 6), named metelosides A-E, and four known compounds (4, 7-9). Their structures were elucidated by extensive spectroscopic methods, including 1D and 2D NMR and MS spectra. The structures of metelosides A and B were found to be unusual among the reported spirostane-type steroidal saponins due to the presence of the acetamide groups in the molecules. Compounds 2, 4, 5, and 6 were shown to be cytotoxic against three cancer cell lines, including HepG2, MCF-7, and SK-Mel-2 cells. Furthermore, compounds 3, 4, and 7 exhibited modest anti-inflammatory effects through inhibition of NO production in LPS-stimulated BV cells.

Sesquiterpene Quinones and Diterpenes from Smenospongia cerebriformis and Their Cytotoxic Activity.

Using various chromatographic methods, one new sesquiterpene quinone named smenohaimien F (1) and five known, neodactyloquinone (2), dactyloquinone C (3), dactyloquinone D (4), isoamijiol (5), and amijiol (6), were isolated from the marine sponge Smenospongia cerebriformis Duchassaing & Michelotti, 1864. Their structures were elucidated by ID-, 2D-NMR spectroscopic analysis, HR-ESI-MS, and by comparing with the NMR data reported in the literature. The cytotoxic activities of the all compounds were evaluated on five human cancer cell lines, LU-1, HL-60, SK-Mel-2, HepG-2, and MCF-7. Compound 4 was found to exhibit significant cytotoxic activities on all tested human cancer cell lines with IC50 values ranging from 0.7 to 1.6 µg/mL.

New Alkaloids and Anti-inflammatory Constituents from the Leaves of Antidesma ghaesembilla.

Using various chromatographic methods, two new alkaloids, antidesoic acids A (1) and B (2) along with fourteen known compounds (3-16) were isolated from the leaves of Antidesma ghaesembilla Gaertn. Their chemical structures were elucidated by physical and chemical methods. All the isolated compounds were evaluated for their inhibitory activity on LPS-stimulated nitric oxide (NO) production in BV2 cells and RAW 264.7 macrophages. Bisflavone 8 significantly inhibited LPS- stimulated NO production in BV2 cells and RAW 264.7 macrophages with IC50 values of 5.4 and 8.0 µM, respectively. Compounds 1-3, 7, 10, 12, 14, and 16 showed moderate inhibitory activities with IC50 values ranging from 11.7 to 77.4 µM.

New Lignans from Antidesma hainanensis Inhibit NO Production in BV2 Microglial Cells.

Two new lignans (7S,7'R,8S,8'R)-3,3'-dimethoxy-7,7'-epoxylignan-4,4',9-triol 4-O-ß-D-glucopyranoside (1) and 9-O-formylaviculin (2) together with other thirteen known secondary metabolites were isolated from the leaves of Antidesma hainanensis. Their chemical structures were determined using NMR, electrospray ionization (ESI)-MS, circular dichroism (CD) spectroscopic methods, and as well as by comparison with those reported in the literature. Neuro-inflammatory activity of isolated compounds was evaluated by their inhibition on nitric oxide (NO) production in activated BV2 microglial cells. At concentration of 40 µM, compounds 1-3, 5, 7, 8, 9, 14, and 15 exhibited inhibitory effects over 50%, suggesting that they could be potential candidate drugs for the cure of neuro-inflammation. In addition, compounds 1, 8, 14, and 15 significantly inhibited 16.23, 27.76, 21.23, and 29.44% NO production at diluted concentration as low as 2.5 µM.

New naphthalene derivatives and isoquinoline alkaloids from Ancistrocladus cochinchinensis with their anti-proliferative activity on human cancer cells.

Five new compounds, named ancistronaphtosides A and B (1 and 2), anciscochine (3), anciscochine 6-O-ß-d-glucopyranoside (4), and 4'-methoxy-5-epi-ancistecrorine A1 (5), together with tortoside A (6) and 4-hydroxy-2-methoxyphenyl-6-O-syringoyl-ß-d-glucopyranoside (7) were isolated from the methanolic extract of Ancistrocladus cochinchinensis. Their chemical structures were established using HR-ESI-MS, NMR spectroscopic, and chiroptical methods. Compound 5 significantly exhibited anti-proliferation against HL-60, LU-1, and SK-MEL-2 cells with IC50 values of 5.0±1.2, 6.5±1.6, and 6.8±2.0µg/mL, respectively.

Bis-sesquiterpene from the Marine Sponge Dysidea fragilis.

Two new sesquiterpenes and one new bis-sesquiterpene, named dysinidins C-E (1-3) along with three known sterols, dysideasterol F, 9α,l lα-epoxycholest-7-en-3ß,5α,6α-triol, and 9α,11α-epoxycholest-7-en-3ß,5α,6α,19-tetrol 6-acetate (4-6) were isolated from the Vietnamese marine sponge Dysidea fragilis (Montagu, 1814). Their structures were determined by 1D- and 2D-NMR spectroscopies and HR-ESI-MS, as well as by comparison with reported literature data. Compounds 4-6 were found to inhibit eight human cancer cell lines (KB, LU-1, HL-60, LNCaP, SK-Mel-2, HepG-2, MCF-7, and PC-3), with IC50 values ranging from 7.3 to 31.5 µM.

Two New Compounds from the Leaves of Glochidion obliquum.

Using combined chromatographic methods, two new compounds, 6ß,9ß:9,13-diepoxymegastig-4-en-3ß-ol (1), 5a,6a-epoxy D:C-friedoolean-8-en-3ß-ol (2) were isolated from the methanol extract of the leaves of Glochidion obliquum Decne. Their structures were elucidated by 1D- and 2D-NMR spectra and in comparison with those reported in the literature.

Spirostanol saponins from Tacca vietnamensis and their anti-inflammatory activity.

Using various chromatographic methods, five new steroidal saponins named taccavietnamosides A-E (1-5) and three known, (24S,25R)-spirost-5-en-3ß,24-diol 3-O-α-l-rhamnopyranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→3)]-ß-d-glucopyranoside (6), (24S,25R)-spirost-5-en-3ß,24-diol 3-O-α-l-rhamnopyranosyl-(1→2)-[ß-d-glucopyranosyl-(1→4)-α-l-rhamnopyranosyl-(1→3)]-ß-d-glucopyranoside (7), and chantrieroside A (8) were isolated from the rhizomes of Tacca vietnamensis Thin et Hoat. Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for the inhibitory activities of nitric oxide production in LPS-stimulated RAW 264.7 macrophages and BV2 cells. As the results, compounds 3-5 showed moderate inhibition on NO production in LPS-stimulated BV2 cells and RAW 264.7 macrophages with the IC50 values ranging from 37.0 to 60.7µM.