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1.
Yakugaku Zasshi ; 143(12): 1039-1046, 2023.
Article Ja | MEDLINE | ID: mdl-38044109

Selenium is an essential trace element and its deficiency causes myositis, myocardial damage, and other symptoms. Patients receiving long-term intravenous nutrition or tube-feeding in particular are deficient in essential trace elements, including selenium, and require regular supplementation. In Japan, injectable selenium-containing products are listed on the National Health Insurance drug price list, and oral solutions are prepared and used in hospitals. However, these formulations have problems related to preservation and require complicated administration procedures. In this study, we developed a new fast-disintegrating tablet formulation of selenium, using SmartEx® (D-mannitol·low substituted hydroxypropylcellulose (L-HPC)·fully hydrolyzed polyvinyl alcohol (PVA) mixture) as a coprocessing additive, that can be administered orally or by feeding tube. The tablet formulation had excellent disintegrable capability, sufficient hardness, and did not cause tube blockage when administered in the simple suspension method. In addition, the tablet formulation showed no changes in properties in an accelerated test without packaging for 42 d, indicating that it could be stored for a long period. Fast-disintegrating tablets prepared with SmartEx® are expected to improve the adherence and quality of life of patients who require selenium supplementation.


Selenium , Humans , Quality of Life , Mannitol , Tablets , Drug Packaging , Administration, Oral , Solubility , Drug Compounding
2.
Biochem Biophys Rep ; 35: 101530, 2023 Sep.
Article En | MEDLINE | ID: mdl-37637942

Aberrant melanin overproduction can significantly impact an individual's appearance and cause mental and psychological distress. Current inhibitors of melanin production exert harmful side effects due to inadequate selectivity; thus a need to develop more selective melanin synthesis inhibitors is necessary. Extracellular vesicles are important agents of intercellular signalling in prokaryotes and eukaryotes. Recently, plant-derived nanoparticles, similar to mammalian exosomes, have attracted attention for their use in health research. In this study, to investigate the potential of plant-derived exosome-like nanoparticles (ELNs) as inhibitors of melanin production, we used hot water to extract ELNs from the rhizome of Atractylodes lancea (A-ELNs). The size of A-ENLs ranged from 34 to 401 nm and carried three microRNA: ath-miR166f, ath-miR162a-5p, and ath-miR162b-5p. These A-ENLs were applied to B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH). After A-ELNs were taken up by B16-F10 cells, their melanin levels were significantly reduced. Furthermore, A-ELNs significantly reduced tyrosinase activity in B16-F10 cells and mRNA expression of microphthalmia-associated transcription factor (Mitf), tyrosinase, tyrosinase-related protein 1, and DOPA chrome tautomerase. These results suggest that A-ELN suppresses melanogenic enzymes expression by downregulating Mitf, thereby inhibiting melanin synthesis. Hence, A-ELN can be developed into a novel topical drug after additional studies and optimization.

3.
J Pharm Pharmacol ; 75(10): 1322-1331, 2023 Oct 05.
Article En | MEDLINE | ID: mdl-37390476

OBJECTIVE: Exosome-like nanoparticles (ELNs), which are plant-derived extracellular membrane vesicles, can regulate mammalian gene expression. ELNs can cross the blood-brain barrier, making them potential therapeutic agents or drug-delivery carriers for neuroinflammation-related diseases. Here, we investigated the anti-neuroinflammatory potential of ELNs extracted from Allium tuberosum (A-ELNs). METHODS: A-ELNs were extracted, and their miRNA profile was characterized. A-ELNs were also applied to BV-2 microglial and MG-6 cells derived from C57/BL6 mice stimulated with lipopolysaccharide (LPS), followed by an examination of levels of inflammatory-related factors. To test their drug-carrying potential, A-ELNs were mixed with dexamethasone, an anti-inflammatory drug, to prepare dexamethasone-incorporated A-ELNs (Dex-A-ELNs). KEY FINDINGS: A-ELNs showed a particle size of 145 ± 2 nm and characteristic miRNAs. A-ELNs significantly decreased the LPS-induced nitric oxide (NO) and inflammatory cytokines levels in BV-2 and MG-6 cells. The mRNA expression of heme oxygenase-1 was significantly increased, and that of inducible NO synthase and inflammatory cytokines was significantly decreased by A-ELNs in BV-2 cells. Dex-A-ELNs inhibited NO production in BV-2 cells more potently than either A-ELNs or dexamethasone alone. CONCLUSION: A-ELNs can alleviate microglial inflammation. Their effects can be potentiated by incorporating anti-inflammatory drugs, such as dexamethasone, making them potential therapeutic agents or drug-delivery carriers for neuroinflammation.


Chive , Exosomes , Nanoparticles , Mice , Animals , Microglia , Chive/metabolism , Neuroinflammatory Diseases , Exosomes/metabolism , Lipopolysaccharides/pharmacology , Inflammation/drug therapy , Inflammation/prevention & control , Inflammation/metabolism , Anti-Inflammatory Agents/therapeutic use , Cytokines/metabolism , Dexamethasone/pharmacology , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide/metabolism , NF-kappa B/metabolism , Mammals/metabolism
4.
J Nat Med ; 77(3): 561-571, 2023 Jun.
Article En | MEDLINE | ID: mdl-37115471

Nerve inflammation is linked to the development of various neurological disorders. This study aimed to examine whether Glycyrrhizae Radix effectively influences the duration of the pentobarbital-induced loss of righting reflex, which may increase in a mouse model of lipopolysaccharide (LPS)-induced nerve inflammation and diazepam-induced γ-aminobutyric acid receptor hypersensitivity. Furthermore, we examined the anti-inflammatory effects of Glycyrrhizae Radix extract on LPS-stimulated BV2 microglial cells, in vitro. Treatment with Glycyrrhizae Radix significantly decreased the duration of pentobarbital-induced loss of righting reflex in the mouse model. Furthermore, treatment with Glycyrrhizae Radix significantly attenuated the LPS-induced increases in interleukin-1ß, interleukin-6, and tumor necrosis factor-alpha at the mRNA level, and it significantly reduced the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus 24 h after LPS treatment. Treatment with Glycyrrhizae Radix also suppressed the release of nitric oxide, interleukin-1ß, interleukin-6, and tumor necrosis factor protein in culture supernatants of LPS-stimulated BV2 cells. In addition, glycyrrhizic acid and liquiritin, active ingredients of Glycyrrhizae Radix extract, reduced the duration of pentobarbital-induced loss of righting reflex. These findings suggest that Glycyrrhizae Radix, as well as its active ingredients, glycyrrhizic acid and liquiritin, may be effective therapeutic agents for the treatment of nerve inflammation-induced neurological disorders.


Drugs, Chinese Herbal , Glycyrrhiza , Mice , Animals , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Glycyrrhizic Acid/pharmacology , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Diazepam/therapeutic use , Reflex, Righting , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Hippocampus/metabolism , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Drugs, Chinese Herbal/pharmacology
5.
Medicina (Kaunas) ; 59(1)2023 Jan 13.
Article En | MEDLINE | ID: mdl-36676789

Background and Objectives: Hyponatremia is among the most prevalent electrolyte abnormalities observed in patients with cancer during chemotherapy. Therefore, managing hyponatremia is crucial since it causes a severe electrolyte imbalance that can lead to significant mortality, and this study aimed to investigate the relationship between hyponatremia, anticancer drugs, and cancer types. Materials and Methods: Reported odds ratios were calculated and evaluated based on adverse event reports submitted to the Japanese Adverse Drug Event Report (JADER) database. Results: Overall, 2943 patients had hyponatremia. Notably, cisplatin, pemetrexed, and etoposide had marked hyponatremia signals. In addition, significant hyponatremia signals were detected for oesophageal, lung, and renal cancers. Conclusions: Hyponatremia has been reported in women and patients with lung cancer receiving cisplatin, with a growing trend in the number of elderly patients receiving cisplatin. Furthermore, since the onset of hyponatremia during cisplatin administration is frequently reported within 10 days, patient information should be thoroughly examined before and monitored throughout the administration, which can contribute to the early detection and prevention of hyponatremia.


Antineoplastic Agents , Hyponatremia , Kidney Neoplasms , Lung Neoplasms , Aged , Female , Humans , Antineoplastic Agents/adverse effects , Cisplatin/adverse effects , Electrolytes/adverse effects , Hyponatremia/chemically induced , Hyponatremia/epidemiology , Lung Neoplasms/drug therapy , Risk Factors
6.
Biol Pharm Bull ; 45(12): 1805-1811, 2022.
Article En | MEDLINE | ID: mdl-36450533

Bevacizumab is an inhibitor of vascular endothelial growth factor (VEGF) that prevents tumor growth. While bevacizumab is therapeutically effective, it induces several adverse events. Among these, central nervous system (CNS) ischemia can lead to death or permanent disability. In this study, we reviewed the Japanese Adverse Drug Event Report database to analyze the occurrence of CNS ischemia after bevacizumab administration. Significant associations between the occurrence of CNS ischemia and bevacizumab use were detected (adjusted reporting odds ratios (ROR): 2.68, 95% confidence interval (CI): 2.00-3.59, p < 0.001). Furthermore, an association between diagnosis of glioma and bevacizumab use was also detected (p < 0.001). These events occurred early after the start of treatment and then gradually decreased; however, more than half of CNS ischemia events were reported beyond 30 d after the first administration. In addition, a logistic regression suggested that CNS ischemia caused by bevacizumab was associated with glioma, underlying hypertension and aging. A poor prognosis was reported for several cases occurring in elderly patients (over 60 years of age). Although bevacizumab is a useful pharmacological treatment for cancer, caution should be taken to avoid severe adverse events. Accordingly, the patient's general and medical condition should be carefully examined before initiating treatment, and blood pressure should be continuously assessed throughout treatment with bevacizumab to prevent CNS ischemia.


Drug-Related Side Effects and Adverse Reactions , Glioma , Aged , Humans , Middle Aged , Pharmaceutical Preparations , Bevacizumab/adverse effects , Japan/epidemiology , Vascular Endothelial Growth Factor A , Central Nervous System , Ischemia
7.
Medicina (Kaunas) ; 58(10)2022 Oct 20.
Article En | MEDLINE | ID: mdl-36295654

Background and Objectives: The aim of this study is to investigate the characteristics of gastrointestinal bleeding events associated with BCR-ABL tyrosine kinase inhibitor (TKI) treatment, using the reporting odds ratio (ROR) of the adverse event reports submitted to the Japanese Adverse Drug Event Report database between 2004 and 2020, and to examine the number of reported TKI-related gastrointestinal bleeding cases according to sex and age, as well as the actual number of TKI prescriptions issued in Japan. Materials and Methods: The RORs and 95% confidence intervals (CIs) of gastrointestinal bleeding events related to TKIs were calculated using the data of the 595,121 included cases. Results: Significant gastrointestinal bleeding events were detected for dasatinib (crude ROR: 4.47, 95% CI: 3.77-5.28) and imatinib (crude ROR: 1.22, 95% CI: 1.01-1.46). In multiple logistic regression analyses, significant gastrointestinal bleeding events were detected for dasatinib (adjusted ROR: 8.02, 95% CI: 5.75-10.2), imatinib (adjusted ROR: 1.81, 95% CI: 1.2-2.72), age (≥60 years, adjusted ROR: 2.22, 95% CI: 2.1-2.36), reporting year (adjusted ROR: 1.04, 95% CI: 1.04-1.05), and male sex (adjusted ROR: 1.47, 95% CI: 1.37-1.57). Interaction analysis revealed that the association of gastrointestinal bleeding with dasatinib was affected by age (≥60 years) and sex (female), with the number and proportion of dasatinib-related gastrointestinal bleeding cases increasing among those aged ≥60 years. Conclusions: Specific TKIs and patient characteristics were associated with gastrointestinal bleeding. Our results aid the prompt identification and treatment of TKI-related gastrointestinal bleeding.


Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Male , Female , Humans , Dasatinib/adverse effects , Imatinib Mesylate/adverse effects , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/chemically induced , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Pyrimidines/pharmacology , Protein Kinase Inhibitors/therapeutic use , Gastrointestinal Hemorrhage/chemically induced , Gastrointestinal Hemorrhage/epidemiology
8.
Biol Pharm Bull ; 45(7): 888-894, 2022.
Article En | MEDLINE | ID: mdl-35786596

In obese patients with type 2 diabetes, reduced insulin sensitivity, increased production of inflammatory cytokines, and increased oxidative stress were observed, which lead to decreased protein synthesis and increased proteolysis in the skeletal muscles. Juzentaihoto (JTT) is herbal medicine and we have previously reported that the administration of JTT hot water extract alleviates skeletal muscle atrophy in a mouse model with streptozotocin-induced type 1 diabetes. In this study, we evaluated the inhibitory effects of JTT on muscle atrophy in a mouse model with obesity and type 2 diabetes. JTT was administered to KKAy mice with type 2 diabetic obesity and its effects on the skeletal muscles were evaluated. After JTT administration in KKAy mice, the wet weight and muscle fibre cross-sectional area of gastrocnemius increased and the time duration of exercise in the rotarod test improved. In addition, the serum levels of tumour necrosis factor-α and interleukin-6 decreased, adiponectin levels increased, and homeostasis model assessment for insulin resistance improved. Furthermore, JTT administration decreased the mRNA levels of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1), increased the mRNA levels of Sirtuin1 in gastrocnemius. Our results suggest that JTT improves insulin resistance, suppresses inflammation, and reduces oxidative stress in KKAy mice, thereby suppressing skeletal muscle atrophy. JTT administration in clinical practice is expected to improve muscle atrophy in patients with obesity and type 2 diabetes.


Diabetes Mellitus, Type 2 , Insulin Resistance , Animals , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drugs, Chinese Herbal , Mice , Muscular Atrophy/drug therapy , Obesity/complications , Obesity/drug therapy , RNA, Messenger
9.
J Nat Med ; 76(3): 634-644, 2022 Jun.
Article En | MEDLINE | ID: mdl-35257304

Neuroinflammation is associated with the development of hypoactive delirium, which results in poor clinical outcomes. Drugs effective against hypoactive sur have not yet been established. Yokukansan has an anti-neuroinflammatory effect, making it potentially effective against hypoactive delirium. This study aimed to examine the effect of Yokukansan on the pentobarbital-induced loss of righting reflex duration extended with lipopolysaccharide (LPS)-induced neuroinflammation and diazepam-induced gamma-aminobutyric acid receptor stimulation in a mouse model. The active ingredients in Yokukansan and its anti-neuroinflammatory effect on the hippocampus were also investigated. Furthermore, we examined the in vitro anti-inflammatory effects of Yokukansan on LPS-stimulated BV2 cells, a murine microglial cell line. Findings revealed that treatment with Yokukansan significantly decreased the duration of pentobarbital-induced loss of righting reflex by attenuating the LPS-induced increase in interleukin-6 and tumor necrosis factor-alpha levels in the hippocampus. Moreover, treatment with Yokukansan significantly decreased the number of ionized calcium-binding adapter molecule-1-positive cells in the hippocampal dentate gyrus after 24 h of LPS administration. In addition, glycyrrhizic acid, an active ingredient in Yokukansan, partially decreased the duration of pentobarbital-induced loss of righting reflex. Treatment with Yokukansan also suppressed the expression of inducible nitric oxide, interleukin-6, and tumor necrosis factor mRNA in LPS-stimulated BV2 cells. Thus, these findings suggest that Yokukansan and glycyrrhizic acid may be effective therapeutic agents for treating neuroinflammation-induced hypoactive delirium.


Delirium , Lipopolysaccharides , Animals , Delirium/metabolism , Diazepam/metabolism , Diazepam/pharmacology , Diazepam/therapeutic use , Drugs, Chinese Herbal , Glycyrrhizic Acid/pharmacology , Hippocampus , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/pharmacology , Mice , NF-kappa B/metabolism , Neuroinflammatory Diseases , Pentobarbital/metabolism , Pentobarbital/pharmacology , Pentobarbital/therapeutic use , Reflex, Righting , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolism
10.
J Nat Med ; 76(2): 379-388, 2022 Mar.
Article En | MEDLINE | ID: mdl-34997408

Sarcopenic obesity is associated with increased visceral fat and decreased muscle mass, resulting in decreased insulin sensitivity, increased production of inflammatory cytokines, and oxidative stress. In this study, we first evaluated the effects of herbal medicines on the transcriptional activity of the Sirtuin 1 (sirt1) promoter in vitro as an indicator of their therapeutic effect. Our data suggested that hot water Saikokeishikankyoto (SKK) extracts increased sirt1 transcriptional activity in vitro, identifying it as a candidate therapeutic for evaluation in the KKAy type 2 diabetic obesity mouse model. These in vivo evaluations revealed that SKK treatment increased the wet weight and muscle fiber content in cross sections of the gastrocnemius muscle (GA) and restored motor function in these animals. In addition, SKK treatment reduced tumor necrosis factor-α (TNFα) expression in the sera and suppressed Atrogin1 and MuRF1 transcription in the GA samples. This treatment also increased sirt1 expression in these tissues. These results suggest that SKK inhibits skeletal muscle atrophy and improves motor function in KKAy mice by suppressing inflammation. In actual clinical practice, SKK is expected to inhibit muscle atrophy and improve motor dysfunction in sarcopenic obesity.


Muscle, Skeletal , Muscular Atrophy , Plant Extracts/pharmacology , Sarcopenia/drug therapy , Animals , Diabetes Mellitus, Experimental/complications , Mice , Muscle Fibers, Skeletal , Muscle, Skeletal/metabolism , Muscle, Skeletal/pathology , Muscular Atrophy/drug therapy , Obesity/complications , Promoter Regions, Genetic , Sirtuin 1/genetics , Sirtuin 1/metabolism
11.
J Med Food ; 19(5): 435-41, 2016 May.
Article En | MEDLINE | ID: mdl-26829513

Bangle (Zingiber purpureum) is a tropical ginger that is used as a spice in Southeast Asia. Phenylbutenoid dimers isolated from Bangle have exhibited neurotrophic effects in primary cultured rat cortical neurons and PC12 cells. Furthermore, chronic treatment with phenylbutenoid dimers enhances hippocampal neurogenesis in olfactory bulbectomized mice. In this study, we investigated the effects of Bangle extract on behavior and hippocampal neurogenesis in vivo. SAMP8 mice, which are an established model for accelerated aging, with age-related learning and memory impairments, were given a Bangle-containing diet for 1 month, and subsequent behavioral tests and immunohistochemistry for Ki67, a proliferating cell marker, were performed. We found that the Bangle-containing diet improved spatial learning and memory deficits in the Morris water maze and significantly increased the numbers of Ki67-positive cells in the dentate gyrus of the SAMP8 mice. In addition, the Bangle extract exhibited a neurotrophin-like activity as indicated by the induction of neurite sprouting in PC12 cells. Our results suggest that Bangle is beneficial for the prevention of age-related progression of cognitive impairment.


Aging/drug effects , Memory Disorders/drug therapy , Neurogenesis/drug effects , Neurons/drug effects , Spatial Learning/drug effects , Zingiberaceae/chemistry , Aging/psychology , Animals , Dentate Gyrus/drug effects , Dentate Gyrus/physiopathology , Disease Models, Animal , Humans , Male , Memory/drug effects , Memory Disorders/physiopathology , Memory Disorders/psychology , Mice , Mice, Transgenic , Neurons/cytology , PC12 Cells , Rats
12.
Food Chem ; 138(4): 2210-8, 2013 Jun 15.
Article En | MEDLINE | ID: mdl-23497878

This study investigated the influence of Goishi-tea on visceral fat weight in induced obese mice. Mice were divided into two main groups, normal and obesity. In obesity group, mice were fed with high-fat diet. Goishi-tea including its fractions (ethyl-acetate layer and water layer) was administrated in normal and obesity three sub-groups. Results showed no influence of Goishi-tea in normal group. However, visceral fat weight, size of adipose cell and cholesterol level were significantly decreased in obesity group fed Goishi-tea compared to control group. Moreover, adiponectin levels tended to increase and adipocytokines has significant values lower in obesity group fed Goishi-tea compared to control group. Interestingly, Goishi tea involved in the high-fat diet induced-obese mice can inhibit fat accumulation and maintain adiponectins without increasing tumor necrosis factor-alpha and interleukin-6. It would be beneficial for the prevention of metabolic syndrome and obesity-related disorder.


Adipokines/metabolism , Adipose Tissue/drug effects , Adipose Tissue/metabolism , Camellia sinensis/chemistry , Plant Extracts/administration & dosage , Adipose Tissue/physiopathology , Animals , Body Weight/drug effects , Female , Humans , Intra-Abdominal Fat/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Obese , Obesity/metabolism , Phytotherapy , Tea/chemistry
13.
Biol Pharm Bull ; 35(4): 639-42, 2012.
Article En | MEDLINE | ID: mdl-22466574

It has been reported that dogs are capable of identifying cancer in humans by detecting a specific odor: bladder cancer by detecting urine odor and other cancers by detecting exhaled breath odor. However, no odor recognized by dogs that indicates cancer has been identified. In this study, we examined whether bladder cancer could be detected by gas chromatography-mass spectrometry (GC-MS)-based metabolomics analysis of urine odor. Nine patients with bladder cancer and 7 healthy controls were recruited as participants. Patients collected urine 3 d before and for 3-7 d after surgery. The concentrated urine odor was analyzed by GC-MS and principal component analysis (PCA). Results indicated 12 metabolites of urine odor. Score plots of 7 of the preoperative bladder cancer patients were clearly different from those of controls on the PCA map. The distribution of controls was in the negative domain of principal component (PC) 1, whereas the distribution of preoperative patients was in the positive domain of PC1. Bladder cancer was diagnosed in 5 of the 9 patients on the basis of urinary cytology. The findings indicate the potential to screen bladder cancer by analyzing urine odor. Moreover, diagnosis of bladder cancer on the basis of urine odor might have higher sensitivity than screening by urinary cytology.


Biomarkers, Tumor/urine , Early Detection of Cancer/methods , Odorants/analysis , Urinary Bladder Neoplasms/urine , Case-Control Studies , Gas Chromatography-Mass Spectrometry , Humans , Metabolomics , Neoplasm Staging , Urinary Bladder Neoplasms/diagnosis , Urinary Bladder Neoplasms/pathology
14.
J Nat Med ; 65(1): 9-17, 2011 Jan.
Article En | MEDLINE | ID: mdl-20640522

We have previously reported that Eriobotrya japonica seed extract (ESE) is effective for the treatment of various gastric mucosal injuries. For the pharmaceutical preparation of ESE, we are evaluating deep sea water (DSW), which contains trace elements and has a homeostasis-enhancing effect, as the solvent. In this study, we prepared DSW containing ESE (ESE + DSW) and evaluated its usefulness for the prevention of gastric mucosal injuries using non-steroidal anti-inflammatory drug-induced acute gastric mucosal injury models in male Wistar/ST rats. Gastric mucosal injury models were prepared by administering indomethacin at 30 mg/kg orally to the rats after a 24-h fast. ESE was prepared by a routine procedure and administered at the same concentration as in the administration to humans. The rats were divided into the following 6 groups: ESE, DSW, ESE + DSW, tap water (control), rebamipide (positive control), or untreated. Gastric mucosal injuries were evaluated by measuring the injury area, lipid peroxide (LPO) level, antioxidative enzyme level, and volume of mucus. The injury area and LPO levels in plasma and gastric tissue were significantly reduced in the ESE and ESE + DSW groups compared with the control and DSW group. The plasma and gastric tissue antioxidative enzyme levels were significantly higher in the ESE and ESE + DSW groups than in the control group. These results suggest that DSW, when combined with ESE, inhibits antioxidative enzymes, and enhances the gastric mucosal protecting effect of ESE.


Eriobotrya/chemistry , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Indomethacin/toxicity , Plant Extracts/pharmacology , Seawater , Seeds/chemistry , Animals , Gastric Acid/metabolism , Male , Oxidation-Reduction/drug effects , Plant Extracts/chemistry , Rats , Rats, Wistar
15.
J Nutr Sci Vitaminol (Tokyo) ; 56(2): 145-9, 2010.
Article En | MEDLINE | ID: mdl-20495297

We examined the immunomodulatory effect of Eriobotrya japonica seed extract (ESE) on rat allergic dermatitis elicited by repeated dinitrofluorobenzene (DNFB) application on the ear. Oral administration of ESE significantly inhibited development of allergic dermatitis based on lower ear thickness and serum immunoglobulin E (IgE) levels. Th1 cytokine interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), Th2 cytokine interleukin-4 (IL-4) and interleukin-10 (IL-10) in the lesional skin were determined. Oral administration of ESE significantly decreased IL-4 while significantly increasing IL-10 in lesional skin, and the lower levels of IFN-gamma and IL-2 were reversed by oral administration of ESE. The infiltration of eosinophils in the lesional skin was decreased by oral administration of ESE. These results suggested that ESE exerts anti-allergic actions by improving the balance of Th1/Th2 in allergic dermatitis.


Dermatitis, Allergic Contact/prevention & control , Eriobotrya , Immunosuppressive Agents/pharmacology , Plant Extracts/pharmacology , Seeds , Administration, Oral , Analysis of Variance , Animals , Cytokines/blood , Cytokines/drug effects , Dermatitis, Allergic Contact/blood , Dermatitis, Allergic Contact/complications , Disease Models, Animal , Ear , Edema/etiology , Edema/prevention & control , Enzyme-Linked Immunosorbent Assay/methods , Immunoglobulin E/blood , Immunosuppressive Agents/blood , Male , Plant Extracts/blood , Rats , Rats, Sprague-Dawley
16.
J Pharm Pharmacol ; 62(2): 241-6, 2010 Feb.
Article En | MEDLINE | ID: mdl-20487204

OBJECTIVES: Non-alcoholic steatohepatitis is associated with the deposition of lipid droplets in the liver, and is characterised histologically by the infiltration of inflammatory cells, hepatocellular degeneration and liver fibrosis. Oxidative stress may play an important role in the onset and deterioration of non-alcoholic steatohepatitis. We previously reported that an Eriobotrya japonica seed extract, extracted in 70% ethanol, exhibited antioxidant actions in vitro and in vivo. In this study, we examined the effect of this extract in a rat model of non-alcoholic steatohepatitis. METHODS: The seed extract was given in the drinking water to fats being fed a methionine-choline-deficient diet for 15 weeks. KEY FINDINGS: Increases in alanine aminotransferase and aspartate aminotransferase levels were significantly inhibited in rats fed the seed extract compared with the group on the diet alone. Formation of fatty droplets in the liver was also inhibited. Antioxidant enzyme activity in liver tissue was higher than in the diet-only group and lipid peroxidation was reduced compared with rats that also received the extract. Expression of 8-hydroxy-2'-deoxyguanosine and 4-hydroxy-2-nonenal was lower in the rats given the seed extract than in the diet-only group. In the former, liver tissue levels of transforming growth factor-beta and collagen were also decreased. CONCLUSIONS: Thus, the E. japonica seed extract inhibited fatty liver, inflammation and fibrosis, suggesting its usefulness in the treatment of non-alcoholic steatohepatitis.


Antioxidants/therapeutic use , Eriobotrya/chemistry , Fatty Liver/drug therapy , Liver/drug effects , Oxidative Stress/drug effects , Plant Extracts/therapeutic use , 8-Hydroxy-2'-Deoxyguanosine , Aldehydes/metabolism , Animals , Antioxidants/isolation & purification , Antioxidants/pharmacology , Body Weight/drug effects , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/biosynthesis , Disease Models, Animal , Fatty Liver/etiology , Fatty Liver/metabolism , Fatty Liver/pathology , Liver/metabolism , Liver/pathology , Liver Cirrhosis, Experimental/etiology , Liver Cirrhosis, Experimental/metabolism , Liver Cirrhosis, Experimental/pathology , Liver Cirrhosis, Experimental/prevention & control , Liver Function Tests , Male , Organ Size/drug effects , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Rats , Rats, Wistar , Seeds/chemistry , Transforming Growth Factor beta/biosynthesis
17.
J Pharm Biomed Anal ; 53(1): 98-102, 2010 Sep 21.
Article En | MEDLINE | ID: mdl-20371156

A metabonomics approach, consisting of gas chromatography coupled to mass spectrometry (GC/MS) and a multivariate statistical technique, was developed to estimate the protective effects of Lonicera japonica extract (LJE) on acute liver injury. A high dose of dimethylnitrosamine (DMN) was used to induce an acute stage of hepatic injury in 21 male Wistar rats. The rats were divided into three groups: normal, model and treatment. Pathological changes, particularly fibrosis, were also examined by Azan staining. The results indicate that clear and consistent biochemical changes occur. Nine candidate biomarkers for DMN treatment and LJE intervention under controlled conditions were identified using chemometric analysis. Pathological analysis suggests that LJE has a protective effect to the liver. This work suggests that a metabonomics approach can be used to estimate pharmacodynamic action of naturally occurring drugs in a dynamic and non-invasive way.


Biomarkers, Pharmacological/urine , Chemical and Drug Induced Liver Injury/prevention & control , Drugs, Chinese Herbal/therapeutic use , Lonicera/chemistry , Metabolomics/methods , Animals , Chemical and Drug Induced Liver Injury/pathology , Chemical and Drug Induced Liver Injury/urine , Dimethylnitrosamine/toxicity , Drugs, Chinese Herbal/chemistry , Fibrosis/pathology , Fibrosis/prevention & control , Flowers/chemistry , Gas Chromatography-Mass Spectrometry/methods , Phytotherapy , Rats , Rats, Wistar , Time Factors
18.
J Nat Med ; 64(3): 288-94, 2010 Jul.
Article En | MEDLINE | ID: mdl-20306146

The aim of this study is to investigate effects of Flos lonicera extract (FLE) on acute liver injury model rats which induced by 35 mg/kg dimethylnitrosamine (DMN). Model rats were divided into hepatic injury control group (administrated with water), FLE group (administrated with FLE) and silymarin group (administrated with silymarin which is hepatotherapeutic drug) as positive control. They were examined including ALT, AST, ALP, gamma-GT, ALB and TP levels in serum, and MDA, GPx levels in liver tissue. In addition, pathologic changes, particularly fibrosis, were examined by Azan staining. The results revealed that the ALT, AST, ALP, gamma-GT, MDA GPx and liver fibrosis degree in the LJE group were lower than the silymarin group and control group, ALB and TP were higher than the silymarin group and control group. These results suggested that LJE may help in inhibiting of acute liver injury greater than silymarin.


Dimethylnitrosamine/toxicity , Drugs, Chinese Herbal/therapeutic use , Flowers/chemistry , Liver Diseases/drug therapy , Lonicera/chemistry , Animals , Chromatography, High Pressure Liquid , Chromatography, Liquid , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Lipid Peroxidation/drug effects , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Liver Diseases/etiology , Liver Diseases/metabolism , Male , Mass Spectrometry , Rats , Rats, Wistar
19.
J Pharm Pharmacol ; 61(2): 237-41, 2009 Feb.
Article En | MEDLINE | ID: mdl-19178772

OBJECTIVES: The potent antioxidant activity of Eriobotrya japonica seed extract (ESE) and its usefulness in the prevention and treatment of various disorders has been reported previously. Its antioxidant activity associated with beta-sitosterol and polyphenols contained in the extract was also validated. In this study, anti-allergic activity of Eriobotrya japonica seed extract was investigated. METHODS: The inhibition of histamine release-mediated type 1 allergy by Eriobotrya japonica seed extract was used as an index. KEY FINDINGS: The administration of this extract inhibited histamine release from rat mast cells, suggesting its usefulness in allergic disease treatment. In an experiment using a guinea-pig allergic rhinitis model, this extract reduced the frequency of sneezing and nose-scratching. CONCLUSIONS: These results suggest that Eriobotrya japonica seed extract may contribute to the relief of allergic disease-related symptoms.


Eriobotrya/chemistry , Mast Cells/drug effects , Plant Extracts/pharmacology , Animals , Capillary Permeability/drug effects , Chromatography, High Pressure Liquid/methods , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Guinea Pigs , Histamine Release/drug effects , L-Lactate Dehydrogenase/analysis , L-Lactate Dehydrogenase/metabolism , Male , Mast Cells/cytology , Mast Cells/immunology , Peritoneal Cavity/cytology , Plant Extracts/chemistry , Rats , Rhinitis, Allergic, Perennial/prevention & control , Rhinitis, Allergic, Seasonal/prevention & control , Seeds/chemistry , Skin/blood supply , Skin/drug effects , Sneezing/drug effects
20.
Yakugaku Zasshi ; 128(7): 1037-44, 2008 Jul.
Article Ja | MEDLINE | ID: mdl-18591872

Since lipid oxidation is involved in the deterioration of hypercholesterolemia-related atherosclerosis, ingestion of drinks and foods with antioxidant actions is useful for preventing lipid oxidation. Goishi-tea is a post-fermented-tea manufactured by a unique method in Japan, and may be useful for preventing various disorders. However, there is no scientific evidence. In this study, we compared the radical scavenging activity of goishi-tea with that of other teas, and administered this tea to a rabbit model of hypercholesteremia to evaluate its usefulness in the inhibition of hypercholesteremia and atherosclerosis. The radical scavenging activity of goishi-tea was similar to that of green-tea, and was higher than that of other types of fermented-teas. On the other hand, some difference of components was found between goishi-tea and green-tea. In cholesterol-fed rabbits, low-density lipoprotein (LDL)-cholesterol level in the goishi-tea-group was lower than that in the green-tea-group. Plasma lipidperoxide value was also lower in the goishi-tea-group than in the green-tea and tap-water-groups. On aortic endothelial staining, fat area in the goishi-tea-group was lower than that in the tap-water-group. Furthermore, fat accumulation in the aortic intima in the goishi-tea-group was very low. Goishi-tea has higher antioxidant activities than the other fermented-teas tested, which were generally low, and decreased serum lipid levels, suggesting that goishitea is a very peculiar fermented-tea with usefulness in the prevention of hypercholesterolemia and atherosclerosis.


Atherosclerosis/prevention & control , Hypercholesterolemia/prevention & control , Phytotherapy , Plant Extracts/therapeutic use , Tea , Adipose Tissue/metabolism , Animals , Atherosclerosis/metabolism , Cholesterol, LDL/blood , Disease Models, Animal , Fermentation , Hypercholesterolemia/metabolism , Lipid Peroxides/blood , Male , Rabbits , Tunica Intima/metabolism
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