Effects of Steaming and SiO2 Surface Passivation on SSZ-13 Zeolites in the Ethylene to Propylene Reaction.

SSZ-13 zeolite was modified by two kinds of post-treatment methods such as steaming and SiO2 surface passivation (silylation) for ETP catalyst with high activity. The former steaming treatment was conducted in the range of 400-700 °C, whereas the latter surfaces passivation was applied to a chemical liquid deposition (CLD) technique that uses various silylation agents such as tetramethylorthosilicate (TMOS), tetraethylorthosilicate (TEOS), and tetrabuthylorthosilicate (TBOS). Catalysts were characterized by powder-XRD, ICP, Ar-phsisorption, solid-state 27Al MAS NMR, and NH3-TPD, and their activities were tested in fixed bed reaction system. Regarding the effects of steaming temperature, the results show that a relatively higher selectivity is observed in SSZ-13 catalysts treated at proper steaming temperatures such as 450 and 500 °C compared to parent and other steam treated catalysts. For optimum surface passivation treatments for ETP reactions, one-step surface passivation using TEOS agents among various passivation agents led to enhanced propylene selectivity to 80% when compared with parent and other silylated SSZ-13 catalysts. However, a sequential passivation treatment with a TEOS agent was not highly affected by the reaction activity.

Evaluation of in vitro anti-oxidant and anti-inflammatory activities of Korean and Chinese Lonicera caerulea.

BACKGROUND/OBJECTIVES: The honeysuckle berry (HB) contains ascorbic acid and phenolic components, especially anthocyanins, flavonoids, and low-molecular-weight phenolic acids. In order to examine the potential of HB as a hepatoprotective medicinal food, we evaluated the in vitro anti-oxidant and anti-inflammatory activities of Korean HB (HBK) and Chinese HB (HBC). MATERIALS/METHODS: Antioxidant and anti-inflammatory effects of the extracts were examined in HepG2 and RAW 264.7 cells, respectively. The anti-oxidant capacity was determined by DPPH, SOD, CAT, and ARE luciferase activities. The production of nitric oxide (NO) as an inflammatory marker was also evaluated. The Nrf2-mediated mRNA levels of heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase [quinone] 1 (Nqo1), and glutamate-cysteine ligase catalytic subunit (Gclc) were measured. The concentrations of HB extracts used were 3, 10, 30, 100, and 300 µg/mL. RESULTS: The radical scavenging activity of all HB extracts increased in a concentration-dependent manner (P < 0.01 or P < 0.05). SOD (P < 0.05) and CAT (P < 0.01) activities were increased by treatment with 300 µg/mL of each HB extract, when compared to those in the control. NO production was observed in cells pretreated with 100 or 300 µg/mL of HBC and HBK (P < 0.01). Treatment with 300 µg/mL of HBC significantly increased Nqo1 (P < 0.01) and Gclc (P < 0.05) mRNA levels compared to those in the control. Treatment with 300 µg/mL of HBK (P < 0.05) and HBC (P < 0.01) also significantly increased the HO-1 mRNA level compared to that in the control. CONCLUSIONS: Thus, the Korean and Chinese HBs were found to possess favorable in vitro anti-oxidant and anti-inflammatory activities. Nrf2 and its related anti-oxidant genes were associated with both anti-oxidant and anti-inflammatory activities in HB-treated cells. Further studies are needed to confirm these in vivo effects.

Immunomodulatory Effects of Kuseonwangdogo-Based Mixed Herbal Formula Extracts on a Cyclophosphamide-Induced Immunosuppression Mouse Model.

AIM: Kuseonwangdogo is a traditional Korean immunomodulatory polyherbal prescription. However, there are no systemic findings on its complex immunomodulatory effects on in vivo models. In this study, we observed the immunomodulatory effects of Kuseonwangdogo-based mixed herbal formula aqueous extracts (MHFe) on cyclophosphamide- (CPA-) induced immunosuppression mouse model. METHODS: In total, 60 male 6-week-old ICR mice (10 mice/group) were selected based on body weight 24 h after the second CPA treatment and used in this experiment. Twelve hours after the end of the last (fourth) oral administration of MHFe, the animals were sacrificed. RESULTS: Following CPA treatment, a noticeable decrease in the body, thymus, spleen, and submandibular lymph node (LN) weights; white blood cell, red blood cell, platelet number, hemoglobin, and hematocrit concentrations; serum interferon-γ levels; splenic tumor necrosis factor-α, interleukin- (IL-) 1ß, and IL-10 content; and peritoneal and splenic natural killer cell activities was observed. Depletion of lymphoid cells in the thymic cortex, splenic white pulp, and submandibular LN-related atrophic changes were also observed. However, these CPA-induced myelosuppressive signs were markedly and dose-dependently inhibited by the oral administration of 125, 250, and 500 mg/kg MHFe. CONCLUSION: MHFe can be a promising, potent immunomodulatory therapeutic agent for various immune disorders.

Protective effects of guggulsterone against colitis are associated with the suppression of TREM-1 and modulation of macrophages.

Triggering receptor expressed on myeloid cells 1 (TREM-1)-expressing intestinal macrophages are significantly increased in the colons of patients with inflammatory bowel disease (IBD). We focused here on the effects of guggulsterone on macrophage modulation in colitis as a potential therapeutic molecule in human IBD and explore the underlying mechanisms. Gene expression in macrophages was examined and wound-healing assay using HT-29 cells was performed. Colitis in wild-type and IL-10-, Toll-like receptor 4 (TLR4)-, and myeloid differentiation primary response 88 (MyD88)-deficient mice was induced via the administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) into the colon. In both in vitro and in vivo experiments, guggulsterone suppressed intestinal inflammation amplified by TREM-1 stimulation, in which the suppression of NF-κB, activating protein-1, and proteasome pathways was involved. In the TNBS-induced colitis model, guggulsterone reduced disease activity index scores and TREM-1 expression, stimulated IL-10 production, and improved survival in wild-type mice. These effects were not observed in IL-10-, TLR4-, and MyD88-deficient mice. Guggulsterone also suppressed M1 polarization, yet induced the M2 phenotype in macrophages from IBD patients as well as from mice. These findings indicate that guggulsterone blocks the hyperactivation of macrophages via TREM-1 suppression and induces M2 polarization via IL-10 mediated by the TLR4 signaling pathway. Furthermore, this study provides a new rationale for the therapeutic potential of guggulsterone in the treatment of IBD. NEW & NOTEWORTHY We found that guggulsterone attenuates triggering receptor expressed on myeloid cells 1 (TREM-1)-mediated hyperactivation of macrophages and polarizes macrophages toward the M2 phenotype. This was mediated by IL-10 and partly Toll-like receptor 4 signaling pathways. Overall, these data support that guggulsterone as a natural plant sterol modulates macrophage phenotypes in colitis, which may be of novel therapeutic importance in inflammatory bowel disease treatment.

Molecular mechanisms of cutis laxa- and distal renal tubular acidosis-causing mutations in V-ATPase a subunits, ATP6V0A2 and ATP6V0A4.

The a subunit is the largest of 15 different subunits that make up the vacuolar H+-ATPase (V-ATPase) complex, where it functions in proton translocation. In mammals, this subunit has four paralogous isoforms, a1-a4, which may encode signals for targeting assembled V-ATPases to specific intracellular locations. Despite the functional importance of the a subunit, its structure remains controversial. By studying molecular mechanisms of human disease-causing missense mutations within a subunit isoforms, we may identify domains critical for V-ATPase targeting, activity and/or regulation. cDNA-encoded FLAG-tagged human wildtype ATP6V0A2 (a2) and ATP6V0A4 (a4) subunits and their mutants, a2P405L (causing cutis laxa), and a4R449H and a4G820R (causing renal tubular acidosis, dRTA), were transiently expressed in HEK 293 cells. N-Glycosylation was assessed using endoglycosidases, revealing that a2P405L, a4R449H, and a4G820R were fully N-glycosylated. Cycloheximide (CHX) chase assays revealed that a2P405L and a4R449H were unstable relative to wildtype. a4R449H was degraded predominantly in the proteasomal pathway, whereas a2P405L was degraded in both proteasomal and lysosomal pathways. Immunofluorescence studies disclosed retention in the endoplasmic reticulum and defective cell-surface expression of a4R449H and defective Golgi trafficking of a2P405L Co-immunoprecipitation studies revealed an increase in association of a4R449H with the V0 assembly factor VMA21, and a reduced association with the V1 sector subunit, ATP6V1B1 (B1). For a4G820R, where stability, degradation, and trafficking were relatively unaffected, 3D molecular modeling suggested that the mutation causes dRTA by blocking the proton pathway. This study provides critical information that may assist rational drug design to manage dRTA and cutis laxa.

Ameliorating effects of herbal formula hemomine on experimental subacute hemorrhagic anemia in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Hemomine (HM) is an herbal mixture consisting of 5 varieties of the hematopoietic herbal extracts (Angelica gigas Nakai, Cnidium officinale Makino, Paeonia lactiflora Pall., Rehmannia glutinosa Liboschitz ex Stueudel, Glycyrrhiza uralensis Fischer). AIM OF THE STUDY: Anemia has been treated with iron supplements, whereas it could cause adverse side effects such as digestive discomfort. In the present study, HM was applied to SHA rats to test for several activities so as to verify its therapeutic potentials on anemia and digestive discomfort. MATERIALS AND METHODS: Sprague-Dawley rats were assigned to seven groups: (Two controls, two references (ferric hydroxide polymatose (FM) and ferritin extract glycerin hydrate (FA)), three different concentrations of HM, n=8 per groups), and induced subacute hemorrhagic anemia (SHA) through blood exsanguinations once a day for 7 days. RESULTS: The SHA animal model showed changes in the markers related to classic iron-deficient and regenerative anemia in this experiment. However, the SHA related anemic signs were dose-dependently inhibited by the administration of HM 2, 1, and 0.5ml/kg for 7 days, and more favorably than the equal dosages of FM and FA. In addition, FM and FA showed the typical constipation signs, including reduction of in thickness of the colonic mucosa, in contrast, HM 2, 1, and 0.5ml/kg groups had no effects on the gastrointestinal motilities and the colonic mucous components when compared to the controls. The results suggested that the HM significantly showed to have therapeutic effects in the experimental SHA in rats, and is more potent than the commercial iron supplement through the proliferation of hematopoietic stem cells with reduced digestive discomfort. CONCLUSIONS: Therefore, Hemomine may prove to be a promising hematopoietic and therapeutic agent for anemia.

The Effects of Topical Application of Polycal (a 2:98 (g/g) Mixture of Polycan and Calcium Gluconate) on Experimental Periodontitis and Alveolar Bone Loss in Rats.

The aim of this study was to observe whether Polycal has inhibitory activity on ligation-induced experimental periodontitis and related alveolar bone loss in rats following topical application to the gingival regions. One day after the ligation placements, Polycal (50, 25, and 12.5 mg/mL solutions at 200 µL/rat) was topically applied to the ligated gingival regions daily for 10 days. Changes in bodyweight, alveolar bone loss index, and total number of buccal gingival aerobic bacterial cells were monitored, and the anti-inflammatory effects were investigated via myeloperoxidase activity and levels of the pro-inflammatory cytokines IL-1ß and TNF-α. The activities of inducible nitric oxide synthase (iNOS) and lipid peroxidation (MDA) were also evaluated. Bacterial proliferation, periodontitis, and alveolar bone loss induced by ligature placements were significantly inhibited after 10 days of continuous topical application of Polycal. These results indicate that topical application of Polycal has a significant inhibitory effect on periodontitis and related alveolar bone loss in rats mediated by antibacterial, anti-inflammatory, and anti-oxidative activities.

Effect of Polycalcium, a mixture of Polycan and calcium lactate-gluconate in a 1:9 weight ratio, on rats with surgery-induced osteoarthritis.

In the present study, the beneficial and synergistic effects of Polycalcium, a mixture of Polycan and calcium (Ca) lactate-gluconate in a 1:9 weight ratio, on a rat model of osteoarthritis (OA) were explored. Polycalcium (50, 100 and 200 mg/kg) was administered orally once per day for 28 days from 1 week after the OA-modeling surgery. Diclofenac sodium (2 mg/kg) was administered as a reference drug. Following the OA surgery, increases in the maximum extension angles, edematous changes in knee and capsule thickness, reductions in chondrocyte proliferation and cartilage glycosaminoglycan (GAG) levels, as well as changes in cartilage degeneration were observed. However, these OA-related symptoms were inhibited after 28 days of continuous oral treatment with Polycalcium. Anti-OA effects, including the induction of chondrocyte proliferation, were detected in the Polycalcium-treated rats and were more favorable compared with those in rats treated with Polycan or Ca lactate-gluconate alone (100 mg). Therefore, a mixture of Polycan and Ca lactate-gluconate was demonstrated to have beneficial synergistic effects on OA.

The administration of Fructus Schisandrae attenuates dexamethasone-induced muscle atrophy in mice.

In the present study, we aimed to determine whether ethanol extracts of Fructus Schisandrae (FS), the dried fruit of Schizandra chinensis Baillon, mitigates the development of dexamethasone-induced muscle atrophy. Adult SPF/VAT outbred CrljOri:CD1 (ICR) mice were either treated with dexamethasone to induce muscle atrophy. Some mice were treated with various concentrations of FS or oxymetholone, a 17α-alkylated anabolic-androgenic steroid. Muscle thickness and weight, calf muscle strength, and serum creatine and creatine kinase (CK) levels were then measured. The administration of FS attenuated the decrease in calf thickness, gastrocnemius muscle thickness, muscle strength and weight, fiber diameter and serum lactate dehydrogenase levels in the gastrocnemius muscle bundles which was induced by dexamethasone in a dose-dependent manner. Treatment with FS also prevented the dexamethasone-induced increase in serum creatine and creatine kinase levels, histopathological muscle fiber microvacuolation and fibrosis, and the immunoreactivity of muscle fibers for nitrotyrosine, 4-hydroxynonenal, inducible nitric oxide synthase and myostatin. In addition, the destruction of the gastrocnemius antioxidant defense system was also inhibited by the administration of FS in a dose-dependent manner. FS downregulated the mRNA expression of atrogin-1 and muscle ring-finger protein-1 (involved in muscle protein degradation), myostatin (a potent negative regulator of muscle growth) and sirtuin 1 (a representative inhibitor of muscle regeneration), but upregulated the mRNA expression of phosphatidylinositol 3-kinase, Akt1, adenosine A1 receptor and transient receptor potential cation channel subfamily V member 4, involved in muscle growth and the activation of protein synthesis. The overall effects of treatment with 500 mg/kg FS were comparable to those observed following treatment with 50 mg/kg oxymetholone. The results from the present study support the hypothesis that FS has a favorable ameliorating effect on muscle atrophy induced by dexamethasone, by exerting anti-inflammatory and antioxidant effects on muscle fibers, which may be due to an increase in protein synthesis and a decrease in protein degradation.

Essential oils purified from Schisandrae semen inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 activation and migration of human aortic smooth muscle cells.

BACKGROUND: The migration of vascular smooth muscle cells from the tunica media to the subendothelial region may be a key event in the development of atherosclerosis after arterial injury. In this study, we investigated the potential mechanisms underlying the anti-atherosclerotic effects of Schisandrae Semen essential oil (SSeo) in human aortic smooth muscle cells (HASMCs). METHODS: Metalloproteinase-2/9 (MMP-2/9) activity was evaluated by gelatin zymography and gelatinase activity assay kit. The possible mechanisms underlying SSeo-mediated reduction of by tumor necrosis factor (TNF)-α-induced cell invasion and inhibition of secreted and cytosolic MMP-9 production in HASMCs were investigated. RESULTS: Our results indicate that SSeo treatment has an inhibitory effect on activation as well as expression of MMP-9 induced by TNF-α in HASMCs in a dose-dependent manner without significant cytotoxicity. SSeo attenuated nuclear translocation of TNF-α-mediated nuclear factor-kappa B (NF-κB) and blocked degradation of the NF-κB inhibitor proteins as well as the production of reactive oxygen species. SSeo also reduced TNF-α-induced production of pro-inflammatory mediators such as nitric oxide and prostaglandin E2 and inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression in HASMCs. Furthermore, the Matrigel migration assay showed that SSeo effectively reduced TNF-α-induced HASMC migration compared with that in the control group. CONCLUSIONS: Taken together, these results suggest that SSeo treatment suppresses TNF-α-induced HASMC migration by selectively inhibiting MMP-9 expression, which was associated with suppression of the NF-κB signaling pathway. Taken together, these results suggest that SSeo has putative potential anti-atherosclerotic activity.

Genotoxicity of rice bran oil extracted by supercritical CO2 extraction.

Rice bran oil extracted by supercritical CO2 extraction (RB-SCE) reportedly exhibits pharmacological activities such as antioxidant and in vivo hair growth-inducing effects. Such activities raise the possibility of the development of novel hair growth-inducing agents using RB-SCE. The aim of this study was to investigate the potential genotoxic effects of RB-SCE in three short-term mutagenicity assays (bacterial reverse mutation assay, in vitro mammalian chromosomal aberration test, and in vivo micronucleus assay). RB-SCE showed no genotoxicity in the bacterial reverse mutation assay up to 5000 mg/plate and in the in vivo micronucleus test up to 600 mg/kg body weight. However, at 120 µg/mL with S9 mix and 200 µg/mL without S9 mix RB-SCE showed significantly different genotoxicity than the negative control in the in vitro chromosome aberration test. The induction of chromosomal aberrations under the present conditions may have no biological significance. We have herein demonstrated that RB-SCE can be regarded as a non-genotoxic material based on the available in vivo and in vitro results.

Protective effects of calcium gluconate on osteoarthritis induced by anterior cruciate ligament transection and partial medial meniscectomy in Sprague-Dawley rats.

BACKGROUND: This study aimed to determine whether calcium gluconate exerts protective effects on osteoarthritis (OA) induced by anterior cruciate ligament (ACL) transection and partial medial meniscectomy. METHODS: Calcium gluconate was administered by mouth daily for 84 days to male ACL transected and partial medial meniscectomized Sprague-Dawley rats 1 week after operation. RESULTS: Eighty-four days of treatment with 50 mg/kg calcium gluconate led to a lower degree of articular stiffness and cartilage damage compared to the OA control, possibly through inhibition of overexpressed cyclooxygenase (COX)-2 and related chondrocyte apoptosis. Similar favorable effects on stiffness and cartilage were detected in calcium gluconate-administered rats. Additionally, calcium gluconate increased 5-bromo-2'-deoxyuridine (BrdU) uptake based on observation of BrdU-immunoreactive cells on both the femur and tibia articular surface cartilages 84 days after intra-joint treatment with calcium gluconate. CONCLUSIONS: Taken together, our results demonstrate that calcium gluconate has a protective effect against OA through inhibition of COX-2 and related chondrocyte apoptosis.

In vivo hair growth-promoting effect of rice bran extract prepared by supercritical carbon dioxide fluid.

The potential hair growth-promoting activity of rice bran supercritical CO2 extract (RB-SCE) and major components of RB-SCE, linoleic acid, policosanol, γ-oryzanol, and γ-tocotrienol, were evaluated with the histological morphology and mRNA expression levels of cell growth factors using real-time reverse transcriptase-polymerase chain reaction (PCR) in C57BL/6 mice. RB-SCE showed hair growth-promoting potential to a similar extent as 3% minoxidil, showing that the hair follicles were induced to be in the anagen stage. The numbers of the hair follicles were significantly increased. In addition, mRNA expression levels of vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), and keratinocyte growth factor (KGF) were also significantly increased and that of transforming growth factor-ß (TGF-ß) decreased in RB-SCE-treated groups. Among the major components of RB-SCE, linoleic acid and γ-oryzanol induced the formation of hair follicles according to examination of histological morphology and mRNA expression levels of cell growth factors. In conclusion, our results demonstrate that RB-SCE, particularly linoleic acid and γ-oryzanol, promotes hair growth and suggests RB-SCE can be applied as hair loss treatment.

Safety and efficacy of polycalcium for improving biomarkers of bone metabolism: a 4-week open-label clinical study.

Polycalcium is a mixture of Polycan and calcium lactate-gluconate 1:9 (w/w) with demonstrated antiosteoporosis activity in vitro and in vivo studies. These studies were a 4-week open-label, single-center trial to evaluate the efficacy of oral Polycalcium on bone metabolism and safety. In total, 30 healthy women (range 40-60 years) were administered 400 mg of Polycalcium for 4 weeks. The primary efficacy parameter was urinary deoxypyridinoline (DPYR) levels, and serum osteocalcin (OSC), bone-specific alkaline phosphatase (BALP), urinary cross-linked C-telopeptide of type-1 collagen (CTx), urinary cross-linked N-telopeptide of type-1 collagen (NTx), calcium (Ca), and phosphorus (P) levels, which were evaluated for comparison before and after administration of Polycalcium. After 4 weeks of Polycalcium administration, 27 subjects completed the test plan. Three subjects withdrew their consent to participate. The values of blood OSC, BALP, serum Ca, and serum P from baseline to 4 weeks of treatment were changed by -28.44%, 14.37%, 6.11%, and 1.42%, respectively. Biomarkers of bone resorption: urinary DPYR, serum CTx, serum NTx, urinary Ca, and urinary P, at baseline after 4 weeks of treatment were changed by -13.40%, 6.67%, -5.13%, -22.43%, and -3.04%, respectively. Additionally, when considering the subjects' adverse effects and the results of the blood and urine tests over the 4-week trial period, the dose of 400 mg Polycalcium showed efficacy for improving bone metabolism and was well tolerated and safe. Polycalcium was apparently safe and efficacious.

Efficacy test of Polycan, a beta-glucan originated from Aureobasidium pullulans SM-2001, on anterior cruciate ligament transection and partial medial meniscectomy-induced-osteoarthritis rats.

The object of this study was to assess the efficacy of Polycan from Aureobasidium pullulans SM-2001, which is composed mostly of beta-1,3-1,6-glucan, on osteoarthritis (OA)-induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT&PMM). Three different dosages of Polycan (85, 42.5, and 21.25 mg/kg) were orally administered once a day for 84 days to male rats a week after ACLT&PMM surgery. Changes in the circumference and maximum extension angle of each knee, and in cartilage histopathology were assessed using Mankin scores 12 weeks after Polycan administration. In addition, cartilage proliferation was evaluated using bromodeoxyuridine (BrdU). As the result of ACLT&PMM, classic OA was induced with increases in maximum extension angles, edematous knees changes, and capsule thickness, as well as decreases in chondrocyte proliferation, cartilages degenerative changes, and loss of articular cartilage. However, these changes (except for capsule thickness) were markedly inhibited in all Polycan- and diclofenac sodium-treated groups compared with OA control. Although diclofenac sodium did not influence BrdU uptake, BrdU-immunoreactive cells were increased with all dosages of Polycan, which means that Polycan treatment induced proliferation of chondrocytes in the surface articular cartilage of the tibia and femur. The results obtained in this study suggest that 84 days of continuous oral treatment of three different dosages of Polycan led to lesser degrees of articular stiffness and histological cartilage damage compared with OA controls 91 days after OA inducement, suggesting that the optimal Polycan dosage to treat OA is 42.5 mg/kg based on the present study.

Immunomodulatory effects of Aureobasidium pullulans SM-2001 exopolymers on the cyclophosphamide-treated mice.

The immunomodulatory effects of exopolymers of Aureobasidium pullulans SM-2001 containing beta-1,3/1,6-glucan were evaluated on the cyclophosphamide (CPA)-treated mice. To induce immunosuppress, 150 and 110 mg/kg of CPA were intraperitoneally injected at 1 and 3 days before start of test material administrations, respectively. Exopolymers were subcutaneously or orally administered in a volume of 10 ml/kg, 4 times; 12-hr intervals from 24 hrs after second treatment of CPA. After treatment of exopolymers, the changes of thymus and spleen weights, splenic amounts of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-10, thymic and splenic CD3+, CD4+, CD8+ and TNF-alpha+ cells were monitored in CPA-treated mice. As results of CPA treatment, dramatical decreases of the CD3+, CD4+, CD8+ and TNF-alpha+ cells were detected in thymus and spleen with decreases of thymus and spleen weights. In addition, decreases of splenic TNF-alpha, IL-1beta and IL-10 contents were also detected at flow cytometrical observations. However, oral and subcutaneous treatment of exopolymers effectively reduced the immunosuppressive changes induced by CPA. Therefore, it is concluded that exopolymers of A. pullulans can be effectively prevent the immunosuppress mediated, at least partially, recruitment of T cells and TNF-alpha+ cells or enhancement of their activity, and can provide effective prevention or treat regimes for the immunosuppress and related diseases such as cancer, sepsis and high-dose chemotherapy or radiotherapy.