Esophageal hematoma mimicking esophageal varices after chewing betel nut: a case report.

BACKGROUND: Betel nut chewing is very common in Southeast Asia and other tropical countries. Much clinical evidence suggests that chewing betel nut has pro-inflammatory and carcinogenic effects, but there are few clinical reports of acute toxicity caused by it, especially involving esophageal damage. CASE PRESENTATION: We presented a case of a 72-year-old female who was admitted to our hospital for chest pain and hematemesis within several minutes after chewing betel nut. Gastroscopy showed two longitudinal ridge-like mucosal eminences in the esophagus located 20 cm from the incisors down to the gastric cardia, which was similar to varices. At last, a CT scan showed concentric-circle thickening of the esophagus wall, suggesting hematomas. Our treatment included fasting, inhibiting gastric acid and maintaining blood volume. After one week of medical treatment, rechecked gastroscopy showed that esophageal hematomas were gradually absorbed, with the formation of multiple shallow ulcers. CONCLUSIONS: The acute toxicity of chewing betel nut can be easily overlooked. Patients who experience chest pain or hematemesis after chewing betel nut products,especially those who take aspirin at the same time, need to be alert to esophageal hematoma.

Alkaloids and Polyacetylenes from Hippobroma longiflora with Antiangiogenesis Properties.

Four new alkaloids, hippobrines A-D (1-4), along with three new polyacetylenes, hippobrenes A-C (5-7), were isolated from Hippobroma longiflora. Compounds 1-3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by single-crystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds (1-7) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 µg/mL.

2,6-Disubstituted Piperidine Alkaloids with Neuroprotective Activity from Hippobroma longiflora.

Three new alkaloids, hipporidine A (1: ), hipporidine B (2: ), and (-)-lobeline N-oxide (3: ), were discovered from the whole plant of Hippobroma longiflora together with five known compounds (4: -8: ). Their 2,6-disubstituted piperidine structures were established based on the HRESIMS, NMR (COSY, HMBC, HSQC, NOESY), and UV spectroscopic data. Hipporidines A (1: ) and B (2: ) possess a rare 1,3-oxazinane moiety. Compound 3: is the N-oxide derivative of (-)-lobeline (6: ). Moreover, the absolute configuration of norlobeline (5: ) was established by single-crystal X-ray diffraction analysis. Three major secondary metabolites (6: -8: ) were evaluated for their neuroprotective effect against paclitaxel-induced neurotoxicity. Consequently, pretreatment with compound 8: at a concentration of 1.0 µM displayed significant attenuation on paclitaxel-damaged neurite outgrowth of dorsal root ganglion neurons without interfering with the cytotoxicity of paclitaxel on cervical cancer SiHa cells.

Components with Anti-Diabetic Activity Isolated from the Leaves and Twigs of Glycosmis pentaphylla Collected in Vietnam.

A phytochemical investigation of the leaves and twigs of Glycosmis pentaphylla (Rutaceae), collected in Vietnam, yielded three new compounds named glyfuran (1), glyphyllamide (2), and glyphyllazole (3), along with twenty-five known compounds (4-28). The structures of isolates were determined by IR, MS, NMR, and UV data analyses. In the anti-diabetic activity screening, (+)-isoaltholacton (4), glycoborinine (17), 2',4'-dihydroxy-4,6'-dimethoxychalcone (24), and flavokawain A (25) simultaneously exhibited inhibition of dipeptidyl peptidase-4 (DPP4) and stimulation of the glucagon-like peptide-1 (GLP-1) secretion on the murine intestinal secretin tumor cell line (STC-1).

Antiproliferation Effects of Marine-Sponge-Derived Methanol Extract of Theonella swinhoei in Oral Cancer Cells In Vitro.

The purpose of this study aimed to assess the antiproliferation effects of methanol extract of T. swinhoei (METS) and explore the detailed responses of oral cancer cells compared to normal cells. METS effectively inhibits the cell proliferation of oral cancer cells but does not affect normal cell viability, exhibiting preferential antiproliferation function. METS exerted more subG1 accumulation, apoptosis induction, cellular and mitochondrial oxidative stress, and DNA damage than normal cells, reverted by oxidative stress inhibitor N-acetylcysteine. This METS-caused oxidative stress was validated to attribute to the downregulation of glutathione. METS activated both extrinsic and intrinsic caspases. DNA double-strand breaks (γH2AX) and oxidative DNA damage (8-hydroxy-2-deoxyguanosine) were stimulated by METS. Therefore, for the first time, this investigation shed light on exploring the functions and responses of preferential antiproliferation of METS in oral cancer cells.

Biosynthesis of Piperazine-Derived Diazabicyclic Alkaloids Involves a Nonribosomal Peptide Synthetase and Subsequent Tailoring by a Multifunctional Cytochrome P450 Enzyme.

Piperazine-derived diazabicycles are privileged structures found in natural products and synthetic chemical entities, including therapeutic agents. Herein, we deciphered the biosynthesis of two unique classes of diazabicyclic alkaloids, fischerazines A-C. Notably, we characterized a multifunctional P450 monooxygenase NfiC that installs ortho-dihydroxyl groups on the dibenzyl-piperazines, in turn triggering a range of NfiC-catalyzed and spontaneous cyclization events.

Pomegranate Extract (POMx) Induces Mitochondrial Dysfunction and Apoptosis of Oral Cancer Cells.

The anticancer effect of pomegranate polyphenolic extract POMx in oral cancer cells has rarely been explored, especially where its impact on mitochondrial functioning is concerned. Here, we attempt to evaluate the proliferation modulating function and mechanism of POMx against human oral cancer (Ca9-22, HSC-3, and OC-2) cells. POMx induced ATP depletion, subG1 accumulation, and annexin V/Western blotting-detected apoptosis in these three oral cancer cell lines but showed no toxicity to normal oral cell lines (HGF-1). POMx triggered mitochondrial membrane potential (MitoMP) disruption and mitochondrial superoxide (MitoSOX) generation associated with the differential downregulation of several antioxidant gene mRNA/protein expressions in oral cancer cells. POMx downregulated mitochondrial mass, mitochondrial DNA copy number, and mitochondrial biogenesis gene mRNA/protein expression in oral cancer cells. Moreover, POMx induced both PCR-based mitochondrial DNA damage and γH2AX-detected nuclear DNA damage in oral cancer cells. In conclusion, POMx provides antiproliferation and apoptosis of oral cancer cells through mechanisms of mitochondrial impairment.

Effect of N, N-Dimethylglycine on Homocysteine Metabolism in Rats Fed Folate-Sufficient and Folate-Deficient Diets.

OBJECTIVE: This study aimed to investigate the effects of N,N-dimethylglycine (DMG) on the concentration and metabolism of plasma homocysteine (pHcy) in folate-sufficient and folate-deficient rats. METHODS: In this study, 0.1% DMG was supplemented in 20% casein diets that were either folate-sufficient (20C) or folate-deficient (20CFD). Blood and liver of rats were subjected to assays of Hcy and its metabolites. Hcy and its related metabolite concentrations were determined using a liquid chromatographic system. RESULTS: Folate deprivation significantly increased pHcy concentration in rats fed 20C diet (from 14.19 ± 0.39 µmol/L to 28.49 ± 0.50 µmol/L; P < 0.05). When supplemented with DMG, pHcy concentration was significantly decreased (12.23 ± 0.18 µmol/L) in rats fed 20C diet but significantly increased (31.56 ± 0.59 µmol/L) in rats fed 20CFD. The hepatic methionine synthase activity in the 20CFD group was significantly lower than that in the 20C group; enzyme activity was unaffected by DMG supplementation regardless of folate sufficiency. The activity of hepatic cystathionine ß-synthase (CBS) in the 20CFD group was decreased but not in the 20C group; DMG supplementation enhanced hepatic CBS activity in both groups, in which the effect was significant in the 20C group but not in the other group. CONCLUSION: DMG supplementation exhibited hypohomocysteinemic effects under folate-sufficient conditions. By contrast, the combination of folate deficiency and DMG supplementation has deleterious effect on pHcy concentration.

Targeted Isolation of Xenicane Diterpenoids from Taiwanese Soft Coral Asterospicularia laurae.

Application of LC-MS/MS-based molecular networking indicated the ethanol extract of octocoral Asterospicularia laurae is a potential source for the discovery of new xenicane derivatives. A natural product investigation of this soft coral resulted in the isolation of four new xenicane diterpenoids, asterolaurins O‒R (1‒4), together with six known compounds, xeniolide-A (5), isoxeniolide-A (6), xeniolide-B (7), 7,8-epoxyxeniolide-B (8), 7,8-oxido-isoxeniolide-A (9), and 9-hydroxyxeniolide-F (10). The structures of isolated compounds were characterized by employing spectroscopic analyses, including 2D-NMR (COSY, HMQC, HMBC, and NOESY) and high-resolution electrospray ionization mass spectrometry (HRESIMS). Asterolaurin O is the first case of brominated tricarbocyclic type floridicin in the family Xeniidae. Concerning bioactivity, the cytotoxic activity of those isolates was evaluated. As a result, compounds 1 and 2 demonstrated a selective cytotoxic effect against the MCF-7 cell line at IC50 of 14.7 and 25.1 µM, respectively.

Additional alkaloids from Zoanthus vietnamensis with neuroprotective and anti-angiogenic effects.

A chemical investigation of the zoantharian Zoanthus vietnamensis, collected off Taiwan, yielded eleven new alkaloids, 7α-hydroxykuroshine J (1), 18ß-hydroxykuroshine J (2), 5α-hydroxyzoanthenamine (3), 5ß-hydroxyzoanthenamine (4), 14α-hydroxyzoanthenamine (5), 30-hydroxyzoanthenamine (6), 11-dehydroxy-18-epi-kuroshine A (7), 5α-hydroxykuroshine A (8), 7ß-hydroxykuroshine A (9), 11-keto-oxyzoanthamine (10), and 30-hydroxyzoanthamine (11), along with eight known compounds (12-19). The structures of these compounds were identified by detailed spectroscopic data, including HRESIMS, IR, NMR, and UV spectra. All secondary metabolites isolated from Z. vietnamensis were investigated for the anti-angiogenic effect in human endothelial progenitor cells (EPCs). Compounds 6, 7, 11, and 13 exhibited mild anti-angiogenic effect by blocking cell growth and tube formation of EPCs. The neuroprotective potential of four major compounds 12, 14, 15, and 19 against paclitaxel-induced neurotoxicity was evaluated. Pretreatment of 14 and 15 protected paclitaxel-damaged neurite outgrowth of dorsal root ganglion (DRG) neurons, without interfering the cytotoxic activity of paclitaxel on cervical cancer SiHa cells.

Correction: Ou-Yang, F. et al. Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima). Int. J. Mol. Sci. 2019, 20, 3238.

The authors would like to make corrections to their published paper [...].

New Hydroquinone Monoterpenoid and Cembranoid-Related Metabolites from the Soft Coral Sarcophyton tenuispiculatum.

Chemical investigation of the marine soft coral Sarcophyton tenuispiculatum resulted in the isolation of a 1,4-dihydrobenzoquinone, sarcotenuhydroquinone (1), three new cembranoids, sarcotenusenes A‒C (2‒4), and ten previously reported metabolites 5-14. The chemical structures of all isolated metabolites were determined by detailed spectroscopic analyses. In biological assays, anti-inflammatory, cytotoxic, and peroxisome proliferator-activated receptor γ (PPAR-γ) transcription factor assays of all compounds were performed. None of the isolated compounds were found to exhibit activity in the PPAR-γ transcription factor assay. The anti-inflammatory assays showed that (+)-7α,8ß-dihydroxydeepoxysarcophine (13) inhibited the production of IL-1ß to 56 ± 1% at a concentration of 30 µM in lipopolysaccharide (LPS)-stimulated J774A.1 macrophage cells. In addition, 1 and 2 were found to exhibit cytotoxicity towards a panel of cancer cell lines.

Aleuritin, a novel dinor-diterpenoid from the twigs of Aleurites moluccanus with an anti-lymphangiogenic effect.

A phytochemical investigation of Aleurites moluccanus yielded one novel dinor-diterpenoid, aleuritin (1), along with a rare diterpenoid, aleuritone (2). Compound 1 has an unprecedented skeleton with a 6/6/5-fused tricyclic ring system. Compound 2 possesses a rare 6/6/5/3-fused tetracyclic skeleton, which is probably an artifact formed photochemically by the Norrish reaction. The structures of 1 and 2 were determined by spectroscopic methods (ECD, IR, mass, and NMR) and confirmed by single-crystal X-ray diffraction analyses. A plausible biogenetic pathway of 1 is proposed. Pharmacological study showed that these two compounds possessed mild in vitro anti-lymphangiogenic activity, which suppressed tube formation with IC50 values of 48.1 ± 1.8 and 34.2 ± 0.8 µg mL-1, respectively.

Zoanthamine Alkaloid Derivatives from the Zoantharian Zoanthus vietnamensis with Antimetastatic Activity.

A novel compound zoanone A (1), together with eight new alkaloids, 3ß,14α-dihydroxy-28-deoxyzoanthenamine (2), 7α-hydroxy-28-deoxyzoanthenamine (3), 3α-hydroxyzoanthenamine (4), 7ß-hydroxyzoanthenamine (5), 28α-methoxyzoanthenamine (6), 28α-methoxykuroshine A (7), 30-hydroxykuroshine A (8), and 3ß-hydroxy-11-deketo-kuroshine B (9), was isolated from the zoantharian Zoanthus vietnamensis. Their structures were elucidated by the comprehensive analyses of IR, mass spectrometry, NMR, and UV spectroscopic data. The absolute configuration of 1 was established by single-crystal X-ray crystallographic analysis using Cu Kα radiation. A plausible biosynthetic pathway of 1 was proposed. Antiangiogenic and antilymphangiogenic activities of the isolated metabolites were tested and evaluated. The results showed that all isolated compounds had weak antimetastatic activity.

Clerodane Diterpenoids from Callicarpa hypoleucophylla and Their Anti-Inflammatory Activity.

Plants of the genus Callicarpa are known to possess several medicinal effects. The constituents of the Taiwan endemic plant Callicarpa hypoleucophylla have never been studied. Therefore, C. hypoleucophylla was selected for our phytochemical investigation. Two new clerodane-type diterpenoids, named callihypolins A (1) and B (2), along with seven known compounds were isolated from the leaves and twigs of the Lamiaceae plant C. hypoleucophylla and then characterized. The structures of compounds 1 and 2 were elucidated by spectroscopic data analysis, specifically, two-dimension nuclear magnetic resonance (NMR). The anti-inflammatory activity of compounds 1-9 based on the suppression of superoxide anion generation and elastase release was evaluated. Among the isolates, compounds 2-4 showed anti-inflammatory activity (9.52-32.48% inhibition at the concentration 10 µm) by suppressing superoxide anion generation and elastase release. Our findings not only expand the description of the structural diversity of the compounds present in plants of the genus Callicarpa but also highlight the possibility of developing anti-inflammatory agents from Callicarpa endemic species.

Cytotoxic and anti-inflammatory effects of lignans and diterpenes from Cupressus macrocarpa.

Cupressus macrocarpa is a windbreak tree and is reported to have various cytotoxic effects. A natural product study on the leaves of C. macrocarpa has yielded ten secondary metabolites, including three new diterpenoids (1-3), four known diterpenoids (4-7), and three known lignans (8-10). The structures of all isolated compounds were elucidated via the interpretation of spectroscopic methods, especially 2D NMR and mass analyses. In the cytotoxic assays, compounds 1-3 and 7-10 showed inhibition effect against HepG2, MDA-MB-231, and A549 cells with IC50 values ranging from 0.004 to 19.9 µg/mL. Moreover, the anti-inflammatory assays revealed that (-)-matairesinol (8) had significant inhibitory activities on superoxide anion generation (IC50 = 2.7 ± 0.3 µM) and elastase release (IC50 = 6.6 ± 0.7 µM).

Anti-Lymphangiogenic Alkaloids from the Zoanthid Zoanthus vietnamensis Collected in Taiwan.

Eleven new secondary metabolites [kuroshines H-J (1-3), 27-methyl glycinate zoanthenamine (4), 27-hydroxyzoanthenamine (5), 27-methyl glycinate kuroshine A (6), 27-hydroxykuroshine A (7), 3ß-hydroxy-28-deoxyzoanthenamine (8), 14α-hydroxy-28-deoxyzoanthenamine (9), 27-hydroxy-28-deoxyzoanthenamine (10), and kuroshine K (11)], along with seven known compounds (12-18), were isolated from the zoantharian Zoanthus vietnamensis. The structures of all isolated components were elucidated by spectroscopic data (IR, MS, NMR, and UV), especially 2D NMR analyses. The relative configurations of 1 and 2 were confirmed by using single-crystal X-ray crystallography. Compounds 1-3 were found to have an unprecedented ether linkage between C-15 and C-28, while the unusual substituent methyl glycinate, attached at C-27 in compounds 4 and 6, was found for the first time in zoanthamine-type alkaloids. The anti-lymphangiogenic activities of 17 isolated compounds were evaluated. Compounds 4, 5, and 10 exerted promising anti-lymphangiogenic functions by reducing cell growth and tube formation of human lymphatic endothelial cells (LECs). In addition, the structure-activity relationships of the isolated alkaloids against lymphangiogenesis of LECs are discussed.

Antiproliferation for Breast Cancer Cells by Ethyl Acetate Extract of Nepenthes thorellii x (ventricosa x maxima).

Extracts from the Nepenthes plant have anti-microorganism and anti-inflammation effects. However, the anticancer effect of the Nepenthes plant is rarely reported, especially for breast cancer cells. Here, we evaluate the antitumor effects of the ethyl acetate extract of Nepenthes thorellii x (ventricosa x maxima) (EANT) against breast cancer cells. Cell viability and flow cytometric analyses were used to analyze apoptosis, oxidative stress, and DNA damage. EANT exhibits a higher antiproliferation ability to two breast cancer cell lines (MCF7 and SKBR3) as compared to normal breast cells (M10). A mechanistic study demonstrates that EANT induces apoptosis in breast cancer cells with evidence of subG1 accumulation and annexin V increment. EANT also induces glutathione (GSH) depletion, resulting in dramatic accumulations of reactive oxygen species (ROS) and mitochondrial superoxide (MitoSOX), as well as the depletion of mitochondrial membrane potential (MMP). These oxidative stresses attack DNA, respectively leading to DNA double strand breaks and oxidative DNA damage in γH2AX and 8-oxo-2'deoxyguanosine (8-oxodG) assays. Overall these findings clearly revealed that EANT induced changes were suppressed by the ROS inhibitor. In conclusion, our results have shown that the ROS-modulating natural product (EANT) has antiproliferation activity against breast cancer cells through apoptosis, oxidative stress, and DNA damage.

Anti-Lymphangiogenesis Components from Zoanthid Palythoa tuberculosa.

Three new compounds, tuberazines A-C (1-3), and eleven known compounds (4-14) were obtained from the ethanolic extract of Taiwanese zoanthid Palythoa tuberculosa. Compounds 1-4 are rare marine natural products with a pyrazine moiety, and compound 5 is a tricyclic tryptamine derivative isolated from nature for the first time. The structures of all isolated metabolites were determined by analyzing their IR, Mass, NMR, and UV spectrometric data. The absolute configuration of 1 was confirmed by comparing the trend of experimental electronic circular dichroism (ECD) with calculated ECD spectra. The anti-lymphangiogenic activities of new compounds were evaluated in human lymphatic endothelial cells (LECs). Of these, new compound 3 displayed the most potent anti-lymphangiogenesis property by suppressing cell growth and tube formation of LECs.

Novel 11-norbetaenone isolated from an entomopathogenic fungus Lecanicillium antillanum.

A novel nor-betaenone compound, 11-norbetaenone (1), was isolated from the culture broth of an entomopathogenic fungus Lecanicillium antillanum. The structure was determined on the basis of 1D and 2D NMR spectroscopic data. The absolute stereochemistry of 1 was further confirmed by X-ray single crystallography analysis. It is the first secondary metabolite reported from the species Lecanicillium antillanum. And it is also the first time that a betaenone-type compound was isolated from the genus Lecanicillium. Furthermore, 11-norbetaenone (1) displayed significant anti-angiogenic effect by suppressing tube formation.