ABSTRACT
Vascular wall aging has been strongly associated with cardiovascular diseases. Thus, this study aimed to investigate the efficacy of USCP-GVH-014, a mixed extract of Salvia miltiorrhiza Bunge and Paeonia lactiflora Pall., in inhibiting vascular wall aging through in vitro and in vivo experiments. The results revealed that USCP-GVH-014 inhibited abnormal cell proliferation, collagen overproduction, and MMP-2 and MMP-9 overexpression caused by various stimuli and recovered the antioxidant enzyme superoxide dismutase on human aortic smooth muscle cells. In addition, it inhibited the increase in ICAM-1 and VCAM-1 expression induced by tumor necrosis factor alpha on human aortic endothelial cells and prevented the aging of the vascular wall by regulating related proteins such as epidermal growth factor and interleukin-1ß. Furthermore, it reduced vascular aging in in vivo studies. These results demonstrate that USCP-GVH-014 effectively reduces vascular aging, thereby rendering it a potential therapeutic candidate for cardiovascular diseases.
Subject(s)
Cardiovascular Diseases , Paeonia , Salvia miltiorrhiza , Humans , Endothelial Cells , AgingABSTRACT
BACKGROUND: Halitosis, the unpleasant odor in the oral cavity, has garnered increased attention and concern due to the growing significance of social interaction. SGE-107, a blend of 3 botanical drugs-Korean goat's beard, Cirsium tanakae, and Basil-with caffeic acid as its indicator component. This study aims to investigate the efficacy of SGE-107 in treating halitosis in patients with mild gastrointestinal symptoms. METHODS: We enrolled 25 participants with oral malodor and dyspeptic symptoms. We assessed the severity of halitosis using the visual analog scale. Throughout a 4-week period of administering SGE-107, we evaluated both objective and subjective parameters, including the halitosis-associated life-quality test, the Korean gastrointestinal symptom rating scale, levels of volatile sulfur compounds, salivary flow rate, oral moisture, tongue index, Winkel tongue coating index, and tongue temperature. RESULTS: After the intervention period, both the visual analog scale (5.88â ±â 1.03 vs 2.38â ±â 0.93, Pâ <â .001) and the scores of the halitosis-associated life-quality test (31.21â ±â 11.78 vs 13.83â ±â 6.38, Pâ <â .001) showed significant reductions. The proportion of participants with abnormal levels of methyl mercaptan (a volatile sulfur compound) also significantly decreased (17, 70.8% vs 9, 37.5%, Pâ =â .039). Furthermore, there were significant improvements in reflux, constipation, diarrhea, and the total scores on the Korean gastrointestinal symptom rating scale. Throughout the study period, only 2 participants experienced mild adverse events. CONCLUSION: SGE-107 appears to be a safe and effective treatment for halitosis-associated with gastrointestinal symptoms; nevertheless, the limited sample size necessitates further large-scale randomized, controlled studies to confirm our findings.
Subject(s)
Cirsium , Halitosis , Ocimum basilicum , Humans , Halitosis/drug therapy , Sulfur Compounds , Mouth , TongueABSTRACT
BACKGROUND: Previous research demonstrated that the crude saponins of Platycodi radix improve glucose metabolism by enhancing insulin sensitivity in type 2 diabetic animals; however, which individual saponins are the most potent insulin sensitizers is unknown. OBJECTIVES: This study investigated which saponin(s) have anti-diabetic action in vitro and in vivo. METHODS: The insulin-stimulated glucose uptake and PPAR-γ agonistic actions of six saponins from Platycodi radix were investigated in 3T3-L1 adipocytes, and glucose-stimulated insulin secretion was determined in Min6 cells. Four individual saponins (20 mg/kg body weight) were orally administered to low-dose streptozotocin-injected diabetic mice fed a high-fat diet for 8 weeks to evaluate glucose tolerance by oral glucose tolerance testing (OGTT), insulin sensitivity by insulin tolerance testing, and insulin signaling in the liver and adipose tissues. RESULTS: Platyconic acid (PA) most effectively increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes, possibly in part by working as a peroxisome proliferator-activated receptors (PPAR)-γ activator; however, none of the saponins improved glucose-stimulated insulin secretion in insulinoma cells. PA-treated diabetic mice exhibited the lowest peak serum glucose levels and highest serum insulin levels during the first part of OGTT. PA also improved insulin sensitivity: PA increased glycogen accumulation and decreased triacylglycerol storage in liver, which was associated with enhanced hepatic insulin signaling, while PA potentiated the expression of adiponectin and PPAR-γ in adipose tissue, and improved insulin signaling and increased GLUT4 translocation into the membranes. CONCLUSIONS: PA improves glucose homeostasis in type 2 diabetic mice, partly by enhancing hepatic and adipocyte insulin sensitivity, possibly by activating PPAR-γ.
Subject(s)
Blood Glucose/drug effects , Insulin Resistance , Plant Extracts/pharmacology , Saponins/pharmacology , Triterpenes/pharmacology , 3T3-L1 Cells , Adipocytes/drug effects , Adipocytes/metabolism , Adiponectin/genetics , Adiponectin/metabolism , Animals , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/pathology , Diet, High-Fat , Glucose Tolerance Test , Glucose Transporter Type 4/genetics , Glucose Transporter Type 4/metabolism , Homeostasis , Hypoglycemic Agents/pharmacology , Insulin/blood , Liver/cytology , Liver/drug effects , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , PPAR gamma/agonists , PPAR gamma/metabolism , Protein Transport/genetics , Signal TransductionABSTRACT
Recent studies suggest that phytoestrogens may exert a protective effect against osteoporosis. This study examined whether treatment with phytoestrogen extracts from Saururus chinensis (SC) exerted a preventive effect on estrogen-deficiency-induced osteoporosis. Six- to seven-month-old female Sprague-Dawley rats were randomly assigned into either a sham-operated group or one of three ovariectomy (OVX) subgroups: OVX treated with vehicle, OVX with alendronate, and OVX with SC extract (SC). Rats began receiving treatment 4 weeks before the OVX treatment and continued receiving treatment for an additional 10 weeks after OVX (for a combined total of 14 weeks). The results showed that the SC treatment prevented loss of femur bone mineral density after OVX, as determined by a significant decrease in the levels of serum bone turnover markers osteocalcin and alkaline phosphatase as well as urinary deoxypyridinoline. Micro-computed tomography analysis showed that the SC treatment significantly prevented decreases in bone volume/tissue volume, trabecular number and trabecular thickness, while also preventing an increase in trabecular separation. It was concluded that SC treatment could prevent OVX-induced loss of bone mass and deterioration in trabecular microarchitecture by suppressing bone turnover, thereby maintaining bone structural integrity. Further, no stimulation of proliferation of uterine tissue was noted. Therefore, it is suggested that treatment with S. chinensis extracts might be a potential alternative therapy for treating postmenopausal osteoporosis.
Subject(s)
Bone Density Conservation Agents/therapeutic use , Osteoporosis/drug therapy , Ovariectomy , Phytotherapy , Saururaceae/chemistry , Alendronate/pharmacology , Alkaline Phosphatase/blood , Amino Acids/urine , Animals , Biomarkers/chemistry , Body Weight , Bone Density/drug effects , Cell Proliferation , Drug Evaluation, Preclinical , Female , Femur/drug effects , Femur/metabolism , Femur/pathology , Organ Size , Osteocalcin/blood , Osteoporosis/chemically induced , Osteoporosis/pathology , Plant Extracts/pharmacology , Rats , Rats, Sprague-Dawley , Uterus/drug effects , Uterus/metabolism , Uterus/pathology , X-Ray Microtomography/methodsABSTRACT
Decursin (De), an active component of Angelica gigas, is known to exert anticancer and neuroprotective effects. However, its antiobesity and antidiabetic potential has not yet been investigated. This study evaluated the antiobesity effect of decursin, particularly focusing on its ability to inhibit adipocyte differentiation in 3T3-L1 cells. Decursin treatment resulted in the inhibition of adipocyte differentiation and the expression of fatty acid synthase. The study further investigated these antiobesity effects using mice fed a normal diet (ND), a high-fat diet (HFD) and a HFD plus decursin 200 mg/kg diet (HFD + De) for 7 weeks. Mice administered HFD plus decursin showed a drastic decrease in weight gain, triglyceride content, total cholesterol content and fat size compared with those that received the HFD alone; this was observed despite similar quantities of total food intake. Furthermore, decursin improved glucose tolerance in mice fed a HFD. Finally, administration of decursin along with the HFD significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1. These results suggest that decursin might be useful for the treatment of obesity and diabetes.
Subject(s)
Adipokines/blood , Adipose Tissue/metabolism , Angelica/chemistry , Anti-Obesity Agents/pharmacology , Benzopyrans/pharmacology , Butyrates/pharmacology , Hypoglycemic Agents/pharmacology , 3T3-L1 Cells , Adipokines/antagonists & inhibitors , Adipokines/metabolism , Animals , Anti-Obesity Agents/chemistry , Anti-Obesity Agents/isolation & purification , Benzopyrans/chemistry , Benzopyrans/isolation & purification , Blood Glucose/metabolism , Body Weight/drug effects , Butyrates/chemistry , Butyrates/isolation & purification , Cholesterol/analysis , Diet, High-Fat/adverse effects , Glucose Tolerance Test , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/isolation & purification , Insulin Resistance , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Obesity/chemically induced , Obesity/physiopathology , Weight Gain/drug effectsABSTRACT
Farnesylation of the activated RAS oncogene product by protein farnesyltransferase (FTase) is a critical step for its oncogenic function. Bioassay-guided purification of Ferula asafoetida (Umbelliferae) extract led to the isolation of the coumarin-derived sesquiterpene galbanic acid (1) as an active principal for FTase inhibitory activity, together with the four structurally related sesquiterpenes karatavicinol (2), umbelliprenin (3), farnesiferol B (4), and farnesiferol C (5). The 50 % inhibitory concentration (IC (50)) of 1 against FTase in an enzyme-based assay was calculated as 2.5 µM. Compound 1 also demonstrated potent inhibition of the proliferation of oncogenic RAS-transformed NIH3T3/Hras-F in a dose-dependent manner. The IC (50) value of 1 on the proliferation of oncogenic RAS-transformed NIH3T3/Hras-F cells was calculated as 16.2 µM, whereas its IC (50) value on control vector-transfected normal RAS-containing NIH3T3/ZIPneo cells was 58.5 µM.
Subject(s)
Coumarins/pharmacology , Cytostatic Agents/pharmacology , Farnesyltranstransferase/antagonists & inhibitors , Ferula/chemistry , Animals , Brain/enzymology , Coumarins/chemistry , Coumarins/isolation & purification , Cytostatic Agents/chemistry , Cytostatic Agents/isolation & purification , Farnesyltranstransferase/isolation & purification , Inhibitory Concentration 50 , Mice , NIH 3T3 Cells , Prenylation/drug effects , RatsABSTRACT
Three new guaiane-type sesquiterpene lactones (1-3), together with nine related sesquiterpenes (4-12), were isolated from the whole extract of Ixeris dentata (Asteraceae). The chemical structures of isolates 1-12 were established by spectroscopic analyses as 3 ß,8 ß-dihydroxy-guaia-10(14)-en-1 α,4 α,5 α,6 ß,7 α,11 ßH-12,6 α-olide (1), ixerin N 6'- O-acetate (2), ixerisoside A 6'- O-acetate (3), ixerin N ( 4), ixerisoside A (5), ixerin M (6), tectroside (7), 8-epidesacylcynaropicrin glucoside (8), 8-epiisolipidiol (9), 11 ßH-11,13-dihydrointegrifolin (10) 8 ß-hydroxy-4 ß,15-dihydrozaluzanin C (11), and integrifolin (12). Compounds 1-12 were evaluated for their inhibitory effect on the proliferation of the cultured human tumor cell lines MES-SA, MES-SA/DX5, HCT-15, and HCT15/CL02 in vitro.
Subject(s)
Antineoplastic Agents, Phytogenic/isolation & purification , Asteraceae/chemistry , Lactones/isolation & purification , Plant Extracts/chemistry , Sesquiterpenes/isolation & purification , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/therapeutic use , Cell Line, Tumor , Humans , Lactones/chemistry , Lactones/pharmacology , Molecular Structure , Neoplasms/drug therapy , Phytotherapy , Plant Extracts/pharmacology , Plant Extracts/therapeutic use , Sesquiterpenes/chemistry , Sesquiterpenes/pharmacologyABSTRACT
A new resveratrol oligomer (1) together with eight related components (2- 9) were isolated from the seed extract of Paeonia lactiflora (Paeoniaceae) as active principles responsible for the inhibition of beta-site APP-cleaving enzyme 1 (BACE-1) in vitro. The chemical structure of 1 was established as (-)-7a,8a- CIS- ε-viniferin with the aid of spectroscopic analyses including NOESY experiments. All isolated resveratrol oligomers (1- 9) demonstrated significant inhibition on baculovirus-expressed BACE-1 in a dose-dependent manner, which was assessed by the FRET assay using Rh-EVNLDAEFK as a substrate in vitro.
Subject(s)
Amyloid Precursor Protein Secretases/antagonists & inhibitors , Aspartic Acid Endopeptidases/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Paeonia/chemistry , Plant Extracts/pharmacology , Stilbenes/pharmacology , Baculoviridae , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/isolation & purification , Molecular Structure , Plant Extracts/chemistry , Resveratrol , Seeds , Stilbenes/chemistry , Stilbenes/isolation & purificationABSTRACT
Cancer cells in poorly vascularized solid tumors are constantly or intermittently exposed to stressful microenvironments, including glucose deprivation, hypoxia, and other forms of nutrient starvation. These tumor-specific conditions, especially glucose deprivation, activate a signaling pathway called the unfolded protein response (UPR), which enhances cell survival by induction of the stress proteins. We have established a screening method to discover anticancer agents that could preferentially inhibit tumor cell viability under glucose-deprived conditions. Here we identify arctigenin (ARC-G) as an active compound that shows selective cytotoxicity and inhibits the UPR during glucose deprivation. Indeed, ARC-G blocked expression of UPR target genes such as phosphorylated-PERK, ATF4, CHOP, and GRP78, which was accompanied by enhanced phosphorylation of eIF2 alpha during glucose deprivation. The UPR inhibition led to apoptosis involving a mitochondrial pathway by activation of caspase-9 and -3. Furthermore, ARC-G suppressed tumor growth of colon cancer HT-29 xenografts. Our results demonstrate that ARC-G can be served as a novel type of antitumor agent targeting the UPR in glucose-deprived solid tumors.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Colonic Neoplasms/drug therapy , Furans/pharmacology , Glucose/deficiency , Lignans/pharmacology , Unfolded Protein Response/drug effects , Animals , Apoptosis/drug effects , Cell Survival/drug effects , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Dose-Response Relationship, Drug , Endoplasmic Reticulum Chaperone BiP , Gene Expression Regulation, Neoplastic/drug effects , HT29 Cells , HeLa Cells , Humans , Mice , Mice, Nude , Time Factors , Tumor Burden/drug effects , Unfolded Protein Response/genetics , Xenograft Model Antitumor AssaysABSTRACT
Three new triterpenoid saponins, platyconic acid B lactone (1), deapio-platyconic acid B lactone (2), and deapio-platycodin D(2) (3), together with 17 known triterpenoid saponins, were isolated from a root extract of Platycodon grandiflorum. The structures of 1-3 were determined on the basis of spectroscopic data interpretation and chemical transformation. Saponins with a platycodigenin or polygalacic acid unit as a sapogenin demonstrated significant inhibitory effects on the proliferation of a small panel of cultured human tumor cells.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Platycodon/chemistry , Saponins/isolation & purification , Saponins/pharmacology , Triterpenes/isolation & purification , Triterpenes/pharmacology , Antineoplastic Agents/chemistry , Drug Screening Assays, Antitumor , Humans , Molecular Structure , Plant Roots/chemistry , Saponins/chemistry , Triterpenes/chemistry , Tumor Cells, CulturedABSTRACT
Pancreatic cancer cells are sometimes exposed to stressful microenvironments such as glucose deprivation, hypoxia, and starvation of other nutrients. These stresses, which are characteristic of poorly vascularized solid tumors, activate the unfolded protein response (UPR). The UPR is a stress-signaling pathway present in tumor cells that is associated with molecular chaperone GRP78. Induction of GRP78 has been found to increase cell survival and decrease apoptotic potential through genetic alterations. Thus GRP78 may represent a novel target in the development of anticancer drugs. Here we established a novel screening program to identify chaperone modulators that exhibit preferential cytotoxic activity in glucose-deprived pancreatic cancer cells. During the course of our screening, we isolated an active substance, Ponciri Fructus (PF), from an herbal medicine source and identified it as a down-regulator of GRP78. As expected, PF inhibited expression of the GRP78 protein under glucose-deprivation conditions in a dose-dependent manner. Furthermore, it induced selective cytotoxicity against glucose-deprived cancer cells; this effect was not observed under normal growth conditions. We also detected apoptotic bodies on Hoechst staining and attempted to determine whether PF-induced apoptosis involved caspase-3 activation. Our results suggest that the GRP78-inhibitory action of PF was dependent on strict hypoglycemic conditions and that it resulted in the selective death of glucose-deprived pancreatic cancer cells.
Subject(s)
Antineoplastic Agents/pharmacology , Glucose/deficiency , Heat-Shock Proteins/antagonists & inhibitors , Heat-Shock Proteins/metabolism , Pancreatic Neoplasms/pathology , Plant Extracts/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Endoplasmic Reticulum Chaperone BiP , HumansABSTRACT
A new resveratrol dimer, (+)-vitisinol E (1) which demonstrated inhibitory activity on BACE-1 (beta-site APP-cleaving enzyme 1) in vitro, was isolated from the stembark extract of Vitis vinifera (Vitaceae) together with four known resveratrol oligomers, (+)-epsilon-viniferin (2), (+)-ampelopsin A (3), (+)-vitisin A (4) and (-)-vitisin B (5). The chemical structure of 1 was established by MR spectroscopic analyses, including HMBC. All isolated resveratrol derivatives (1-5) demonstrated significant inhibition on baculovirus-expressed BACE-1 in a dose-dependent manner, which was assessed with the FRET assay using Rh-EVNLDAEFK as a substrate in vitro.
Subject(s)
Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Plant Extracts/pharmacology , Stilbenes/pharmacology , Vitis/chemistry , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Antioxidants/isolation & purification , Aspartic Acid Endopeptidases/antagonists & inhibitors , Baculoviridae , Enzyme Inhibitors/isolation & purification , Molecular Structure , Plant Bark , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Plant Stems , Resveratrol , Stilbenes/isolation & purificationABSTRACT
Glucose deprivation, a pathophysiological cell condition, causes up-regulation of GRP78 and induction of etoposide resistance in human cancer cells. The induction of drug resistance can be partly explained by the fact that GRP78 can block activation of caspase-7 induced by treatment with etoposide. Therefore, downregulating GRP78 expression may be a novel strategy anticancer drug development. Based on that premise, we established a screening program for anticancer agents that exhibit preferential cytotoxic activity for etoposide-resistant cancer cells under glucose-deprived conditions. We recently isolated an active compound, AR-054, from the culture broth of Streptomyces sp., which prevents stress-induced etoposide resistance in vitro. AR-054 was identified as piericidin A, a prototypical compound, by ESI-MS analysis and various NMR spectroscopic methods. Here, we showed that piericidin A suppressed the accumulation of GRP78 protein and was also highly toxic to etoposide-resistant HT-29 cells, with IC50 values for colony formation of 6.4 and 7.7 nM under 2-deoxyglucose supplemented and glucose-deprived conditions, respectively. Interestingly, piericidin A had no effect under normal growth conditions. Therefore, we suggest that piericidin A prevents up-regulation of GRP78, and exhibits cytotoxicity in glucose-deprived HT-29 cells that are resistant to etoposide.
Subject(s)
Colonic Neoplasms/pathology , Down-Regulation/drug effects , Drug Resistance, Neoplasm/drug effects , Etoposide/pharmacology , Glucose/deficiency , Heat-Shock Proteins/metabolism , Molecular Chaperones/metabolism , Pyridines/pharmacology , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Caspase 7/metabolism , Cell Death/drug effects , Colonic Neoplasms/enzymology , Endoplasmic Reticulum Chaperone BiP , Enzyme Activation/drug effects , HT29 Cells , Humans , Pyridines/isolation & purification , Up-Regulation/drug effectsABSTRACT
A genuine triterpenoid saponin, platyconic acid A (1) was isolated from the roots extract of Platycodon grandiflorum, together with five known saponins: deapioplatycoside E (2), platycoside E (3), platycodin D(3) (4), platycodin D(2) (5) and platycodin D (6). The structure of 1 was determined on the basis of spectral analysis and chemical evidence.
Subject(s)
Platycodon/chemistry , Saponins/chemistry , Saponins/isolation & purification , Magnetic Resonance Spectroscopy , Molecular Structure , Plant Roots/chemistryABSTRACT
Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR) which is a stress-signaling pathway in tumor cells that is associated with the molecular chaperone GRP78 and induction of GRP78 has been shown to protect them against programmed cell death. Thus, targeting glucose-deprived conditions may be a novel strategy in anticancer drug development. Based on that, we established a novel screening program for chaperone modulators that preferentially cytotoxic activity in cancer cells under glucose-deprived conditions. During the course of our screening system, we recently isolated an active compound, 326-2, from Penicillium verrucosum var. cyclopium and identified it as a down-regulator of the grp78 gene. As expected, 326-2 inhibited the expression of the GRP78 promoter under glucose-deprived conditions in a dose-dependent manner with an IC(50) value of 50nM. Furthermore, 326-2 was identified as verrucosidin, a pyrone-type polyketide, by ESI-MS analyses and various NMR spectroscopic methods. We found that verrucosidin prevents UPR-induced expression of protein, such as GRP78, whose expression is induced by glucose-deprived or by 2-deoxyglucose; this effect is not seen under normal growth conditions. The GRP78-inhibitory action of verrucosidin was dependent on strict hypoglycemic conditions and resulted in selective cell death of glucose-deprived HT-29 human colon cancer cells.
Subject(s)
Glucose/deficiency , Heat-Shock Proteins/metabolism , Molecular Chaperones/metabolism , Mycotoxins/toxicity , Pyrones/toxicity , Cell Survival/drug effects , Colonic Neoplasms , Down-Regulation , Endoplasmic Reticulum Chaperone BiP , HT29 Cells , HumansABSTRACT
Colorectal cancer is the third most common cause of cancer-related deaths in the world. Surgical intervention followed by chemotherapy remains the primary approach to treatment since colon cancers remain refractory to most chemotherapeutic agents. Based on that, we established a program to screen natural products for cytotoxic activity, employing the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay system utilizing HT-29 human colon cancer cells. During the course of our screening, we found that the methanolic extract of silkworm droppings (SDME) has cytotoxic effects on HT-29 cells. In the present study, we investigated the possible mechanisms by which SDME exerts its antiproliferative activity in HT-29 cells. As expected, SDME inhibited growth of HT-29 cells in a dose-dependent manner as assessed by the MTT reduction assay, the lactate dehydrogenase release assay, and the colony formation assay. We also investigated whether the apoptotic effects induced by SDME involve the caspase pathway using the caspase colorimetric assay. Interestingly, caspase-9 and -3, but not caspase-8, were activated in response to SDME treatment. Taken together, these results clearly indicate that the induction of apoptosis by SDME involves a mitochondrial-mediated pathway and strongly suggest that SDME may potentially be a chemotherapeutic agent for human colon cancer.
Subject(s)
Bombyx/metabolism , Caspases/metabolism , Cell Division/drug effects , Colonic Neoplasms/enzymology , Colonic Neoplasms/pathology , Methanol , Animals , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 9/metabolism , Colonic Neoplasms/drug therapy , Enzyme Activation/drug effects , Feces/chemistry , HT29 Cells , HumansABSTRACT
Natural marine products have recently become the focus of increased research interest, due to their potential pharmacological activities. Therefore, we have screened 50 varieties of marine seaweed and determined that the methanolic extracts from Plocamium telfairiae (PTE) exhibited a cytotoxic effect against HT-29 human colon carcinoma cells. In this study, we report on the cytotoxic activity and mechanism of PTE-induced apoptosis in HT-29 cells. The treatment of HT-29 cells with various PTE concentrations resulted in the inhibition of growth and the induction of apoptosis in a dose-dependent manner, as determined by the results of a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay, a lactate dehydrogenase release assay, a morphological assay, and a colony formation assay. Interestingly, we also detected apoptotic bodies on Hoechst staining and attempted to determine whether the PTE-induced apoptosis involved the caspase pathway, using a caspase colorimetric assay. The activation of caspases-8, -9, -3, and -7 and the specific proteolytic cleavage of poly(ADP-ribose) polymerase were detected over the course of apoptosis induction. Our results showed that PTE may function as a chemopreventive and/or chemotherapeutic agent in colon carcinoma cells via the reduction of cell viability and the induction of apoptosis.
Subject(s)
Apoptosis/drug effects , Caspases/metabolism , Plant Extracts/pharmacology , Plocamium/chemistry , Caspase 8/metabolism , Caspase 9/metabolism , Enzyme Activation , HT29 Cells , Humans , Methanol , Poly(ADP-ribose) Polymerases/metabolismABSTRACT
Red peppers and red pepper paste are reported to have anti-obesity, analgesic and anti-inflammatory effects in animals and humans due to the capsaicin in red pepper. We investigated whether consuming capsaicin and capsiate, a nonpungent capsaicin analogue, modifies glucose-stimulated insulin secretion, pancreatic ß-cell survival and insulin sensitivity in 90% pancreatectomized (Px) diabetic rats, a moderate and non-obese type 2 diabetic animal model. Px diabetic rats were divided into 3 treatment groups: 1) capsaicin (Px-CPA), 2) capsiate (Px-CPI) or 3) dextrose (Px-CON) and provided high fat diets (40 energy % fat) containing assigned components (0.025% capsaicin, capsiate, or dextrose) for 8 weeks. Both capsaicin and capsiate reduced body weight gain, visceral fat accumulation, serum leptin levels and improved glucose tolerance without modulating energy intake in diabetic rats. In comparison to the control, both capsaicin and capsiate potentiated first and second and phase insulin secretion during hyperglycemic clamp. Both also increased ß-cell mass by increasing proliferation and decreasing apoptosis of ß-cells by potentiating insulin/IGF-1 signaling. However, only capsiate enhanced hepatic insulin sensitivity during euglycemic hyperinuslinemic clamp. Capsiate reduced hepatic glucose output and increased triglyceride accumulation in the hyperinsulinemic state and capsiate alone significantly increased glycogen storage. This was related to enhanced pAktâPEPCK and pAMPK signaling. Capsaicin and capsiate reduced triglyceride storage through activating pAMPK. In conclusion, capsaicin and capsiate improve glucose homeostasis but they differently enhance insulin sensitivity in the liver, insulin secretion patterns, and islet morphometry in diabetic rats. Capsiate has better anti-diabetic actions than capsaicin.
Subject(s)
Capsaicin/analogs & derivatives , Diabetes Mellitus, Experimental/metabolism , Hypoglycemic Agents/pharmacology , Insulin Resistance , Animals , Blood Glucose/metabolism , Capsaicin/pharmacology , Cell Survival , Diabetes Mellitus, Experimental/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Glucose Clamp Technique , Insulin/blood , Insulin/metabolism , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Male , Rats , Rats, Sprague-DawleyABSTRACT
Ultraviolet B (UVB) irradiation causes skin damage and inflammation by inducing the secretion of various cytokines, which are immune regulators produced by cells. To prevent skin inflammation, keratinocytes that have been irreversibly damaged by UVB must be eliminated through apoptosis. Ixeris dentata (I. dentata) (family Asteraceae) is a perennial medicinal herb indigenous to Korea. It is used in Korea, China and Japan to treat indigestion, pneumonia, diabetes, hepatitis, contusions and tumors. Guaiane-type sesquiterpene lactones were isolated from the whole extract of I. dentata. This led to the isolation of the anti-inflammatory sesquiterpene lactone compound tectroside (TES), which was tested on a human keratinocyte cell line. To determine the anti-inflammatory effects of TES, we examined its influence on UVB-induced pro-inflammatory cytokine production in human keratinocytes (HaCaT cells) by observing these cells in the presence or absence of TES. In the present study, pro-inflammatory cytokine production was determined by performing enzyme-linked immunosorbent assay, reverse transcription-polymerase chain reaction and western blot analysis to evaluate the activation of mitogen-activated protein kinases (MAPKs). TES inhibited UVB-induced production of the pro-inflammatory cytokines interleukin (IL)-6 and IL-8 in a dose-dependent manner. In addition, TES inhibited the expression of cyclooxygenase (COX)-2 and the phosphorylation of c-Jun NH2-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) MAPKs, suggesting that it inhibits the secretion of the pro-inflammatory cytokines IL-6 and IL-8 and COX-2 expression by blocking MAPK phosphorylation. These results suggest that TES can potentially protect against UVB-induced skin inflammation.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Keratinocytes/drug effects , Keratinocytes/radiation effects , Lactones/pharmacology , Sesquiterpenes, Guaiane/pharmacology , Ultraviolet Rays/adverse effects , Anti-Inflammatory Agents/chemistry , Asteraceae/chemistry , Cell Line , Cell Survival/drug effects , Cell Survival/radiation effects , Cyclooxygenase 2/genetics , Gene Expression Regulation/drug effects , Humans , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Keratinocytes/metabolism , Lactones/chemistry , Mitogen-Activated Protein Kinases/metabolism , Phosphorylation , Plant Extracts/chemistry , Plant Extracts/pharmacology , RNA, Messenger/genetics , Sesquiterpenes, Guaiane/chemistryABSTRACT
An effective HPLC method to analyse platycosides from the balloon flower root was developed using ELSD. The optimum resolution of the platycosides was achieved on an ODS column with gradient elution of eluent A, 30mM ammonium acetate buffer (pH 4.81): methanol: acetonitrile=75:5:20 (v/v/v), and B, 69:5:26 (v/v/v). Amongst 18 platycosides, platycoside E showed the highest content, followed by polygalacin D2 and 3â³-O-acetylplatyconic acid A. The sum of these three compounds was recommended for quality control of balloon flower root for medicinal purposes. The samples could be clustered into groups based on platycoside content. Group I, characterised by a high concentration of platycosides, was located near the west coast of Korea, whereas group II, characterised by a low concentration of platycosides, was located inland or in mountainous area. The method could be used to control the quality of balloon flower root.