Anti-Atopic Dermatitis Activity of Epi-Oxyzoanthamine Isolated from Zoanthid.

Atopic dermatitis (AD, eczema) is a condition that causes dry, itchy, and inflamed skin and occurs most frequently in children but also affects adults. However, common clinical treatments provide limited relief and have some side effects. Therefore, there is a need to develop new effective therapies to treat AD. Epi-oxyzoanthamine is a small molecule alkaloid isolated from Formosan zoanthid. Relevant studies have shown that zoanthamine alkaloids have many pharmacological and biological activities, including anti-lymphangiogenic functions. However, there are no studies on the use of epi-oxyzoanthamine on the skin. In this paper, epi-oxyzoanthamine has been shown to have potential in the treatment of atopic dermatitis. Through in vitro studies, it was found that epi-oxyzoanthamine inhibited the expression of cytokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Atopic dermatitis-like skin inflammation was induced in a mouse model using 2,4-dinitrochlorobenzene (DNCB) in vivo. The results showed that epi-oxyzoanthamine significantly decreased skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly reduced transepidermal water loss (TEWL), erythema, ear thickness, and spleen weight, while also increasing surface skin hydration. These results indicate that epi-oxyzoanthamine from zoanthid has good potential as an alternative medicine for treating atopic dermatitis or other skin-related inflammatory diseases.

Physapruin A Exerts Endoplasmic Reticulum Stress to Trigger Breast Cancer Cell Apoptosis via Oxidative Stress.

Physalis plants are commonly used traditional medicinal herbs, and most of their extracts containing withanolides show anticancer effects. Physapruin A (PHA), a withanolide isolated from P. peruviana, shows antiproliferative effects on breast cancer cells involving oxidative stress, apoptosis, and autophagy. However, the other oxidative stress-associated response, such as endoplasmic reticulum (ER) stress, and its participation in regulating apoptosis in PHA-treated breast cancer cells remain unclear. This study aims to explore the function of oxidative stress and ER stress in modulating the proliferation and apoptosis of breast cancer cells treated with PHA. PHA induced a more significant ER expansion and aggresome formation of breast cancer cells (MCF7 and MDA-MB-231). The mRNA and protein levels of ER stress-responsive genes (IRE1α and BIP) were upregulated by PHA in breast cancer cells. The co-treatment of PHA with the ER stress-inducer (thapsigargin, TG), i.e., TG/PHA, demonstrated synergistic antiproliferation, reactive oxygen species generation, subG1 accumulation, and apoptosis (annexin V and caspases 3/8 activation) as examined by ATP assay, flow cytometry, and western blotting. These ER stress responses, their associated antiproliferation, and apoptosis changes were partly alleviated by the N-acetylcysteine, an oxidative stress inhibitor. Taken together, PHA exhibits ER stress-inducing function to promote antiproliferation and apoptosis of breast cancer cells involving oxidative stress.

Severinia buxifolia-isolated acridones inhibit lung cancer invasion and decrease HIFα protein synthesis involving 5'UTR-mediated translation inhibition.

BACKGROUND: Lung cancer is one of the most common cancers worldwide and is by far the leading cause of cancer death attributed to its rapid metastasis and poor prognosis. Given that hypoxia-inducible factors (HIFs) are associated with cancer metastasis, discovering agents to inhibit HIF-mediated invasive cancer is highly desired. PURPOSE: This study aimed to investigate the natural acridone compounds isolated from Severinia buxifolia for the potential to delay hypoxia-induced lung cancer invasiveness by HIF inhibition. METHODS: Using a hypoxia-responsive element (HRE) luciferase reporter, cell migration and invasion assays, real-time PCR, Western blot, and DNA recombinant clones, compound effect on HIF activity, cancer metastasis, HIF-1α mRNA transcription, HIFs protein stability, and HIF-1α translation were observed under hypoxia conditions. RESULTS: Atalaphyllidine (Sbs-A) and atalaphyllinine (Sbs-B) were found to show the most potent effects on HIF transcriptional activity and HIF-1α protein expression in NSCLC cell line A549, although Sbs-A and Sbs-B might not attribute decreasing HIF-1α mRNA expression to potent inhibition of HIF activity. HIF-1α protein stability was not affected by Sbs-A; also, prolyl hydroxylase and proteasome inhibitors could not reverse the inhibitory effect from compounds. Furthermore, 3 - 10 µM low concentrations of Sbs-A inhibited HIF target gene expression, gelatin zymography activity, and A549 cancer invasion. Ultimately, Sbs-A inhibited HIF-1α 5'UTR-mediated translation independent of oxygen concentration, underlying the mechanism of compounds inhibiting HIF-1α protein expression. CONCLUSION: Our study proposed Severinia buxifolia-isolated acridone compounds inhibited 5'-mRNA HIFA-mediated translation and provided evidence supporting the ability of acridone compounds in targeting HIFα for delayed lung cancer metastasis.

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.

Juglone prevents human platelet aggregation through inhibiting Akt and protein disulfide isomerase.

BACKGROUND/PURPOSE: Juglone, a natural compound widely found in Juglandaceae plants, has been suggested as a potential drug candidate for treating cancer, inflammation, and diabetic vascular complications. In the present study, the antiplatelet effect and underlying mechanisms of juglone were investigated for the first time. STUDY DESIGN/METHODS: Human platelet aggregation and activation were measured by turbidimetric aggregometry, flow cytometry, and Western blotting. In vitro antithrombotic activity of juglone was assessed using collagen-coated flow chambers under whole-blood flow conditions. The effect of juglone on protein disulfide isomerase (PDI) activity was determined by the dieosin glutathione disulfide assay. RESULTS: Juglone (1 - 5 µM) inhibited platelet aggregation and glycoprotein (GP) IIb/IIIa activation caused by various agonists. In a whole blood flow chamber system, juglone reduced thrombus formation on collagen-coated surfaces under arterial shear rates. Juglone abolished intracellular Ca2+ elevation and protein kinase C activation caused by collagen, but had no significant effect on that induced by G protein-coupled receptor agonists. In contrast, Akt activation caused by various agonists were inhibited in juglone-treated platelets. Additionally, juglone showed inhibitory effects on both recombinant human PDI and platelet surface PDI at concentrations similar to those needed to prevent platelet aggregation. CONCLUSION: Juglone exhibits potent in vitro antiplatelet and antithrombotic effects that are associated with inhibition of Akt activation and platelet surface PDI activity.

Anti-inflammatory, hepatoprotective and antioxidant activity of ellagitannin isolated from Melaleuca styphelioides.

Ellagitannins have a marked antioxidant effect and can prevent liver injury induced by free radicals. An undescribed ellagitannin named styphelioidin was isolated from Melaleuca styphelioides Sm. The structure of styphelioidin was elucidated by using various spectroscopic methods. The hepatoprotective activity of styphelioidin (25, 50, and 100 µM) was tested using the CCl4-challenged HepG2 cell model by measuring alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in HepG2 cells treated with styphelioidin for 1 h followed by 40 mM CCl4. Glutathione (GSH), superoxide dismutase activity (SOD) and lipid peroxidation (MDA) were evaluated to determine the mechanisms of the hepatoprotective activity. Styphelioidin significantly reduced the levels of ALT, AST, and MDA at all tested concentrations. Moreover, it conferred a marked increase in the GSH levels and the SOD activity compared to the CCl4-treated groups. Styphelioidin also exerted DPPH· radical-scavenging effects with an IC50 value of 3.67 µM. Results indicated the hepatoprotective therapeutic potential of styphelioidin comparable to silymarin. Moreover, anti-inflammatory activity was assessed and styphelioidin inhibited fMLF/CB-induced elastase release in human neutrophils with IC50 2.51 µM. Cell-free experiments with human neutrophil elastase indicated a direct enzymatic inhibitory effect of styphelioidin on the enzyme activity (IC50 2.58 µM). The potential of styphelioidin to interact with human neutrophil elastase binding sites was further confirmed by molecular docking of styphelioidin into human neutrophil elastase crystal structure using AutoDock 4.2. Styphelioidin represents a potent hepatoprotective and antioxidant agent with effects on ALT, AST, MDA, GSH, and SOD comparable to silymarin. The beneficial anti-elastase properties hold the potential for drug development against elastase-related inflammatory diseases. This study highlights a promising natural hepatoprotective and anti-inflammatory candidate derived from M. styphelioides.

Ethyl acetate extracts of Nepenthes ventricosa x sibuyanensis leaves cause growth inhibition against oral cancer cells via oxidative stress.

Introduction: The genus Nepenthes of the pitcher plants contains several natural and hybrid species that are commonly used in herbal medicine in several countries, but its possible use in cancer applications remains unknown as yet. Methods: In this study, we investigated the antioral cancer properties using ethyl acetate extracts of the Nepenthes hybrid (Nepenthes ventricosa x sibuyanensis), namely EANS. The bioactivity was detected by a MTS-based cell proliferation assay and flow cytometric or Western blot analysis for apoptosis, oxidative stress, and DNA damage. Results: Treatment for 24 hrs of EANS inhibited all three types of oral cancer cells that were tested (Ca9-22, CAL 27, and SCC9), with just a small difference to normal oral cells (HGF-1). This antiproliferation was inhibited by pretreatments with the reactive oxygen species (ROS) scavenger N-acetylcysteine (NAC), and the apoptosis inhibitor (Z-VAD). EANS treatment increased the subG1 population and it also dose- and time-dependently induced annexin V- and pancaspase-detected apoptosis as well as cleaved caspases 3 and 9 overexpressions in the oral cancer cells (Ca9-22). After EANS treatment of Ca9-22 cells, intracellular ROS and mitochondrial superoxide (MitoSOX) were overexpressed and mitochondrial membrane potential (MMP) was disrupted. Moreover, DNA damages such as γH2AX and 8-oxo-2'-deoxyguanosine (8-oxodG) were increased after EANS treatment to Ca9-22 cells. The EANS-induced effects (namely, oxidative stress, apoptosis, and DNA damage) were suppressed by ROS scavenger. Conclusion: Our findings demonstrated that EANS inhibits ROS-mediated proliferation against oral cancer cells.

Ethyl Acetate Extract of Nepenthes ventricosa x maxima Exerts Preferential Killing to Oral Cancer Cells.

Nepenthes plants are a folk medicine in many Southeast Asia countries for curing diseases but its anticancer effect is rarely investigated. The objectives of this study were to investigate the antioral cancer ability of ethyl acetate extract of Nepenthes ventricosa x maxima (EANV). The preferential killing ability of EANV was determined by MTS-based cell viability assays. The bioactive effects were further screened by flow cytometry for apoptosis, oxidative stress, and DNA damage. At 24 h treatment, EANV dose dependently decreased six types of oral cancer cells, but the normal oral cells (HGF-1) kept a 90% viability. EANV also showed chronic antiproliferative effects and inhibited 3D sphere formation ability of oral cancer cells. Ca9-22 and CAL 27 oral cancer cells with high response to EANV increased subG1 populations and enhanced Annexin V- and pancaspase-detected apoptosis in these cells. EANV also induced the generation of reactive oxygen species (ROS) and mitochondrial superoxide and the dysfunction of mitochondrial membrane potential. Moreover, the oxidative DNA damage level such as 8-oxo-2'deoxyguanosine was increased in EANV-treated oral cancer cells. Taken together, EANV has a preferential killing effect against oral cancer cells associated with oxidative stress, apoptosis, and DNA damage, suggesting EANV as a potential antioral cancer agent.

Ethyl acetate extract of Nepenthes adrianii x clipeata induces antiproliferation, apoptosis, and DNA damage against oral cancer cells through oxidative stress.

Nepenthes plants are regarded as a kind of Traditional Chinese Medicine for several diseases but its anticancer activity remain unclear. The subject of this study is to evaluate the antiproliferation effects on oral cancer cells by Nepenthes plants using ethyl acetate extract of Nepenthes adrianii x clipeata (EANA). Cell viability was detected using MTS assay. Its detailed mechanisms including cell cycle, apoptosis, oxidative stress, and DNA damage were explored by flow cytometry or western blotting. For 24 hours EANA treatment, five kinds of oral cancer cells (CAL 27, Ca9-22, OECM-1, HSC-3, and SCC9) show IC50 values of cell viability ranging from 8 to 17 µg/mL but the viability of normal oral cells (HGF-1) remains over 80%. Subsequently, CAL 27 and Ca9-22 cells with high sensitivity to EANA were chosen to investigate the detailed mechanism. EANA displays the time course and concentration effects for inducing apoptosis based on flow cytometry (subG1 and annexin V analyses) and western blotting [cleaved poly (ADP-ribose) polymerase (c-PARP)]. Oxidative stress and DNA damage were induced by EANA treatments in oral cancer cells through reactive oxygen species (ROS), mitochondrial membrane potential disruption, mitochondrial superoxide, and γH2AX. All these changes of EANA treatments in oral cancer cells were reverted by the ROS scavenger N-acetylcysteine pretreatment. Therefore, EANA induces preferential killing, apoptosis, and DNA damage against oral cancer cells through oxidative stress.

Components from the Leaves and Twigs of Mangrove Lumnitzera racemosa with Anti-Angiogenic and Anti-Inflammatory Effects.

One new neolignan, racelactone A (1), together with seven known compounds (2-8) were isolated from the methanolic extract of the leaves and twigs of Lumnitzera racemosa. The structure of racelactone A (1) was determined on the basis of the mass and NMR spectroscopic data interpretation. With respect to bioactivity, compound 1 displayed an anti-angiogenic effect by suppressing tube formation. Furthermore, compounds 1, 4, and 5 showed significant anti-inflammatory effects with IC50 values of 4.95 ± 0.89, 1.95 ± 0.40, and 2.57 ± 0.23 µM, respectively. The plausible biosynthesis pathway of racelactone A (1) was proposed.

Ethyl Acetate Extract of Scindapsus cf. hederaceus Exerts the Inhibitory Bioactivity on Human Non-Small Cell Lung Cancer Cells through Modulating ER Stress.

Unfolded protein response (UPR) is a cytoprotective mechanism that alleviates the protein-folding burden in eukaryotic organisms. Moderate activation of UPR is required for maintaining endoplasmic reticulum (ER) homeostasis and profoundly contributes to tumorigenesis. Defects in UPR signaling are implicated in the attenuation of various malignant phenotypes including cell proliferation, migration, and invasion, as well as angiogenesis. This suggests UPR as a promising target in cancer therapy. The pharmacological effects of the plant Scindapsus cf. hederaceus on human cancer cell lines is not understood. In this study, we identified an ethyl acetate extract from Scindapsus cf. hederaceus (SH-EAE), which markedly altered the protein expression of UPR-related genes in human non-small cell lung cancer (NSCLC) cells. Treatment with the SH-EAE led to the dose-dependent suppression of colony forming ability of both H1299 and H460 cells, but not markedly in normal bronchial epithelial BEAS-2B cells. SH-EAE treatment also attenuated the migration and invasion ability of H1299 and H460 cells. Moreover, SH-EAE strikingly suppressed the protein expression of two ER stress sensors, including inositol requiring enzyme-1α (IRE-1α) and protein kinase R-like ER kinase (PERK), and antagonized the induction of C/EBP homologous protein (CHOP) expression by thapsigargin, an ER stress inducer. SH-EAE induced the formation of massive vacuoles which are probably derived from ER. Importantly, SH-EAE impaired the formation of intersegmental vessels (ISV) in zebrafish larvae, an index of angiogenesis, but had no apparent effect on the rate of larval development. Together, our findings demonstrate, for the first time, that the ability of SH-EAE specifically targets the two sensors of UPR, with significant anti-proliferation and anti-migration activities as a crude extract in human NSCLC cells. Our finding also indicates potential applications of SH-EAE in preventing UPR activation in response to Tg-induced ER stress. We suggest that SH-EAE attenuates UPR adaptive pathways for rendering the NSCLC cells intolerant to ER stress.

Bioactive Triterpenoids from the Leaves and Twigs of Lithocarpus litseifolius and L. corneus.

Phytochemical investigation of the leaves and twigs of Lithocarpus litseifolius and Lithocarpus corneus resulted in the isolation of four new triterpenoids (1: -4: ), three triterpenoids (5: -7: ) isolated from a natural source for the first time, and six known compounds (8: -13: ). In addition, four known triterpenoids (14: -17: ) were isolated from L. corneus. Compound 1: is a 3,4-seco-lupane-type triterpenoid, and compounds 2: -4: are lupane-type triterpenoids in different oxidation states. The structures of all isolated compounds were identified by spectroscopic methods, especially NMR and mass spectrometry data. The absolute configuration of 2: and 3: was confirmed by X-ray single crystallographic analysis. The anti-inflammatory activities of 1: -17: and anti-HIV activities of 2: -17: were evaluated. Among them, 3-epi-betulinic acid (8: ) showed a strong anti-HIV activity comparable to abacavir, a drug used for treating HIV/AIDS. 3,4-seco-4(23),20(29)-lupadiene-3,28-dioic acid (5: ) exhibited potent inhibition of superoxide-anion generation with 86.9 ± 2.8% inhibition at 1 µM.

Hexane fraction of Pluchea indica root extract inhibits proliferation and induces autophagy in human glioblastoma cells.

Pluchea indica (L.) Less. is a perennial plant known for its versatile uses in traditional medicine. Previous findings have shown that the extracts of Pluchea indica possess significant anti-inflammatory, anti-ulcer and anti-tuberculosis activity. The aim of this study was to demonstrate the anticancer activity of the hexane fraction of P. indica root extract (H-PIRE) in human glioblastoma cells using flow cytometric and western blot analysis. The results shoewd that, H-PIRE suppressed the growth of glioblastoma cells in a dose-dependent manner. H-PIRE treatment markedly decreased the population of cells in S and G2/M phases. The significant upregulation of acidic vesicular organelle (AVO) was detected during H-PIRE treatment. The expression levels of microtubule-associated light chain 3-II (LC3-II) protein, phosphorylated JNK and phosphorylated p38 were significantly increased, confirming the occurrence of autophagy during the process. Finally, the combination treatment of H-PIRE and LY294002, a pan PI3K inhibitor, further decreased cell viability, suggesting an additive anticancer effect. Taken together, our results suggest that H-PIRE suppresses the proliferation of glioblastoma cells by inducing cell cycle arrest and autophagy.

Indonesian herbal medicine prevents hypertension-induced left ventricular hypertrophy by diminishing NADPH oxidase-dependent oxidative stress.

Indonesian herbal medicine Centella asiatica, Justicia gendarussa and Imperata cylindrica decoction (CJID) are known to be efficacious for hypertension. Oxidative stress plays an important role in hypertension-induced left ventricular hypertrophy (H-LVH). This study evaluated whether CJID inhibit cardiac remodeling in spontaneously hypertensive rats (SHRs) through mechanism of oxidative stress-related cardiac-NADPH oxidase (NOXs) pathway: NOX1, NOX2 and NOX4. Forty-weeks-old SHRs and normotensive-WKY rats, were both randomly divided into 2 groups: CJID and control. All rats were treated for 5 weeks. Systolic blood pressure (SBP) and heart rate (HR) were measured. LV morphology, function and performance were assessed by histological staining and echocardiography. Serum and cardiac superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were assessed. Cardiac superoxide and hydrogen peroxide (H2O2) productions, protein expressions of SOD2, SOD3, NOX1, NOX2 and NOX4 were also determined. We found that SBP and HR were significantly decreased in SHRs-treated group. Echocardiography showed that CJID significantly improved LV morphometry and function. CJID decreased MDA level, but increased SOD activity. Cardiac superoxide and H2O2 generation were decreased in SHRs-treated group. CJID caused cardiac SODs expressions to be increased but NOXs expressions to be suppressed. In conclusion, CJID prevents H-LVH by reducing reactive oxygen species production via the NOXs-dependent pathway.

Anti-allergic Hydroxy Fatty Acids from Typhonium blumei Explored through ChemGPS-NP.

Increasing prevalence of allergic diseases with an inadequate variety of treatment drives forward search for new alternative drugs. Fatty acids, abundant in nature, are regarded as important bioactive compounds and powerful nutrients playing an important role in lipid homeostasis and inflammation. Phytochemical study on Typhonium blumei Nicolson and Sivadasan (Araceae), a folk anti-cancer and anti-inflammatory medicine, yielded four oxygenated fatty acids, 12R-hydroxyoctadec-9Z,13E-dienoic acid methyl ester (1) and 10R-hydroxyoctadec-8E,12Z-dienoic acid methyl ester (2), 9R-hydroxy-10E-octadecenoic acid methyl ester (3), and 12R*-hydroxy-10E-octadecenoic acid methyl ester (4). Isolated compounds were identified by spectroscopic methods along with GC-MS analysis. Isolated fatty acids together with a series of saturated, unsaturated and oxygenated fatty acids were evaluated for their anti-inflammatory and anti-allergic activities in vitro. Unsaturated (including docosahexaenoic and eicosapentaenoic acids) as well as hydroxylated unsaturated fatty acids exerted strong anti-inflammatory activity in superoxide anion generation (IC50 2.14-3.73 µM) and elastase release (IC50 1.26-4.57 µM) assays. On the other hand, in the anti-allergic assays, the unsaturated fatty acids were inactive, while hydroxylated fatty acids showed promising inhibitory activity in A23187- and antigen-induced degranulation assays (e.g., 9S-hydroxy-10E,12Z-octadecadienoic acid, IC50 92.4 and 49.7 µM, respectively). According to our results, the presence of a hydroxy group in the long chain did not influence the potent anti-inflammatory activity of free unsaturated acids. Nevertheless, hydroxylation of fatty acids (or their methyl esters) seems to be a key factor for the anti-allergic activity observed in the current study. Moreover, ChemGPS-NP was explored to predict the structure-activity relationship of fatty acids. The anti-allergic fatty acids formed different cluster distant from clinically used drugs. The bioactivity of T. blumei, which is historically utilized in folk medicine, might be related to the content of fatty acids and their metabolites.

6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice.

The anti-diabetic activity of ginger powder (Zingiber officinale) has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.

Constituents of the Leaves of Pandanus utilis.

Nineteen compounds, including seven triterpenoids (1-7), five steroids (8-12), four cyclohexenone derivatives (13-16), two benzenoid glycosides (17 and 18) and one lignan (19), were isolated and separated from the leaves of Pandanus utilis through bioactivity-guided fractionation. Among them, one new lanosterol- type triterpenoid was found and named as (24R)-24-methyl-5a-4-demethyllanosta-9(11),25-dien-3ß-ol (1). The structures of the isolates were determined by mass and spectroscopic analyses, and the compounds were subjected to anti-inflammatory, anti-oxidative and cytotoxic assays.

Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis.

The Aquilaria malaccensis (Thymelaeaceae) tree is a source of precious fragrant resin, called agarwood, which is widely used in traditional medicines in East Asia against diseases such as asthma. In our continuous search for active natural products, A. malaccensis seeds ethanolic extract demonstrated antiallergic effect with an IC50 value less than 1 µg/mL. Therefore, the present research aimed to purify and identify the antiallergic principle of A. malaccensis through a bioactivity-guided fractionation approach. We found that phorbol ester-rich fraction was responsible for the antiallergic activity of A. malaccensis seeds. One new active phorbol ester, 12-O-(2Z,4E,6E)-tetradeca-2,4,6-trienoylphorbol-13-acetate, aquimavitalin (1) was isolated. The structure of 1 was assigned by means of 1D and 2D NMR data and high-resolution mass spectrometry (HR-MS). Aquimavitalin (1) showed strong inhibitory activity in A23187- and antigen-induced degranulation assay with IC50 values of 1.7 and 11 nM, respectively, with a therapeutic index up to 71,000. The antiallergic activities of A. malaccensis seeds and aquimavitalin (1) have never been revealed before. The results indicated that A. malaccensis seeds and the pure compound have the potential for use in the treatment of allergy.

Chemical Constituents and LC-profile of Fresh Formosan Lonicera japonica Flower Buds.

One new secoiridoid glucoside, ethylsecologanin dimethyl acetal (1), along with 15 known compounds, comprising six iridoid glucosides (2-7), six flavonoids (8-13), two sterol glucosides (14 and 15), and chlorogenic acid (16) were isolated from the flower buds of Formosan Lonicera japonica. The structures of these isolates were determined on the basis of mass and spectroscopic analyzes. In addition, the chemical profiles of fresh Formosan honeysuckle buds and the dried Chinese one were compared by HPLC with a PDA detector. The calibration curve of the active component, chlorogenic acid, was also provided. As a result of the constituent similarity, Formosan L.japonica can be an alternative to the Chinese honeysuckles.

Alkaloids from Pandanus amaryllifolius: Isolation and Their Plausible Biosynthetic Formation.

Pandanus amaryllifolius Roxb. (Pandanaceae) is used as a flavor and in folk medicine in Southeast Asia. The ethanolic crude extract of the aerial parts of P. amaryllifolius exhibited antioxidant, antibiofilm, and anti-inflammatory activities in previous studies. In the current investigation, the purification of the ethanolic extract yielded nine new compounds, including N-acetylnorpandamarilactonines A (1) and B (2); pandalizines A (3) and B (4); pandanmenyamine (5); pandamarilactones 2 (6) and 3 (7), and 5(E)-pandamarilactonine-32 (8); and pandalactonine (9). The isolated alkaloids, with either a γ-alkylidene-α,ß-unsaturated-γ-lactone or γ-alkylidene-α,ß-unsaturated-γ-lactam system, can be classified into five skeletons including norpandamarilactonine, indolizinone, pandanamine, pandamarilactone, and pandamarilactonine. A plausible biosynthetic route toward 1-5, 7, and 9 is proposed.