Association of periodontal disease treatment with mortality in patients with dementia: a population-based retrospective cohort study (2002-2018).

Dementia is one of the leading causes of death worldwide. In this study, we analyzed the association of periodontal treatment with the risk of death in patients with dementia. The analyzed data were obtained by linking the National Health Insurance Corporation claims data between 2002 and 2018 to the Statistics Korea death registry. In total, 1,131,406 patients with dementia aged ≥ 65 years had undergone dental treatment during the study period. Time-dependent Cox proportional hazards model was performed. The mortality rate was approximately 10% among the patients with dementia. The 17-years cumulative survival rates for patients who received periodontal treatment and their untreated counterparts were 83.5% and 71.5%, respectively. The crude hazard ratio of the periodontal group was approximately twice as high as that of the non-periodontal group (1.99; P < 0.001). Furthermore, in the regression model that was adjusted for socio-demographic variables and systematic chronic diseases, the risk of death in the non-periodontal group was approximately 1.83 times higher than that of the periodontal group (P < 0.00). These findings suggest that preventive periodontal treatment may decrease mortality risk in older people with dementia.

Evaluating a shared care pathway intervention for people receiving chemotherapy to reduce post-treatment unplanned hospital presentations: a randomised controlled trial.

PURPOSE: The aim of this randomised controlled trial (RCT) was to explore whether a community nursing intervention for outpatients receiving systemic therapy reduced unplanned hospital presentations and improved physical and psychosocial health outcomes over the first three cycles of treatment compared to a control group receiving standard care. METHODS: The number of and reasons for unplanned presentations were obtained for 170 intervention and 176 control group adult patients with solid tumours starting outpatient chemotherapy. Poisson regression was used to compare the number of presentations between the intervention and control groups. Patients self-completed the Hospital Anxiety and Depression Scale, the Cancer Behavior Inventory and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire core 30 (EORTC QLQ-C30) at the start of the first four cycles. Linear regression techniques were used to compare quality of life outcomes. RESULTS: The reduction in unplanned presentations in the intervention group relative to the control group was 12% (95% CI, - 25%, 37%; P = 0.48). At the start of cycle 4, there was no difference in anxiety (difference = 0.47 (95% CI, - 0.28, 1.22; P = 0.22)), depression (difference = 0.57 (95% CI, - 0.18, 1.31; P = 0.13)) or EORTC QLQ-C30 summary score (difference = 0.16 (95% CI, - 2.67, 3.00; P = 0.91)). Scores for self-efficacy as measured by the Cancer Behavior Inventory were higher in the intervention group (difference = 4.3 (95% CI, 0.7, 7.9; P = 0.02)). CONCLUSION: This RCT did not demonstrate a benefit in reducing unplanned presentations to hospital. The trial identified improved cancer-based self-efficacy in patients receiving the intervention. TRIAL REGISTRATION: Registered at Australian and New Zealand Clinical Trials Registry: ACTRN12614001113640, registered 21/10/2014.

Euglena gracilis (Euglena) powder supplementation enhanced immune function through natural killer cell activity in apparently healthy participants: A randomized, double-blind, placebo-controlled trial.

Euglena gracilis (Euglena) is a microalgae found in most freshwater environments that produces paramylon, an insoluble ß-1,3-glucan linked to human immunity. We hypothesized that Euglena powder has effects on immune function in apparently healthy adults. The study included male or female volunteers between the ages of 20 and 70 years who had white blood cell counts ranging from 4 × 103/µL to 10 × 103/µL, a "severe" rating on the stress questionnaire from the Korea National Health and Nutrition Examination Survey, and at least 2 upper respiratory infections with cold-like symptoms in the previous year. Participants received either a placebo or 700 mg of Euglena powder daily for 8 weeks. The study measured natural killer cell activity, cytokine concentrations, and blood lipid profiles to confirm the immune effect of Euglena consumption. In conclusion, Euglena improved immunological function through natural killer cell activity. Safety assessment showed no significant changes in vital signs or clinical chemistry indicators, and there were no adverse events associated with Euglena consumption. Euglena supplementation may help boost the immune systems of healthy individuals.

In vivo Guinea Pig Model Study for Evaluating Antifungal Effect of a Dual-Diode Laser with Wavelengths of 405 Nm and 635 Nm on Dermatophytosis.

Background: Various laser- and light-based devices have been introduced as complementary or alternative treatment modalities for dermatophytosis, particularly for finger or toenail onychomycosis. Objective: This study aimed to comparatively evaluate the antifungal effects of 405-nm and 635-nm dual-band diode lasers using an in vivo guinea pig model of dermatophytosis. Materials and Methods: A guinea pig model was developed by the repetitive application of fungal spore preparations to the back skin of guinea pigs. Dual-diode laser treatment was delivered to the guinea pig skin at a power of 24 mW at a wavelength of 405 nm and 18 mW at 635 nm for 12 min. The treatments were administered three times weekly for 2 weeks, and a mycological study was performed. Results: Mycological studies using scraped samples obtained from treatment groups A (N = 8) and B (N = 8) after dual-diode laser treatment revealed that seven of eight (87.5%) samples in each group had negative results for direct potassium hydroxide microscopy and fungal culture studies. Skin specimens from each infected laser-untreated guinea pig exhibited spongiotic psoriasiform epidermis with parakeratosis. Meanwhile, skin specimens from infected laser-treated guinea pigs in groups A and B demonstrated thinner epidermal thickness than those from infected untreated controls but thicker than those from uninfected treated controls without noticeable inflammatory cell infiltration in the dermis. Conclusion: The guinea pig dermatophytosis model can be used to comparatively evaluate the efficacy and safety of various treatment modalities, including dual-diode lasers, for superficial fungal skin infection.

Travel Time for Dental Care Services Based on Patient Preference in South Korea.

This study analyzed patient preferences using travel time from residence to dental institution when selecting dental care services. We used data from the Korean Health Panel from 2008 to 2017 and analyzed each dental service episode. Since the distribution of travel time was skewed to the left, median travel time was analyzed. The association of travel time with services was analyzed via the population-averaged generalized estimating equation (GEE) with the Poisson family. The median of the average travel time per episode was longer for non-National Health Insurance (NHI)-covered services and shorter for NHI-covered services. The first quintile of low-income subjects traveled the longest for all services and utilized dental care the most. In the GEE analysis, travel time was approximately three times longer for implant treatment and gold inlay/resin fillings and >2 times longer for orthodontic care than for NHI-covered services. Patients residing in rural counties traveled for longer than residents of large cities. Income was statistically significant; however, the coefficient was close to zero. Travel time was related to the type of service and reflected patient preference. This was more prominent for expensive non-NHI-covered services than for NHI-covered services. The findings suggest patients' subjective preferences for dental clinic selection are expressed as rational deliberation considering each individual's situation.

Neuroprotective and Anti-Inflammatory Effects of Pinus densiflora Bark Extract in Gerbil Hippocampus Following Transient Forebrain Ischemia.

Korean red pine (Pinus densiflora) belongs to the Genus Pinus, and its bark contains a great amount of naturally occurring phenolic compounds. Until now, few studies have been conducted to assess the neuroprotective effects of Pinus densiflora bark extract against brain ischemic injury. The aim of this study was to investigate the neuroprotective effects of pre-treatment with the extract in the hippocampus following 5-min transient forebrain ischemia in gerbils. Furthermore, this study examined the anti-inflammatory effect as a neuroprotective mechanism of the extract. Pinus densiflora bark was extracted by pure water (100 °C), and this extract was quantitatively analyzed and contained abundant polyphenols, flavonoids, and proanthocyanidins. The extract (25, 50, and 100 mg/kg) was orally administered once a day for seven days before the ischemia. In the gerbil hippocampus, death of the pyramidal neurons was found in the subfield cornu ammonis 1 (CA1) five days after the ischemia. This death was significantly attenuated by pre-treatment with 100 mg/kg, not 25 or 50 mg/kg, of the extract. The treatment with 100 mg/kg of the extract markedly inhibited the activation of microglia (microgliosis) and significantly decreased the expression of pro-inflammatory cytokines (interleukin 1ß and tumor necrosis factor α). In addition, the treatment significantly increased anti-inflammatory cytokines (interleukin 4 and interleukin 13). Taken together, this study clearly indicates that pre-treatment with 100 mg/kg of Pinus densiflora bark extract in gerbils can exert neuroprotection against brain ischemic injury by the attenuation of neuroinflammatory responses.

Transient forebrain ischemia under hyperthermic condition accelerates memory impairment and neuronal death in the gerbil hippocampus by increasing NMDAR1 expression.

Altered expression levels of N­methyl­D­aspartate receptor (NMDAR), a ligand­gated ion channel, have a harmful effect on cellular survival. Hyperthermia is a proven risk factor of transient forebrain ischemia (tFI) and can cause extensive and severe brain damage associated with mortality. The objective of the present study was to investigate whether hyperthermic preconditioning affected NMDAR1 immunoreactivity associated with deterioration of neuronal function in the gerbil hippocampal CA1 region following tFI via histological and western blot analyses. Hyperthermic preconditioning was performed for 1 h before tFI, which was developed by ligating common carotid arteries for 5 min. tFI­induced cognitive impairment under hyperthermia was worse compared with that under normothermia. Loss (death) of pyramidal neurons in the CA1 region occurred fast and was more severe under hyperthermia compared with that under normothermia. NMDAR1 immunoreactivity was not observed in the somata of pyramidal neurons of sham gerbils with normothermia. However, its immunoreactivity was strong in the somata and processes at 12 h post­tFI. Thereafter, NMDAR1 immunoreactivity decreased with time after tFI. On the other hand, NMDAR1 immunoreactivity under hyperthermia was significantly increased in the somata and processes at 6 h post­tFI. The change pattern of NMDAR1 immunoreactivity under hyperthermia was different from that under normothermia. Overall, accelerated tFI­induced neuronal death under hyperthermia may be closely associated with altered NMDAR1 expression compared with that under normothermia.

Topical Application of Aronia melanocarpa Extract Rich in Chlorogenic Acid and Rutin Reduces UVB-Induced Skin Damage via Attenuating Collagen Disruption in Mice.

Aronia melanocarpa, a black chokeberry, contains high levels of phenolic acids and polyphenolic flavonoids and displays antioxidative and anti-inflammatory effects. Through high-performance liquid chromatography for extracts from Aronia melanocarpa, we discovered that the extract contained chlorogenic acid and rutin as major ingredients. In this study, we examined the protective effects of the extract against ultraviolet B- (UVB)-induced photodamage in the dorsal skin of institute of cancer research (ICR) mice. Their dorsal skin was exposed to UVB, thereafter; the extract was topically applied once a day for seven days. Photoprotective properties of the extract in the dorsal skin were investigated by clinical skin severity score for skin injury, hematoxylin and eosin staining for histopathology, Masson's trichrome staining for collagens. In addition, we examined change in collagen type I and III, and matrix metalloproteinase (MMP)-1 and MMP-3 by immunohistochemistry. In the UVB-exposed mice treated with the extract, UVB-induced epidermal damage was significantly ameliorated, showing that epidermal thickness was moderated. In these mice, immunoreactivities of collagen type I and III were significantly increased, whereas immunoreactivities of MMP-1 and 3 were significantly decreased compared with those in the UVB-exposed mice. These results indicate that treatment with Aronia melanocarpa extract attenuates UV-induced photodamage by attenuating UVB-induced collagen disruption: these findings might be a result of the chlorogenic acid and rutin contained in the extract. Based on the current results, we suggest that Aronia melanocarpa can be a useful material for developing photoprotective adjuvant.

Effects of Decursin and Angelica gigas Nakai Root Extract on Hair Growth in Mouse Dorsal Skin via Regulating Inflammatory Cytokines.

This current study investigates the facilitative effects and mechanisms of decursin, a major component of Angelica gigas Nakai (AGN), and AGN root extract on hair growth in mice. We perform high-performance liquid chromatography on AGN extract to show it contains 7.3% decursin. Hairs in mouse dorsal skin are shaved distilled in water, 0.15% decursin, and 2% AGN root extract (0.15% decursin in the diluted extract) and topically applied twice a day for 17 days. Hematoxylin and eosin staining are done to examine the morphological changes in the hair follicles. To compare the effects of decursin and AGN extract on inflammatory cytokines in the dorsal skin, Western blot analysis and immunohistochemistry for tumor necrosis factor α (TNF-α) and interleukin (IL)-1ß as pro-inflammatory cytokines, and IL-4 and IL-13 as anti-inflammatory cytokines are conducted. The results show that the application of decursin and AGN extract confer effects on hair growth. Hair growth is significantly facilitated from seven days after the treatments compared to that in the control group, and completely grown hair was found 17 days after the treatments. The protein levels and immunoreactivity of TNF-α and IL-1ß in this case are significantly decreased, whereas the IL-4 and IL-13 levels and immunoreactivity are significantly increased compared to those in the control group. Additionally, high-mobility group box 1, an inflammatory mediator, is elevated by the topical application of decursin and AGN extract. Taken together, the treatment of mouse dorsal skin with AGE root extract containing decursin promotes hair growth by regulating pro- and/or anti-inflammatory cytokines. We, therefore, suggest that AGN root extract as well as decursin can be utilized as materials for developing hair growth-facilitating treatments.

Pycnogenol® Supplementation Attenuates Memory Deficits and Protects Hippocampal CA1 Pyramidal Neurons via Antioxidative Role in a Gerbil Model of Transient Forebrain Ischemia.

Pycnogenol® (an extract of the bark of French maritime pine tree) is used for dietary supplement and known to have excellent antioxidative efficacy. However, there are few reports on neuroprotective effect of Pycnogenol® supplementation and its mechanisms against ischemic injury following transient forebrain ischemia (TFI) in gerbils. Now, we examined neuroprotective effect and its mechanisms of Pycnogenol® in the gerbils with 5-min TFI, which evokes a significant death (loss) of pyramidal cells located in the cornu ammonis (CA1) region of gerbil hippocampus from 4-5 days post-TFI. Gerbils were pretreated with 30, 40, and 50 mg/kg of Pycnogenol® once a day for 7 days before TFI surgery. Treatment with 50 mg/kg, not 30 or 40 mg/kg, of Pycnogenol® potently protected learning and memory, as well as CA1 pyramidal cells, from ischemic injury. Treatment with 50 mg/kg Pycnogenol® significantly enhanced immunoreactivity of antioxidant enzymes (superoxide dismutases and catalase) in the pyramidal cells before and after TFI induction. Furthermore, the treatment significantly reduced the generation of superoxide anion, ribonucleic acid oxidation and lipid peroxidation in the pyramidal cells. Moreover, interestingly, its neuroprotective effect was abolished by administration of sodium azide (a potent inhibitor of SODs and catalase activities). Taken together, current results clearly indicate that Pycnogenol® supplementation can prevent neurons from ischemic stroke through its potent antioxidative role.

One-pot selective production of levulinic acid and formic acid from spent coffee grounds in a catalyst-free biphasic system.

This study introduces the catalyst-free production of levulinic acid (LA) and formic acid (FA) from spent coffee grounds (SCGs) as a starting material in a biphasic system of 1,2-dichloroethane (DCE)-water at temperatures above 160 °C. In addition to the advantage of using the biphasic system attributed to the product equilibrium, DCE served as a source of hydrogen induced by subcritical water (SCW). The effect of temperature, the amount of DIW and DCE, and the pretreatment on SCG (raw or lipid extracted SCG (LE-SCG)) on the overall reaction and humin formation were studied. The maximum conversion of LA and FA was 47 and 29 w/w% of the total convertible monosaccharides in raw SCGs while 43 and 28 w/w% of the conversion were obtained at 180 °C when LE-SCG was used. The solvothermal effects of two media provides a non-catalytic route to utilize undried SCG for the production of LA and FA.

Chemical Composition of a Novel Distillate from Fermented Mixture of Nine Anti-Inflammatory Herbs and Its UVB-Protective Efficacy in Mouse Dorsal Skin via Attenuating Collagen Disruption and Inflammation.

Since ancient times, various herbs have been used in Asia, including Korea, China, and Japan, for wound healing and antiaging of the skin. In this study, we manufactured and chemically analyzed a novel distillate obtained from a fermented mixture of nine anti-inflammatory herbs (Angelica gigas, Lonicera japonica, Dictamnus dasycarpus Turcz., D. opposita Thunb., Ulmus davidiana var. japonica, Hordeum vulgare var. hexastichon Aschers., Xanthium strumarium L., Cnidium officinale, and Houttuynia cordata Thunb.). The fermentation of natural plants possesses beneficial effects in living systems. These activities are attributed to the chemical conversion of the parent plants to functional constituents which show more potent biological activities. In our current study, the distillate has been manufactured after fermenting the nine oriental medical plants with Lactobacillus fermentum, followed by distilling. We analyzed the chemical ingredients involved in the distillate and evaluated the effects of topical application of the distillate on ultraviolet B (UVB)-induced skin damage in Institute of Cancer Research (ICR) mice. Topical application of the distillate significantly ameliorated the macroscopic and microscopic morphology of the dorsal skin against photodamage induced by UVB radiation. Additionally, our current results showed that topical application of the distillate alleviated collagen disruption and reduced levels of proinflammatory cytokines (tumor necrosis factor alpha and interleukin 1 ß expressions) in the dorsal skin against UVB radiation. Taken together, our current findings suggest that the distillate has a potential to be used as a material to develop a photoprotective adjuvant.

Identification of novel compounds, oleanane- and ursane-type triterpene glycosides, from Trevesia palmata: their biocontrol activity against phytopathogenic fungi.

Plants contain a number of bioactive compounds that exhibit antimicrobial activity, which can be recognized as an important source of agrochemicals for plant disease control. As part of our search for new antimicrobial agents from natural sources, we found that a crude methanol extract of Trevesia palmata exhibited a promising antifungal activity against phytopathogenic fungi, such as Magnaporthe oryzae and Botrytis cinerea. Furthermore, based on activity-guided fractionation, we isolated five antifungal compounds from the methanol extract of T. palmata: two new triterpene glycosides (TPGs), TPG1 (hederagenin-3-O-ß-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranoside) and TPG5 (3-O-α-L-rhamnopyranosyl asiatic acid), along with three known TPGs (TPG2 [macranthoside A], TPG3 [α-hederin], and TPG4 [ilekudinoside D]). The chemical structures of the TPGs were determined by spectroscopic analyses and by comparison with literature data. An in vitro antifungal bioassay revealed that except for TPG4 (ilekudinoside D; IC50 >256 µg/ml), the other TPGs exhibited strong antifungal activities against the rice blast pathogen M. oryzae with IC50 values ranging from 2-5 µg/ml. In particular, when the plants were treated with compound TPG1 (500 µg/ml), disease control values against rice blast, tomato grey mold, tomato late blight, and wheat leaf rust were 84, 82, 88, and 70%, respectively, compared to the non-treatment control. Considering the in vitro and in vivo antifungal activities of the TPGs and the T. palmata methanol extracts, our results suggest that T. palmata can be a useful source to develop new natural fungicides.

Wet in situ transesterification of spent coffee grounds with supercritical methanol for the production of biodiesel.

This work introduces biodiesel production from wet spent coffee grounds (SCGs) with supercritical methanol without any pre-drying process. Supercritical methanol and subcritical water effectively produced biodiesel via in situ transesterification by inducing more porous SCG and enhancing the efficiency of lipid extraction and conversion. It was also found that space loading was one of the critical factors for biodiesel production. An optimal biodiesel yield of 10.17 wt% of dry SCG mass (86.33 w/w% of esterifiable lipids in SCG) was obtained at reaction conditions of 270 °C, 90 bars, methanol to wet SCG ratio 5:1, space loading 58.4 ml/g and reaction time 20 min. Direct use of wet SCG waste as feedstock for supercritical biodiesel production eliminates the conventional dying process and the need of catalyst and also reduces environmental problems caused by landfill accumulation.

Solvo-thermal in situ transesterification of wet spent coffee grounds for the production of biodiesel.

This work addresses non-catalytic biodiesel production from spent coffee ground (SCG) by integrating solvo-thermal effect of 1,2-dichloroethane (DCE) with in situ transesterification over 160 °C. The SCG water content has a positive effect on the DCE hydrolysis up to 60 wt% due to the bimolecular substitution mechanism. The hydrolysis gives an acidic environment favorable for cellulose decomposition, SCG particle size reduction and lipid conversion. The optimal fatty acid ethyl ester yield was 11.8 wt% based on the mass of dried SCG with 3.36 ml ethanol and 3.16 ml DCE at 196.8 °C through the response surface methodology. Using the solvo-thermal effect, direct utilization of wet SCG as a biodiesel feedstock provides not only economic feasibility without using drying process and additional acid catalyst but also environmental advantage of recycling the municipal waste.

Regulation of RANKL-Induced Osteoclastogenesis by 635-nm Light-Emitting Diode Irradiation Via HSP27 in Bone Marrow-Derived Macrophages.

OBJECTIVE: This study was designed to investigate the effect of 635-nm irradiation from a light-emitting diode (LED) on osteoclastogenesis in receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-stimulated mouse bone marrow-derived macrophages (BMMs). We determined whether 635-nm irradiation modulated the RANKL-induced osteoclastic signaling pathway in heat shock protein-27 (HSP27)-silenced cells and analyzed the functional cross talk between these factors in osteoclastic differentiation and activation. BACKGROUND: HSP27, a member of the small HSP family, regulates oxidative stress. Clinical reports suggest that low-level laser therapy or LED therapy (LEDT) could be an effective alternative treatment for osteolytic bone disease. METHODS: In control or HSP27-siRNA-treated BMMs, the effects of LED irradiation with 635 nm and 5 mW/cm2 on RANKL-induced osteoclastic differentiation and activity were assessed by measuring tartrate-resistant acid phosphatase (TRAP) and resorption pit formation. Quantitative real-time polymerase chain reaction and western blot assays were carried out to assess the mRNA expression of osteoclastogenesis-related genes and phosphorylation of c-Jun-N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), AKT, and p38, respectively. Intracellular reactive oxygen species (ROS) generation was measured using the 2',7'-dichlorodihydrofluorescein diacetate (H2DCF-DA) detection method. RESULTS: The 635-nm irradiation treatment significantly increased HSP27 expression and decreased intracellular ROS generation, as well as p38 and AKT phosphorylation, leading to reductions in the expression of c-fos, NFATc1, and DC-STAMP and TRAP activation and osteoclastic bone resorption in RANKL-induced BMMs. However, in HSP27-silenced BMMs, no change was observed. CONCLUSIONS: Thus, 635-nm irradiation modulates RANKL-induced osteoclastogenesis via HSP27 in BMMs. Thus, HSP27 may play a role in regulating the osteoclastic response to LEDT.

In-situ transesterification of wet spent coffee grounds for sustainable biodiesel production.

This work addresses in-situ transesterification of wet spent coffee grounds (SCGs) for the production of biodiesel. For in-situ transesterification process, the methanol, organic solvent and acid catalyst were mixed with wet SCG in one pot and the mixture was heated for simultaneous lipid extraction and transesterification. Maximum yield of fatty acid methyl esters (FAME) was 16.75wt.% based on the weight of dry SCG at 95°C. Comprehensive experiments were conducted with varying temperatures and various amounts of moisture, methanol, co-solvent and acid catalyst. Moderate polar and alcohol-miscible organic solvent is suitable for the high FAME yield. Unsaturated FAMEs are subject to oxidative cleavage by nitric acid and shorter chain (C6 and C10) FAMEs were mainly produced while sulfuric acid yielded long chain unsaturated FAMEs (C16 and C18). Utilization of wet SCGs as a biodiesel feedstock gives economic and environmental benefits by recycling the municipal waste.

Eruca sativa and its flavonoid components, quercetin and isorhamnetin, improve skin barrier function by activation of peroxisome proliferator-activated receptor (PPAR)-α and suppression of inflammatory cytokines.

Atopic dermatitis, which is related to dermatologic disorders and is associated with skin barrier dysfunction, represents an epidemic problem demanding effective therapeutic strategies. In the present study, we showed that the treatment with Eruca sativa extract resulted in a significant increase in the transactivation activity of peroxisome proliferator-activated receptor (PPAR) response element such as PPAR-α and suppression in the expression of inflammatory cytokine and antimicrobial peptides. In addition, E. sativa extract promotes the expression of filaggrin related to skin barrier protection. Quercetin and isorhamnetin, flavonoids' constituents of E. sativa, also promoted PPAR-α activity. These results indicate that E. sativa extract may be an appropriate material for improving skin barrier function as a skin therapeutic agent for atopic dermatitis.

Gintonin, a ginseng-derived lysophosphatidic acid receptor ligand, potentiates ATP-gated P2X1 receptor channel currents.

Ginseng, the root of Panax ginseng C.A. Meyer, is used as a general tonic. Recently, we isolated a novel ginsengderived lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity in cells endogenously expressing LPA receptors, e.g., Xenopus oocytes. P2X receptors are ligandgated ion channels activated by extracellular ATP, and 7 receptor subtypes (P2X1-P2X7) have been identified. Most of the P2X1 receptors are expressed in the smooth muscles of genitourinary organs involved in reproduction. A main characteristic of the P2X1 receptor is rapid desensitization after repeated ATP treatment of cells or tissues expressing P2X1 receptors. In the present study, we examined the effect of gintonin on P2X1 receptor channel activity. P2X1 receptors were heterologously expressed in Xenopus oocytes. ATP treatment of oocytes expressing P2X1 receptors induced large inward currents (I ATP ), but repetitive ATP treatments induced a rapid desensitization of I ATP . Gintonin treatment after P2X1 receptor desensitization potentiated I ATP in a concentration-dependent manner. We further examined the signaling transduction pathways involved in gintonin-mediated potentiation of I ATP . Gintoninmediated I ATP potentiation was blocked by Ki16425, an LPA1/3 receptor antagonist, a PKC inhibitor, a PLC inhibitor, and a PI4-Kinase inhibitor but not by a calcium chelator. In addition, mutations of the phosphoinositide binding site of the P2X1 receptor greatly attenuated the gintonin-mediated I ATP potentiation. These results indicate that G protein-coupled LPA receptor activation by gintonin is coupled to the potentiation of the desensitized P2X1 receptor through a phosphoinositide-dependent pathway.

Combined treatment of betulinic acid, a PTP1B inhibitor, with Orthosiphon stamineus extract decreases body weight in high-fat-fed mice.

Leptin resistance is a common feature of obesity and is accompanied by hyperleptinemia. Although leptin sensitizers improve leptin resistance, they also decrease plasma leptin levels that attenuate the leptin-associated antiobesity effect. We hypothesized that the combinational treatment of leptin sensitizer and endogenous leptin expression stimulant would synergistically induce an antiobesity effect in high-fat-fed obese animals. Betulinic acid (BA) isolated from Saussurea lappa suppressed the hypothalamic protein tyrosine phosphatase 1B in mice and enhanced the antiobesity effect of leptin in obese rats. Ethanol extract of Orthosiphon stamineus (OS) induced leptin expressions in both 3T3-L1 adipocytes and mice in a dose-dependent manner. To evaluate our hypothesis, we treated obese mice induced by 6 weeks of high-fat-diet feeding with BA and OS for 2 weeks. Although BA or OS alone did not decrease body weight in obese mice, the combinational treatment of BA and OS decreased body weight significantly compared to either BA- or OS-treated obese mice. These results suggest that combinational treatment of BA and OS would be effective for the treatment of obesity.