Iron deficiency anemia is one of the most common micronutrient deficient conditions around the globe with various consequences, including the weakened immune system. Quercetin is widely distributed bioflavonoid; it has been debated for its dual roles in iron regulation. Quercetin-iron interaction in the body is a complex mechanism which has not been completely understood. The present study aimed to investigate the effect of quercetin on iron supplementation in iron deficiency anemia and on iNOS expression in splenic macrophages. The rat model of iron deficiency anemia was induced by feeding low iron diet to weanling rats for 20 days. The animals were then administered with ferrous sulfate, quercetin, and their combination for 30 days. Blood parameters, histopathological analysis, iron storage, CD68, iNOS and SLC40 expression in rat spleen were investigated. Our results showed that quercetin regulated iron absorption, despite SLC40 down-expression, indicating possible alternate route of iron transport, and that quercetin modulated iNOS production in splenic macrophages.
Anemia, Iron-Deficiency ; drug therapy ; genetics ; metabolism ; Animals ; Dietary Supplements ; analysis ; Female ; Homeostasis ; drug effects ; Humans ; Iron ; deficiency ; Macrophages ; drug effects ; metabolism ; Nitric Oxide Synthase Type II ; genetics ; metabolism ; Quercetin ; administration & dosage ; Rats ; Rats, Sprague-Dawley ; Spleen ; drug effects ; enzymology

The present study sought to investigate the anti-inflammation and immunoloregulation effect of 17 Guizhi Fuling capsule ingredients. The anti-inflammatory ingredients on LPS-induced RAW264. 7 cell injury were assessed with ELISA and immunofluorescence. The release of IL-1β, TNF-α, PGE2 were detected with ELISA and the expression of COX-2 was detected with immunofluorescence. The effects of them on promoting splenic lymphocyte proliferation were assessed with MTT and Hoechst 33342 staining method. The results showed that 15 ingredients had obviously anti-inflammatory activity on LPS- induced injury and play the immunoloregulation roles. This study suggested that the 15 ingredients may be the active ingredients on pelvic infection.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Capsules ; pharmacology ; Cyclooxygenase 2 ; immunology ; Drugs, Chinese Herbal ; administration & dosage ; Immunologic Factors ; pharmacology ; Inflammation ; drug therapy ; Interleukin-1beta ; immunology ; Macrophages ; drug effects ; enzymology ; immunology ; Male ; Mice ; Mice, Inbred BALB C ; Spleen ; cytology ; drug effects ; immunology ; Tumor Necrosis Factor-alpha ; immunology

OBJECTIVETo confirm the anticancer effect of total annonaceous acetogenins (TAAs) abstracted from Annona squamosa Linn. on human hepatocarcinoma.

METHODSThe inhibitory effect of TAAs was demonstrated in H22-bearing mice. The potency of TAAs was confirmed as its 50% inhibiting concentration (IC50) on Bel-7402 cell under Sulfur Rhodamine B staining. Both underlying mechanisms were explored as cellular apoptosis and cell cycle under flow cytometry. Mitochondrial and recipient apoptotic pathways were differentiated as mitochondrial membrane potential under flow cytometry and caspases activities under fluorescence analysis.

RESULTSThe inhibitory rate of TAAs in mice was 50.98% at 4 mg/kg dose. The IC50 of TAAs on Bel-7402 was 20.06 µg/mL (15.13-26.61µg/mL). Effective mechanisms of TAAs were confirmed as both of arresting cell cycle at G1 phase and inducing apoptosis dose- and time-dependently. Mitochondrial and recipient pathways involved in apoptotic actions of TAAs.

CONCLUSIONTAAs is effective for hepatocarcinoma, via inhibiting proliferation and inducing apoptosis.

Acetogenins ; chemistry ; pharmacology ; therapeutic use ; Animals ; Annona ; chemistry ; Antineoplastic Agents, Phytogenic ; chemistry ; pharmacology ; therapeutic use ; Apoptosis ; drug effects ; Carcinoma, Hepatocellular ; drug therapy ; enzymology ; pathology ; Caspases ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, High Pressure Liquid ; Dose-Response Relationship, Drug ; Humans ; Liver Neoplasms ; drug therapy ; enzymology ; pathology ; Male ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Organ Specificity ; drug effects ; Spleen ; drug effects ; Thymus Gland ; drug effects ; Xenograft Model Antitumor Assays

OBJECTIVETo observe the dynamic time-phase expressions of key genes of brain-gut CaM signal pathway of spleen Qi deficiency rats and the intervention effect of Sijunzi decoction.

METHODMale Wistar rats were randomly divided into the normal control group, model 14 d, 21 d, 28 d groups, and Sijunzi decoction 14 d, 21 d, 28 d groups. Except for the normal control group, the remaining groups were included into the spleen Qi deficiency model with the bitter cold breaking Qi method (ig 7.5 g · kg⁻¹ · d⁻¹ of Rheum officinale, Fructus aurantii immaturus, Magnolia officinalis preparation) and the exhaustive swimming method. On the 7th day after the modeling, the Sijunzi decoction groups were orally administered with Sijunzi decoction 20 g · kg⁻¹ · d⁻¹. The expressions of key genes CaM/CaMK II of CaM signaling pathway in hippocampus and intestine at different time points by immunohistochemical method and Western blot. At the same time, the intervention effect of Sijunzi decoction on spleen Qi deficiency rats and its mechanism were analyzed.

RESULTSpleen Qi deficiency rats showed higher intestinal CaM/CaMK II expression and lower hippocampus CaM/CaMK II expression than normal rats (P < 0.05, P < 0.01). After the treatment of Sijunzi decoction, spleen Qi deficiency rats showed reduction in intestinal CaM/CaMK II expression and increase in hippocampus CaM/CaMK II expression (P < 0.05, P < 0.01).

CONCLUSIONThe formation of spleen Qi deficiency syndrome may be related to the high expression of CaM/CaMK II in small intestine tissues and its low expression in hippocampus tissues. Sijunzi decoction may achieve the therapeutic effect in spleen Qi deficiency syndrome by reducing the CaM/CaMK II expression in intestinal tissues and increasing it in hippocampus tissues.

Animals ; Brain ; drug effects ; enzymology ; metabolism ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 ; genetics ; metabolism ; Calmodulin ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Intestines ; drug effects ; enzymology ; metabolism ; Male ; Qi ; Rats ; Rats, Wistar ; Spleen ; drug effects ; Splenic Diseases ; drug therapy ; enzymology ; genetics ; metabolism

OBJECTIVETo explore the effect of Buzhong Yiqi decoction on PI3K/AKT signaling pathway in spleen, stomach and lung of nude mice with lung adenocarcinoma transplantation tumor.

METHODTotally 60 nude mice were randomly divided into the blank control group, the tumor-bearing control group, the cisplatin group, the low-dose Buzhong Yiqi decoction group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. After the corresponding interventions, efforts were made to measure the transplanted tumor volume and calculate the tumor inhibiting rate. The immunohistochemical method and real time PCR were used to detect the expression of PI3K and AKT level in nude mice spleen, stomach and lung.

RESULTBuzhong Yiqi decoction of different concentrations combined with cisplatin could inhibit the growth of the transplanted tumor, with the strongest inhibitory effect in the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group. All of the expressions of PI3K and AKT protein and gene in the spleen, stomach and lung increased, with the most significant increase in the tumor-bearing group. Along with the increase of the concentration of cisplatin and Buzhong Yiqi decoction, the expressions of PI3K and AKT gradually reduced. Compared with the tumor-bearing control group, there were statistical differences in spleen and stomach tissues (P < 0.05). Compared with the cisplatin group, the middle-dose Buzhong Yiqi decoction group and the high-dose Buzhong Yiqi decoction group showed statistical differences (P < 0.05), but without statistical difference compared with the blank control group.

CONCLUSIONAmong nude mice with lung adenocarcinoma transplantation tumor, the PI3K and AKT protein and gene expressions in spleen, stomach and lung tissues increased, which might indicated the effect of cisplatin and Buzhong Yiqi decoction in reducing PI3K and AKT expressions and the relations between the reduction degree and the concentrations of Buzhong Yiqi decoction. Cisplatin combined with Buzhong Yiqi decoction could decrease the PI3K and AKT protein and gene expression in spleen, stomach and lung, and make the pathway closer to normal, so as to protect the functions of spleen, stomach and lung, there may be target spots of Buzhong Yiqi decoction in PI3K/AKT signal pathway.

Adenocarcinoma ; drug therapy ; enzymology ; genetics ; Animals ; Cell Line, Tumor ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lung ; drug effects ; enzymology ; Lung Neoplasms ; drug therapy ; enzymology ; genetics ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Oncogene Protein v-akt ; genetics ; metabolism ; Phosphatidylinositol 3-Kinases ; genetics ; metabolism ; Signal Transduction ; drug effects ; Spleen ; drug effects ; enzymology

OBJECTIVEThrough establishing different blood deficiency animal model, to evaluate enriching blood effect changes of the drug pair of Angelicae Sinensis Radix and Chuanxiong Rhizoma and each single herb, and to explore the effect characteristics of their compatibility.

METHODThree different methods of acetyl phenylhydrazine (APH) hemolytic method, cyclophosphamide (CTX) chemical damage method, APH-CTX complex method were used respectively to copy different blood deficiency model mice. Changes of orbit blood routine, thymus index, spleen index and ATPase activity of red cell membrane of model mice were tested.

RESULTCompared with normal group, all indexes had significant differences in three model mice. The drug pair and each single herb had significant impact on most indexes of the APH-CTX complex model mice, and on the individual indexes of APH hemolytic model mice and CTX chemical damage model mice. Therefore, APH and CTX complex blood deficiency model was more suitable for the enriching blood mechanism study of the drug pair of Angelicae Sinensis Radix and Chuanxiong Rhizoma. Compared with the single herb of Angelicae Sinensis Radix and Chuanxiong Rhizoma, the drug pair of them had presented enriching blood effect at different extent with strengthening trend in regulating the invigorating blood indexes, immune organs and energy metabolic enzymes.

CONCLUSIONThe results of this research have provided scientific basis for revealing the mutual promotive composition law of the drug pair of Angelicae Sinensis Radix and Chuanxiong Rhizoma, and responded effectively the mult-link and mult-target effect characteristics of Chinese medicine bio-effect, to offer reference for the bio-effect research of the complicated substance group of Chinese medicine and traditional Chinese medicine formulae, and to supply demonstrative reference for researching the formulae compatibility law which takes the single drug-drug pair-formulae as main line.

Administration, Oral ; Angelica sinensis ; chemistry ; Animals ; Ca(2+) Mg(2+)-ATPase ; drug effects ; metabolism ; Cyclophosphamide ; pharmacology ; Drug Therapy, Combination ; Drugs, Chinese Herbal ; chemistry ; Erythrocytes ; drug effects ; enzymology ; Female ; Hematologic Diseases ; drug therapy ; etiology ; Hemoglobins ; drug effects ; Leukocytes ; drug effects ; Medicine, Chinese Traditional ; Mice ; Models, Animal ; Phenylhydrazines ; pharmacology ; Plant Roots ; chemistry ; Random Allocation ; Rhizome ; chemistry ; Sodium-Potassium-Exchanging ATPase ; drug effects ; metabolism ; Spleen ; drug effects ; immunology ; Thymus Gland ; drug effects ; immunology

Many immune down-regulatory molecules have been isolated from parasites, including cystatin (cystain protease inhibitor). In a previous study, we isolated and characterized Type I cystatin (CsStefin-1) of the liver fluke, Clonorchis sinensis. To investigate whether the CsStefin-1 might be a new host immune modulator, we induced intestinal inflammation in mice by dextran sodium sulfate (DSS) and treated them with recombinant CsStefin-1 (rCsStefin-1). The disease activity index (DAI) increased in DSS only-treated mice. In contrast, the DAI value was significantly reduced in rCsStefin-1-treated mice than DSS only-treated mice. In addition, the colon length of DSS only-treated mice was shorter than that of rCsStefin-1 treated mice. The secretion levels of IFN-gamma and TNF-alpha in the spleen and mesenteric lymph nodes (MLNs) were significantly increased by DSS treatment, but the level of TNF-alpha in MLNs was significantly decreased by rCsStefin-1 treatment. IL-10 production in both spleen and MLNs was significantly increased, and IL-10+F4/80+ macrophage cells were significantly increased in the spleen and MLNs of rCsStefin-1 treated mice after DSS treatment. In conclusion, rCsStefin-1 could reduce the intestinal inflammation occurring after DSS treatment, these effects might be related with recruitment of IL-10 secreting macrophages.
Animals ; Antigens, Differentiation/analysis ; Clonorchis sinensis/*enzymology ; Colon/pathology ; Cystatins/*metabolism ; Cytokines/secretion ; Dextran Sulfate/toxicity ; Female ; Helminth Proteins/*metabolism ; Immunologic Factors/*metabolism ; Inflammation/chemically induced/*pathology ; Interleukin-10/analysis ; Intestines/*drug effects/pathology ; Lymph Nodes/immunology ; Macrophages/chemistry/*immunology ; Mice ; Mice, Inbred C57BL ; Severity of Illness Index ; Spleen/immunology

OBJECTIVETo investigate the influence of Weichang'an pill on the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) in model rats.

METHODAnimal model of compound diarrhea was induced by a lactose enriched diet in the Wistar rat, combining with restraint stress. Twenty four female Wistar rats were randomly divided into normal group, model group and 60 mg x kg(-1) x d(-1) Weichang'an pill group. The rate of weight increase, the incubation period of diarrhea and the diarrhea index were observed. Then 45 female Wistar rats randomly divided into five groups: control group, model group and Weichang'an pill groups of high, medium and low doses (80, 60, 40 mg x kg(-1) x d(-1)). The indexes of thymus and spleen were calculated. The activities of LDH, MDH and disaccharidase in intestinal organization were inspected. Serum D-xylose content and the AQP4 concentration in proximal colon were detected.

RESULTAfter taking Weichang'an pill for 4 days, the rate of weight increase in Weichang'an pill group was higher than the model group's. While the rate of diarrhea was lower significantly. So the best cycle of taking medicine was 4 days. The indexes of thymus and spleen of model group were decreased than that of control group. And the activities of LDH, MDH and disaccharidase in intestinal organization were also decreased. But the AQP4 concentration in proximal colon was increased. Compared with the model group, the indexes of thymus and spleen increased remarkably in the group of medium doses. Meanwhile, the activities of LDH, MDH and disaccharidase increased. But the AQP4 concentration didn't change.

CONCLUSIONWeichang'an pill has the effect of antidiarrhea. It can adjust the sugar's catabolism through increasing the activity of intestinal digestive ferment.

Animals ; Aquaporin 4 ; genetics ; metabolism ; Colon ; drug effects ; metabolism ; Disaccharidases ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Intestines ; drug effects ; enzymology ; Irritable Bowel Syndrome ; drug therapy ; enzymology ; genetics ; metabolism ; L-Lactate Dehydrogenase ; genetics ; metabolism ; Malate Dehydrogenase ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Spleen ; drug effects ; metabolism

OBJECTIVE: To examine the effects of cocaine on the activities of ATPase, LDH and SDH in cultured mouse splenocytes in vitro. METHODS: The ATPase, LDH and SDH activities in mouse splenocytes were detected at day 7 after continuous culturing the mouse cells exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL in vitro. RESULTS: The activities of ATPase, LDH and SDH in mouse splenocytes exposed to cocaine hydrochloride in final concentration of 10, 20 and 100 microg/mL were significantly decreased after continuous culturing for 7 days. CONCLUSION The present study demonstrated that cocaine could inhibit the activities of ATPase, LDH and SDH in cultured splenocytes in vitro.
Adenosine Triphosphatases/metabolism* ; Animals ; Cells, Cultured ; Cocaine/pharmacology* ; Dose-Response Relationship, Drug ; L-Lactate Dehydrogenase/metabolism* ; Male ; Mice ; Mice, Inbred Strains ; Spleen/enzymology* ; Succinate Dehydrogenase/metabolism*

OBJECTIVE: To investigate the protective effect of abnormal savda munzip on the radiation-induced damaged in mice. METHODS: The mice were randomly divided into 2 groups: a control group and a drug group; the latter was again divided into a low dosage group (6.25%), a moderate dosage group (12.5%) and a high dosage group (25%) according to the drug concentration. All mice were given general radiation emitted by 6 Gy MV-X liner accelerator once, which resulted in the acute radiation damage. The different administrations of abnormal savda munzip were fed to the mice in the drug group orally for 7 days consecutively before and after the radiation. On the day of the last administration, 10 mice were sacrificed, and white blood cells, red cells and blood plates of the peripheral blood, spleen index, and spleen SOD were detected; while the 20 remaining mice were fed continually till 30 days, and the 30 day survival ratio of the mice was calculate. RESULTS: (1) Although the mice weight in the drug groups was higher than that in the control group, no significant difference existed (P>0.05). Spleen index in the control group was higher than that in the drug group. (2) Spleen SOD was significantly increased by the drugs compared with that of the control group (P<0.01), which was positively related to the drug concentration. (3) Pre-treatment of mice with the extract of abnormal savda munzip significantly increased the white cells and red cells in the peripheral blood compared with the control group (P<0.05). The blood cells were positively related to the drug concentration (P<0.05). Although the counts of blood plates in all drug groups were higher than those in the control group, no significant difference existed (P>0.05). (4) Compared with the control group, a marked improvement of 30 day survival rate in all drug groups was observed (P<0.0001). Both the concentration and the survival rate were increased (P<0.01). (5) The SOD level and leukocyte counts in the irradiated mice were positively related to the survival ratio (r=0.612, P<0.005; r=0.32, P<0.05, respectively). CONCLUSION The abnormal savda munzip has significant protective function on the mice irradiated by 7 Gy MV-X liner accelerator.
Administration, Oral ; Animals ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; therapeutic use ; Male ; Mice ; Radiation Injuries, Experimental ; drug therapy ; mortality ; Radiation-Protective Agents ; administration & dosage ; therapeutic use ; Random Allocation ; Spleen ; drug effects ; enzymology ; Superoxide Dismutase ; metabolism ; Survival Rate ; Time Factors ; Whole-Body Irradiation