ABSTRACT
Context: Mortality from severe sepsis has been declining in recent years but remains a challenge worldwide because it remains the most frequent cause of death in ICUs. High-quality nursing care during a patient's CBP can play an important role in promoting a patient's physical condition. Objective: The study intended to explore the effects of nursing based on a humanistic care concept on continuous blood purification (CBP) treatment for patients with severe sepsis in an intensive care unit (ICU). Design: The research team performed a prospective randomized controlled study. Setting: The study took place at Minhang Hospital at Fudan University in Shanghai, China. Participants: Participants were 80 patients with severe sepsis who had been admitted to the ICU of the hospital and who were receiving CBP between April 2021 and December 2022. Intervention: The research team randomly divided participants into two groups according to their admission sequence, with 40 participants in each group: (1) an intervention group, the humanistic care group, who received CBP under humanistic care, and (2) a control group who received CBP under routine nursing. Outcome Measures: At baseline and postintervention, the research team: (1) measured participants' negative emotions using the Self-rating Anxiety Scale (SAS) and the Self-rating Depression scale (SDS), (2) assessed participants' hope levels using the Herth Hope Index (HHI), and (3) evaluated participants' health statuses using the Acute Physiology and Chronic Health Evaluation (APACHE-II). The team also measured the complication rate and determined participants' treatment compliance. Results: Postintervention compared to the control group, the humanistic care group's: (1) SAS and SDS scores were significantly lower, with P < .001 and P < .001, respectively; (2) HHI score was significantly higher, with P < .001; (3) APACHE-II scores and complication rate were significantly lower, with P < .001 and < .001, respectively; and (4) treatment compliance was significantly higher, with P = .0186. Conclusions: Nursing based on a humanistic care concept in ICUs can effectively alleviate the negative mood of patients with severe sepsis receiving CBP, enhance their hope levels and the treatment effect, improve their health statuses and treatment compliance, and reduce the occurrence of complications.
Subject(s)
Intensive Care Units , Sepsis , Humans , Sepsis/therapy , Sepsis/psychology , Female , Male , Middle Aged , Prospective Studies , China , Aged , Adult , HumanismABSTRACT
Inflammation is a key contributor to diabetic kidney disease pathogenesis, including reactive oxidation stress (ROS)-mediated nuclear factor-κB (NF-κB) signaling pathway. In this study, we examined the effect of Astragaloside IV (AS-IV) on anti-inflammatory and anti-oxidative properties under high glucose (HG) condition and the potential mechanism in glomerular mesangial cells (GMCs). We showed that AS-IV concentration-dependently reduced GMCs proliferation, restrained ROS release and hydrogen peroxide content, and suppressed pro-inflammatory cytokines as well as pro-fibrotic factors expression, which were associated with the inhibition of NF-κB and nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling activation. Accordingly, both NF-κB overexpression by using RNA plasmid and Nrf2 gene silencing by using RNA interference weakened the ability of AS-IV to ameliorate HG-induced oxidative stress, inflammation, and cell proliferation. Furthermore, phosphatidylinositide 3-kinases (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein kinases (ERK) signaling pathway regulated the process of AS-IV-induced Nrf2 activation and antioxidant capacity, which evidenced by using PI3K inhibitor LY294002 or ERK inhibitor PD98059 that largely abolished the AS-IV efficacy. Taken together, these results indicated that AS-IV protected against HG-induced GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation.
Subject(s)
NF-kappa B , Proto-Oncogene Proteins c-akt , Humans , NF-kappa B/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , NF-E2-Related Factor 2/metabolism , Antioxidants/pharmacology , Mesangial Cells/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction , Phosphatidylinositol 3-Kinase/metabolism , Oxidative Stress , Cytokines/metabolism , Glucose/metabolism , Inflammation/metabolismABSTRACT
Zuogui Wan (ZGW), a well-known traditional Chinese medicine (TCM), has been used to nourish "Kidney-Yin" for a long time in China, implying a protective effect on the kidney. The aim of the present study is to investigate the effect of ZGW on high glucose-induced podocyte apoptosis and diabetic nephropathy (DN) in db/db mice. ZGW (1 g/kg-1/day-1) was administered intragastrically to db/db mice for 8 weeks. HPLC was used for identifying the components of ZGW, biochemical and histopathological approaches were used for evaluating its therapeutic effects, and cultured mouse podocytes were used for further exploring its underlying mechanism in vitro. ZGW improved renal function and podocyte loss and also normalized kidney reactive oxygen species production in db/db mice. The cytotoxicity of ZGW on mouse podocytes was assessed by the LDH assay. The effect of ZGW on podocyte viability and apoptosis was determined with CCK-8 and Annexin-V/PI staining by treatment with high glucose. ZGW attenuated podocyte apoptosis, and oxidative stress was detected by the peroxide-sensitive fluorescent probe 2',7'-dichlorodihydrofluorescein diacetate (DCF-DA) staining in a dose-dependent manner. Furthermore, ZGW decreased the expression of caspase-3 and phospho-p38 in both the kidney cortex and high glucose-treated podocytes. Thus, our data from in vivo and in vitro studies demonstrated that ZGW improved renal injury in diabetes by inhibiting oxidative stress and podocyte apoptosis.
ABSTRACT
BACKGROUND/AIMS: Huangqi Decoction (HQD) has been traditionally used to treat diabetes mellitus in China. The present study was carried out to assess the protective effect of HQD on diabetic nephropathy (DN) using the streptozotocin-induced (STZ) diabetic rats. METHODS: Diabetes was induced by a single intraperitoneal injection of STZ (60 mg/kg) in male Wistar rats. 40 diabetic rats were divided into 5 groups: vehicle-treated (DN group), 0.45, 0.15, 0.05 g/kg HQD-treated diabetic group (HQD group) and 1 mg/kg rosiglitazone-treated diabetic group (RGZ group). 16 normal rats were randomly divided into 2 groups: vehicle-treated normal control group (NC) and 0.45 g/kg HQD-treated normal control group (NC+0.45 g/kg HQD). At the end of 8-week experiment, we measured changes of renal pathological morphology, function, antioxidant enzyme levels and the activation of TGF-ß/PPAR-γ/MAPK signaling pathway. RESULTS: After HQD treatment, renal function, including blood urea nitrogen (BUN), 24-h albuminuria and blood glucose level were improved significantly; meanwhile, impaired kidney redox balance was diminished in diabetic rats. The activation of TGF-ß, phospho-JNK, phospho-p44/42, p47 and p42 phox was blocked and the decrease in PPAR-γ in diabetic rats was attenuated by treatment with HQD in a dose-dependent manner. CONCLUSION: These results suggest that HQD shows therapeutic efficacy in DN characterized by renal dysfunction and pathological changes through hypoglycemic and antioxidant effects.
Subject(s)
Diabetic Nephropathies/prevention & control , Drugs, Chinese Herbal/therapeutic use , Mitogen-Activated Protein Kinases/metabolism , PPAR gamma/metabolism , Transforming Growth Factor beta/metabolism , Albumins/analysis , Animals , Blood Glucose/analysis , Blood Urea Nitrogen , Diabetes Mellitus, Experimental/chemically induced , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Diabetic Nephropathies/pathology , Drugs, Chinese Herbal/pharmacology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Kidney/drug effects , Kidney/metabolism , Kidney/pathology , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Signal Transduction/drug effects , Streptozocin/toxicity , Up-Regulation/drug effectsABSTRACT
OBJECTIVE: Traditional Chinese Medicine compound HuangQi decoction is widely used in clinical treatment of chronic kidney disease, but its role on renal interstitial fibrosis and the underlying mechanism remains unclear. The aim of this study is to investigate the effect of HuangQi decoction on renal interstitial fibrosis and its association with the TGF-ß/Smad signaling pathway Methods: A total of 120 C57/BL mice were randomly divided into six groups: sham group, sham plus high-dose HuangQi decoction (1.08g/kg) group, unilateral ureteral obstruction (UUO) model group, and UUO model plus low to high doses of HuangQi decoction (0.12g/kg, 0.36g/kg and 1.08g/kg respectively) groups. Animals were sacrificed 14 days after the administration and ipsilateral kidney tissue was sampled for pathologic examinations. Immunohistochemistry, PCR and western blot were used to detect the expressions of related molecules in the TGF-ß/Smad signaling pathway. TGF-ß1 was used in in vitro experiments to induce human kidney proximal tubule epithelial cells (HK2). RESULTS: HuangQi decoction improved ipsilateral kidney fibrosis in UUO mice and downregulated the expressions of TGF-ß1, TßRI, TßRII, Smad4, Smad2/3, P-Smad2/3, α-SMA, collagen type I, III and IV in a dose-dependent manner while upregulated the expression of Smad7 in the same fashion. Similar results were found in in vitro studies. CONCLUSION: The protective effect of HuangQi decoction for unilateral ureteral obstruction kidney damage in mice was mediated by downregulating the TGF-ß/Smad signaling pathway.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Fibrosis/drug therapy , Kidney Diseases/drug therapy , Signal Transduction/drug effects , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism , Animals , Astragalus propinquus , Cell Line , Cell Transdifferentiation/drug effects , Collagen Type I/genetics , Collagen Type I/metabolism , Collagen Type III/genetics , Collagen Type III/metabolism , Disease Models, Animal , Down-Regulation/drug effects , Drugs, Chinese Herbal/therapeutic use , Fibrosis/metabolism , Fibrosis/pathology , Humans , Kidney/metabolism , Kidney/pathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Medicine, Chinese Traditional , Mice , Mice, Inbred C57BL , Protein Serine-Threonine Kinases/genetics , Protein Serine-Threonine Kinases/metabolism , Receptor, Transforming Growth Factor-beta Type II , Receptors, Transforming Growth Factor beta/genetics , Receptors, Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/genetics , Transforming Growth Factor beta1/metabolism , Up-Regulation/drug effects , Ureteral Obstruction/drug therapy , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathologyABSTRACT
OBJECT: To explore the effects of HuangQi decoction on tubulointerstitial fibrosis in mice and the Wnt/ß-catenin signaling pathway. METHODS: Unilateral ureteral obstruction (UUO) model was used. A total of 120 C57/BL mice were randomly divided into 6 groups, sham group, sham+HuangQi decoction group (1.08 g/kg), UUO group, UUO+HuangQi decoction group (0.12, 0.36, 1.08 g/kg). Immunohistochemical analysis, RT-PCR and Western blot were employed to examine the proteins and genes related to the Wnt/ß-catenin signaling pathway. RESULTS: In UUO mice models, expression levels of Wnt3,4, Frizzled4, LRP5,6, ß-catenin, LEF-1, TCF-1, Snail, MMP2,7 genes were positively correlated with the degree of renal tubulointerstitial fibrosis, while expression levels of GSK-3ß, Axin, APC, CK1 were negatively correlated. HuangQi decoction could down-regulate expression levels of Wnt3,4, Frizzled4, LRP5,6, ß-catenin, LEF-1, TCF-1, Snail, Twist, MMP2,7 and up-regulate expression levels of GSK-3ß, Axin, APC, CK1 and E-cadherin. CONCLUSION: HuangQi decoction could effectively inhibit the up-regulation of Wnt/ß-catenin signaling pathway induced by UUO, implying a possible role in improving renal interstitial fibrosis.
Subject(s)
Drugs, Chinese Herbal/therapeutic use , Kidney Diseases/drug therapy , Kidney/drug effects , Up-Regulation/drug effects , Wnt Signaling Pathway/drug effects , Animals , Fibrosis , Kidney/metabolism , Kidney/pathology , Kidney Diseases/metabolism , Kidney Diseases/pathology , Male , Mice , Mice, Inbred C57BLABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: You-gui Pill (YGP), a traditional Chinese medicinal prescription, was widely used to warm and recuperate "kidney-yang" clinically for hundreds of years in China. Recent studies found that YGP had a potential benefit for renoprotection. AIM OF THE STUDY: The present study aimed to elucidate the in vivo and in vitro efficacy of YGP on renal tubulointerstitial fibrosis, and the molecular mechanism is also investigated. MATERIALS AND METHODS: Rat renal tubulointerstitial fibrosis model was elicited by unilateral ureteral obstruction (UUO). Sprague-Dawley rats underwent UUO and were studied after 14 days. Animals were randomly subjected to six groups: sham, UUO, UUO/YGP (0.14, 0.42, 1.26g/kg/d), and UUO/enalapril (10mg/kg/d). HE, Masson and ELISA were used for evaluate renal injury and function. Immunohistochemical analysis and western blot were used to detect the expressions of α-SMA, fibronectin, collagen matrix and Smads. In vitro studies were investigated in TGF-ß1-stiumlated NRK-49F cell line. RESULTS: Oral administration of YGP significantly decreased UUO-induced inflammatory cell infiltration, tubular atrophy and interstitial fibrosis, and there was no significant difference between YGP at 1.26g/kg and enalapril at 10mg/kg treatment (P>0.05). Meanwhile, serum creatinine and blood urea nitrogen levels were reduced dramatically (P<0.01). In coincide with the decreased of TGF-ß1, α-SMA, fibronectin and collagen matrix expressions were also declined with YGP treatment in both UUO kidneys and TGF-ß1-stimulated NRK-49F cell line. Additionally, nuclear translocation of p-Smad2/3 was markedly down-regulated by YGP (P<0.001), with a relative mild up-regulated expression of Smad7 (P<0.05). CONCLUSIONS: Our findings demonstrate that YGP had a renoprotective effect in ameliorating renal tubulointerstitial fibrosis, and this activity possibly via suppression of the TGF-ß and its downstream regulatory signaling pathway, including Smad2/3.
Subject(s)
Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Fibrosis/drug therapy , Signal Transduction/drug effects , Smad Proteins/metabolism , Transforming Growth Factor beta/metabolism , Actins , Animals , Cells, Cultured , Dose-Response Relationship, Drug , Down-Regulation , Enalapril/pharmacology , Enalapril/therapeutic use , Fibrosis/pathology , Kidney Diseases/drug therapy , Kidney Diseases/pathology , Kidney Diseases/physiopathology , Male , Rats , Transforming Growth Factor beta/pharmacology , Up-RegulationABSTRACT
A traditional Chinese medicine (TCM) formula, Zuo Jin Wan (ZJW), has been found as an anticancer drug in human cancer. In this study, we investigated the synergistic effect of ZJW extracts on DDP-induced apoptosis in human gastric cancer SGC-7901/DDP cells. Our results demonstrated that ZJW extracts could increase the sensitivity of SGC-7901/DDP cells to DDP by increasing the concentration of DDP in cytoplasm and enhance the proapoptosis of DDP by upregulating the JNK and Bax expression, downregulating the Bcl-2 expression, increasing the accumulation of Cytochrome C in cytoplasm, and promoting the activities of caspase-3 and caspase-9. In vivo, ZJW extracts enhanced the inhibiting effect of DDP on tumor growth in SGC-7901/DDP xenograft model and upregulated the expression of p-JNK and Bax but downregulated the Bcl-2 expression in xenograft tumors. In conclusion, in vitro and in vivo, ZJW extracts could enhance the proapoptotic effect of DDP by promoting the activation of JNK and the expression of Bcl-2, inhibiting the Bax expression, followed by increasing the release of Cytochrome C from mitochondria to cytoplasm, and finally activating the caspase cade reaction. Our results implied that ZJW might serve as a synergistic drug with chemotherapeutic drugs DDP in the treatment of gastric cancer.
ABSTRACT
In the present study, we investigate the effect of curcumin, a major active component isolated from rhizomes of Curcuma longa, on the cytotoxicity of three human carcinoma cell lines (AGS, HT-29 and MGC803) in gastrointestinal tract and a normal gastric epithelial cell line GES-1, and the mechanism of curcumin-induced apoptosis. The results indicated that curcumin inhibited the gastrointestinal carcinoma cell growth in a dose-dependent manner and cytotoxicity was more towards the gastric carcinoma cell AGS and colon carcinoma cell HT-29 compared to normal gastric cell GES-1, and increased externalization of phosphatidylserine residue was observed by Annexin V/PI staining in the two cell lines. Treatment of AGS and HT-29 cells with curcumin enhanced the cleavage of procaspase-3, -7, -8 and -9. Meanwhile, curcumin induced endoplasmic reticulum (ER) stress and mitochondrial dysfunction as evidenced by up-regulation of CCAAT/enhancer binding protein homologous protein (CHOP), phosphorylation of JNK and down-regulation of SERCA2ATPase, release of cytochrome c, decrease of Bcl-2 and reduction of mitochondrial membrane potential in both AGS and HT-29 cells. Overexpression of bax, total JNK, phospho-FADD and total FADD were also observed in curcumin-treated HT-29 cells. Moreover, curcumin decreased cytosolic and ER Ca(2+), but increased mitochondrial Ca(2+) in the two cell lines. 2-Aminoethoxydiphenyl borate, an antagonist of inositol 1, 4, 5-triphosphate receptor, partly blocked curcumin-induced cytosolic Ca(2+) decrease in AGS and HT-29 cells. Additionally, carbonyl cyanide m-chlorophenylhydrazone, an inhibitor of mitochondrial Ca(2+) uptake, reversed curcumin-triggered AGS and HT-29 cells growth inhibition. siRNA to CHOP markedly reduced curcumin-induced apoptosis. These results suggest that curcumin can impact on ER stress and mitochondria functional pathways in AGS and HT-29 cells, death receptor pathway was also involved in curcumin-treated HT-29 cells, thus identifying specific well-defined molecular mechanisms that may be targeted by therapeutic strategies.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Curcumin/pharmacology , Endoplasmic Reticulum Stress , Gene Expression Regulation, Neoplastic , Mitochondria/drug effects , Annexin A5 , Calcium/metabolism , Caspases/genetics , Caspases/metabolism , Cell Line, Tumor , Cell Proliferation/drug effects , Coloring Agents , Curcuma/chemistry , Fas-Associated Death Domain Protein/genetics , Fas-Associated Death Domain Protein/metabolism , Humans , MAP Kinase Kinase 4/genetics , MAP Kinase Kinase 4/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/metabolism , Plant Extracts/chemistry , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism , Sarcoplasmic Reticulum Calcium-Transporting ATPases/genetics , Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism , Signal Transduction , Transcription Factor CHOP/antagonists & inhibitors , Transcription Factor CHOP/genetics , Transcription Factor CHOP/metabolismABSTRACT
BACKGROUND: Zedoary (Curcumae Rhizoma, Ezhu), a Chinese medicinal herb, has been reported to show anticancer activity. This study aims to investigate the effect of zedoary oil (Ezhu You) on the proliferation of AGS cells which is one gastric cancer cell line. METHODS: The main ingredients of the herb were detected by GC-MS for herbal quality control. Cell viability was measured by MTT assay and cell proliferation was investigated by immunocytochemical staining for proliferating cell nuclear antigen (PCNA) protein. In addition, the cell cycle distributions were detected by flow cytometry with propidium iodine (PI) staining and the apoptosis rates were evaluated by flow cytometry with annexin V/PI double-staining. The morphological changes associated with apoptosis were observed by Hoechst 33342/PI double-staining. Protein expression was determined by western blot analysis. RESULTS: The main ingredients of the herb, including curzerene (26.45%), eucalyptol (12.04%), curcumol (9.04%), pyridine (7.97%), germacrone (7.89%), ß-elemene (7.36%), τ-elemene (4.11%) and 28 other ingredients, including curdione, were consistent with the chemical profiles of zedoary. Zedoary oil significantly decreased the cell viability of AGS cells (P < 0.01) and MGC 803 cells (P < 0.01), and the inhibitory effects were attenuated by elevated concentrations of FBS. At high concentrations (≥90 µg/mL), zedoary oil killed GES-1 cells. At low concentrations (≤60 µg/mL), zedoary oil was less inhibitory toward normal gastric epithelial cells than gastric cancer cell lines. In AGS cells, zedoary oil inhibited cell proliferation in a dose- and time-dependent manner, with decreased PCNA protein expression in the zedoary oil-treated cells, and arrested the cell cycle at S, G2/M and G0/G1 stages after treatment for 6-48 h. At concentrations of 30, 60 and 90 µg/mL, which resulted in significant inhibition of proliferation and cell cycle arrest, zedoary oil induced cell apoptosis. In addition, Hoechst 33342/PI double-staining confirmed the morphological characteristics of cell apoptosis at 24 h. Zedoary oil upregulated the ratio of Bax/Bcl-2 protein expression (P < 0.01). CONCLUSIONS: Zedoary oil inhibited AGS cell proliferation through cell cycle arrest and cell apoptosis promotion, which were related to Bax/Bcl-2 protein expression.
ABSTRACT
OBJECTIVES: Postoperative ileus is major cause of postoperative complication and prolonged hospitalization. Jatrorrhizine, which is a protoberberine alkaloid isolated from the medicinal plants Berberis aristata and Coptis chinensis, has been found to increase contractility of gastric antral and ileum smooth muscles of rat gastrointestinal tract. We have investigated whether jatrorrhizine could offset gastrointestinal transit in rat with postoperative ileus. METHODS: Postoperative ileus was induced by laparotomy with intestinal manipulation under anaesthesia. Gastrointestinal transit was evaluated by measurement of gastric emptying, geometric centre and the migration of Evans blue. KEY FINDINGS: Postoperative ileus significantly delayed gastric emptying and intestinal transit. Jatrorrhizine dose-dependently (0.1, 0.3 and 1 mg/kg) offset delayed gastric emptying and intestinal transit (geometric centre and the migration of Evans blue) in postoperative ileus. Pretreatment of animals with atropine inhibited the action of jatrorrhizine on gastric emptying and intestinal transit, but pretreatment of animals with SB204070 did not influence the effect of jatrorrhizine on gastric emptying and intestinal transit in postoperative ileus. CONCLUSIONS: Jatrorrhizine offset postoperative ileus-induced delayed gastric emptying and intestinal transit in rats, an action mediated via the cholinergic pathway, but not involving activation of 5-HT(4) receptors.
Subject(s)
Berberine/analogs & derivatives , Cholinergic Fibers/drug effects , Gastrointestinal Transit/drug effects , Ileus/drug therapy , Postoperative Complications/drug therapy , Animals , Atropine/therapeutic use , Berberine/therapeutic use , Dose-Response Relationship, Drug , Drug Interactions , Evans Blue , Gastric Emptying/drug effects , Gastric Emptying/physiology , Gastrointestinal Transit/physiology , Laparotomy/adverse effects , Male , Muscarinic Agonists/therapeutic use , Plant Extracts/therapeutic use , Plants, Medicinal , Rats , Rats, Wistar , Receptors, Serotonin, 5-HT4/metabolism , Serotonin 5-HT4 Receptor Antagonists/therapeutic use , Time FactorsABSTRACT
OBJECTIVE: To study the effects and mechanisms of sinensetin on proliferation and apoptosis of human AGS gastric cancer cells. METHOD: MTT assay was used to detect the growth inhibition rates of human AGS gastric cancer cells treated with sinsesectin in different concentrations and times. The cell cycle distribution was measured by flow cytometry. The apoptosis was examined by Annexin-FITC/PI staining and DNA fragment analysis. The apoptosis morphology was observed by inverted fluorescence microscope after Hoechst 33342 staining. The protein expressions of p21 and p53 were detected by western blot. RESULT: MTT assay showed that sinensetin inhibited the growth of AGS gastric cancer cells in a dose- and time-dependent manner. Sinensetin blocked AGS cells in G2/ M and increased the apoptosis rates of AGS cells in a dose-dependent manner. DNA ladder was observed in cells treated with 60 micromol x L(-1) sinensetin for 48 h. The typical apoptotic morphological changes including cell nucleus shrinkage, chromatin condensation and apoptotic bodies were observed when treated with different dose of sinensetin. Western blot showed that sinensetin increased expressions of p53 and p21 in a dose-dependent manner. CONCLUSION: Sinensetin could inhibit human AGS gastric cancer cells proliferation and induce cell cycle block in G2/M phase and apoptosis. The up regulation of p53 and p21 protein might be one of the mechanisms.
Subject(s)
Apoptosis/drug effects , Flavonoids/pharmacology , Stomach Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Cyclin-Dependent Kinase Inhibitor p21/analysis , Dose-Response Relationship, Drug , Humans , Stomach Neoplasms/pathology , Tumor Suppressor Protein p53/analysisABSTRACT
OBJECTIVE: The main ingredients and the inhibitory effects of essential oil of a compound Chinese herbal medicine Weiqi Decoction (WQD) on AGS cell proliferation were to be investigated. METHODS: Chemical compounds of WQD essential oil were detected by gas chromatography and mass spectrometry analysis. Cell viability was measured by methyl thiazolyl tetrazolium method. Cell cycle distribution was detected by flow cytometry. Apoptosis and necrosis of AGS cells were determined by Hoechst 33342/propidium iodine staining. RESULTS: Chemical analysis showed that the main ingredients of WQD essential oil were bornylene and 3-n-butylphthalide. Ligustilide, which is the effective compound of Danggui (Radix Angelicae Sinensis), was not detected in WQD essential oil. The essential oil inhibited cell proliferation in a dose- and time-dependent manner, and blocked cell cycle progression at G(2)/M stage. At the concentrations that resulted in significant inhibition of cell proliferation and cell cycle arrest, essential oil induced both apoptosis and necrosis. CONCLUSION: The results suggest that WQD essential oil contains some effective ingredients for treating chronic atrophic gastritis and functional dyspepsia, and also has an antiproliferative effect on AGS cells through cell cycle arrest and apoptosis promotion in vitro. Therefore, essential oil should be retained as much as possible during stewing this decoction.