diospyros and Disease-Models--Animal

Diabetes mellitus is a global disorder, and a major issue for health care systems. The current review outlooks the use of fruit flavonoids as natural remedy in the prevention of diabetes mellitus. The onset of diabetes mainly depends upon genetics and lifestyle issues. Currently used therapeutic options for the control of diabetes, like dietary amendments, oral hypoglycemic drugs, and insulin, have their own limitations. Fruit flavonoids possess various antidiabetic, anti-inflammatory, and antioxidant potentials and act on various cellular signaling pathways in pancreas, white adipose tissue, skeletal muscle, and liver function, which in result induces antidiabetic effects. Recently, antidiabetic effect of fruit flavonoids has been studied using various animal models and clinical trials. Research studies revealed a statistically significant potential of fruit flavonoids in managing the altered glucose and oxidative metabolisms in diabetes. Unlike synthetic antidiabetic agents, fruit flavonoids manage diabetes without compromising cellular homeostasis thereby posing no side effects. Further studies are required in purification and characterization of different fruit flavonoids with respect to their beneficial effect for diabetic patients.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Biological Availability; Carica; Citrus; Diabetes Complications; Diabetes Mellitus, Type 2; Diospyros; Disease Models, Animal; Flavonoids; Fruit; Humans; Hypoglycemic Agents; Insulin; Pancreas; Phytotherapy; Plant Extracts; Psidium

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread across the world. Inactivating the virus in saliva and the oral cavity represents a reasonable approach to prevent human-to-human transmission because the virus is easily transmitted through oral routes by dispersed saliva. Persimmon-derived tannin is a condensed type of tannin that has strong antioxidant and antimicrobial activity. In this study, we investigated the antiviral effects of persimmon-derived tannin against SARS-CoV-2 in both in vitro and in vivo models. We found that persimmon-derived tannin suppressed SARS-CoV-2 titers measured by plaque assay in vitro in a dose- and time-dependent manner. We then created a Syrian hamster model by inoculating SARS-CoV-2 into hamsters' mouths. Oral administration of persimmon-derived tannin dissolved in carboxymethyl cellulose before virus inoculation dramatically reduced the severity of pneumonia with lower virus titers compared with a control group inoculated with carboxymethyl cellulose alone. In addition, pre-administration of tannin to uninfected hamsters reduced hamster-to-hamster transmission of SARS-CoV-2 from a cohoused, infected donor cage mate. These data suggest that oral administration of persimmon-derived tannin may help reduce the severity of SARS-CoV-2 infection and transmission of the virus.

Topics: Administration, Oral; Animals; Antiviral Agents; COVID-19; COVID-19 Drug Treatment; Cricetinae; Diospyros; Disease Models, Animal; Interleukin-1beta; Interleukin-6; Lung; Male; Mesocricetus; SARS-CoV-2; Severity of Illness Index; Tannins; Viral Load

In this work, a bioactive persimmon extract was produced from discarded fruits. A central composite design was used to evaluate the effect of different extraction parameters and ripeness stages of persimmon fruits on the total phenolic content and antioxidant activity of the resulting extracts. Significantly greater phenolic contents were obtained from immature persimmon (IP) fruits. The optimum IP extract with the conditions set by the experimental design was industrially up-scaled and its composition and functional properties were evaluated and compared with those obtained under lab-scale conditions. Both extracts contained significant protein (>20%) and phenolic contents (∼11-27 mg GA/g dry extract) and displayed significant antiviral activity against murine norovirus and hepatitis A virus. Moreover, the extract showed no toxicity and significantly reduced the fat content and the cellular ageing of Caenorhabditis elegans (C. elegans) without affecting the worm development. These effects were mediated by down-regulation of fat-7, suggesting an anti-lipogenic activity of this extract.

Topics: Animals; Antioxidants; Antiviral Agents; Caenorhabditis elegans; Diospyros; Disease Models, Animal; Food Handling; Mice; Norovirus; Phenols; Plant Extracts; Proteins; Waste Products

Analgesic, anti-inflammatory, and sedative drugs are available with potential side effects such as peptic ulcer and addiction among other things. In this regard, research is underway to find safe, effective, and economical drugs free of these side effects. In this study, an isolated natural product from Diospyros lotus, was tested for the aforementioned bioactivities.. To evaluate analgesic, anti-inflammatory, and sedative potential of D. lotus extracts in animal paradigms using BALB/c mice as experimental model.. Analgesic, anti-inflammatory and sedative activities of dinaphthodiospyrol G (1) isolated from the chloroform fraction of D. lotus were evaluated using different experimental procedures. Anti-inflammatory effect was evaluated using the carrageenan and histamine-induced paw edema, whereas the antinociceptive effect was quantified by means of the hot plate analgesiometer. On the other hand, the sedative effect was determined using animal assay for screening the locomotors effects of compound 1. Compound 1 was also subjected to molecular modeling studies against cyclooxygenase enzymes.. Results from this investigation showed that the extract is devoid of anti-inflammatory and antinociceptive potentials but has a significant sedative effect, whereas the tested compound exhibited 55.23 and 78.34% attenuation in paw edema by carrageenan and histamine assays, respectively. A significant (p < 0.001) and dose-dependent antinociceptive and sedative effects were demonstrated by the isolated compound. Molecular docking and dynamics simulation studies of the isolated compound against cyclooxygenase enzyme indicated that compound 1 forms specific interactions with key residues in the active site of the target receptor, which validates the potential use of the isolated compound as cyclooxygenase inhibitor.. Compound 1 exhibited remarkable analgesic, anti-inflammatory, and sedative activities. These findings strongly justify the traditional use of D. lotus in the treatment of inflammation, pain, and insomnia.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Diospyros; Disease Models, Animal; Hypnotics and Sedatives; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Molecular Structure; Pakistan; Plant Extracts; Plant Roots

Synapse dysfunction is an early hallmark of Alzheimer's disease (AD), and was considered to be closely related to memory loss. The molecular mechanisms that trigger synapse loss and dysfunction remain poorly understood. Increasing evidence shows a link between Rho GTPases and synapse plasticity. Rho GTPases play a role in controlling synapse function by regulating actin cytoskeleton and dendritic spines. Observations have suggested that phytochemicals, such as flavonoids, alleviate cognition impairment in AD. However, to date, the link between the protective effect of flavonoids on AD and the activity of Rho GTPases remains uninvestigated. In this study, APP/PS1 mice were used as an AD model, and we found that synapse loss occurred in AD mice brain. Flavonoids extracted from leaves of Diospyros kaki (FLDK) were used to investigate whether its protective effects on synapse were related to Rho GTPases activity in AD mice. The Rho GTPases Activation Kit showed that Ras homologous member A (RhoA)-GTP was significantly higher and Ras-related C3 botulinum toxin substrate 1 (Rac1)-GTP was significantly lower in APP/PS1 mice than in normal mice, and RhoA-GTP activity was significantly inhibited by FLDK. We also found that FLDK improved learning and memory function, and antagonized the downregulation expressions of synapse-related proteins such as synaptophysin and drebrin. These findings suggest that FLDK is a potential therapeutic agent for AD, and modulation of Rho GTPases activity might contribute toward its protective effect.

Topics: Alzheimer Disease; Amyloid beta-Protein Precursor; Animals; Diospyros; Disease Models, Animal; Down-Regulation; Flavonoids; Male; Mice, Transgenic; Plant Extracts; Presenilin-1; rho GTP-Binding Proteins; rhoA GTP-Binding Protein; Spatial Learning; Spatial Memory; Synapses; Up-Regulation

Topics: Animals; Antineoplastic Agents, Immunological; Antineoplastic Agents, Phytogenic; Carcinoma, Hepatocellular; Cell Line, Tumor; Cyclophosphamide; Diospyros; Disease Models, Animal; Drug Screening Assays, Antitumor; Female; Flavonoids; Humans; Killer Cells, Natural; Liver Neoplasms; Macrophages; Male; Mice; Phagocytosis; Plant Extracts; Plant Leaves

Persimmon (

Topics: Animals; Bone Density Conservation Agents; Cell Differentiation; Cells, Cultured; Diospyros; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Humans; Mice, Inbred ICR; Mitogen-Activated Protein Kinases; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteoporosis, Postmenopausal; Ovariectomy; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Polysaccharides; Proto-Oncogene Proteins c-fos; RANK Ligand; Signal Transduction; Time Factors

Retinal ganglion cell (RGC) death is part of many retinal diseases. Here, we report that the ethanol extract of Diospyros kaki (EEDK) exhibits protective properties against retinal degeneration, both in vitro and in vivo. Upon exposure to cytotoxic compounds, RGC-5 cells showed approximately 40% cell viability versus the control, while pre-treatment with EEDK markedly increased cell viability in a concentration-dependent manner. Further studies revealed that cell survival induced by EEDK was associated with decreased levels of apoptotic proteins, such as poly (ADP-ribose) polymerase, p53, and cleaved caspase-3. In addition to apoptotic pathways, we demonstrated that expression levels of antioxidant-associated proteins, such as superoxide dismutase-1, glutathione S-transferase, and glutathione peroxidase-1, were positively modulated by EEDK. In a partial optic nerve crush mouse model, EEDK had similar ameliorating effects on retinal degeneration resulting from mechanical damages. Therefore, our results suggest that EEDK may have therapeutic potential against retinal degenerative disorders, such as glaucoma.

Topics: Animals; Apoptosis; Diospyros; Disease Models, Animal; Male; Mice; Nerve Crush; Optic Nerve Injuries; Oxidative Stress; Plant Extracts; Plant Leaves; Protective Agents; Reactive Oxygen Species; Retinal Degeneration; Retinal Ganglion Cells

Atopic dermatitis (AD) is a common chronic inflammatory skin disease, affecting 10-20% of individuals worldwide. Therefore, the discovery of drugs for treating AD is an attractive subject and important to human health. Diospyros kaki and Diospyros kaki (D. kaki) folium exert beneficial effects on allergic inflammation. However, the effect of D. kaki calyx on AD remains elusive. The present study evaluated the effects of an aqueous extract of D. kaki calyx (AEDKC) on AD-like skin lesions using mouse and keratinocyte models. We used a mouse AD model by the repeated skin exposure of house dust mite extract [Dermatophagoides farinae extract (DFE)] and 2,4-dinitrochlorobenzene (DNCB) to the ears. In addition, to determine the underlying mechanism of its operation, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)-activated keratinocytes (HaCaT) were used. Oral administration of AEDKC decreased AD-like skin lesions, as demonstrated by the reduced ear thickness, serum immunoglobulin E (IgE), DFE-specific IgE, IgG2a, histamine level and inflammatory cell infiltration. AEDKC inhibited the expression of pro-inflammatory cytokines and a chemokine via downregulation of nuclear factor-κB and signal transducer and activator of transcription 1 in HaCaT cells. On examination of the AD-related factors in vivo and in vitro, it was confirmed that AEDKC decreased AD-like skin lesions. Taken together, the results suggest that AEDKC is a potential drug candidate for the treatment of AD.

Topics: Animals; Anti-Inflammatory Agents; Dermatitis, Atopic; Dinitrochlorobenzene; Diospyros; Disease Models, Animal; Female; Immunoglobulin G; Keratinocytes; Mice; Mice, Inbred BALB C; Plant Extracts; Pyroglyphidae; Skin

Nontuberculous mycobacteria (NTM), including Mycobacterium avium complex (MAC), cause opportunistic chronic pulmonary infections. Notably, MAC susceptibility is regulated by various factors, including the host immune system. Persimmon (Ebenaceae Diospyros kaki Thunb.) tannin is a condensed tannin composed of a polymer of catechin groups. It is well known that condensed tannins have high antioxidant activity and bacteriostatic properties. However, it is hypothesized that condensed tannins might need to be digested and/or fermented into smaller molecules in vivo prior to being absorbed into the body to perform beneficial functions. In this study, we evaluated the effects of soluble persimmon-derived tannins on opportunistic MAC disease. Soluble tannins were hydrolyzed and evaluated by the oxygen radical absorbance capacity (ORAC) method. The ORAC value of soluble tannin hydrolysate was approximately five times greater than that of soluble tannin powder. In addition, soluble tannin hydrolysate exhibited high bacteriostatic activity against MAC in vitro. Furthermore, in an in vivo study, MAC infected mice fed a soluble tannin-containing diet showed significantly higher anti-bacterial activity against MAC and less pulmonary granuloma formation compared with those fed a control diet. Tumor necrosis factor α and inducible nitric oxide synthase levels were significantly lower in lungs of the soluble tannin diet group compared with the control diet group. Moreover, proinflammatory cytokines induced by MAC stimulation of bone marrow-derived macrophages were significantly decreased by addition of soluble tannin hydrolysate. These data suggest that soluble tannin from persimmons might attenuate the pathogenesis of pulmonary NTM infection.

Topics: Animals; Anti-Bacterial Agents; Diospyros; Disease Models, Animal; Female; Inflammation; Mice; Mice, Inbred BALB C; Mycobacterium avium-intracellulare Infection; Tannins

The purpose of this study was to evaluate the effect of ethanol extract of Diospyros kaki (EEDK) leaves on corneal neovascularization (CoNV) in rats. One week after the alkali burns in the corneas, the CoNV area coverage in the CoNV-positive control group, 100 mg/kg EEDK group, and 200 mg/kg EEDK group was 43.3% ± 5.5%, 337.7% ± 2.5%, and 27.2% ± 4.3%, respectively. The areas of CoNV in the EEDK-treated groups were significantly different from those of the CoNV group. EEDK significantly attenuated the upregulation of vascular endothelial growth factor, fibroblast growth factor, interleukin-6, and matrix metalloproteinase-2 (MMP-2) protein levels. Orally administrated D. kaki inhibited CoNV development in rats.

Topics: Alkalies; Animals; Burns, Chemical; Corneal Neovascularization; Diospyros; Disease Models, Animal; Humans; Interleukin-6; Male; Matrix Metalloproteinase 2; Plant Extracts; Rats; Vascular Endothelial Growth Factor A

In this study, the beneficial effects of the oral administration of ethanol extract of Diospyros kaki (EEDK) were tested on a mouse dry eye model induced by benzalkonium chloride (BAC).. A solution of 0.2% BAC was administered topically to mouse eyes for 14 days, twice daily, to induce dry eye. Various concentrations of EEDK were administrated daily by oral gavage for 14 days after BAC treatment. Preservative-free eye drops were instilled in the positive-control group. The tear secretion volume (Schirmer's test), tear break-up time (BUT), and fluorescein score were measured on the ocular surface. BAC-induced corneal damage was tested with hematoxylin-eosin staining. Moreover, apoptotic cell death in the corneal epithelial layer was investigated with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining. The protein expression level of interleukin-1alpha (IL-1α), IL-1β, IL-6, tumor necrosis factor- alpha (TNF-α), and monocyte chemotactic protein-1 (MCP-1) was determined with western blot analysis. Furthermore, squamous metaplasia in the corneal epithelial layer was detected with immunofluorescent staining for cytokeratine-10. The cellular proliferation in the cornea was examined with immunohistochemical staining for Ki-67.. EEDK treatment resulted in prolonged BUT, decreased fluorescein score, increased tear volume, and smoother epithelial cells compared with BAC treatment alone in the cornea. Moreover, EEDK treatment inhibited the inflammatory response and corneal epithelial cell death in a BAC-induced murine dry eye model, and changes in squamous cells were inhibited. Proliferative activity in the corneal epithelium cells was improved with EEDK.. EEDK could be a potential therapeutic agent in the clinical treatment of dry eye.

Topics: Administration, Oral; Animals; Apoptosis; Benzalkonium Compounds; Blotting, Western; Cornea; Cytokines; Diospyros; Disease Models, Animal; Dry Eye Syndromes; Fluorescent Antibody Technique, Indirect; In Situ Nick-End Labeling; Male; Mice; Mice, Inbred BALB C; Ophthalmic Solutions; Plant Extracts; Plant Leaves; Tears

The total flavonoids from Persimmon leaves (PLF), extracted from the leaves of Diospyros kaki L. Dispryosl and Ebenaceae, is reported to possess many beneficial health effects. However, the oral bioavailability of PLF is relatively low due to its poor solubility. In the present study, the phospholipid complexes of total flavonoids from Persimmon leaves (PLF-PC) was prepared to enhance the oral bioavailability of PLF and to evaluate its antiatherosclerotic properties in atherosclerosis rats in comparison to PLF. A HPLC-MS method was developed and validated for the determination of quercetin and kaempferol in rats plasma to assess the oral bioavailability of PLF-PC. The effect of PLF (50mg/kg/d) and PLF-PC (equivalent to PLF 50mg/kg/d) on atherosclerosis rats induced by excessive administration of vitamin D (600,000IU/kg) and cholesterol (0.5g/kg/d) was assessed after orally administered for 4 weeks. The relative bioavailabilities of quercetin and kaempferol in PLF-PC relative to PLF were 242% and 337%, respectively. The levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) in serum were measured by an automatic biochemistry analyzer. The morphological changes of aorta were observed with optical microscopy. According to the levels of biochemical parameters in serum and the morphological changes of aorta, PLF-PC showed better therapeutic efficacy compared to PLF. Thus, PLF-PC holds a promising potential for increasing the oral bioavailability of PLF. Moreover, PLF-PC exerts better therapeutic potential in the treatment of atherosclerotic disease than PLF.

Topics: Administration, Oral; Animals; Aorta; Aortic Diseases; Atherosclerosis; Biological Availability; Biomarkers; Chromatography, Liquid; Diospyros; Disease Models, Animal; Drug Compounding; Flavonoids; Hypolipidemic Agents; Lipids; Male; Mass Spectrometry; Phospholipids; Phytotherapy; Plant Extracts; Plant Leaves; Plants, Medicinal; Plaque, Atherosclerotic; Rats, Sprague-Dawley; Vitamin D

The purpose of the study was to investigate the protective effects of the ethanol extract of Diospyros kaki (EEDK) persimmon leaves to study N-methyl-N-nitrosourea (MNU)-induced retinal degeneration in mice. EEDK was orally administered after MNU injection. Retinal layer thicknesses were significantly increased in the EEDK-treated group compared with the MNU-treated group. The outer nuclear layer was preserved in the retinas of EEDK-treated mice. Moreover, EEDK treatment reduced the MNU-dependent up-regulation of glial fibrillary acidic protein (GFAP) and nestin expression in Müller and astrocyte cells. EEDK treatment also inhibited MNU-dependent down-regulation of rhodopsin expression. Quercetin exposure significantly attenuated the negative effects of H2O2 in R28 cells, suggesting that quercetin can act in an antioxidative capacity. Thus, EEDK may be considered as an agent for treating or preventing degenerative retinal diseases, such as retinitis pigmentosa and age-related macular degeneration.

Topics: Animals; Diospyros; Disease Models, Animal; Glial Fibrillary Acidic Protein; Humans; Male; Methylnitrosourea; Mice; Mice, Inbred C57BL; Nerve Tissue Proteins; Nestin; Plant Extracts; Plant Leaves; Retinal Degeneration

Diospyros kaki (D. kaki) has been cultivated throughout Eastern Asia for hundreds of years. D. kaki contains various biological active compounds, such as amino acids, carotenoids, flavonoids, tannins, catechins and vitamin A. Previous studies have shown that D. kaki has beneficial effects on homeostasis, constipation, hypertension, atherosclerosis and allergic dermatitis and is a good source of antioxidants, polyphenols and dietary fiber. However, the anti-allergic and anti-inflammatory effects of D. kaki have not yet been elucidated. This study aimed to investigate the protective effects of the aqueous extract of Diospyros kaki (AEDK) on mast cell-mediated allergic inflammation and to determine its possible mechanisms of action by using in vitro and in vivo mast cell-based models. The cAMP and intracellular calcium levels were measured to clarify the mechanisms by which AEDK inhibits the release of histamine from mast cells. AEDK inhibited the release of histamine and β-hexosaminidase from mast cells by modulating cAMP and intracellular calcium levels. We also measured the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. AEDK decreased gene expression and the secretion of the pro-inflammatory cytokines, TNF-α and IL-1β by inhibiting nuclear factor-κB. In addition, AEDK inhibited systemic and cutaneous allergic reaction. The inhibitory effects of AEDK on allergic reaction and the release of histamine were found to be similar to those of disodium cromoglycate, a known anti-allergic drug. To isolate the active component of AEDK, activity-guided fractionation was performed, based on the inhibitory effects on systemic anaphylaxis. Catechin was identified as an active compound. The present findings provide evidence that AEDK inhibits allergic inflammation and suggest the therapeutic application of AEDK in allergic inflammatory disorders.

Topics: Animals; Anti-Asthmatic Agents; Calcium; Cell Line; Cromolyn Sodium; Diospyros; Disease Models, Animal; Histamine Release; Humans; Hypersensitivity; Inflammation; Interleukin-1beta; Interleukin-6; Male; Mast Cells; Mice; Mice, Inbred ICR; NF-kappa B; Plant Extracts; Tumor Necrosis Factor-alpha

Asthma is a complex disease linked to various pathophysiological events, including proteinase activity. In this study, we examined whether a Diospyros blancoi methanolic extract (DBE) exerts protective effects on allergic asthma in a murine asthma model. To investigate the specific role of DBE, we employed a murine model of allergic airway inflammation. BALB/c mice sensitized and challenged with ovalbumin (OVA) were orally administered 20 or 40 mg/kg DBE for 3 days during OVA challenge. DBE induced significant suppression of the number of OVA-induced total inflammatory cells, including eosinophils, macrophages, and lymphocytes, in bronchoalveolar lavage fluid (BALF). Moreover, treatment with DBE led to significant decreases in interleukin (IL)-4, IL-5, and eotaxin levels in BALF and OVA-specific immunoglobulin (Ig)E and IgG1 levels in serum. Histological examination of lung tissue revealed marked attenuation of allergen-induced lung eosinophilic inflammation and mucus-producing goblet cells in the airway. Additionally, DBE suppressed matrix metalloproteinase-9 activity and induced heme oxygenase-1 expression. The present findings collectively suggest that DBE exhibits anti-inflammatory activity in an airway inflammation mouse model, supporting its therapeutic potential for the treatment of allergic bronchial asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchoalveolar Lavage Fluid; Diospyros; Disease Models, Animal; Eosinophils; Female; Heme Oxygenase-1; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-5; Lung; Lymphocytes; Macrophages; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts

Senescence-accelerated mouse prone/8 (SAMP8), a murine model of accelerated senescence, shows age-related deficits in learning and memory. We investigated the effect of oligomeric proanthocyanidins (oligomers) on memory impairment using the SAMP8 model involving the oral administration of oligomers for 5 weeks. To analyse memory improvement in SAMP8, we performed Morris water maze, object location and object recognition tests. The oral administration of oligomers improved spatial and object recognition impairment in SAMP8. Expressions of phosphorylated neurofilament-H (P-NF-H, axon marker), microtubule-associated proteins (MAP) 2a and 2b (MAP2; dendrite marker) and synaptophysin were increased in the brains of SAMP8-administered oligomers. In particular, the expression of P-NF-H was significantly elevated in the hippocampal CA1. This indicates that oligomers result in an increase in the densities of axons, dendrites and synapses. To investigate the protective mechanisms of oligomers against brain dysfunction with ageing, we carried out a receptor tyrosine kinase phosphorylation antibody array, and clarified that the administration of oligomers led to an increase in the phosphorylation of vascular endothelial growth factor receptor (VEGFR)-2, suggesting the neuroprotective role of oligomers. The phosphorylation of VEGFR-2 was more greatly increased in the hypothalamus and choroid plexus than in other brain regions of SAMP8. Memory in oligomer-treated mice was impaired by SU1498, a VEGFR-2-specific antagonist. Elucidating the relationship between memory impairment with ageing and VEGFR-2 signalling may provide new suggestions for protection against memory deficit in the ageing brain.

Topics: Aging; Animals; Brain; Cinnamates; Diospyros; Disease Models, Animal; Fruit; Male; Maze Learning; Memory Disorders; Mice; Mice, Inbred Strains; Microtubule-Associated Proteins; Neurofilament Proteins; Neurons; Neuroprotective Agents; Phosphorylation; Phytotherapy; Plant Extracts; Proanthocyanidins; Spatial Behavior; Synaptophysin; Vascular Endothelial Growth Factor Receptor-2

The anti-aging activities of persimmon oligomeric proanthocyanidins (POPs), reported to improve life span and behavioral characteristics associated with the aging process, were investigated using the senescence-accelerated mouse (SAM) P8, which is a good model for studies on aging-related behavioral changes as well as life span. We demonstrated that the administration of POPs extended the life span of SAMP8. In addition, POPs elevated Sirt1 expression, which is recognized as an essential factor for life span extension in the brain. On the other hand, the administration of POPs did not induce stereotypical behaviors such as rearing, jumping, and hanging from the lid of a cage, whereas food restriction increased these frequencies without a significant change in motor function. The present study suggests a promising role of POPs as anti-aging agents to extend life span, although further studies elucidating their anti-aging mechanisms acting are needed.

Topics: Aging; Animals; Behavior, Animal; Diospyros; Disease Models, Animal; Gene Expression; Humans; Life Expectancy; Male; Mice; Plant Extracts; Proanthocyanidins; Random Allocation; Sirtuin 1

Derivatisation of diospyrin, a bisnaphthoquinonoid isolated from Diospyros montana Roxb., led to the modification of its inhibitory activity, in vitro, towards a murine tumour model, Ehrlich ascites carcinoma (EAC), and two human cancer cell lines, viz., malignant skin melanoma (A375) and epidermoid laryngeal carcinoma (Hep2). Among the novel derivatives, an epoxide exhibited the maximum antiproliferative activity (IC(50) values in the range of 0.03-0.21 microM) and a comparatively lower toxicity (IC(50) approximately 98 microM) in normal human peripheral blood mononuclear cells (PBMC). This compound might provide a novel 'lead' for the development of clinically effective antiproliferative agents against cancer.

Topics: Animals; Antineoplastic Agents; Cell Proliferation; Diospyros; Disease Models, Animal; Humans; Inhibitory Concentration 50; Leukocytes, Mononuclear; Mice; Naphthoquinones; Plant Bark; Tumor Cells, Cultured

The objective of this study was to investigate the hypolipidemic effects of powdered whole persimmon leaf supplement in rats fed high-fat diet. Three groups of male Sprague-Dawley rats during 6 weeks were fed different diet: normal control (NC), high-fat (HF), and high-fat supplemented with powdered whole persimmon leaf (PL; 5%, wt/wt) groups. Body weight and relative weight of interscapular brown adipose tissue were significantly lower in the PL group than in the HF group, while plasma leptin concentration was higher. The supplementation of persimmon leaf significantly lowered the plasma total cholesterol and triglyceride concentrations, whereas elevated the ratio of HDL-C/total-C and improved the atherogenic index. Persimmon leaf supplementation led the hepatic cholesterol and triglyceride values to similar levels to the NC group. Accumulation of hepatic lipid droplets and the epididymal white adipocyte size of PL group were diminished comparing to the HF group. Hepatic HMG-CoA and ACAT activities were significantly higher in the PL group than in other groups. Contents of fecal triglyceride, cholesterol and acidic sterol were significantly higher in the PL group than in the HF group. Accordingly, we suggest that supplementation of the powdered whole persimmon leaf improves plasma and hepatic lipid levels profile partly via the increased fecal lipids in high-fat fed rats. These beneficial effects may be due to the properties of its phenolic compounds (1.15 g/100g) and high fiber (63.48 g/100g) content in the powdered persimmon leaf.

Topics: Acyl Coenzyme A; Adipose Tissue, Brown; Animals; Cholesterol; Dietary Fats; Diospyros; Disease Models, Animal; Epididymis; Hypolipidemic Agents; Lipid Metabolism; Lipoproteins; Liver; Male; Organ Size; Plant Extracts; Plant Leaves; Rats; Rats, Sprague-Dawley; Sterol O-Acyltransferase; Triglycerides; Weight Gain

We have previously shown that persimmon leaf extract and its major flavonoid constituent, astragalin, inhibited histamine release by basophils and that oral administration of these substances prior to the onset into an atopic dermatitis (AD) model mouse, NC/Nga, prevented development of dermatitis.. This study was designed to assess the clinical therapeutic effect of persimmon leaf extract and astragalin in NC/Nga mice suffering from dermatitis and the dose-response preventive effects of persimmon leaf extract on dermatitis and transepidermal water loss (TEWL).. The efficacy of persimmon leaf extract or astragalin in NC/Nga mice was judged by measurement of skin severity, scratching behaviour, serum IgE levels or TEWL.. Oral administration of persimmon leaf extract (250 mg kg(-1)) or astragalin (1.5 mg kg-1) for 4 weeks into NC/Nga mice with overt dermatitis resulted in a decrease in the severity of the condition. The preventive effect of persimmon leaf extract on the dermatitis was dose-dependent and continuous intake of persimmon leaf extract significantly decreased its onset and development. In addition, TEWL was also suppressed at a persimmon leaf extract dose of 250 mg kg(-1). No significant adverse reaction by these substances could be observed.. These observations suggest that persimmon leaf extract or the flavonoid astragalin may be alternative substances for the management of AD.

Topics: Administration, Oral; Animals; Dermatitis, Atopic; Diospyros; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Drugs, Chinese Herbal; Flavonoids; Kaempferols; Mice; Mice, Inbred Strains; Phytotherapy; Plant Leaves; Water Loss, Insensible