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Gallarhois (GR) is a traditional oriental herbal medicine with various pharmacological effects; however, its effect on gastric ulcer has not been previously explored. We firstly investigated the component and antioxidant activity of GR extract (EtGR) by HPLC analysis and 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results showed that EtGR consisted of gallotannin (68.7%), gallic acid (27.2%) and methyl gallate (4.1%) and that it had a high antioxidant value (IC50 value; 1.93 µg/mL). To evaluate the possible anti-gastric ulcer potential of EtGR, we investigated the effects of EtGR in the model of ethanol/hydrochloric acid (EtOH/HCl)-induced gastric ulcer. Gross and histological gastric lesions, biochemical and gene expression parameters were taken into consideration. The results showed that EtOH/HCl treatment produced mucosal injuries with morphological and histological damage, whereas EtGR co-treatment reduced the gastric injuries. EtGR treatment also decreased the contents of malonaldehyde (MDA) activity relative to the vehicle group. Moreover, EtGR decreased the levels of interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and cyclo-oxygenase-2 (COX-2) expression. Finally, EtGR did not induce any specific toxicity in the livers or kidneys of the EtOH/HCl-induced gastric ulcer model. These results suggest that EtGR had stronger antioxidant activity and could be a new useful natural drug for gastroprotection against gastric ulcer. Moreover, these findings provide a scientific basis for the development of drugs from traditional oriental herbal medicines.
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PURPOSE: Aims of this study is to evaluate the therapeutic effects and toxicity of Se-loaded cellulose film originated from Styela clava tunic (SeSCTF) on cutaneous wounds during diabetic conditions. MATERIALS AND METHODS: Alterations in skin regeneration, angiogenesis and toxicity were examined using streptozotocine (STZ)-induced diabetic Sprague Dawley® (SD) rats with surgical skin wounds after application of SeSCTF for 12 days. RESULTS: SCTF showed high tensile strength (1.64 MPa), low elongation (28.59%), low water vapor transmission rate (WVTR) and outstanding porous structure. Although SeSCTF application did not induce any significant alterations in glucose concentration or toxicity, wound morphology was rapidly recovered in the SeSCTF treated group relative to the gauze (GZ) and SCTF treated group. Moreover, recovery of re-epithelization, wound contraction and number of blood vessel was observed in SeSCTF treated groups when compared with all other groups. Furthermore, the SeSCTF treated group showed complete recovery of key protein expressions of the downstream signaling pathway of vascular endothelial growth factor (VEGF), angiopoietin-2/1 (Ang-2/1), the signaling pathway of insulin receptors and anti-oxidative status. CONCLUSIONS: Overall, the results of this study suggest that SeSCTF accelerates the healing process of cutaneous wounds in STZ-induced diabetic SD rats through stimulation of angiogenesis and the glucose receptor signaling pathway.
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Vendajes , Celulosa/química , Cordados no Vertebrados/metabolismo , Selenio/química , Animales , Antioxidantes/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/patología , Masculino , Malondialdehído/metabolismo , Ratas , Ratas Sprague-Dawley , Receptor de Insulina/metabolismo , Regeneración/efectos de los fármacos , Selenio/farmacología , Transducción de Señal/efectos de los fármacos , Piel/patología , Estreptozocina , Resistencia a la Tracción , Cicatrización de Heridas/efectos de los fármacosRESUMEN
The Styela clava tunic (SCT) is known as a good raw material for preparing anti-inflammatory compounds, wound healing films, guided bone regeneration, and food additives. To investigate whether ethanol extracts of the SCT (EtSCT) could protect against hepatic injury induced by carbon tetrachloride (CCl4) in ICR mice, alterations in serum biochemical indicators, histopathology, hepatic apoptosis, inflammation, and fibrosis were observed in ICR mice pretreated with EtSCT for 5 days before CCl4 injection. EtSCT contained 15.6 mg/g of flavonoid and 37.5 mg/g phenolic contents with high 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (93.3%) and metal chelation activity (46.5%). The EtSCT+CCl4-treated groups showed decreased levels of ALT, LDH, and AST, indicating toxicity and a necrotic area in the liver, while the level of ALP remained constant. The formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the EtSCT+CCl4-treated groups. Furthermore, the levels of pro- and anti-inflammatory cytokines and the phosphorylation of p38 in the TNF-α downstream signaling pathway rapidly recovered in the EtSCT+CCl4-treated groups. The EtSCT+CCl4-treated groups showed a significant decrease in hepatic fibrosis markers including collagen accumulation, MMP-2 expression, TGF-ß1 concentration, and phosphorylation of Smad2/3. Moreover, a significant decline in malondialdehyde (MDA) concentration and enhancement of superoxide dismutase (SOD) expression were observed in the EtSCT+CCl4-treated groups. Taken together, these results indicate that EtSCT can protect against hepatic injury induced by CCl4-derived reactive intermediates through the suppression of hepatic apoptosis, inflammation, and fibrosis.
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BACKGROUND: Gall (Galla Rhois [GR]) is known to have antibacterial, anti-inflammatory, antimetastatic, and anti-invasion activities and exert hepatoprotective effects. However, the hepatoprotective effects of gallotannin-enriched GR (GEGR) and their mechanisms have not yet been investigated. OBJECTIVE: The potential protective effect of GEGR against hepatotoxicity induced by hydrogen peroxide (H2O2) was investigated. MATERIALS AND METHODS: Changes in cell viability, apoptosis protein expression, and reactive oxygen species (ROS) generation were determined in HepG2 cells that were pretreated with four different concentrations of GEGR (6.25-50 µg/ml) for 24 h before H2O2 exposure. RESULTS: GEGR consisted of gallotannin (69.2%), gallic acid (26.6%), and methyl gallate (4.2%) and showed remarkable 2,2-diphenyl-1-picrylhydrazyl scavenging activity (inhibitory concentration 50% = 0.212 µg/ml). The lethal dose 50% and effective dose 50% values for the response of HepG2 cells to GEGR were determined to be 178 and 6.85 µg/ml, respectively. Significant reductions in the immunofluorescence intensity indicating apoptosis were also detected in the nuclei of HepG2 cells stained with 4',6-diamidino-2-phenylindole and Annexin V after GEGR treatment. The Bax/Bcl-2 ratio and active caspase-3 level were higher in H2O2 + vehicle-treated cells. However, these levels gradually decreased to those of the No-treated group in the GEGR pretreated group even though little or no decrease was observed in response to low GEGR concentrations. Furthermore, the GEGR pretreated group showed a reduced level of 2',7'-dichlorofluorescein diacetate stained cells, indicating ROS generation relative to the H2O2 + vehicle-treated group. CONCLUSION: The results of this study provide strong evidence that GEGR can prevent cell death induced by H2O2 in HepG2 cells through the induction of antioxidant conditions. SUMMARY: The gallotannin (69.2%), gallic acid (26.6%), and methyl gallate (4.2%) are the main constituents of water extracts of GRGEGR was more potent in DPPH scavenging, and gallotannin contributes to this extract activityGEGR significantly reduced the increase of apoptosis, Bax/Bcl-2 ratio, and active caspase-3 level after H2O2 treatmentGEGR pretreatment showed protection against H2O2-induced ROS production in DCFH-DA staining analysis. Abbreviations used: COX: Cyclooxygenase; DAPI: 4',6-diamidino-2-phenylindole; DMSO: Dimethyl sulfoxide; DPPH: 2,2-diphenyl-1-picrylhydrazyl; GEGR: Gallotannin-enriched Galla Rhois; GR: Galla Rhois; HPLC: High-performance liquid chromatography; H2O2: Hydrogen peroxide; MMP: Metallopeptidase; MTT: 3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; ROS: Reactive oxygen species; UV-Vis: Ultraviolet-visible.
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Asparagus cochinchinesis (A. cochinchinesis) is a medicine traditionally used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although numerous studies of the antiinflammatory effects of A. cochinchinesis have been conducted, the underlying mechanisms of such effects in macrophages remain to be demonstrated. To investigate the mechanism of suppressive effects on the inflammatory response in macrophages, alterations of the nitric oxide (NO) level, the cell viability, inducible nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) expression levels, inflammatory cytokine expression, the mitogen-activated protein kinase (MAPK) signaling pathway, cell cycle arrest and reactive oxygen species (ROS) levels were measured in lipopolysaccharide (LPS)-activated RAW264.7 cells following treatment with ethyl acetate extract from A. cochinchinesis root (EaEAC). RAW264.7 cells pretreated two different concentrations of EaEAC prior to LPS treatment exhibited no significant toxicity. The concentration of NO was significantly decreased in the EaEAC + LPS treated group compared with the vehicle + LPS treated group. A similar decrease in mRNA transcript level of COX2, iNOS, pro-inflammatory cytokines [tumor necrosis factorα and interleukin (IL)1ß] and antiinflammatory cytokines (IL6 and IL10) was detected in the EaEAC + LPS treated group compared with the vehicle + LPS treated group, although the decrease rate varied. Enhancement of the phosphorylation of MAPK family members following LPS treatment was partially rescued in the EaEAC pretreated group, and the cell cycle was arrested at the G2/M phase. Furthermore, the EaEAC pretreated group exhibited a reduced level of ROS generation compared with the vehicle + LPS treated group. Taken together, these results suggest that EaEAC suppresses inflammatory responses through inhibition of NO production, COX2 expression and ROS production, as well as differential regulation of inflammatory cytokines and cell cycle in RAW264.7 cells. In addition, these results provide strong evidence to suggest that EaEAC may be considered as an important candidate for the treatment of particular inflammatory diseases.
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Antiinflamatorios/farmacología , Asparagus/química , Ciclo Celular/efectos de los fármacos , Ciclooxigenasa 2/metabolismo , Citocinas/metabolismo , Macrófagos/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Extractos Vegetales/farmacología , Acetatos/química , Animales , Antioxidantes/metabolismo , Depuradores de Radicales Libres/farmacología , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Ratones , Óxido Nítrico/biosíntesis , Células RAW 264.7 , Especies Reactivas de Oxígeno/metabolismoRESUMEN
The aim of this study was to investigate the therapeutic effects of three different cellulose membranes (CMs) manufactured from Styela clava tunics (SCTs) on the healing of cutaneous wounds. We examined the physical properties and therapeutic effects of three CMs regenerated from SCTs (referred to as SCT CMs), including normal CM (SCTCM), freeze-dried SCTCM (FSCTCM) and sodium alginate-supplemented SCTCM (ASCTCM) on skin regeneration and angiogenesis using Sprague-Dawley (SD) rats. FSCTCM exhibited an outstanding interlayered structure, a high tensile strength (1.64 MPa), low elongation (28.59%) and a low water vapor transmission rate (WVTR) compared with the other SCT-CMs, although the fluid uptake rate was maintained at a medium level. In the SD rats with surgically wounded skin, the wound area and score of wound edge were lower in the FSCTCM-treated group than in the gauze (GZ)-treated group on days 3-6 and 12-14. In addition, a significant attenuation in the histopathological changes was observed in the FSCTCM-treated group. Furthermore, the expression level of collagen-1 and the signaling pathway of transforming growth factor (TGF)-ß1 were significantly stimulated by the topical application of FSCTCM. However, no signs of toxicity were detected in the livers or kidneys of the three SCTCM-treated groups. Overall, our data indicate that the FSCTCM may accelerate the process of wound healing in the surgically wounded skin of SD rats through the regulation of angiogenesis and connective tissue formation without inducing any specific toxicity.
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Celulosa , Membranas Artificiales , Urocordados/química , Cicatrización de Heridas , Animales , Biomarcadores , Celulosa/química , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Masculino , Modelos Animales , Ratas , Regeneración , Piel , Resistencia a la Tracción , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The laxative effects of aqueous extract of Liriope platyphylla (AEtLP) on loperamide (Lop)induced constipation have been reported; however, the key compounds and the mechanism underlying these effects remain unclear. Therefore, the laxative effects of five candidates derived from L. platyphylla: Diosgenin (DG), 5-hydroxymethylfurfural (5-HMF), adenosine (AD), hydroxypropyl cellulose (HPC) and uridine (UD) were investigated by examining the alteration of G protein α (Gα) expression, protein kinase C (PKC) phosphorylation and inositol triphosphate (IP3) concentration levels in the 5-hydroxytryptamine (5HT; serotonin) receptor signaling pathway. Primary rat intestine smooth muscle cells (pRISMCs), intestinal epithelial cells (IEC)18 and B35 cells were cotreated with Lop and the five compounds in order to screen the candidates. AEtLP, prucalopride (PCP) and bisacodyl (BS) served as positive controls. In pRISMCs, Gα expression levels were recovered in the majority of candidatetreated groups, whereas PKC phosphorylation recovery was observed only in the DG, 5HMF and AD treatment groups. In IEC18 cells, the AD treatment group mimicked the effects of PCP on PKC phosphorylation levels, whereas the DG, 5HMF, HPC and UD treatment groups mimicked the effects of AEtLP and BS. In B35 cells, a greater upregulation of PKC phosphorylation levels were observed in the UD treatment group compared with the PCP and BS treatment groups, whereas DG, 5HMF and AD treatment reduced the PKC phosphorylation levels to a greater extent than AEtLP treatment. However, effects similar to AEtLP, PCP and BS on Gα expression levels were not detected in any treatment groups in IEC18 and B35 cells. Furthermore, the level of IP3 was enhanced only in pRISMCs, in which all five candidates were effective, while the greatest concentration was observed in the UD treatment group. In conclusion, the results of the present study suggest that UD may be considered the compound with the greatest laxative activity, which may regulate the 5HT receptor signaling pathway.
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Colon Transverso/efectos de los fármacos , Laxativos/química , Laxativos/farmacología , Liriope (Planta)/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Receptores de Serotonina/metabolismo , Animales , Células Cultivadas , Colon Transverso/citología , Colon Transverso/metabolismo , Estreñimiento/tratamiento farmacológico , Estreñimiento/metabolismo , Femenino , Laxativos/aislamiento & purificación , Extractos Vegetales/aislamiento & purificación , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacosRESUMEN
α-Isocubebenol (ICO) isolated from Schisandra chinensis fruit was recently shown to exert neuroprotective properties with significant anti-neuroinflammatory effects. Here, we present evidence of the novel effects of ICO on alleviation of cognitive impairment. To confirm these effects, ICR mice were pretreated with two different doses of ICO for 3 weeks and scopolamine (SP) to induce memory impairment for the last 7days of the period. A passive avoidance test showed that ICO pretreatment recovered memory impairment in SP treated mice, although there was no difference between the two doses. Acetylcholinesterase (AChE) activity was significantly decreased in the SP+ICO treated group compared with the SP+Vehicle treated group. Additionally, significant recovery of the number of apoptotic cells and the ratio of apoptosis proteins (Bcl-2/Bax) were detected in the SP+ICO treated group than the SP+Vehicle treated group. Moreover, ICO treatment attenuated the decrease of ERK phosphorylation by SP treatment. These results indicate that ICO from S. chinensis fruit could be applied as an active pharmaceutical ingredient for cognitive improvement in Alzheimer's disease (AD).
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Acetilcolinesterasa/metabolismo , Inhibidores de la Colinesterasa/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Escopolamina , Sesquiterpenos/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/enzimología , Trastornos del Conocimiento/patología , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Hipocampo/patología , Masculino , Memoria a Largo Plazo/efectos de los fármacos , Ratones Endogámicos ICR , Neuronas/patología , FosforilaciónRESUMEN
During the last few decades, considerable research on diabetic wound healing strategies has been performed, but complete diabetic wound healing remains an unsolved problem, which constitutes an enormous biomedical burden. Herein, hyaluronic acid (HA)/poly(lactic-co-glycolic acid, PLGA) core/shell fiber matrices loaded with epigallocatechin-3-O-gallate (EGCG) (HA/PLGA-E) are fabricated by coaxial electrospinning. HA/PLGA-E core/shell fiber matrices are composed of randomly-oriented sub-micrometer fibers and have a 3D porous network structure. EGCG is uniformly dispersed in the shell and sustainedly released from the matrices in a stepwise manner by controlled diffusion and PLGA degradation over four weeks. EGCG does not adversely affect the thermomechanical properties of HA/PLGA-E matrices. The number of human dermal fibroblasts attached on HA/PLGA-E matrices is appreciably higher than that on HA/PLGA counterparts, while their proliferation is steadily retained on HA/PLGA-E matrices. The wound healing activity of HA/PLGA-E matrices is evaluated in streptozotocin-induced diabetic rats. After two weeks of surgical treatment, the wound areas are significantly reduced by the coverage with HA/PLGA-E matrices resulting from enhanced re-epithelialization/neovascularization and increased collagen deposition, compared with no treatment or HA/PLGA. In conclusion, the HA/PLGA-E matrices can be potentially exploited to craft strategies for the acceleration of diabetic wound healing and skin regeneration.
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Catequina/análogos & derivados , Diabetes Mellitus Experimental/tratamiento farmacológico , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/química , Ácido Poliglicólico/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Catequina/administración & dosificación , Catequina/química , Colágeno/metabolismo , Fibroblastos/efectos de los fármacos , Neovascularización Fisiológica/efectos de los fármacos , Ácido Poliglicólico/administración & dosificación , Ratas , Ratas Sprague-Dawley , Piel/efectos de los fármacosRESUMEN
Several natural products containing tannins are used as traditional medicines for treatment of constipation; however, their pharmacological mechanism is not well understood. The laxative effects of gallotannin-enriched extract isolated from Galla Rhois (GEGR) were investigated using a constipation model induced by loperamide (Lop) injection. After analysis for antioxidant activity of GEGR, alterations in the excretion parameters, histological structure, mucin secretion, and related protein levels were measured in the transverse colon of Sprague Dawley (SD) rats with Lop-induced constipation following treatment with 250, 500 and 1,000 mg/ml of GEGR. The number and weight of feces increased significantly by 48-79% and 128-159%, respectively, in the Lop+GEGR treated group relative to the Lop+vehicle treated group, while food intake and water consumption were maintained at a constant level. The thickness of mucosa, muscle and flat luminal surface, as well as the number of goblet cells and crypt of lieberkuhn were enhanced in the Lop+GEGR treated group. Moreover, mucin secretion increased significantly in a dose dependent manner in the Lop+GEGR treated group. Furthermore, the downstream signaling pathway of the muscarinic acetylcholine receptors (mAChR) M2 and M3 was recovered by GEGR treatment, although the expression level varied. The levels of Gα expression and inositol triphosphate (IP3) concentration were also recovered in the Lop+GEGR treated group relative to the Lop+vehicle treated group. The results of the present study provide strong evidence that tannins distributed in various medicinal plants are important candidates for improving chronic constipation induced by Lop treatment in animal models.
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Antidiarreicos/efectos adversos , Productos Biológicos/química , Estreñimiento/tratamiento farmacológico , Taninos Hidrolizables/uso terapéutico , Laxativos/uso terapéutico , Loperamida/efectos adversos , Extractos Vegetales/uso terapéutico , Animales , Colon/efectos de los fármacos , Estreñimiento/inducido químicamente , Heces , Conducta Alimentaria/efectos de los fármacos , Proteínas de Unión al GTP/metabolismo , Taninos Hidrolizables/farmacología , Mucinas/metabolismo , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacología , Ratas Sprague-Dawley , Receptores Muscarínicos/efectos de los fármacos , Receptores Muscarínicos/metabolismo , Transducción de SeñalRESUMEN
Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCTtreated groups compared with the UV + vehicletreated group, and the expression of collagen I increased. The attenuation of mitogenactivated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCTtreated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT-treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for use as therapeutic drug which protects against skin aging by regulating the skin morphology, histopathological structures, ER stress, inflammation and oxidative conditions.
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Antioxidantes/farmacología , Envejecimiento de la Piel/efectos de los fármacos , Piel/efectos de los fármacos , Extractos de Tejidos/farmacología , Urocordados/química , Animales , Western Blotting , Estrés del Retículo Endoplásmico/efectos de los fármacos , Estrés del Retículo Endoplásmico/efectos de la radiación , Epidermis/efectos de los fármacos , Epidermis/patología , Epidermis/efectos de la radiación , Etanol/química , Flavonoides/análisis , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de la radiación , Masculino , Ratones Pelados , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fenoles/análisis , Sustancias Protectoras/farmacología , Piel/metabolismo , Piel/efectos de la radiación , Envejecimiento de la Piel/fisiología , Envejecimiento de la Piel/efectos de la radiación , Superóxido Dismutasa/metabolismo , Extractos de Tejidos/aislamiento & purificación , Rayos Ultravioleta , Pérdida Insensible de Agua/efectos de los fármacos , Pérdida Insensible de Agua/efectos de la radiaciónRESUMEN
To investigate the beneficial effects of diosgenin (DG) on the multiple types of brain damage induced by Aß-42 peptides and neurotoxicants, alterations in the specific aspects of brain functions were measured in trimethyltin (TMT)-injected transgenic 2576 (TG) mice that had been pretreated with DG for 21 days. Multiple types of damage were successfully induced by Aß-42 accumulation and TMT injection into the brains of TG mice. However, DG treatment significantly reduced the number of Aß-stained plaques and dead cells in the granule cells layer of the dentate gyrus. Significant suppression of acetylcholinesterase (AChE) activity and Bax/Bcl-2 expression was also observed in the DG treated TG mice (TG+DG group) when compared with those of the vehicle (VC) treated TG mice (TG+VC group). Additionally, the concentration of nerve growth factor (NGF) was dramatically enhanced in TG+DG group, although it was lower in the TG+VC group than the non-transgenic (nTG) group. Furthermore, the decreased phosphorylation of downstream members in the TrkA high affinity receptor signaling pathway in the TG+VC group was significantly recovered in the TG+DG group. A similar pattern was observed in p75(NTR) expression and JNK phosphorylation in the NGF low affinity receptor signaling pathway. Moreover, superoxide dismutase (SOD) activity was enhanced in the TG+DG group, while the level of malondialdehyde (MDA), a marker of lipid peroxidation, was lower in the TG+DG group than the TG+VC group. These results suggest that DG could exert a wide range of beneficial activities for multiple types of brain damage through stimulation of NGF biosynthesis.
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Animal models for gastric ulcers produced by physical, pharmacological and surgical methods have been widely employed to evaluate therapeutic drugs and investigate the mechanism of action of this disease. ICR mice were selected to produce this model, even though several mice and rats have been widely used in studies of gastric ulcers. To compare the responses of ICR mice obtained from three different sources to gastric ulcer inducers, alterations in gastric injury, histopathological structure, and inflammation were measured in Korl:ICR (Korea NIFDS source), A:ICR (USA source) and B:ICR (Japan source) treated with three concentrations of ethanol (EtOH) (50, 70, and 90%) in 150 mM hydrochloric acid (HCl) solution. Firstly, the stomach lesion index gradually increased as the EtOH concentration increased in three ICR groups. Moreover, a significant increase in the level of mucosal injury, edema and the number of inflammatory cells was similarly detected in the EtOH/HCl treated group compared with the vehicle treated group in three ICR groups. Furthermore, the number of infiltrated mast cells and IL-1ß expression were very similar in the ICR group derived from three different sources, although some differences in IL-1ß expression were detected. Especially, the level of IL-1ß mRNA in 50 and 90EtOH/HCl treated group was higher in Korl:ICR and A:ICR than B:ICR. Overall, the results of this study suggest that Korl:ICR, A:ICR and B:ICR derived from different sources have an overall similar response to gastric ulcer induced by EtOH/HCl administration, although there were some differences in the magnitude of their responses.
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To quantitatively evaluate the therapeutic effects of diosgenin (DG) and investigate the role of IL-4 on skin inflammation, alterations in luciferase-derived signal and general phenotype biomarkers were measured in IL-4/Luc/CNS-1 transgenic mice with phthalic anhydride (PA)-induced skin inflammation after treatment with DG for 4 weeks. High levels of luciferase-derived signal detected in the abdominal region and submandibular lymph node (SL) of the PA treated group was significantly decreased by 67-88% in the PA + DG cotreated group. Furthermore, the weight of the lymph node and spleen, IgE concentration, epidermis thickness, and number of infiltrated mast cells were lower in the PA + DG treated group than the PA + Vehicle treated group. Moreover, expression of IL-6 and vascular endothelial growth factor (VEGF) also decreased in the PA + DG cotreated group. These results suggest that PA-induced skin inflammation could be successfully suppressed by DG treatment in IL-4/Luc/CNS-1 Tg mice through attenuation of IL-4 and IL-6 expression, as well as decreased IgE concentration and mast cells infiltration.
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Antiinflamatorios/farmacología , Dermatitis Atópica/tratamiento farmacológico , Diosgenina/farmacología , Interleucina-4/genética , Interleucina-6/genética , Piel/efectos de los fármacos , Animales , Movimiento Celular/efectos de los fármacos , Dermatitis Atópica/inducido químicamente , Dermatitis Atópica/inmunología , Dermatitis Atópica/patología , Expresión Génica , Genes Reporteros , Inmunoglobulina E/genética , Interleucina-4/antagonistas & inhibidores , Interleucina-4/inmunología , Interleucina-6/antagonistas & inhibidores , Interleucina-6/inmunología , Luciferasas/genética , Luciferasas/inmunología , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/inmunología , Ganglios Linfáticos/patología , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Mastocitos/patología , Ratones , Ratones Transgénicos , Tamaño de los Órganos/efectos de los fármacos , Anhídridos Ftálicos , Piel/inmunología , Piel/patología , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/patología , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/inmunologíaRESUMEN
To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-ß1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system.
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Antioxidantes/farmacología , Áfidos/metabolismo , Productos Biológicos/farmacología , Tetracloruro de Carbono , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Taninos Hidrolizables/farmacología , Cirrosis Hepática Experimental/prevención & control , Hígado/efectos de los fármacos , Rhus/parasitología , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Productos Biológicos/metabolismo , Biomarcadores/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/sangre , Enfermedad Hepática Inducida por Sustancias y Drogas/genética , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Citocinas/genética , Citocinas/metabolismo , Citoprotección , Regulación de la Expresión Génica , Taninos Hidrolizables/metabolismo , Mediadores de Inflamación/metabolismo , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/sangre , Cirrosis Hepática Experimental/genética , Cirrosis Hepática Experimental/patología , Masculino , Ratones Endogámicos ICR , Necrosis , Estrés Oxidativo/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVES: This study aimed to investigate the beneficial effects of Cheonggukjang (CGK) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on neurotoxic damages. METHODS: The specific aspects of brain functions were measured in Institute for Cancer Research (ICR) mice that had been pretreated for 4 weeks with three difference doses of CGK before trimethyltin (TMT) treatment. RESULTS: The short- and long-term memory loss induced by TMT treatment was significantly improved in the CGK-pretreated group in a dose-dependent manner. The number of dead cells in the granule cell layer of the dentate gyrus was decreased in the TMT/CGK-cotreated group relative to the TMT/vehicle-treated group, whereas significant suppression of acetylcholinesterase (AChE) activity was observed in the same group. Additionally, a dose-dependent increase in nerve growth factor (NGF) concentration, activation of the NGF receptor signaling pathway including the TrkA high affinity receptor and p75(NTR) low affinity receptor, and decline in Bax/Bcl-2 level was measured in all TMT/CGK-treated groups, although a decrease in the active form of caspase-3 was observed in the TMT/H-CGK-treated group. Furthermore, superoxide dismutase (SOD) activity was enhanced in the TMT/CGK-treated group, whereas the level of malondialdehyde (MDA), a marker of lipid peroxidation, was 43-58% lower in the TMT/CGK-treated group than the TMT/vehicle-treated group. DISCUSSION: These results demonstrate that CGK fermented by mixed culture of B. subtilis and L. sakei could exert a wide range of beneficial activities for neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington disease.
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Bacillus subtilis/metabolismo , Trastornos del Conocimiento/prevención & control , Suplementos Dietéticos , Latilactobacillus sakei/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Alimentos de Soja/análisis , Animales , Biomarcadores/metabolismo , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/metabolismo , Trastornos del Conocimiento/patología , Giro Dentado/efectos de los fármacos , Giro Dentado/enzimología , Giro Dentado/patología , Suplementos Dietéticos/análisis , Fermentación , Alimentos Funcionales/análisis , Alimentos Funcionales/microbiología , Intoxicación del Sistema Nervioso por Metales Pesados/fisiopatología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Trastornos de la Memoria/etiología , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/patología , Trastornos de la Memoria/prevención & control , Ratones , Ratones Endogámicos ICR , Proteínas del Tejido Nervioso/agonistas , Proteínas del Tejido Nervioso/antagonistas & inhibidores , Proteínas del Tejido Nervioso/metabolismo , Neuronas/efectos de los fármacos , Neuronas/enzimología , Neuronas/patología , Fármacos Neuroprotectores/química , Extractos Vegetales/química , Organismos Libres de Patógenos Específicos , Compuestos de Trimetilestaño/toxicidadRESUMEN
To evaluate the hepatotoxicity and nephrotoxicity of Galla Rhois (GR) toward the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed after oral administration of 250, 500 and 1,000 mg/kg body weight/day of gallotannin-enriched extract of GR (GEGR) for 14 days. GEGR contained 68.7±2.5% of gallotannin, 25.3±0.9% of gallic acid and 4.4±0.1% of methyl gallate. Also, the level of malondialdehyde (MDA), a marker of lipid peroxidation, was decreased with 19% in the serum of high dose GEGR (HGEGR)-treated mice. The body and organ weight, clinical phenotypes, urine parameters and mice mortality did not differ among GEGR-treated groups and the vehicle-treated group. Furthermore, no significant increase was observed in alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and the serum creatinine (Cr) in the GEGR-treated group relative to the vehicle-treated group. Moreover, the specific pathological features induced by most toxic compounds such as CCl4 were not observed upon liver and kidney histological analysis. Overall, the results of the present study suggest that GEGR does not induce any specific toxicity in liver and kidney organs of ICR at doses of 1,000 mg/kg body weight/day, indicating that this is no observed adverse effect level (NOAEL).
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Some polymers and bioactive compounds derived from Styela clava tunic (SCT) have been reported as traditional medicine for the treatment of inflammation, oxidative stress and surgical wounds although there is little scientific evidence of their liver and kidney toxicity. To investigate the toxicity of ethanol extracts of SCT (EtSCT) in the liver and kidney of ICR mice, alterations in related markers including body weight, organ weight, urine composition, liver pathology and kidney pathology were analyzed following oral administration of 50 and 100 mg/kg body weight/day of EtSCT for 14 days. EtSCT showed a high level of free radical scavenging activity for DPPH (93.1%) and NO (16.2%) as well as the presence of 14.8 mg/mL of flavonoids and 36.2 mg/mL of phenolics, while EtSCT treated groups did not show any significant alterations in the body and organ weight, clinical phenotypes, urine parameters or mice mortality when compared with the vehicle treated group. In addition, constant levels of serum biochemical markers including alanine phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN) and serum creatinine (CRE) were maintained. Moreover, no specific histopathological features induced by most toxic compounds were observed in liver and kidney sections stained with hematoxilin and eosin. Therefore, the present results indicate that EtSCT with strong antioxidant activity cannot induce any specific toxicity in liver and kidney organs of ICR at doses of 100 mg/kg body weight/day.
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To characterize the changes in global gene expression in the distal colon of constipated SD rats in response to the laxative effects of aqueous extracts of Liriope platyphylla (AEtLP), including isoflavone, saponin, oligosaccharide, succinic acid and hydroxyproline, the total RNA extracted from the distal colon of AEtLP-treated constipation rats was hybridized to oligonucleotide microarrays. The AEtLP treated rats showed an increase in the number of stools, mucosa thickness, flat luminal surface thickness, mucin secretion, and crypt number. Overall, compared to the controls, 581 genes were up-regulated and 216 genes were down-regulated by the constipation induced by loperamide in the constipated rats. After the AEtLP treatment, 67 genes were up-regulated and 421 genes were down-regulated. Among the transcripts up-regulated by constipation, 89 were significantly down-regulated and 22 were recovered to the normal levels by the AEtLP treatment. The major genes in the down-regulated categories included Slc9a5, klk10, Fgf15, and Alpi, whereas the major genes in the recovered categories were Cyp2b2, Ace, G6pc, and Setbp1. On the other hand, after the AEtLP treatment, ten of these genes down-regulated by constipation were up-regulated significantly and five were recovered to the normal levels. The major genes in the up-regulated categories included Serpina3n, Lcn2 and Slc5a8, whereas the major genes in the recovered categories were Tmem45a, Rerg and Rgc32. These results indicate that several gene functional groups and individual genes as constipation biomarkers respond to an AEtLP treatment in constipated model rats.
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Colon/metabolismo , Estreñimiento/tratamiento farmacológico , Regulación hacia Abajo/efectos de los fármacos , Laxativos/uso terapéutico , Liriope (Planta)/química , Extractos Vegetales/uso terapéutico , Regulación hacia Arriba/efectos de los fármacos , Animales , Colon/patología , Estreñimiento/inducido químicamente , Quinasa 2 del Receptor Acoplado a Proteína-G , Liriope (Planta)/metabolismo , Loperamida/toxicidad , Análisis de Secuencia por Matrices de Oligonucleótidos , Extractos Vegetales/química , Raíces de Plantas/química , Raíces de Plantas/metabolismo , Ratas , Ratas Sprague-Dawley , Proteínas Tirosina Quinasas Receptoras/genética , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
Rapid healing of dermatological wounds is of vital importance in preventing infection and reducing post-treatment side-effects. Here we report the therapeutic effects of phytochemically stabilized gold nanoparticles (pAuNPs) coated on a hydrocolloid membrane (HCM) for curing cutaneous wounds. Furthermore, the remedial effects of pAuNPs on skin regeneration and angiogenesis were examined using Sprague Dawley® (SD) rats with skin injuries after a pAuNP-deposited hydrocolloid membrane (pAuNP-HCM) had been applied for 15 days. The rate of wound closure was 4 times faster in the pAuNP-HCM-treated group than in the gauze (GZ)- or HCM-treated groups in the first 5 days. Moreover, wound widths in the pAuNP-HCM-treated group were significantly reduced after 5-15 days of treatment following the injury, compared with the other groups. In addition, a significant increase in collagen expression and a decrease in matrix metalloproteinase (MMP)-1 expression and transforming growth factor (TGF-ß1) concentration were observed in the pAuNP-HCM-treated group on day 5. Wound tissue applied with the pAuNP-HCM showed enhancement of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang-1), and angiopoietin 2 (Ang-2) expression. Furthermore, the activity of superoxide dismutases (SODs) was significantly increased in the skin tissue of the pAuNP-HCM-treated group, compared with the GZ- or HCM-treated groups. It is probable that the accelerated process of wound healing in the injured skin of SD rats via pAuNP-HCM results from the synergistic regulation of angiogenesis and connective tissue formation, as well as the stimulation of antioxidant effects.