Sophflarine A, a novel matrine-derived alkaloid from Sophora flavescens with therapeutic potential for non-small cell lung cancer through ROS-mediated pyroptosis and autophagy.

BACKGROUND: Novel compounds and more efficient treatment options are urgently needed for the treatment of non-small cell lung cancer (NSCLC). The decoction of Sophora flavescens has been used to treat NSCLC in the clinic, and matrine-type alkaloids are generally considered to be the key pharmacodynamic material basis. But the previous study showed that common matrine-type alkaloids exhibit significant cytotoxicity only when at concentrations close to the millimolar (mM) level. The key antitumor alkaloids in S. flavescens seem to have not yet been revealed. PURPOSE: The aim of this study was to screen water-soluble matrine alkaloid with novel skeleton and enhanced activity from S. flavescens, and to reveal the pharmacological mechanism of its therapeutic effect on NSCLC. METHODS: Alkaloid was obtained from S. flavescens by chromatographic separation methods. The structure of alkaloid was determined by spectroscopic methods, and single-crystal X-ray diffraction. The mechanism of anti-NSCLC in vitro with cellular models was evaluated by MTT assay, western blotting, cell migration and invasion assay, plate colony-formation assay, tube formation assay, immunohistochemistry assay, hematoxylin and eosin staining. The antitumor efficacy in vivo was test in NSCLC xenograft models. RESULTS: A novel water-soluble matrine-derived alkaloid incorporating 6/8/6/6 tetracyclic ring system, named sophflarine A (SFA), was isolated from the roots of S. flavescens. SFA had significantly enhanced cytotoxicity compared with the common matrine-type alkaloids, having an IC50 value of 11.3 µM in A549 and 11.5 µM in H820 cells at 48 h. Mechanistically, SFA promoted NSCLC cell death by inducing pyroptosis via activating the NLRP3/caspase-1/GSDMD signaling pathway, and inhibited cancer cell proliferation by increasing the ROS production to activate autophagy via blocking the PI3K/AKT/mTOR signaling pathway. Additionally, SFA also inhibited NSCLC cell migration and invasion by suppressing EMT pathway, and inhibited cancer cell colony formation and human umbilical vein endothelial cell angiogenesis. In concordance with the above results, SFA treatment blocked tumor growth in an A549 cell-bearing orthotopic mouse model. CONCLUSION: This study revealed a potential therapeutic mechanism of a novel matrine-derived alkaloid, which not only described a rational explanation for the clinical utilization of S. flavescens, but also provided a potential candidate compound for NSCLC treatment.

Isolation, structural characterization and anti-oxidant activity of a novel polysaccharide from garlic bolt.

Allium sativum L. is a widely distributed plant used as a spice, vegetable and medicine. In this study, one novel water-soluble polysaccharide (GBP-1a), with a molecular weight of 15.0 kDa, was isolated from the scape of A. sativum (garlic bolt). GBP-1a consists of galactose, glucose and arabinose at a ratio of 73.29:4.36:1.70. It has a backbone, which is composed of 1,4-linked Galp, with 1,2,6-linked Galp branches and 1-linked Glcp residue. In addition, the anti-oxidant activities of GBP-1a, as well as the two main polysaccharide fractions on ABTS radicals, metal ions and superoxide anion radicals, were evaluated in vitro. This study added new data to the study of polysaccharides from garlic bolt.

Two new isoquinoline alkaloids from the seeds of Nandina domestica.

Two new isoquinoline alkaloids, 6 R,6aS-N-nantenine Nß-oxide (1), 6S,6aS-N-nantenine Nα-oxide (2), along with nine known alkaloids, nantenine (3), oxonantenine (4), protopine (5), nornantenine (6), N-methyl-laurotetanine (7), isocorydine (8), O-methyflavinantine (9), N-methyl-2,3,6-trimethoxymorphinan-dien-7-one Nß-oxide (10) and (+)-10-O-methylhernovine Nß-oxide (11) were isolated from the seeds of Nandina domestica. Their structures were elucidated by extensive analyses of spectroscopic data (IR, UV, HRESIMS, 1 D and 2 D NMR), ECD calculation and comparison with the related literatures. In addition, the cytotoxicity against A549 cells of these alkaloids was determined by the MTT assay.

ß-Carboline Alkaloids from the Seeds of Peganum harmala and Their Anti-HSV-2 Virus Activities.

Pegaharines A-G (1-6), six novel ß-carboline alkaloids representing three types of skeleton, were isolated from the seeds of Peganum harmala. Compound 1 is a peculiar ß-carboline alkaloid characterized by the unprecedented carbon skeleton of an azepine-indole system. Compounds 3-6 represent the first examples of heterodimers constructed from rare tetracyclic ß-carboline and classic tricyclic ß-carboline alkaloids. Compounds 1 and 2 were characterized by X-ray crystallography. Compound 4 exhibited strong antiviral activity against HSV-2, with an IC50 value of 2.12 ± 0.14 µM.

Six New Acylphloroglucinols from Dryopteris championii.

Six new acylphloroglucinols (1 - 6) were isolated from Dryopteris championii. Their structures were established on the basis of extensive analysis of spectroscopic data and comparison with reported data. The antibacterial activities of the isolates were evaluated against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Dickeya zeae.

Sesquiterpene lactones from Elephantopus mollis and their anti-inflammatory activities.

Seven sesquiterpene lactones, 8-O-methacryloylelephanpane, 2,4-bis-O-methyl-8-O-methacryloylelephanpane, 4-O-ethyl-8-O-methacryloylelephanpane, 8-O-methacryloylisoelephanpane, 2-O-demethyltomenphantopin C, molephantin A, molephantin B, along with ten known ones, were isolated from Elephantopus mollis (Asteraceae). Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolates were evaluated for their anti-inflammatory activities on LPS-stimulated RAW 264.7 cells, and all tested compounds exhibited potent anti-inflammatory effects with IC50 values of 0.57 ± 0.17 to 14.34 ± 1.61 µM, except that compound tomenphantopin C exhibited moderate anti-inflammatory activity with IC50 values of 59.97 ± 1.53 µM.

Diterpenoid Alkaloids from Delphinium ajacis and Their Anti-RSV Activities.

Five new diterpenoid alkaloids, ajacisines A-E (1-5), were isolated from Delphinium ajacis, along with seven known alkaloids (6-12). On the basis of their spectral data (IR, UV, HR-ESI-MS, 1D and 2D NMR) and chemical properties, the structures of compounds 1-12 were identified. All isolated compounds were evaluated for their in vitro antiviral activities against respiratory syncytial virus, and compounds 3-5 and 8 exhibited moderate to weak effects with IC50 values of 75.2 ± 1.1, 35.1 ± 0.6, 10.1 ± 0.3, and 50.2 ± 0.5 µM, respectively.

Three new ent-kaurane diterpenes from the herbs of Wedelia prostrata.

Three new ent-kaurane diterpenes, 3α-angeloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (1), 3α-tigloyloxy-17-hydroxy-ent-kaur-15-en-19-oic acid (2) and 3α-cinnamoyloxykaur-9(11),16-dien-19-oic acid (3), along with five known compounds (4-8), were isolated from the herbs of Wedelia prostrata (Asteraceae). The structures were determined by extensive analysis of their spectroscopic data (IR, UV, HRESIMS, 1D and 2D NMR). The isolated compounds were evaluated for their cytotoxic activity on human hepatocellular carcinoma HepG2 cells. Among them, all isolates exhibited cytotoxic activities with IC50 values ranging from 9.55 ± 0.45 to 53.92 ± 1.22 µM.

[Chemical Constituents from Syzygium samarangense Branches and Leaves].

OBJECTIVE: To investigate the chemical constituents from the branches and leaves of Syzygium samarangense. METHODS: The dried branches and leaves of Syzygium samarangense were powdered and extracted with 95% ethanol, then partitioned with petroleum ether, chloroform and ethyl acetate. The chloroform fraction was subjected to silica gel, Sephdex L-20 and preparative HPLC. The structures were identified by physicochemical properties and spectral data. RESULTS: 14 compounds were respectively isolated and identified as ursolic aldehyde(1), betulin(2), betulinic aldehyde(3), betulinic acid(4), lupeol(5), ß-sitosterol(6), 5, 7-dihydroxy-6-methylflavanone(7), 2', 4'-dihydroxy-6'-methoxy-3'-methyldihydrochalcone (8), 2', 4'-dihydroxy-6'-methoxy-3'-methylchalcone (9), 5, 7-dihydroxy-6, 8-dimethylflavanone (10), 5, 7-dihydroxyflavanone (11), 2', 4'-dihydroxy-6'-methoxy-3', 5'-dimethyldihydrochalcone (12), 2'-hydroxy-4', 6'-dimethoxy-3'-methylchalcone(13) and p-hydroxyb6nzaldehyde(14). CONCLUSION: Compounds 1 - 4 and 14 are isolated from this plant for the first time.

New Phloroglucinol Derivatives from the Fruit Tree Syzygium jambos and Their Cytotoxic and Antioxidant Activities.

Seven new phloroglucinol derivatives (1-7) were isolated from the fruit tree Syzygium jambos together with four known triterpenoids (8-11) and two known flavones (12 and 13). According to the spectroscopic analyses (infrared, electrospray ionization mass spectrometry (ESIMS), high-resolution ESIMS, 1D and 2D nuclear magnetic resonance), the structures of compounds 1-7 were elucidated as jambone A (1), jambone B (2), jambone C (3), jambone D (4), jambone E (5), jambone F (6), and jambone G (7). All the isolates were determined for their cytotoxic activities on melanoma cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and compounds 10 and 11 showed potent activities. Moreover, compounds 1, 2, 4-7, 12, and 13 exhibited weak antioxidant activities under ferric-reducing antioxidant power and 2,2-diphenyl-1-picryhydrazyl radical-scavenging assays.

Crystal structure of betulinic acid methanol monosolvate.

The title compound [systematic name: 3ß-hy-droxy-lup-20(29)-en-28-oic acid methanol monosolvate], C30H48O3·CH3OH, is a solvent pseudopolymorph of a naturally occurring plant-derived lupane-type penta-cyclic triterpenoid, which was isolated from the traditional Chinese medicinal plant Syzygium jambos (L.) Alston. The dihedral angle between the planes of the carb-oxy-lic acid group and the olefinic group is 12.17 (18)°. The A/B, B/C, C/D and D/E ring junctions are all trans-fused. In the crystal, O-H⋯O hydrogen bonds involving the hy-droxy and carb-oxy-lic acid groups and the methanol solvent mol-ecule give rise to a two-dimensional network structure lying parallel to (001).