Effect of Target Changes on Target Coverage and Dose to the Normal Brain in Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors.

Purpose: We evaluated the dosimetric effect of tumor changes in patients with fractionated brain stereotactic radiation therapy (SRT) on the tumor and normal brain using repeat verification magnetic resonance imaging (MRI) in the middle of the treatment period. Methods and Materials: Fifteen large intracranial metastatic lesions with fractionated SRT were scanned employing standardized planning MRI (MRI-1). Repeat verification MRI (MRI-2) were performed during the middle of the irradiation period. Gross tumor volume (GTV) was defined as the volume of the contrast-enhancing lesion on T1-weighted MRI with gadolinium contrast agent. The doses to the tumor and normal brain were evaluated on the MRI-1 scan. Beam configuration and intensity on the initial volumetric modulated arc therapy plan were used to evaluate the dose to the tumor and the normal brain on MRI-2. We evaluated the effect of D98% (percent dose irradiating 98% of the volume) on the GTV using the plans on the MRI-1 and MRI-2 scans. For the normal brain, the V90%, V80%, and V50% (volume of the normal brain receiving >90%, 80%, and 50% of the prescribed dose, respectively) were investigated. Results: Three (20% of the total) and 4 (26% of the total) tumors exhibited volume shrinkage or enlargement changes of >10%. Five (33% of the total) tumors exhibited volume shrinkage and enlargement changes of <10%. Three tumors (20% of the total) showed no volume changes. D98% of the GTV increased in patients with tumor shrinkage because of dose inhomogeneity and decreased in patients with tumor enlargement, with a coefficient of determination of 0.28. The V90%, V80%, and V50% increase with decreasing tumor volumes and were linearly related to the tumor volume difference with a coefficient of determination values of 0.97, 0.98, and 0.97, respectively. Conclusions: Repeat verification MRI for brain fractionated SRT during the treatment period should be considered to reduce the magnitude of target underdosing or normal brain overdosing.

Impacts of Surface Modification of Pt-Sensing Electrodes with Au on Hydrogen-Sensing Properties and Mechanism of Diode-Type Gas Sensors Based on Anodized Titania.

The impacts of the surface modification of Pt-sensing electrodes with Au on the H2-sensing properties and mechanism of diode-type gas sensors based on anodized titania (TiO2) were discussed in this study. The sensors using Pt electrodes modified with and without Au (Au(n)/Pt/TiO2 (n: sputtering time (s)) and Pt/TiO2 sensors, respectively) were fabricated by employing an anodized TiO2 film on a Ti plate. The surface modification of the Pt electrodes with Au(20) having a thickness of ca. 10 nm was the most drastically enhanced H2 response of the Pt/TiO2 sensor especially in air. The oxidation activity of H2 over the Pt and typical Au(n)/Pt electrodes was investigated to clarify the H2-sensing mechanism, together with analyses of crystal structure and chemical state of these electrodes by X-ray diffraction and X-ray photoelectron spectroscopy, respectively. The oxidation activity of H2 over the Pt electrode decreased with an increase in the amount of the surface-modified Au. Besides, the addition of moisture into the gaseous atmosphere reduced the oxidation activity of H2 in air. The alloying of Pt with Au was confirmed after annealing of the Au(n)/Pt electrodes at 600 °C in air, and the number of oxygen adsorbates on the surface increased with an increase in the amount of the surface-modified Au. On the basis of these results, we can suggest that the large H2 response of the Au(n)/Pt/TiO2 sensors arises from both a decrease in the number of highly active oxygen adsorbates and an increase in dissociatively adsorbed hydrogen species on the surface. The water molecules and/or hydroxy groups adsorbed on the surface by the addition of moisture into the gaseous atmosphere seem to have a crucial role in increasing the dissociatively adsorbed hydrogen species on the surface, to enhance the H2 response.

Effects of Gas Adsorption Properties of an Au-Loaded Porous In2O3 Sensor on NO2-Sensing Properties.

Gas adsorption properties of semiconductor-type gas sensors using porous (pr-) In2O3 powders loaded with and without 0.5 wt % Au (Au/pr-In2O3 and pr-In2O3 sensors, respectively) at 100 °C were examined by using diffuse reflectance infrared Fourier transform spectroscopy, and the effect of the Au loading onto pr-In2O3 on the NO2-sensing properties were discussed in this study. We found the following: the resistance of the Au/pr-In2O3 sensor in dry air is lower than that of the pr-In2O3 sensor; the DRIFT spectra of both the sensors show a broad positive band between 1600 and 1000 cm-1 in dry air (reference: in dry N2 at 100 °C), which mainly originates from oxygen adsorbates and/or lattice oxygen, and that this band is much larger for the Au/pr-In2O3 sensor than for the pr-In2O3 sensor; the Au loading also increases the adsorption amount of H2O and the reactivity of NO2 on the pr-In2O3 surface; and the NO2 response of the Au/pr-In2O3 sensor in dry air is marginally higher than that of the pr-In2O3 sensor in the examined concentration range of NO2 (0.6-5 ppm) in dry air. The obtained results strongly support the enhancement of the NO2 adsorption onto the pr-In2O3 surface by Au loading, which contributed to the improvement of the NO2-sensing properties.

[An Autopsy Case of IGF‒⠡ Secreting Gastric Cancer with Non‒Islet Cell Tumor Hypoglycemia].

We present the case of a 72‒year‒old male patient with anorexia who was diagnosed with advanced gastric cancer with multiple liver metastasis. He had marked hypoglycemia and lightheadedness from the time of admission. The serum insulin level was very low and other endocrinology test results were normal. He was finally diagnosed with non‒islet cell tumor hypoglycemia(NICTH)based on IHC findings that tumor cells expressed insulin‒like growth factor (IGF)Ⅱ. After the patient received intravenous glucocorticoid therapy along with S‒1 plus CDDP combination chemotherapy, the hypoglycemia was quickly resolved. However, he developed septic shock in reaction to the chemotherapy and died on the 35th day of hospitalization. The autopsy showed the presence of IGF‒Ⅱ in the liver metastasis, as well as in the primary tumor.

Identification of pheophorbide a as an inhibitor of receptor for advanced glycation end products in Mallotus japonicus.

Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs (RAGE), RAGE antagonists would provide a useful therapeutic option for various health disorders. Therefore, in this study, we aimed to identify phytochemicals that would inhibit binding of AGEs to RAGE, which may help develop new drug leads and/or nutraceuticals for AGE-RAGE-related diseases. On screening ethanol extracts obtained from 700 plant materials collected in Myanmar, we found that the ethanol extract from the leaves of Mallotus philippensis inhibited the binding of AGEs to RAGE. We also found that the leaves of M. japonicus, which belongs to the same genera and distributes abundantly in Japan, exhibited the inhibitory activity similar to M. philippensis. Activity-guided fractionation and LC/MS analysis of the ethanol extract of M. japonicus helped identify pheophorbide a (PPBa) as a major component in the active fraction, along with some other pheophorbide derivatives. PPBa exhibited potent inhibitory activity against AGE-RAGE binding, with an IC50 value (0.102 µM) comparable to that of dalteparin (0.084 µM). PPBa may be a valuable natural product for use as a therapeutic agent and/or a nutraceutical against various health complications arising from activation of the AGE-RAGE axis.

Eucommia Leaf Extract Induces BDNF Production in Rat Hypothalamus and Enhances Lipid Metabolism and Aerobic Glycolysis in Rat Liver.

BACKGROUND: Mutations in the brain-derived neurotrophic factor (BDNF) gene and its receptor, tyrosine receptor kinase B (TrkB), have been reported to cause severe obesity in rodents. Our previous study demonstrated that the oral administration of 5% Eucommia leaf extract (ELE) or ELE aroma treatment (ELE aroma) produced anti-obesity effects. OBJECTIVE: In this study, we investigated the effects of ELE on glycolysis and lipid metabolism in male Sprague-Dawley rats, as well as the effects of ELE on BDNF in rat hypothalamus. METHODS AND RESULTS: A significant reduction and a reduction tendency in the respiratory quotient were observed in association with 5% ELE and ELE aroma treatment, respectively. Furthermore, RT-qPCR results showed significant increases in Cpt2, Acad, Complex II, and Complex V mRNA levels in the liver with both treatments. In addition, in rat hypothalamus, significant elevations in BDNF, Akt, PLCγ proteins and CREB phosphorylation were observed in the 5% ELE group and the ELE aroma group. Furthermore, the Ras protein was significantly increased in the ELE aroma group. On the other hand, significant dephosphorylation of ERK1/2 was observed by the western blotting in the 5% ELE group and the ELE aroma group. CONCLUSION: These findings suggest that the ELE treatment enhances the lipid metabolism and increases the aerobic glycolytic pathway, while ELE-induced BDNF may affect such energy regulation. Therefore, ELE has the possibility to control metabolic syndrome.

Synergistic Effects of PdOx-CuOx Loadings on Methyl Mercaptan Sensing of Porous WO3 Microspheres Prepared by Ultrasonic Spray Pyrolysis.

In this work, PdOx-CuOx co-loaded porous WO3 microspheres were synthesized with varying loading levels by ultrasonic spray pyrolysis (USP) using polymethyl methacrylate (PMMA) microspheres as a vehicle template. The as-prepared sensing materials and their fabricated sensor properties were characterized by X-ray analysis, nitrogen adsorption, and electron microscopy. The gas-sensing properties were studied toward methyl mercaptan (CH3SH), hydrogen sulfide (H2S), dimethyl sulfide (CH3SCH3), nitric oxide (NO), nitrogen dioxide (NO2), methane (CH4), ethanol (C2H5OH), and acetone (C3H6O) at 0.5 ppm under atmospheric conditions with different operating temperatures ranging from 100 to 400 °C. The results showed that the CH3SH response of USP-made WO3 microspheres was collaboratively enhanced by the creation of pores in the microsphere and co-loading of CuOx and PdOx at low operating temperatures (≤200 °C). More importantly, the CH3SH selectivity against H2S was significantly improved and high selectivity against CH3SCH3, NO, NO2, CH4, C2H5OH, and CH3COCH3 were upheld by the incorporation of PdOx to CuOx-loaded WO3 sensors. Therefore, the co-loading of PdOx-CuOx on porous WO3 structures could be promising strategies to achieve highly selective and sensitive CH3SH sensors, which would be practically useful for specific applications including biomedical and periodontal diagnoses.

Toluene-sensing Properties of Mixed-potential Type Yttria-stabilized Zirconia-based Gas Sensors Attached with Thin CeO2-added Au Electrodes.

Toluene-sensing properties of mixed-potential type yttria-stabilized zirconia (YSZ)-based sensors attached with a thin CeO2-added Au sensing electrode (SE, CeO2 content: 4 - 16 mass%, thickness: 30 - 100 nm), which was fabricated by using a spin-coating method, were examined and the effects of their SE thickness and the additive amount of CeO2 on their toluene response were discussed in this study. The toluene response of the sensors attached with a 16 mass% CeO2-added Au SE increased with an increase in the SE thickness, and the sensor attached with the thickest 16 mass% CeO2-added Au SE showed the largest response, among all the sensors tested. This behavior probably arises from the increase in the number of active sites for electrochemical toluene oxidation in the CeO2-added Au SE.

Transcutaneous Cancer Vaccine Using a Reverse Micellar Antigen Carrier.

Skin dendritic cells (DCs) such as Langerhans cells and dermal dendritic cells have a pivotal role in inducing antigen-specific immunity; therefore, transcutaneous cancer vaccines are a promising strategy to prophylactically prevent the onset of a variety of diseases, including cancers. The largest obstacle to delivering antigen to these skin DC subsets is the barrier function of the stratum corneum. Although reverse micellar carriers are commonly used to enhance skin permeability to hydrophilic drugs, the transcutaneous delivery of antigen, proteins, or peptides has not been achieved to date because of the large molecular weight of drugs. To achieve effective antigen delivery to skin DCs, we developed a novel strategy using a surfactant as a skin permeation enhancer in a reverse micellar carrier. In this study, glyceryl monooleate (MO) was chosen as a skin permeation enhancer, and the MO-based reverse micellar carrier enabled the successful delivery of antigen to Langerhans cells and dermal dendritic cells. Moreover, transcutaneous vaccination with the MO-based reverse micellar carrier significantly inhibited tumor growth, indicating that it is a promising vaccine platform against tumors.

Pharmacokinetic Study of Compound K in Japanese Subjects After Ingestion of Panax ginseng Fermented by Lactobacillus paracasei A221 Reveals Significant Increase of Absorption into Blood.

Compound K (CK) is a metabolite of a saponin in Panax ginseng, formed from ginsenoside, a triterpenoid glycoside, by human intestinal bacteria. Lactobacillus paracasei A221 isolated from fermented food can hydrolyze (deglycosylate) the main ginsenoside, ginsenoside Rb1, and generate CK. However, the pharmacokinetics of L. paracasei A221 fermented ginseng (FG) and nonfermented ginseng (NFG) have not been investigated so far. The aim of this study was to investigate the pharmacokinetics of CK after oral administration of single doses of FG and NFG in healthy Japanese adults. An open-label, randomized, single-dose, two-period, crossover study was conducted in 12 Japanese healthy volunteers (five men and seven women, aged 40-60 years). All subjects were equally allocated into two groups and administered tablets containing FG or NFG. Until 24 h after the administration, blood samples were sequentially collected, plasma concentrations of CK were measured, and the pharmacokinetic parameters were calculated. We also expected restoration of decreased testosterone level as one of the beneficial effects of FG and measured plasma total testosterone concentrations in male volunteers. The means of Tmax, Cmax, and area under the concentration-time curve (AUC) were significantly different between the two groups. In the FG group, AUC0-12h (ng h/mL) and AUC0-24h (ng h/mL) were, respectively, 58.3- and 17.5-fold higher than those in the NFG group. Moreover, mean testosterone concentration in the FG group significantly increased 24 h after administration. These results showed that the main ginsenoside metabolite of ginseng, CK, produced by L. paracasei A221 has potential utility in health maintenance in healthy middle-aged and old Japanese adults.

The Role of Cysteine String Protein α Phosphorylation at Serine 10 and 34 by Protein Kinase Cγ for Presynaptic Maintenance.

Protein kinase Cγ (PKCγ) knock-out (KO) animals exhibit symptoms of Parkinson's disease (PD), including dopaminergic neuronal loss in the substantia nigra. However, the PKCγ substrates responsible for the survival of dopaminergic neurons in vivo have not yet been elucidated. Previously, we found 10 potent substrates in the striatum of PKCγ-KO mice. Here, we focused on cysteine string protein α (CSPα), a protein from the heat shock protein (HSP) 40 cochaperone families localized on synaptic vesicles. We found that in cultured cells, PKCγ phosphorylates CSPα at serine (Ser) 10 and Ser34. Additionally, apoptosis was found to have been enhanced by the overexpression of a phosphorylation-null mutant of CSPα, CSPα(S10A/S34A). Compared with wild-type (WT) CSPα, the CSPα(S10A/S34A) mutant had a weaker interaction with HSP70. However, in sharp contrast, a phosphomimetic CSPα(S10D/S34D) mutant, compared with WT CSPα, had a stronger interaction with HSP70. In addition, total levels of synaptosomal-associated protein (SNAP) 25, a main downstream target of the HSC70/HSP70 chaperone complex, were found to have decreased by the CSPα(S10A/S34A) mutant through increased ubiquitination of SNAP25 in PC12 cells. In the striatum of 2-year-old male PKCγ-KO mice, decreased phosphorylation levels of CSPα and decreased SNAP25 protein levels were observed. These findings indicate the phosphorylation of CSPα by PKCγ may protect the presynaptic terminal from neurodegeneration. The PKCγ-CSPα-HSC70/HSP70-SNAP25 axis, because of its role in protecting the presynaptic terminal, may provide a new therapeutic target for the treatment of PD.SIGNIFICANCE STATEMENT Cysteine string protein α (CSPα) is a protein belonging to the heat shock protein (HSP) 40 cochaperone families localized on synaptic vesicles, which maintain the presynaptic terminal. However, the function of CSPα phosphorylation by protein kinase C (PKC) for neuronal cell survival remains unclear. The experiments presented here demonstrate that PKCγ phosphorylates CSPα at serine (Ser) 10 and Ser34. CSPα phosphorylation at Ser10 and Ser34 by PKCγ protects the presynaptic terminal by promoting HSP70 chaperone activity. This report suggests that CSPα phosphorylation, because of its role in modulating HSP70 chaperone activity, may be a target for the treatment of neurodegeneration.

Enhanced catalytic activity and thermal stability of lipase bound to oxide nanosheets.

The present study reports the effects of binding of lipase, which is an inexpensive digestive enzyme (candida antarctica lipase) that catalyzes the hydrolysis reaction and is frequently utilized for artificial synthesis of a variety of organic molecules, to titanate nanosheets (TNSs) on their biocatalytic activities and stabilities under several lipase concentrations. TNSs were prepared through a hydrolysis reaction of titanium tetraisopropoxide (TTIP) with tetrabutylammonium hydroxide (TBAOH), resulting in formation of a colorless and transparent colloidal solution including TNSs with nanometric dimensions (hydrodynamic diameter: ca. 5.6 nm). TNSs were bound to lipase molecules through electrostatic interaction in an aqueous phase at an appropriate pH, forming inorganic-bio nanohybrids (lipase-TNSs). The enzymatic reaction rate for hydrolysis of p-nitrophenyl acetate (pNPA) catalyzed by the lipase-TNSs, especially in diluted lipase concentrations, was significantly improved more than 8 times as compared with free lipase. On the other hand, it was confirmed that heat tolerance of lipase was also improved by binding to TNSs. These results suggest that the novel lipase-TNSs proposed here have combined enhancements of the catalytic activity and the anti-denaturation stability of lipase.

Premature deaths among individuals with severe mental illness after discharge from long-term hospitalisation in Japan: a naturalistic observation during a 24-year period.

BACKGROUND: Premature death in individuals with severe mental illness (SMI) in countries without nationally collected data, including Japan, is structurally underreported. AIMS: To elucidate excess mortality among individuals with SMI in Japan. METHOD: We retrospectively investigated all deaths among users of a non-clinical community-based mental health service provider in suburban Tokyo from 1992 to 2015. RESULTS: During the study period, 45 individuals died among 254 qualified registrants. Deaths were by natural causes in 33 cases (73.3%). The mean years of life lost was 22.2 years and the overall standard mortality ratio (SMR) was 3.28 (95% CI 2.40-4.39). The cause-specific SMR was 5.09 (95% CI 2.33-9.66) for cardiovascular disease and 7.38 (95% CI 2.40-17.22) for suicide. CONCLUSIONS: Although Japan leads the world in longevity, individuals with SMI suffer premature death and excess mortality due to physical conditions as well as suicide. Revealing this underreported disparity of life is the first step to improving physical care for individuals with SMI. DECLARATION OF INTEREST: S.K. received personal fees from Pfizer and Dainippon-Sumitomo, outside the submitted work, and was a medical adviser to Sudachi-kai. Y.K. received grants from Japan Foundation for Neuroscience and Mental Health (JFNMH), during the conduct of the study, and personal fees from Dainippon-Sumitomo, outside the submitted work. K.K. received grants from Japan Society for the Promotion of Science (JSPS) and Japan Agency for Medical Research and Development (AMED), during the conduct of the study; personal fees from Daiichi-Sankyo, Otsuka, Meiji-Seika Pharma, Yoshitomi, Mochida and Fuji-Film RI Pharma; grants and personal fees from MSD, Astellas, Dainippon-Sumitomo and Eisai; and grants from Lily, Takeda and Tanabe-Mitsubishi, outside the submitted work. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

Multicolour photochromism of colloidal solutions of niobate nanosheets intercalated with several kinds of metal ions.

Colourless and transparent colloidal solutions of niobate nanosheets intercalated with some kinds of metal ions (M-NNS, M: metal) showed quasi-reversible photochromism. Ultraviolet light irradiation of the solutions induced a change in color while maintaining the transparency, and the color change was dependent on the metal ions. The coloured solutions were bleached by exposure to an oxidizing atmosphere. This cycle could be repeated several times.

Clinical assessment of a supplement of Pycnogenol® and L-arginine in Japanese patients with mild to moderate erectile dysfunction.

A double-blind parallel group comparison design clinical study was conducted in Japanese patients with mild to moderate erectile dysfunction to investigate the efficacy of a supplement containing Pycnogenol® and L-arginine. Subjects were instructed to take a supplement (Pycnogenol® 60 mg/day, L-arginine 690 mg/day and aspartic acid 552 mg/day) or an identical placebo for 8 weeks, and the results were assessed using the five-item erectile domain (IIEF-5) of the International Index of Erectile Function. Additionally, blood biochemistry, urinalysis and salivary testosterone were measured. Eight weeks of supplement intake improved the total score of the IIEF-5. In particular, a marked improvement was observed in 'hardness of erection' and 'satisfaction with sexual intercourse'. A decrease in blood pressure, aspartate transaminase and γ-glutamyl transpeptidase (γ-GTP), and a slight increase in salivary testosterone were observed in the supplement group. No adverse reactions were observed during the study period. In conclusion, Pycnogenol® in combination with L-arginine as a dietary supplement is effective and safe in Japanese patients with mild to moderate erectile dysfunction.

Chronic administration of Eucommia leaf stimulates metabolic function of rats across several organs.

Eucommia bark (Eucommia ulmoides Oliver) has been used as an herbal medicine, and more recently, the plant's leaves have been widely used to prepare tea which may have anti-obesity properties. We used a metabolic syndrome-like rat model, produced by feeding a 35% high-fat diet (HFD), to examine potential anti-obesity and anti-metabolic syndrome effects and mechanisms of chronic administration of Eucommia leaf as an extract or green leaf powder. Eighty rats were studied for 3 months in ten groups. Both forms of Eucommia leaves minimised increases in body weight and visceral fat in a dose-dependent fashion. Increases in plasma levels of TAG and NEFA, and insulin resistance secondary to HFD were lessened by both forms of Eucommia leaf. Concomitantly, an increase in plasma adiponectin levels and suppression of plasma resistin and TNF-α levels were confirmed. Real-time PCR studies showed that both forms of Eucommia leaf enhanced metabolic function across several organs, including diminishing ATP production (white adipose tissue), accelerating ß-oxidation (liver) and increasing the use of ketone bodies/glucose (skeletal muscle), all of which may exert anti-obesity effects under HFD conditions. These findings suggest that chronic administration of either form of Eucommia leaves stimulates the metabolic function in rats across several organs. The anti-obesity and anti-metabolic syndrome activity in this rat model may be maintained through secretion and regulation of adipocytokines that depend on the accumulation of visceral fat to improve insulin resistance or hyperlipaemia.

Endothelium-derived hyperpolarizing factor (EDHF) mediates endothelium-dependent vasodilator effects of aqueous extracts from Eucommia ulmoides Oliv. leaves in rat mesenteric resistance arteries.

The vascular effects of an aqueous extract prepared from the leaves of Eucommia ulmoides Oliv. (ELE), a medicinal herb commonly used in antihypertensive herbal prescriptions in China, were investigated in rat mesenteric resistance arteries. The mesenteric vascular bed was perfused with Krebs solution and the perfusion pressure was measured with a pressure transducer. In preparations with an intact endothelium and precontracted with 7 microM methoxamine, perfusion of ELE (107102 mg/ml for 15 min) caused a concentration-dependent vasodilatation, which was abolished by chemical removal of the endothelium. The ELE-induced vasodilatation was inhibited by neither indomethacin (INDO, a cyclooxygenase inhibitor) nor NG-nitro-L-arginine-methyl ester (L-NAME, a nitric oxide inhibitor). The ELE-induced vasodilatation was significantly inhibited by tetraethylammonium (TEA, a K channel blocker) and 18alpha-glycyrrhetinic acid (18alpha-GA, a gap-junction inhibitor), and abolished by high K-containing Krebs' solution. Atropine (a muscarinic acetylcholine receptor antagonist) significantly inhibited the vasodilatation induced by ELE at high concentrations. These results suggest that the ELE-induced vasodilatation is endothelium-dependent but nitric oxide (NO)- and prostaglandin I2 (PGI2)-independent, and is mainly mediated by the endothelium-derived hyperpolarizing factor (EDHF) in the mesenteric resistance arteries. Furthermore, the ELE-induced EDHF-mediated response involves the activation of K-channels and gap junctions.

Iridoids from the green leaves of Eucommia ulmoides.

The bark of Eucommia ulmoides is a well-known crude drug in oriental medicine, and its leaves have been consumed as a beverage. From the green leaves of this plant, three new iridoids (1-3) were isolated, together with 12 known compounds. Compound 1 is the first iridoid possessing a saturated bond between C-3 and C-4 and having an ether linkage between C-3 and C-2 of the glucose unit. Furthermore, 2 and 3 may be regarded as the first naturally occurring conjugates of an iridoid and an amino acid.