ABSTRACT
Yukmijihwang-Tang is widely used in traditional Korean medicine to treat age-related disorders. In the present study, we re-prescribed Gami-Yukmijihwang-Tang (YJT), which is slightly modified from Yukmijihwang-Tang by adding more medicinal plants to evaluate its pharmacological effects on underlying mechanisms against repeated lipopolysaccharide (LPS)-injection-induced neuroinflammation in the hippocampus regions. C57BL/6J male mice (16-24 weeks old) were divided into six groups: (1) the control group (DW with 0.9% saline injection), (2) LPS group (DW with LPS injection), YJT groups ((3) 100, (4) 200, or (5) 400 mg/kg of YJT with LPS injection), and (6) glutathione (GSH) group (100 mg/kg of GSH with LPS injection), respectively. Mice were orally administrated with various doses of YJT or glutathione (GSH) for the first five days. Neuroinflammation in the hippocampus region was induced by repeated injection of LPS during the last three days. As predicted, LPS not only increased oxidative stress-related markers including malondialdehyde, 4-hydroxynonenal, nitrotryptophan, and hydrogen peroxide, but also drastically enhanced inflammatory reactions including nitric oxide, inducible nitric oxide synthase, p65, and toll-like receptor 4, respectively. YJT administration, on the other hand, notably decreased the above pathological alterations by enhancement of antioxidant capacities such as superoxide dismutase and catalase activities. To explain the underlying pharmacological actions of YJT, we focused on a representative epigenetic regulator, a nicotinamide adenine dinucleotide + (NAD+)-dependent chromatin enzyme, Sirtuin 6 (Sirt6). Neuroinflammation in hippocampus regions depleted Sirt6 at the protein level and this alteration directly affected the nuclear factor erythroid 2-related factor (Nrf2)/hemeoxygenase (HO)-1 signaling pathway in the LPS group; however, YJT significantly recovered the Sirt6 protein levels, and it could recover the abnormal status of Nrf2/HO-1 signaling pathways in the hippocampus regions. Additionally, Sirt6 led to the up-regulation of GSH sub-enzymes of mRNA expression and protein levels of total GSH content. These findings suggest that YJT can protect against LPS-induced neuroinflammation and oxidative stress by regulating the Sirt6-related pathways and normalizing the GSH redox cycle.
ABSTRACT
Gochujang, fermented red pepper paste, is a grain-based Korean traditional food. The quality of gochujang produced by cottage industries is not well-documented. Thus, the present study aimed to analyze the quality of gochujang from 35 traditional cottage industries for physicochemical and microbial characteristics, along with volatile compound contents. In addition to microbial characteristics, salinity, pH, free amino nitrogen, and alcohol content were evaluated. Ethanol was detected as the predominant alcohol and 57% of tested gochujang products harbored >1% of total alcohol content, which was above the recommended level for halal products. Gochujang products contained hexadecanoic and linoleic acids predominantly and several volatile compounds belonging to the classes of alcohols, aldehydes, alkanes, nitrogen-containing compounds, and terpenes. A wide range of aerobic mesophilic bacteria (2.79-8.73 log CFU/g) and yeast counts (1.56-7.15 log CFU/g) was observed. Five distinct yeast species were identified, including Zygosaccharomyces rouxii. Eight gochujang products were found to be contaminated with Bacillus cereus (>4 log CFU/g). This study suggests that there is a need to limit B. cereus contamination in cottage industry products and reduce alcohol content to comply with halal food guidelines.
ABSTRACT
Liver fibrosis, which is characterized by excessive accumulation of extracellular matrix (ECM) primarily produced by hepatic stellate cells (HSCs), can eventually lead to cirrhosis. Fibroblast growth factor 18 (FGF18) mediates various biological activities. However, the precise role of FGF18 in the pathological process of liver fibrosis and the underlying mechanisms have not been elucidated. In this study, we found that FGF18 was markedly upregulated in carbon tetrachloride (CCl4)-induced fibrotic mouse liver tissues and transforming growth factor ß (TGF-ß) stimulated LX-2 cells. Furthermore, our studies demonstrated that overexpression of FGF18 in the liver significantly alleviated CCl4-induced fibrosis and inhibited the activation of HSCs, while exacerbated by HSC-specific deletion of FGF18. Mechanistically, FGF18 treatment dramatically activated Hippo signaling pathway by suppressing smoothened (SMO) both in vivo and in vitro. Moreover, the interaction between SMO and LATS1 was crucial for the FGF18 induced protective effects. In conclusion, these results indicated that FGF18 attenuates liver fibrosis at least partially via the SMO-LATS1-YAP signaling pathway and therefore may be a potential therapeutic target for liver fibrosis.
Subject(s)
Hepatic Stellate Cells , Liver Cirrhosis , Animals , Carbon Tetrachloride/adverse effects , Carbon Tetrachloride/metabolism , Fibroblast Growth Factors , Hepatic Stellate Cells/metabolism , Liver/metabolism , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Liver Cirrhosis/metabolism , Mice , Protein Serine-Threonine Kinases , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
Traditional gochujang is well known for its distinguished flavor and taste. However, the safety of cottage industry gochujang products is uncertain, particularly, in terms of biogenic amine (BA) content which is not yet documented. The present study aimed to determine the level of BAs present in 35 traditional gochujang products nationwide. All gochujang products had considerable amounts of total BAs ranging from 52.95 mg/kg to 176.24 mg/kg. Individually, histamine and tyramine were either not detected or detected up to 16.94 mg/kg and 2.15-52.34 mg/kg, respectively. In all the tested gochujang products, putrescine, spermidine, and spermine were detected in the range of 7.60-56.72 mg/kg, 14.96-36.93 mg/kg, and 4.68-16.31 mg/kg, respectively. A total of 22 and 19 gochujang products had less than 1 mg/kg of cadaverine and histamine, respectively. The findings indicate that all the gochujang products tested herein had BA levels below the suggested toxicity limits recommended by the various regulatory authorities, which reveal that they are safe for human consumption.
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis (NASH), affects 25% of the global population. Despite the prevalence of NAFLD worldwide, effective therapeutics are currently lacking. Amomum villosum var. xanthioides (Wall. ex Baker) T.L.Wu & S.J.Chen (AX) is a medicinal herb traditionally used for treating digestive tract disorders in countries across Asia. We aimed to examine the pharmacological effects of the ethyl acetate fraction of AX (AXEF) against tunicamycin (TM)-induced ER stress in a NASH mouse model using C57/BL6J male mice. Following TM injections (2 mg/kg), the mice were orally administrated AXEF (12.5, 25, or 50 mg/kg), silymarin (50 mg/kg), or distilled water daily for 5 days, and the outcomes for fatty liver, inflammation, and oxidative stress were measured in serum or liver tissue levels. AXEF drastically attenuated hepatic ER stress-induced NASH as indicated by decreases in lipid droplet accumulations, serum liver enzymes, hepatic inflammations, and cell death signals in the hepatic tissue and/or serum levels. Interestingly, AXEF showed potent antioxidant effects by quenching reactive oxidative stress and its final product lipid peroxide in the hepatic tissue, specifically an increase in metallothionein (MT). To confirm the underlying actions of AXEF, we observed that AXEF increases MT1 gene promoter activities in the physiological levels. Collectively, AXEF showed antioxidant properties on TM-induced ER stress in a NASH mice model through the improvement of MTs.
ABSTRACT
Deep learning has brought a dramatic development in molecular property prediction that is crucial in the field of drug discovery using various representations such as fingerprints, SMILES, and graphs. In particular, SMILES is used in various deep learning models via character-based approaches. However, SMILES has a limitation in that it is hard to reflect chemical properties. In this paper, we propose a new self-supervised method to learn SMILES and chemical contexts of molecules simultaneously in pre-training the Transformer. The key of our model is learning structures with adjacency matrix embedding and learning logics that can infer descriptors via Quantitative Estimation of Drug-likeness prediction in pre-training. As a result, our method improves the generalization of the data and achieves the best average performance by benchmarking downstream tasks. Moreover, we develop a web-based fine-tuning service to utilize our model on various tasks.
ABSTRACT
BACKGROUND: Various extracts of Hovenia dulcis have been commonly used in Asia for cases of alcohol-related disorders. Fermentation is reported to enhance the level and biological activities of various bio-constituents of plant extracts. Therefore, this study was undertaken to evaluate the effects of fermented H. dulcis extract (FHDE) on ethanol-induced liver injury in mice. METHODS: FHDE was prepared using Bacillus subtilis and Lactobacillus plantarum. The effects of FHDE on ethanol-induced liver injury were evaluated in C57BL/6 N CrSlc mice. A mixed feed preparation containing the fermented extract with and without ethanol was given to mice for 29 days, according to its group. At the end of the experiment, blood and liver samples were collected from all mice in the group. Plasma biochemical analysis and histopathological investigation were performed to evaluate the impacts of treatment on the biomarkers of hepatic damage and inflammatory changes. Besides, the expression of genes that regulate the activities of enzymes associated with alcohol metabolism, antioxidant activity, and fatty acid oxidation was assessed using a quantitative real-time polymerase chain reaction. Moreover, the amino acid contents and the active ingredients of the extract were evaluated before and after fermentation. RESULTS: Fermentation resulted in a marked increase and decrease in the amount of Gamma-Amino-n-butyric acid (GABA) and glutamic acid, respectively. FHDE enhanced the body weight gain of mice compared to ethanol. Besides, plasma levels of triglyceride, low-density lipoprotein, the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were significantly (P < 0.05) reduced in the FHDE-treated groups relative to the ethanol-treated control. FHDE upregulated the expression of genes associated with enzymes involved in alcohol dehydrogenation (Adh1 and Aldh2), antioxidant activity (SOD and CAT), and fatty acid oxidation (PPAR-α and PGC-1α). However, the expressions of Cytochrome peroxidase Cyp2E1 and genes related to lipogenesis (SREBP-1c, FAS, SCD-1, and ACC) were significantly (P < 0.05) downregulated following treatment with the FHDE. Histopathological investigation demonstrated a slight degree of inflammatory cell infiltration and occasional fatty changes in the FHDE-treated groups. CONCLUSION: The GABA-enriched fermented H. dulcis extract prevented ethanol-induced hepatic damage by enhancing the antioxidant defense system, fatty acid oxidation, and reducing lipogenesis.
Subject(s)
Chemical and Drug Induced Liver Injury/drug therapy , Plant Extracts/pharmacology , Rhamnaceae/chemistry , gamma-Aminobutyric Acid/pharmacology , Animals , Chromatography , Disease Models, Animal , Ethanol/adverse effects , Fermentation , Lipogenesis/drug effects , Mass Spectrometry , Mice , Mice, Inbred C57BL , Oxidative Stress/drug effects , Plant Extracts/chemistry , Republic of KoreaABSTRACT
Superhydrophobic surfaces have gained tremendous attention for icephobic properties, including anti-icing and deicing. The former is about how much a surface can delay the ice formation, whereas the latter is about how easy the surface can let the ice go off after freezing. In this study, superhydrophobic surfaces with different surface roughnesses and wettabilities were tested for both anti-icing and deicing purposes to investigate their correlation in association with the different surface properties. Anti-icing test was conducted by utilizing an icing wind tunnel to see how much ice gets accumulated on the surfaces in a dynamic condition (i.e., impacting supercooled water droplets by forced wind). For the deicing test, sessile droplets were frozen on the surfaces in a static condition (i.e., no wind) and then the shear adhesion forces were measured to disconnect the frozen ices off from the surfaces. The experimental results show that higher anti-icing efficacy does not necessarily mean higher deicing efficacy because of the different icing mechanisms. Although a superhydrophobic surface with a lower depinning force (or contact angle hysteresis) delays the ice accumulation in a dynamic condition more effectively, the same surface can require higher shear adhesion force for ice grown in a static condition where condensation and wetting state of a droplet are the key factors.
ABSTRACT
OBJECTIVE: We investigated the effect of using indocyanine green (ICG) gel, a mixture of ICG and Viscoat, on complete removal of the medial wall of the lacrimal sac as well as the success rate of endoscopic endonasal dacryocystorhinostomy (DCR) for primary acquired nasolacrimal duct obstruction. METHODS: Consecutive cases of endoscopic endonasal DCR between January and December 2010 were included in a retrospective, comparative manner. A total of 91 patients with primary acquired nasolacrimal duct obstruction were enrolled. Surgical method was selected according to time period. In the ICG gel group, we used ICG gel, which is a fluorescent-colored viscoelastic substance made of ICG dye (25 mg) and Viscoat. ICG gel was injected into the lacrimal sac via the inferior canaliculus prior to lacrimal sac dissection. The anatomic and functional surgical success rates of endoscopic endonasal DCR in each group were compared. RESULTS: Our study included 49 cases in the ICG gel group and 42 cases in the control group. The functional success rate of endoscopic endonasal DCR reached 93.9% (46 of 49) in the ICG gel group compared with 71.4% (30 of 42) in the control group (Pearson's χ2 test, p value = 0.004). In contrast, there was no statistically significant correlation between use of ICG gel and anatomic success rate of endoscopic endonasal DCR. CONCLUSIONS: Using ICG gel during lacrimal sac dissection may enhance the functional success rate of endoscopic endonasal DCR for primary acquired nasolacrimal duct obstruction by facilitating easier identification and subsequent complete removal of the medial wall of the lacrimal sac.
Subject(s)
Coloring Agents/administration & dosage , Dacryocystorhinostomy/methods , Indocyanine Green/administration & dosage , Lacrimal Duct Obstruction/therapy , Nasolacrimal Duct/surgery , Adult , Aged , Endoscopy , Female , Gels , Humans , Lacrimal Duct Obstruction/diagnosis , Male , Middle Aged , Nasolacrimal Duct/pathology , Retrospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To compare conjunctival staining between lissamine green and fluorescein sodium using a yellow barrier filter. DESIGN: Retrospective cross-sectional study. PARTICIPANTS: Thirteen eyes of 13 patients with dry eyes. METHODS: All patients underwent ocular surface staining with fluorescein sodium and lissamine green. Ocular surface staining with fluorescein sodium was observed through slit-lamp examination under cobalt blue illumination and a yellow filter. Temporal (0-5) and nasal (0-5) conjunctival staining grade was separately graded according to the Oxford scheme. The contrast score was defined as the absolute difference between mean grey values of punctate staining and background. Conjunctival staining grade and contrast scores were compared between these 2 staining methods. RESULTS: The sum of the conjunctival staining grade (0-10) for the nasal and temporal conjunctiva was 4.7 ± 2.5 for fluorescein sodium, which was significantly higher than that of lissamine green, 4.1 ± 2.5 (p = 0.005). The contrast score of temporal and nasal conjunctival staining was 34.6 ± 12.0 and 34.7 ± 10.3, respectively, for fluorescein sodium, which was also significantly greater than for lissamine green (23.4 ± 8.1 and 21.0 ± 9.0, respectively; p = 0.003 and p = 0.003, respectively). CONCLUSIONS: Conjunctival staining with fluorescein sodium and a yellow filter seems to be more sensitive for the detection of conjunctival damage than lissamine green. Fluorescein staining with the yellow filter has the advantage of simultaneous observation of both corneal and conjunctival damage in patients with dry eye without the need for additional vital staining.
Subject(s)
Coloring Agents/administration & dosage , Conjunctiva/pathology , Dry Eye Syndromes/diagnosis , Fluorescein/administration & dosage , Fluorescent Dyes/administration & dosage , Lissamine Green Dyes/administration & dosage , Adult , Coloring Agents/chemistry , Cross-Sectional Studies , Female , Fluorescein/chemistry , Fluorescent Dyes/chemistry , Humans , Lissamine Green Dyes/chemistry , Male , Middle Aged , Retrospective Studies , Staining and Labeling/methods , Young AdultABSTRACT
Neoplasms of the lacrimal drainage system are uncommon, but potentially life-threatening and are often difficult to diagnose. Among primary lacrimal sac tumors, benign mixed tumors are extremely rare. Histologically, benign mixed tumors have been classified as a type of benign epithelial tumor. Here we report a case of benign mixed tumor of the lacrimal sac.
Subject(s)
Adenoma, Pleomorphic/diagnosis , Nasolacrimal Duct/pathology , Salivary Gland Neoplasms/diagnosis , Biopsy , Diagnosis, Differential , Humans , Male , Middle Aged , Tomography, X-Ray ComputedABSTRACT
Portulaca oleracea extracts, known as Ma Chi Hyun in the traditional Korean medicine, show a variety of biomedical efficacies including those in anti-inflammation and anti-allergy. In this study, we investigate the protective activity of the P. oleracea extracts against UVB-induced damage in human epithelial keratinocytes and fibroblasts by several apoptosis-related tests. The results suggest that P. oleracea extracts have protective effects from UVB-induced apoptosis.
Subject(s)
Fibroblasts/drug effects , Fibroblasts/radiation effects , Keratinocytes/drug effects , Keratinocytes/radiation effects , Portulaca , Ultraviolet Rays/adverse effects , Annexin A5/metabolism , Apoptosis/drug effects , Apoptosis/radiation effects , Cell Survival/drug effects , Cell Survival/radiation effects , Cells, Cultured , DNA Fragmentation , Fibroblasts/cytology , Fluorescein-5-isothiocyanate/analogs & derivatives , Fluorescein-5-isothiocyanate/metabolism , Humans , Keratinocytes/pathology , Medicine, Korean Traditional , Phosphatidylserines/metabolism , Plant Extracts/pharmacology , Radiation-Protective Agents/pharmacologyABSTRACT
This study was designed to confirm the applicability of a liposome-based immunochromatographic assay for the rapid detection of Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella Typhimurium) in artificially contaminated tomato samples. To determine the detection limit and pre-enrichment incubation time (10, 12, and 18 h pre-enrichment in 1% buffered peptone water), the tests were performed with different cell numbers of Salmonella Typhimurium (3 × 10(0), 3 × 10(1), 3 × 10(2), and 3 × 10(3) CFU·mL(-1)) inoculated into 25 g of crushed tomato samples. The assay was able to detect as few as 30 Salmonella Typhimurium cells per 25 g of tomato samples (1.2 cells·g(-1)) after 12 h pre-enrichment incubation. Moreover, when the developed assay was compared with traditional morphological and biochemical culture-based methods as well as colloidal gold nanoparticle-based commercial test strips, the developed assay yielded positive results for the detection of Salmonella Typhimurium within a shorter period time. These findings confirm that the developed assay may have practical application for the sensitive detection of Salmonella Typhimurium in various food samples, including raw vegetables, with a relatively low detection limit and shorter analysis time.
Subject(s)
Chromatography/methods , Food Microbiology , Salmonella typhimurium/isolation & purification , Solanum lycopersicum/microbiology , Antibodies, Bacterial/immunology , Bacterial Load , Chromatography/standards , Collodion , Cross Reactions , Immunoglobulin G/immunology , Liposomes , Reagent Strips/standards , Salmonella Food Poisoning/microbiology , Salmonella Food Poisoning/prevention & control , Sensitivity and Specificity , Time FactorsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Myelophil, a combination of extracts taken from Astragali Radix and Salviae Miltiorrhizae Radix, is a traditional Chinese medicine used for the treatment of chronic fatigue-associated disorders. Here we examined the ability of Myelophil to alleviate memory impairment in a mouse model. We aimed to investigate whether Myelophil has the pharmacological effects on memory deficits associated with brain dysfunctions using an animal model. MATERIALS AND METHODS: Ten week-old male C57BL/6N mice were pretreated with Myelophil (50, 100, or 200 mg/kg), or tacrine (10 mg/kg) for 7 days, and then intraperitoneally injected with scopolamine (1 mg/kg). Memory-related behaviors were evaluated using the Morris water maze for 5 days. Levels of biomarkers of oxidative stress, antioxidant activity, acetylcholinesterase (AChE) activity, and extracellular signal-regulated kinase (ERK) were measured in brain tissues. RESULTS: Scopolamine treatment increased the escape latency time and shortened time spent in the target quadrant; these effects were ameliorated by pretreatment with Myelophil. Scopolamine-induced changes in reactive oxygen species (ROS), malondialehyde (MDA), and AChE activity were significantly attenuated in mice pretreated with Myelophil. Recovery of antioxidant capacities, including total glutathione (GSH) content, and the activities of GSH-reductase, GSH-S-transferase, and catalase was also evident in Myelophil-treated mice. The strongest effects were seen for ERK and muscarinic acetylcholine receptor 1 (mAChR1) at both the protein and gene expression levels, with significant amelioration of expression levels in the Myelophil pretreatment group. CONCLUSIONS: These results suggest that Myelophil confers anti-amnesic properties in a mouse model of memory impairment, driven in part by the modulation of cholinergic activity.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Memory Disorders/drug therapy , Neuroprotective Agents/therapeutic use , Phytotherapy , Acetylcholinesterase/metabolism , Animals , Astragalus Plant , Brain/drug effects , Brain/metabolism , Catalase/metabolism , Cells, Cultured , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Ethanol/chemistry , Glutathione/metabolism , Glutathione Transferase/metabolism , MAP Kinase Signaling System/drug effects , Male , Malondialdehyde/metabolism , Maze Learning/drug effects , Memory Disorders/chemically induced , Memory Disorders/metabolism , Mice, Inbred C57BL , Microglia/drug effects , Microglia/metabolism , Neuroprotective Agents/pharmacology , Nitric Oxide/metabolism , Plant Roots , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Receptors, Muscarinic/genetics , Receptors, Muscarinic/metabolism , Salvia miltiorrhiza , Scopolamine , Solvents/chemistry , Superoxide Dismutase/metabolismABSTRACT
BACKGROUNDS: To evaluate the effectiveness of simultaneous medial spindle procedure (MS) and/or lateral tarsal strip procedure (TS) with an endonasal dacryocystorhinostomy (DCR) for treatment of involutional medial punctal ectropion, horizontal eyelid laxity, and nasolacrimal duct obstruction. METHODS: We conducted a retrospective, interventional study of DCR performed from March 2009 to July 2011 by a single surgeon (Baek SH). Patient age, sex, results of medial and lateral distraction test, surgical procedure, time of tube removal, duration of follow-up, functional and anatomical success rate, and causes of failed surgeries were recorded. Lateral lower eyelid laxity was evaluated by a medial distraction test, and medial lid laxity was evaluated by a lateral distraction test. RESULTS: A total of 241 eyes in 175 patients were included in this study. The proportion of combined surgeries to total DCR was 24.5% (59 of 241 eyes). DCR and MS (D + M) were performed on 23 eyes in 17 patients (9.5%) and DCR and TS (D + T) on 29 eyes in 17 patients (12.0%). Concurrent DCR, MS and TS (D + M + T) were performed on seven eyes in four patients (2.9%). Mean age was significantly higher in the combined surgery groups (63.8 ± 10.0 years) than in the DCR group (56.2 ± 10.6 years; p = 0.01, by Mann-Whitney U test). The anatomical success rates were 84.2% in D, 86.9% in D + M, 89.5% in D + T, and 85.7% in D + M + T (p = 0.61 by Kruskal-Wallis test). Functional success rates were 82.4% in D, 86.9% in D + M, 86.2% in D + T, and 85.7% in D + M + T (p = 0.91 by Kruskal-Wallis test). CONCLUSIONS: MS and TS performed concurrently with a DCR may be an effective tool to deal with epiphora due to complex clinical situations such as nasolacrimal duct obstruction, lid laxity, and involutional medial ectropion. It is recommended to examine punctum and lid laxity carefully using slit-lamp biomicroscopy and lid distraction test in patients with epiphora, especially in elderly patients.
Subject(s)
Dacryocystorhinostomy/methods , Ectropion/surgery , Nasolacrimal Duct/surgery , Asian People/ethnology , Ectropion/ethnology , Endoscopy , Female , Humans , Lacrimal Duct Obstruction/ethnology , Male , Middle Aged , Oculomotor Muscles/surgery , Republic of Korea , Retrospective Studies , Tendon Transfer , Treatment OutcomeABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris, also called "InJin" in Korean, has been widely used to treat various hepatic disorders in traditional Oriental medicine. AIMS: The purpose of this study is to evaluate the hepatoprotective effect of Artemisia capillaris (aqueous extract, WAC) on alcoholic liver injury. MATERIALS AND METHODS: Liver injury was induced by oral administration of 30% alcohol (10 mL/kg, twice per day) plus pyrazole (PRZ, 30 mg/kg) with/without WAC (50, 100mg/kg, orally once per day) or silymarin (50mg/kg) for 10 days. The hepatoprotective effects were assessed by observing histopathological changes, hepatic transaminase enzymes, hepatic oxidation and antioxidant parameters, inflammatory cytokines, and alcohol metabolic enzymes in serum and hepatic gene expression level, respectively. RESULTS: Alcohol-PRZ treatment drastically increased the serum levels of aspartate transaminase (AST), alanine transaminase (ALT), and malondialdehyde (MDA) levels in serum and liver tissues while these changes were significantly ameliorated by WAC administration (p<0.05 or 0.01). The prominent microvesicular steatosis and mild necrosis in hepatic histopathology were induced by alcohol-PRZ treatment, but notably attenuated by WAC administration. Moreover, the alcohol-PRZ treatment-induced depletions of the antioxidant components including glutathione content, total antioxidant capacity (TAC), activities of glutathione peroxidase (GSH-Px), reductase (GSH-Rd), catalase, and superoxide dismutase (SOD) were significantly ameliorated by WAC administration (p<0.05, except GSH-Rd). These results were in accordance with the modulation of NF-E2-related factor (Nrf2) and heme oxygenase-1 (HO-1) gene expression. Alcohol-PRZ treatment increased the levels of tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-ß) in hepatic tissues. However they were significantly normalized by WAC administration (p<0.05 or 0.01). In addition, WAC administration significantly attenuated the alterations of aldehyde dehydrogenase (ALDH) level in serum and hepatic gene expressions of ALDH and alcohol dehydrogenase (ADH). CONCLUSIONS: These results support the relevance in clinical use of Artemisia capillaris for alcohol-associated hepatic disorders. The underlying mechanisms may involve both enhancement of antioxidant activities and modulation of proinflammatory cytokines.
Subject(s)
Artemisia , Chemical and Drug Induced Liver Injury/drug therapy , Plant Extracts/therapeutic use , Protective Agents/therapeutic use , Alanine Transaminase/blood , Alkaline Phosphatase/blood , Animals , Aspartate Aminotransferases/blood , Blood Glucose/analysis , Catalase/metabolism , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Ethanol , Glutathione/metabolism , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , L-Lactate Dehydrogenase/blood , Male , Phytotherapy , Plant Extracts/pharmacology , Protective Agents/pharmacology , Pyrazoles , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/blood , Serum Albumin/analysis , Superoxide Dismutase/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/metabolismABSTRACT
PURPOSE: To evaluate the correlation between tear film lipid layer thickness and other objective measurements such as tear film break-up time (TBUT), upper and lower meibomian gland losses, and Schirmer 1 test in patients with obstructive meibomian gland dysfunction (MGD) and normal controls. DESIGN: Cross-sectional study. METHODS: Thirty eyes of 30 patients with obstructive MGD and 25 eyes of 25 normal controls were enrolled. Lipid layer thickness was measured using an interferometer. Tear film stability and tear production were evaluated by TBUT and Schirmer 1 test. Upper and lower meibomian gland losses were evaluated using noncontact meibography. The correlations among variables were evaluated in the obstructive MGD group and the control group. RESULTS: TBUT was significantly shorter in the obstructive MGD group than in the control group (P < .001). Upper and lower meibomian gland losses were higher in the obstructive MGD group than in the control group (P < .001 and P < .001, respectively), and lipid layer thickness was significantly thicker in the control group than in the obstructive MGD group (P = .028). Lipid layer thickness was significantly negatively correlated with upper and lower meibomian gland losses in both groups. CONCLUSIONS: Lipid layer thickness objectively measured with the interferometer was significantly thicker in the control group than in the obstructive MGD group. Lipid layer thickness was negatively correlated with upper and lower meibomian gland losses in the control group as well as in the obstructive MGD group.
Subject(s)
Eyelid Diseases/metabolism , Lipid Metabolism/physiology , Meibomian Glands/metabolism , Tears/metabolism , Adult , Aged , Conjunctiva/metabolism , Cornea/metabolism , Cross-Sectional Studies , Dry Eye Syndromes/metabolism , Eyelid Diseases/pathology , Female , Humans , Interferometry , Male , Meibomian Glands/pathology , Middle AgedABSTRACT
Artemisia capillaris has been widely used as a traditional herbal medicine in the treatment of liver diseases. However, no previous study has investigated whether A. capillaries alone is effective in treating pathological conditions associated with cholestatic liver injury. In the present study, we evaluated the anti-hepatofibrotic effects of A. capillaris (aqueous extract, WAC) in a bile duct ligation (BDL)-induced cholestatic fibrosis model. After BDL, rats were given WAC (25 or 50 mg/kg) or urosodeoxycholic acid (UDCA, 25 mg/kg) orally for 2 weeks (once per day). The serum cholestatic markers, malondialdehyde, and liver hydroxyproline levels were drastically increased in the BDL group, while administering WAC significantly reduced these alterations. Administering WAC also restored the BDL-induced depletion of glutathione content and glutathione peroxidase activity. Cholestatic liver injury and collagen deposition were markedly attenuated by WAC treatment, and these changes were paralleled by the significantly suppressed expression of fibrogenic factors, including hepatic alpha-smooth muscle actin (α-SMA), platelet-derived growth factor (PDGF), and transforming growth factor beta (TGF-ß). The beneficial effects of WAC administration are associated with antifibrotic properties via both upregulation of antioxidant activities and downregulation of ECM protein production in the rat BDL model.
Subject(s)
Artemisia/chemistry , Cholagogues and Choleretics/therapeutic use , Cholestasis/complications , Drugs, Chinese Herbal/therapeutic use , Liver Cirrhosis/prevention & control , Animals , Antioxidants/metabolism , Cholagogues and Choleretics/administration & dosage , Cholagogues and Choleretics/isolation & purification , Cholestasis/pathology , Disease Models, Animal , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/isolation & purification , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Liver Function Tests , Male , Rats , Rats, Sprague-Dawley , Ursodeoxycholic Acid/administration & dosage , Ursodeoxycholic Acid/therapeutic useABSTRACT
Pu-erh tea is produced in China and known to possess medicinal properties. The anticancer and antiangiogenesis effects of fermented Pu-erh tea on HT-29 colon cancer cells and human umbilical vein endothelial cells, respectively, were examined. Two kinds of unfermented and fermented Pu-erh tea (Seven-son tea cake Pu-erh tea and Xiaguan bowl tea [X]) and green tea were used. An MTT assay showed fermented Pu-erh tea X (85% inhibition) possessed more potent anticancer activities than unfermented Pu-erh tea X (67% inhibition) and green tea (53% inhibition) (P < 0.05). Moreover, fermented Pu-erh tea X increased the number of apoptotic bodies determined through DAPI staining and flow cytometric analysis. Fermented Pu-erh tea X induced apoptosis indicated by increased expression of Bax, caspase-9, and caspase-3 messenger RNA and decreased expression of Bcl-2. Fermented Pu-erh tea X also had an anti-inflammation effect, shown in decreased expression of nuclear factor-κB-p65, inducible nitric oxide synthase, COX-2 messenger RNA and increased expression of IκB-α. Further, fermented Pu-erh teas showed stronger antiangiogenesis effects than the 2 other types of tea. After fermentation, the concentrations of gallic acid, resorcylic acid, quercetin, and kaempferol in Pu-erh tea were increased. These results collectively indicated that fermented and unfermented Pu-erh teas possess stronger anticancer and antiangiogenesis effects than green tea. Furthermore, fermented Pu-erh tea showed stronger functional activities than unfermented Pu-erh tea.