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1.
J Pharmacopuncture ; 26(1): 99-104, 2023 Mar 31.
Article in English | MEDLINE | ID: mdl-37007291

ABSTRACT

Our study purpose was to report the clinical application of five different pharmacopunctures (Sweet BV, Scolopendrae Corpus, Chukyu, Cervi Parvum Cornu, and Hominis Placenta) for trigger finger. A patient was admitted to Ba-reun-mom S Korean Medicine Clinic and diagnosed with trigger finger. Because the effects of each pharmacopuncture have been confirmed in various acute to chronic cases, we treated a patient diagnosed with trigger finger using pharmacopunctures Sweet BV and Scolopendrae Corpus at the acute phase, Chukyu pharmacopuncture at the acute to chronic phase, and pharmacopunctures Cervi Parvum Cornu and Hominis Placenta at the chronic phase. This case was measured and assessed by Quinnell's classification of triggering and visual analogue scale (VAS) scores. After treatment, the patient's fifth finger pain and function were improved. The VAS score decreased from 5 to 0. The Quinnell's classification of triggering score decreased from 2 to 0. This case indicated that a patient with trigger finger could be treated by five pharmacopuncture treatments according to the treatment regimen and disease progress.

2.
Biomaterials ; 275: 120925, 2021 08.
Article in English | MEDLINE | ID: mdl-34171755

ABSTRACT

Radiation proctitis is the collateral damage that occurs to healthy cells during radiation treatment of pelvic malignancies. Conservative treatment of radiation proctitis can mitigate inflammatory symptoms, but, to date, no therapeutic options are available for direct recovery of the damaged colonic epithelium. The present study assessed the ability of colon organoid-based regeneration to treat radiation proctitis. Radiation proctitis was induced in mice by irradiating their recta, followed by enema-based transplantation of mouse colon organoids. The transplanted colon organoids were found to successfully engraft onto the damaged rectal mucosa of the irradiated mice, reconstituting epithelial structure and integrity. Lgr5+ stem cells were shown to be pivotal to colon organoid mediated regeneration. Endoscopic examination showed the efficacy of localized transplantation of colon organoids with fibrin glue to irradiated sites. These findings provide useful insights into the use of colon organoid-based regenerative therapy for the treatment of radiation proctitis.


Subject(s)
Proctitis , Radiation Injuries , Animals , Colon , Intestinal Mucosa , Mice , Organoids , Proctitis/therapy , Radiation Injuries/therapy
3.
Ann Med Surg (Lond) ; 63: 102057, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33664939

ABSTRACT

BACKGROUND: The purpose of our study was to investigate the effects of extracorporeal shock wave therapy (ESWT) and hand massage therapy (HMT) on serum lipids and body composition in Korean women. MATERIALS AND METHODS: We randomly classified 60 participants into overweight and obese groups. Subjects received ESWT and HMT twice a week for six weeks (a total of 12 sessions). RESULTS: Body weight and body mass index decreased significantly in obese women from both groups. Waist circumference significantly declined in obese women and overweight women in both treatment groups (p < 0.001). Body fat significantly decreased in the ESWT group of obese women (p < 0.01), while a significant reduction in abdominal obesity was noted only in the HMT group of overweight women (p < 0.01) and the ESWT group of obese women (p < 0.01). There was a significant decrease in triglycerides in the ESWT group of obese women (p < 0.01). CONCLUSIONS: These results suggest that ESWT and HMT could be helpful for the management of people with excess abdominal fat and obesity. Moreover, ESWT is more effective than HMT for improving abdominal obesity and triglyceride levels in obese women as compared to overweight women.

4.
Homeopathy ; 110(2): 108-114, 2021 May.
Article in English | MEDLINE | ID: mdl-33472246

ABSTRACT

BACKGROUND: Rhus toxicodendron (R. tox) has been used as a homeopathic remedy for the treatment of inflammatory conditions. Previously, we reported that R. tox modulated inflammation in the mouse chondrocyte and pre-osteoblastic MC3T3-e1 cell line. During the inflammatory process, cells adhere to the extracellular matrix (ECM) and then migrate to the inflammation site. We examine here the process of cell adhesion in MC3T3-e1 cells after their stimulation with homeopathic R. tox. METHODS: For the cell-substrate adhesion assay, the cultured MC3T3-e1 cells were trypsinized, starved for 1 h in serum-free media, and plated onto culture plates coated with fibronectin (FN), 30c R. tox or gelatin, respectively. The cells were allowed to adhere for 20 min incubation and unattached cells were washed out. Adherent cells were measured using the water-soluble tetrazolium salt-8 assay. The intracellular signals after stimulation of R. tox were examined by analyzing the tyrosine phosphorylation of focal adhesion kinase (FAK), Src kinase, and Paxillin using immunoblot assay. Formation of focal adhesion (FA, an integrin-containing multi-protein structure that forms between intracellular actin bundles and the ECM) was analyzed by immunocytochemistry using NIH ImageJ software. RESULTS: Cell adhesion increased after stimulation with R. tox (FN, 20.50%; R. tox, 44.80%; and gelatin, 17.11% vs. uncoated cells [control]). Tyrosine phosphorylation of FAK, Paxillin, and Src increased compared with that of gelatin when stimulated with R. tox. Additionally, R. tox-stimulated cells formed many FAs (number of FAs per cell, 35.82 ± 7.68) compared with gelatin-stimulated cells (number of FAs per cell, 19.80 ± 7.18) and exhibited extensive formation of actin stress fibers anchored by FAs formed at the cell periphery. CONCLUSION: Homeopathic R. tox promotes the formation of cell adhesions in vitro.


Subject(s)
Cell Adhesion/drug effects , Toxicodendron/metabolism , Animals , Disease Models, Animal , Inflammation/drug therapy , Materia Medica/standards , Materia Medica/therapeutic use , Mice
5.
Liver Transpl ; 24(7): 932-945, 2018 07.
Article in English | MEDLINE | ID: mdl-29710388

ABSTRACT

Both sorafenib and mammalian target of rapamycin inhibitor (mTORi) have antitumor effects. This study aimed to evaluate their antitumor effects in liver transplantation (LT) recipients with hepatocellular carcinoma (HCC) recurrence. We performed a laboratory study using sorafenib and mTORi and subsequently validated their survival benefit in a clinical LT setting. In the laboratory study, the HepG2.2.15 liver tumor cell line and 5 patient-derived graft HCC cell lines were used for in vitro cytotoxic studies. After treatment with everolimus and sorafenib, cell viability and apoptosis assays revealed noticeable cytotoxic effects with individual agents and augmented effects by combination therapy. An in vivo mouse study also demonstrated similar cytotoxic outcomes. In the clinical study including 232 LT recipients with HCC recurrence, the 3-month medication drop-out rate was 35.6% for sorafenib administration and 23.5% for mTORi administration. Postrecurrence survival rates were not different according to sorafenib administration (P = 0.17) but were significantly improved following mTORi administration (P < 0.001). In mTORi subgroups with and without sorafenib, there was no difference in the overall postrecurrence patient survival period (P = 0.26), indicating an absence of synergistic or additional antitumor effect from sorafenib. The median progression-free and overall survival period was 6.4 and 11.8 months, respectively, after sorafenib administration. Time of tumor recurrence and use of mTORi were independent risk factors. In conclusion, our laboratory study demonstrated synergistic antitumor effects of sorafenib and mTORi, but this was not reproduced in our clinical LT study. Our clinical result of mTORi administration showed improved postrecurrence survival, thus administering mTORi in LT recipients with HCC recurrence appears worthwhile. However, the antitumor effect of sorafenib on posttransplant recurrence was not determined in this retrospective study, thus requiring further studies with early start of sorafenib administration. Liver Transplantation 24 932-945 2018. © 2018 AASLD.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Liver Transplantation , Neoplasm Recurrence, Local/drug therapy , Sorafenib/therapeutic use , TOR Serine-Threonine Kinases/antagonists & inhibitors , Animals , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/surgery , Cell Survival/drug effects , Female , Hep G2 Cells , Humans , Liver Neoplasms/mortality , Liver Neoplasms/surgery , Male , Mice, Inbred NOD , Mice, Nude , Mice, SCID , Middle Aged , Neoplasm Recurrence, Local/mortality , Postoperative Period , Progression-Free Survival , Retrospective Studies , Survival Analysis , Time Factors , Xenograft Model Antitumor Assays
6.
Int J Mol Sci ; 18(12)2017 Dec 18.
Article in English | MEDLINE | ID: mdl-29258263

ABSTRACT

Tussilagone, extracted from Tussilago farfara is an oriental medicine used for asthma and bronchitis. We investigated its mechanism of action, its inhibitory effects on lipopolysaccharide-induced inflammation in macrophages, and its impact on viability in a cecal ligation and puncture (CLP)-induced mouse model of sepsis. Tussilagone suppressed the expression of the inflammatory mediators, nitric oxide and prostaglandin E2, and the inflammatory cytokines, tumor necrosis factor-alpha (TNF-α) and high-mobility group box 1 (HMGB1), in lipopolysaccharide-stimulated RAW 264.7 cells and peritoneal macrophages. Tussilagone also reduced the activation of the mitogen-activated protein kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) involved in the activation of various inflammatory mediators in activated macrophages. Moreover, tussilagone administration (1 mg/kg and 10 mg/kg) produced decreased mortality and lung injury in CLP-activated septic mice. Augmented expression of cyclooxygenase (COX)-2 and TNF-α in pulmonary alveolar macrophages of septic mice were attenuated by tussilagone administration. Tussilagone also suppressed the induction of nitric oxide, prostaglandin E2, TNF-α and HMGB1 in the serum of the septic mice. Overall, tussilagone exhibited protective effects against inflammation and polymicrobial sepsis by suppressing inflammatory mediators possibly via the inhibition of NF-κB activation and the MAP kinase pathway. These results suggest the possible use of tussilagone for developing novel therapeutic modalities for sepsis and other inflammatory diseases.


Subject(s)
Inflammation/drug therapy , Sepsis/drug therapy , Sepsis/mortality , Sesquiterpenes/therapeutic use , Animals , Cecum/injuries , Dinoprostone/blood , HMGB1 Protein/blood , Inflammation/blood , Ligation/adverse effects , Macrophages/metabolism , Male , Mice , Mice, Inbred BALB C , Sepsis/blood , Sepsis/immunology , Signal Transduction , Tumor Necrosis Factor-alpha/blood
7.
BMC Complement Altern Med ; 17(1): 222, 2017 Apr 20.
Article in English | MEDLINE | ID: mdl-28427397

ABSTRACT

BACKGROUND: HVC1 consists of Coptidis Rhizoma (dried rhizome of Coptischinensis), Scutellariae Radix (root of Scutellariabaicalensis), Rhei Rhizoma (rhizome of Rheum officinale), and Pruni Cortex (cortex of Prunusyedoensis Matsum). Although the components are known to be effective in various conditions such as inflammation, hypertension, and hypercholesterolemia, there are no reports of the molecular mechanism of its hypolipidemic effects. METHODS: We investigated the hypolipidemic effect of HVC1 in low-density lipoprotein receptor-deficient (LDLR-/-) mice fed a high-cholesterol diet for 13 weeks. Mice were randomized in to 6 groups: ND (normal diet) group, HCD (high-cholesterol diet) group, and treatment groups fed HCD and treated with simvastatin (10 mg/kg, p.o.) or HVC1 (10, 50, or 250 mg/kg, p.o.). RESULTS: HVC1 regulated the levels of total cholesterol, triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol in mouse serum. In addition, it regulated the transcription level of the peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding proteins (SREBP)-2, 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase, lipoprotein lipase (LPL), apolipoprotein B (apo B), liver X receptor (LXR), and inflammatory cytokines (IL-1ß, IL-6, and TNF-α). Furthermore, HVC1 activated 5' adenosine monophosphate-activated protein kinase (AMPK). CONCLUSION: Our results suggest that HVC1 might be effective in preventing high-cholesterol diet-induced hyperlipidemia by regulating the genes involved in cholesterol and lipid metabolism, and inflammatory responses.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Cholesterol/blood , Drugs, Chinese Herbal/pharmacology , Hyperlipidemias , Hypolipidemic Agents/pharmacology , Inflammation , Phytotherapy , AMP-Activated Protein Kinases/metabolism , Animals , Anti-Inflammatory Agents/therapeutic use , Apolipoproteins B/metabolism , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cytokines/metabolism , Diet, High-Fat , Drugs, Chinese Herbal/therapeutic use , Hyperlipidemias/blood , Hyperlipidemias/drug therapy , Hyperlipidemias/etiology , Hypolipidemic Agents/therapeutic use , Inflammation/blood , Inflammation/drug therapy , Lipid Metabolism/drug effects , Liver/drug effects , Liver/metabolism , Male , Mice, Knockout , Receptors, LDL/blood , Receptors, LDL/deficiency , Receptors, LDL/genetics , Transcription Factors/metabolism , Triglycerides/blood
8.
Homeopathy ; 105(1): 42-7, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26827996

ABSTRACT

BACKGROUND: Homeopathic remedy Rhus toxicodendron (Rhus tox) is used for several symptoms including skin irritations, rheumatic pains, mucous membrane afflictions, and typhoid type fever. Previously, we reported that Rhus tox treatment increased the cyclooxygenase-2 (COX-2) mRNA expression in primary cultured mouse chondrocytes. METHODS: A preosteoblastic mouse cell line, MC3T3-e1, was treated with different homeopathic dilutions of Rhus tox and the COX-2 mRNA and protein expression was examined using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblotting. Additionally, nitric oxide (NO) generation was examined in LPS-induced MC3T3-e1 cells using a Griess reaction assay. RESULTS: Stimulation with different concentrations of Rhus tox increased the expression of Cox2 mRNA, with 30X Rhus tox showing the most prominent increase in mRNA expression. In addition, treatment with 30X Rhus tox significantly increased prostaglandin E2 (PGE2) release compared with other homeopathic dilutions. However, the COX-2 protein expression level differed slightly from its mRNA expression, because the 30C Rhus tox treatment increased COX-2 protein to a greater extent compared with other dilutions. NO generation was dramatically decreased in MC3T3-e1 cells after Rhus tox treatment co-stimulated with lipopolysaccharide. CONCLUSION: Homeopathic dilution of Rhus tox has a dual activity that increases COX-2 expression and decreases NO generation, thus modulating inflammation. Further study is needed to examine the cellular signaling mechanisms that are associated with inflammatory regulation by Rhus tox treatment in greater detail.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 2 Inhibitors/therapeutic use , Inflammation Mediators/pharmacology , Plant Extracts/pharmacology , Toxicodendron , Animals , Carrier Proteins/drug effects , Cyclooxygenase 2 Inhibitors/pharmacology , Cytokines/drug effects , Disease Models, Animal , Homeopathy/methods , Mice , Phytotherapy/methods
9.
Molecules ; 21(1): 94, 2016 Jan 15.
Article in English | MEDLINE | ID: mdl-26784157

ABSTRACT

A method for the separation and quantification of three flavonoids and one isocoumarin by reverse-phase high performance liquid chromatography (HPLC) has been developed and validated. Four constituents present in a crude ethanolic extract of the flowers of Coryloposis coreana Uyeki, were analyzed. Bergenin, quercetin, quercitrin and isosalipurposide were used as calibration standards. In the present study, an excellent linearity was obtained with an r² higher than 0.999. The chromatographic peaks showed good resolution. In combination with other validation data, including precision, specificity, and accuracy, this method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of bergenin, quercetin, quercitrin and isosalipurposide in the crude ethanolic extract of C. coreana Uyeki flos. Furthermore, the plant extracts were analyzed with HPLC to determine the four constituents and compositional differences in the extracts obtained under different extraction conditions. Several extracts of them which was dependent on the ethanol percentage of solvent were also analyzed for their antimicrobial and antioxidant activities. One hundred % ethanolic extract from C. coreana Uyeki flos showed the best antimicrobial activity against the methicillin-resistant Staphylococcus aureus (MRSA) strain. Eighty % ethanolic extract showed the best antioxidant activity and phenolic content. Taken of all, these results suggest that the flower of C. coreana Uyeki flos may be a useful source for the cure and/or prevention of septic arthritis, and the validated method was useful for the quality control of C. coreana Uyeki.


Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Inflammatory Agents/isolation & purification , Antioxidants/isolation & purification , Flavonoids/isolation & purification , Hamamelidaceae/chemistry , Isocoumarins/isolation & purification , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Calibration , Chalcones/chemistry , Chalcones/isolation & purification , Chromatography, High Pressure Liquid , Chromatography, Reverse-Phase , Ethanol , Flavonoids/chemistry , Flavonoids/pharmacology , Flowers/chemistry , Humans , Isocoumarins/chemistry , Isocoumarins/pharmacology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/growth & development , Plant Extracts/chemistry , Quercetin/analogs & derivatives , Quercetin/chemistry , Quercetin/isolation & purification , Reference Standards , Sensitivity and Specificity , Solvents
10.
Article in English | MEDLINE | ID: mdl-26413130

ABSTRACT

Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whether Prunus yedoensis (PY) bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity model in vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects.

11.
PLoS One ; 9(8): e105990, 2014.
Article in English | MEDLINE | ID: mdl-25153887

ABSTRACT

The prevalence of metabolic syndrome has been increasing rapidly worldwide. The functions of zinc may have a potential association with metabolic syndrome, but such associations have not been investigated extensively. Therefore, we examined the relationship between serum zinc levels and metabolic syndrome or metabolic risk factors among South Korean adults ≥ 20 years of age. The analysis used data from the Korean National Health and Nutrition Examination Survey, a cross-sectional survey of Korean civilians, conducted from January to December 2010. A total of 1,926 participants were analyzed in this study. Serum zinc levels in men were negatively associated with elevated fasting glucose (adjusted odds ratio [aOR], 0.58; 95% confidence interval [CI], 0.36-0.93) and positively associated with elevated triglycerides (aOR, 1.47; 95% CI, 1.01-2.13). A difference in serum zinc levels was detected in women, depending on the number of metabolic syndrome components (p = 0.002). Furthermore, serum zinc levels showed a decreasing trend with increasing numbers of metabolic syndrome components in women with metabolic syndrome. These findings suggest that serum zinc levels might be associated with metabolic syndrome or metabolic risk factors. Further gender-specific studies are needed to evaluate the effect of dietary or supplemental zinc intake on metabolic syndrome.


Subject(s)
Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Zinc/blood , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Nutrition Surveys , Prevalence , Republic of Korea/epidemiology , Risk Factors , Sex Factors , Young Adult
12.
Article in English | MEDLINE | ID: mdl-24555929

ABSTRACT

The purpose of this study is to optimize ELISA conditions to quantify the colorectal cancer antigen GA733 linked to the Fc antibody fragment fused to KDEL, an ER retention motif (GA733-FcK) expressed in transgenic plant. Variable conditions of capture antibody, blocking buffer, and detection antibody for ELISA were optimized with application of leaf extracts from transgenic plant expressing GA733-FcK. In detection antibody, anti-EpCAM/CD362 IgG recognizing the GA733 did not detect any GA733-FcK whereas anti-human Fc IgG recognizing the human Fc existed in plant leaf extracts. For blocking buffer conditions, 3% BSA buffer clearly blocked the plate, compared to the 5% skim-milk buffer. For capture antibody, monoclonal antibody (MAb) CO17-1A was applied to coat the plate with different amounts (1, 0.5, and 0.25 µg/well). Among the amounts of the capture antibody, 1 and 0.5 µg/well (capture antibody) showed similar absorbance, whereas 0.25 µg/well of the capture antibody showed significantly less absorbance. Taken together, the optimized conditions to quantify plant-derived GA733-FcK were 0.5 µg/well of MAb CO17-1A per well for the capture antibody, 3% BSA for blocking buffer, and anti-human Fc conjugated HRP. To confirm the optimized ELISA conditions, correlation analysis was conducted between the quantified amount of GA733-FcK in ELISA and its protein density values of different leaf samples in Western blot. The co-efficient value R(2) between the ELISA quantified value and protein density was 0.85 (p<0.01), which indicates that the optimized ELISA conditions feasibly provides quantitative information of GA733-FcK expression in transgenic plant.


Subject(s)
Antigen-Antibody Complex/genetics , Antigens, Neoplasm/genetics , Cell Adhesion Molecules/genetics , Colorectal Neoplasms/immunology , Immunoglobulin Fc Fragments/genetics , Plants, Genetically Modified/genetics , Antibodies, Monoclonal/immunology , Antigen-Antibody Complex/analysis , Antigens, Neoplasm/immunology , Cancer Vaccines , Cell Adhesion Molecules/immunology , Colorectal Neoplasms/genetics , Enzyme-Linked Immunosorbent Assay/methods , Epithelial Cell Adhesion Molecule , Humans , Immunoglobulin Fc Fragments/immunology , Immunoglobulin G/immunology , Plant Extracts/immunology , Plant Leaves/metabolism , Receptors, Peptide/genetics , Recombinant Proteins/biosynthesis , Recombinant Proteins/genetics
13.
Nanotechnology ; 24(25): 255602, 2013 Jun 28.
Article in English | MEDLINE | ID: mdl-23723185

ABSTRACT

Mesoporous nanofibers (MSNFs) can be fabricated in the pores of anodic aluminum oxide (AAO) membrane using diverse methods. Among them vapor phase synthesis (VPS) provides several advantages over sol-gel or evaporation-induced self-assembly (EISA) based methods. One powerful advantage is that we can employ multiple surfactants as structural directing agents (SDAs) simultaneously. By adopting diverse pairs of SDAs, we can control the mesopore structures, i.e. pore size, surface area, and even the morphology of mesostructures. Here, we used F127 as a main SDA, which is relatively robust (thus, difficult to change the mesopore structures), and added a series of cationic co-surfactants to observe the systematical changes in their mesostructure with respect to the chain length of the co-surfactant.


Subject(s)
Nanofibers/chemistry , Nanofibers/ultrastructure , Surface-Active Agents/chemistry , Aluminum Oxide/chemistry , Nanotechnology , Porosity , Volatilization
14.
Food Chem Toxicol ; 56: 231-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23485615

ABSTRACT

The purpose of this study was to investigate the anti-fibrotic effects of the aqueous extract of the Platycodi Radix root (Changkil: CK) on dimethylnitrosamine (DMN)-induced liver fibrosis in rats. DMN treatment for 4 weeks led to marked liver fibrosis as assessed by serum biochemistry, histopathological examination, and hepatic lipid peroxidation and collagen content. CK significantly inhibited DMN-induced increases in serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, fibrosis score, and hepatic malondialdehyde and collagen content. CK also inhibited DMN-induced reductions in rat body and liver weights. Reverse transcription polymerase chain reaction (RT-PCR) and western blot analyses revealed that CK inhibited DMN-induced increases in matrix metalloproteinase-13 (MMP-13), tissue inhibitor of metalloproteinase-1 (TIMP-1), and tumor necrosis factor-α (TNF-α) mRNA, and collagen type I and α-smooth muscle actin protein. DMN-induced cyclooxygenase-2 (COX-2) expression and nuclear factor-kappa B (NF-κB) activation was reduced by CK treatment. Furthermore, CK induced activation of nuclear erythroid 2-related factor 2 (Nrf2)-mediated antioxidant enzymes such as γ-glutamylcysteine synthetase (γ-GCS), heme oxygenase-1 (HO-1), NAD(P)H quinone oxidoreductase 1 (NQO1), and glutathione-S-transferase (GST) in HepG2 cells. These results demonstrated that CK attenuates DMN-induced liver fibrosis through the activation of Nrf2-mediated antioxidant enzymes.


Subject(s)
Antioxidants/pharmacology , Dimethylnitrosamine/adverse effects , Liver Cirrhosis/pathology , Plant Extracts/pharmacology , Actins/metabolism , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Collagen Type I/metabolism , Cyclooxygenase 2/metabolism , Glutamate-Cysteine Ligase/metabolism , Glutathione Transferase/metabolism , Heme Oxygenase (Decyclizing)/metabolism , Hep G2 Cells , Humans , Lipid Peroxidation/drug effects , Liver/drug effects , Liver/enzymology , Liver/pathology , Liver Cirrhosis/chemically induced , Liver Cirrhosis/drug therapy , Male , Malondialdehyde/blood , Matrix Metalloproteinase 13/metabolism , NAD(P)H Dehydrogenase (Quinone)/metabolism , NF-E2-Related Factor 2/metabolism , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Plant Roots/chemistry , Platycodon , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Tissue Inhibitor of Metalloproteinase-1/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
Bioorg Med Chem Lett ; 22(24): 7451-5, 2012 Dec 15.
Article in English | MEDLINE | ID: mdl-23142612

ABSTRACT

Ten azo compounds including azo-resveratrol (5) and azo-oxyresveratrol (9) were synthesized using a modified Curtius rearrangement and diazotization followed by coupling reactions with various phenolic analogs. All synthesized compounds were evaluated for their mushroom tyrosinase inhibitory activity. Compounds 4 and 5 exhibited high tyrosinase inhibitory activity (56.25% and 72.75% at 50 µM, respectively). The results of mushroom tyrosinase inhibition assays indicate that the 4-hydroxyphenyl moiety is essential for high inhibition and that 3,5-dihydroxyphenyl and 3,5-dimethoxyphenyl derivatives are better for tyrosinase inhibition than 2,5-dimethoxyphenyl derivatives. Particularly, introduction of hydroxyl or methoxy group into the 4-hydroxyphenyl moiety diminished or significantly reduced mushroom tryosinase inhibition. Among the synthesized azo compounds, azo-resveratrol (5) showed the most potent mushroom tyrosinase inhibition with an IC(50) value of IC(50)=36.28 ± 0.72 µM, comparable to that of resveratrol, a well-known tyrosinase inhibitor.


Subject(s)
Azo Compounds/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Plant Extracts/pharmacology , Stilbenes/pharmacology , Agaricales/enzymology , Azo Compounds/chemical synthesis , Azo Compounds/chemistry , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Molecular Structure , Monophenol Monooxygenase/metabolism , Plant Extracts/chemical synthesis , Plant Extracts/chemistry , Resveratrol , Stilbenes/chemical synthesis , Stilbenes/chemistry , Structure-Activity Relationship
17.
J Med Food ; 12(2): 320-6, 2009 Apr.
Article in English | MEDLINE | ID: mdl-19459732

ABSTRACT

The present study was undertaken to examine the protective effects of an anthocyanin fraction (AF) obtained from purple-fleshed sweet potato on acetaminophen (paraceptamol [APAP])-induced hepatotoxicity in mice and to determine the mechanism involved. Mice pretreated with AF prior to APAP administration showed significantly lower increases in serum alanine aminotransferase and aspartate aminotransferase activities and hepatic malondialdehyde formation than APAP-treated animals without AF. In addition, AF prevented hepatic glutathione (GSH) depletion by APAP, and hepatic GSH levels and GSH S-transferase activities were up-regulated by AF. APAP-induced hepatotoxicity was also prevented by AF, as indicated by liver histopathology findings. In addition, the effects of AF were examined on cytochrome P450 (CYP) 2E1, the major isozyme involved in APAP bioactivation. Treatment of mice with AF significantly and dose-dependently reduced CYP2E1-dependent aniline hydroxylation and CYP2E1 protein levels. Furthermore, AF had an antioxidant effect on FeCl(2)/ascorbate-induced lipid peroxidation in mouse liver homogenates and had superoxide radical scavenging activity. These results suggest that AF protects against APAP-induced hepatotoxicity by blocking CYP2E1-mediated APAP bioactivation, by up-regulating hepatic GSH levels, and by acting as a free radical scavenger.


Subject(s)
Acetaminophen/adverse effects , Anthocyanins/therapeutic use , Chemical and Drug Induced Liver Injury/drug therapy , Ipomoea batatas , Liver Diseases/prevention & control , Liver/drug effects , Plant Extracts/therapeutic use , Alanine Transaminase/metabolism , Aniline Compounds/metabolism , Animals , Anthocyanins/pharmacology , Aspartate Aminotransferases/metabolism , Carcinogens/metabolism , Chemical and Drug Induced Liver Injury/pathology , Cytochrome P-450 CYP2E1/metabolism , Free Radical Scavengers/pharmacology , Free Radical Scavengers/therapeutic use , Glutathione/metabolism , Glutathione Transferase/metabolism , Lipid Peroxidation/drug effects , Liver/pathology , Male , Malondialdehyde/metabolism , Mice , Mice, Inbred ICR , Phytotherapy , Plant Extracts/pharmacology , Protective Agents/pharmacology , Protective Agents/therapeutic use
18.
Immunopharmacol Immunotoxicol ; 31(3): 439-45, 2009.
Article in English | MEDLINE | ID: mdl-19267283

ABSTRACT

Hyperlipidemia has been implicated in atherosclerosis which is the leading cause of death among world population and resulting from lipid metabolic changes is a major cause of atherosclerosis. Bambusae Caulis in Taeniam belongs to Bambusaceae is the stem of Phyllostachys nigra (Lodd.) Munro var. henonis (Bean) Stapf of Phyllostachys bambusoides Siebold et Zuccarini, the perennial evergreen tree. The green middle layer of stem is dried in string-shape I shadow after the bark had been removed. In this study, the effects of middle layer of PN, PB, PP, and BCT on rat with hyperlipidemia, induced by Triton WR-1339 and high cholesterol diet were investigated. We measured plasma levels of triglyceride, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol as measure of its hyperlipidemic effects. As a result, all of the Bambusae Caulis in Taeniam was reduced total cholesterol, LDL. Inhibition rate on LDL-oxidation, hACAT-1, and hACAT-2 was increased dose-dependently. Therefore all of the Bambusae Caulis in Taeniam is a good candidate for the treatment on Triton WR-1339 and high cholesterol diet-induced blood circulatory disorders, obesity, and hyperlipidemia.


Subject(s)
Cholesterol/adverse effects , Detergents/adverse effects , Hyperlipidemias/chemically induced , Hyperlipidemias/drug therapy , Hypolipidemic Agents/pharmacology , Plant Extracts/pharmacology , Poaceae/chemistry , Polyethylene Glycols/adverse effects , Animals , Cholesterol/pharmacology , Detergents/pharmacology , Diet , Hyperlipidemias/blood , Hypolipidemic Agents/chemistry , Male , Plant Extracts/chemistry , Polyethylene Glycols/pharmacology , Rats , Rats, Sprague-Dawley
20.
Cancer Lett ; 268(2): 233-43, 2008 Sep 18.
Article in English | MEDLINE | ID: mdl-18499341

ABSTRACT

The chemopreventive effects of saponin derived from Platycodon grandiflorum (Changkil saponin; CKS) on tumor invasion and migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that CKS reduced 12-O-tetradecanoylphorbol-13-acetate (PMA)-enhanced Matrix metalloproteinases (MMP)-9 and MMP-2 activation in a dose-dependant manner and further inhibited HT-1080 cell invasion and migration. In addition, CKS suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor (NF)-kappaB activation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. CKS also reduced PMA-enhanced MMP-2 active forms through suppression of membrane-type 1 MMP (MT1-MMP) level, but did not alter MMP-2 and TIMP-2 levels. Moreover, reactive oxygen species (ROS) production induced by PMA was partly decreased in the presence of CKS and this suppression of ROS production may be related to diminish NF-kappaB activity. Therefore, our results suggested that the inhibitory effects of CKS on MMP-2 and MMP-9 activation, relation of tumor invasion and migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced NF-kappaB activation through ROS signaling pathway. Overall, CKS may be a valuable anti-invasive drug candidate for cancer therapy.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Enzyme Inhibitors/pharmacology , Matrix Metalloproteinase Inhibitors , NF-kappa B/metabolism , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Signal Transduction/physiology , Cell Movement/drug effects , Humans , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Neoplasm Invasiveness , Plant Roots/chemistry , Platycodon , Tetradecanoylphorbol Acetate/pharmacology , Tissue Inhibitor of Metalloproteinase-1/analysis
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