Cyclophosphamide-induced Immunosuppression Research Articles

Immune-Boosting Potentiating Properties of Brassica nigra Hydroalcoholic Extract in Cyclophosphamide-Induced Immunosuppression in Rats.

The antioxidative and immune-boosting properties of the hydroalcoholic extract of Brassica nigra sprouts in cyclophosphamide-induced immunosuppression in rats were investigated in this study. B. nigra sprouts were prepared in the lab to monitor the bio-changes in bioactive compounds during the sprouting period up to 7 days at 17 ± 1 °C and 90% relative humidity. The total phenolic content (TPC), antioxidant activity (AOA), total flavonoids (TFs), total flavonols (TFLs), and total carotenoids (TCs) were evaluated. Consequently, the identification and quantification of phenolic acids, their derivatives, and flavonoids were carried out using HPLC. Subsequently, the selected BN sprout (6-day-old sprout) was biologically examined, and oxidative stress biomarkers, hematological parameters, immunoglobulins (Igs), and pro-inflammatory and anti-inflammatory cytokines were investigated. An increase in TPC, AOA, TFs, TFLs, and TCs was observed by increasing the sprouting time. The HPLC analysis indicated that the B. nigra seeds contained 10 phenolic acids and 4 flavonoids, predominantly syringic acid and quercetin, respectively. After 3 days, the number of phenolic acids increased to 16, predominantly syringic acid, and the number of flavonoids increased to 7, predominantly quercetin. On the 6th day, 13 phenolic acids were estimated, with the highest being benzoic acid, and 6 flavonoids were estimated, with the highest being quercetin. The greatest rise in phenols was seen on the sixth day of sprouting. These included caffeic acid, chlorogenic acid, cinnamic acid, ferulic acid, coumaric acid, benzoic acid, and rosmarinic acid. Flavonoids such as kaempferol and myricetin increased. The sprouts on day 6 were recorded as having the highest bioactive compounds and AOA content. The selected B. nigra sprouts were examined for antioxidative and immunomodulatory properties in a rat model. Dosing 250 and 500 mg kg-1, the rats exhibited significant improvements in terms of antioxidative stress and the number of white blood cells (WBCs), lymphocytes, and neutrophils in the blood, indicating stimulation of the immune response in a dose-dependent manner. In addition, the production of immune proteins, such as IgG, IgM, and IgA, was enhanced in the blood. Moreover, the 500 mg kg-1 concentration of BN extract stimulated cytokine production in a stronger manner than the 250 mg kg-1 concentration, indicating that the extract significantly increased immune activity. In conclusion, the results indicate that mustard seed extracts have immunosuppressive properties against cyclophosphamide-induced immunosuppression in rats.

Rosmarinic acid improves cyclophosphamide-induced immunosuppression in mice by immunomodulatory and antioxidant effects

Rosmarinic acid (RA) has various pharmacological effects, such as hypolipidemic and antitumor effects; however, its role in immunomodulation is not fully understood. Therefore, in this study, we established a cyclophosphamide-induced immunosuppressive mouse model to study the effects of RA on immune function. The results showed that RA alleviated the slow increase in body weight, increased the immune organ index, and improved the histopathological status of immunosuppressed mice. Furthermore, it can restore peripheral blood levels and enhance the activity of lymphocytes, NK cells, and CTL, as well as the secretion and mRNA expression of immune-related cytokines. Moreover, it improved oxidative stress and promoted phosphorylation of the splenic PI3K/Akt signaling pathway. In summary, RA plays a positive role in the immune response, and its potential mechanism may be related to the regulation of the PI3K/Akt signaling pathway. Thus, RA could be developed as an immunomodulator for functional food and nutraceutical applications.

Fermentation of Ganoderma lucidum and Raphani Semen with a probiotic mixture attenuates cyclophosphamide-induced immunosuppression through microbiota-dependent or -independent regulation of intestinal mucosal barrier and immune responses

BackgroundProbiotic fermentation is a promising strategy for improving the nutritional and functional properties of traditional Chinese medicines (TCMs). Ganoderma lucidum and Raphani Semen are famous TCMs that have been shown to help alleviate immune system disorders. However, few studies have experimentally investigated the effects of probiotic-fermented G.lucidum and Raphani Semen on the immune system. PurposeWe established the in vitro fermentation of G. lucidum and Raphani Semen with a probiotic mixture (Bifidobacterium longum, Lactobacillus acidophilus, and l. fermentum) (GRFB), investigated its ameliorating effect against cyclophosphamide (CTX)-induced immunosuppression, and explored its possible mechanisms. MethodsFirst, the different components in GRFB were identified by high-performance liquid chromatography. Second, its immune-stimulatory activities were evaluated in CTX-treated mice. Lastly, its possible in vitro and in vivo mechanisms were studied. ResultsProbiotic fermentation of G. lucidum and Raphani Semen altered some of its chemical constituents, potentially helping improve the ability of GRFB to alleviate immunosuppression. As expected, GRFB effectively ameliorated CTX-induced immunosuppression by increasing the number of splenic lymphocytes and regulating the secretion of serum and ileum cytokines. GRFB supplementation also effectively improved intestinal integrity in CTX-treated mice by upregulating tight junction proteins. It also protects against CTX-induced intestinal dysbiosis by increasing the abundance of beneficial bacteria and reducing the abundance of harmful bacteria. GRFB could directly promote intestinal immunity but not systemic immunity in vitro, suggesting a microbiota-dependent regulation of GRFB. Interestingly, cohousing CTX-induced immunosuppressed mice with GRFB-treated mice promoted their symptoms recovery. Enhanced CTX-induced immunosuppression by GRFB in vitro depended on the gut microbiota. Remarkably, a Kyoto Encyclopedia of Genes and Genomes analysis showed that the GRFB-reprogrammed microbiota was significantly enriched in DNA damage repair pathways, which contribute to repairing the intestinal mucosal barrier. ConclusionThis is the first study to suggest that compare with unfermented G. lucidum and Raphani Semen, GRFB can more effectively promote intestinal immunity and manipulate the gut microbiota to promote immunostimulatory activity and repair immunosuppression-induced intestinal barrier damage by biotransforming G.lucidum and Raphani Semen components.

Arctoscopus japonicus Lipids Enhance Immunity of Mice with Cyclophosphamide-Induced Immunosuppression.

A lipid extract was obtained from eggs of the sailfin sandfish, Arctoscopus japonicus. Immunostimulatory effects of A. japonicus lipids incorporated with PEG6000 (AJ-PEG) on immunosuppressed mice treated with cyclophosphamide (CY) were investigated. AJ-PEG was administered orally to mice at different concentrations of 25 to 100 mg/kg body weight (BW). CY was injected to mice intraperitoneally at 80 mg/kg BW. Administration of AJ-PEG significantly increased the spleen index of CY-treated mice. AJ-PEG also stimulated the proliferation of splenic lymphocytes and natural killer (NK) activity. Immune-associated cytokines such as IL-1β, IL-2, IL-4, IL-6, TNF-α, and IFN-γ as well as TLR4 were overexpressed in splenic lymphocytes. Furthermore, AJ-PEG significantly increased splenic CD4+ and CD8+ T lymphocytes. In peritoneal macrophages, AJ-PEG administration improved proliferation, nitric oxide (NO) production, and phagocytosis. It also upregulated iNOS, COX-2, IL-1β, IL-6, and TNF-α expression. Taken together, these results suggest that AJ-PEG can be used in animal models with immunosuppressive conditions as a potent immunomodulatory agent.

Discovery of Anti-NRLP3 Inflammasome, Immunomodulatory Phytochemicals from the Extract of Habenaria intermediaD. Don: An Unexplored Plant Species.

The present study describes the isolation, identification, and quantification of biomarker compounds in plant extracts of Habenaria intermedia D. Don (Orchidaceae). The isolation of the compounds was carried out from H. intermedia D. Don by repeated column chromatography of petroleum ether and ethanol fractions of extract of tubers. These compounds were characterized by 1H and 13C NMR and mass spectral data. A new quantitative method was established by using high-performance liquid chromatography (HPLC)-PDA. As a result, seven compounds were isolated and characterized. This is the first report of isolation of these compounds from this plant species H. intermedia D.Don. Out of seven isolated compounds, five were used for the quantitative study. A reliable and suitable HPLC method was developed for the well-resolved chromatogram of compounds. The proposed method was applied successfully to the detection and quantification of compounds. This study also represents the immunomodulatory and anti-inflammasome biological studies of isolated natural products. Loroglossol (HBR-4) has been reported to possess immunomodulatory activity. The immunostimulating assay indicated that HBR-4 could significantly promote the cell proliferation, especially via IL-2, TNF-α, and IFN-γ secretion from spleen cells. These results suggested the potential utilization of HBR-4 as an attractive functional health supplement candidate for hypoimmunity population. Additionally, cyclophosphamide-induced immunosuppression was counteracted by treatment with HBR-4, revealing significant increase in hemagglutinating antibody responses and hemolytic antibody responses. The current work revealed the potential anti-inflammasome and immunomodulatory activities of H. intermedia D. Don compounds and validates the usage of this prominent Rasayna plant.

A cyclophosphamide-induced immunosuppression Swiss Albino mouse model unveils a potential role for cow urine distillate as a feed additive

BackgroundTraditional and natural immunomodulators are increasingly used as supplements in animal feeds and as interventions in the prevention and treatment of disease in animals. ObjectiveThe aim of this study was to examine the immunomodulatory characteristics of distilled cow urine in vivo using two mouse models, a normal mouse model and an immunosuppressive mouse model. MethodologyWe divided 144 Swiss Albino mice weighing between 15 g and 30 g, aged between two and three months, into two groups of 72 mice each. In the first group, we subdivided the animals into six subgroups of 12 each. In this group paramerters such as, body weight, organ weights of liver and kidney, haemagglutination titre, Jerne plaque-forming assay, and bone marrow cellularity were measured. We divided the second group into six subgroups for the assessment of delayed-type hypersensitivity (DTH). ResultsAs compared to normal control mice, immunocompetent and immunosuppressed mice (given cow urine distillate) had significant increases in body weight, spleen weight, liver weight, total leucocyte count, lymphocyte count, serum protein, and globulin contents. In the treatment groups, the titre of antibodies, the number of antibody- producing cells, the cellularity of bone marrow, and foot pad thickness also increased. In the treatment group, both humoral and cellular immunity were altered compared to the control group, suggesting cow urine distillate to be a potential animal feed ingredient for immunoregulation. ConclusionThis study was able to demonstrate the experimental validity of natural compounds as immunomodulators that can be used in feed supplements for animals. Various compounds could be tested for immunomodulatory effects using this technique in experimental animals.

A standardized extract of Echinacea purpurea containing higher chicoric acid content enhances immune function in murine macrophages and cyclophosphamide-induced immunosuppression mice

Context Preparations of Echinacea have been used by herbalists to boost the immune system. Objective In this study, Echinacea purpurea (L.) Moench (Asteraceae) extract with enriched chicoric acid content was investigated for immunomodulation. Materials and methods The standardized hydroalcoholic extract (4% chicoric acid) was prepared from the aerial parts of E. purpurea (SEP). The extract was screened for in vitro antioxidant activities, and immunomodulation in RAW 264.7 cells, at 200 and 400 µg/mL. Further, the male BALB/c mice (20-25 g) were divided into 4 groups (n = 6 per group). All the groups except control, were intraperitoneally injected with 70 mg/kg/day of cyclophosphamide (CTX) for 4 consecutive days. The treatment groups received SEP extract (100 and 200 mg/kg body weight) p.o. from day 5 to 14. Results The SEP extract inhibited DPPH (IC50 = 106.7 µg/mL), ABTS+ (IC50 = 19.88 µg/mL) and nitric oxide (IC50 = 120.1 µg/mL). The SEP extract’s ORAC (oxygen radical absorbance capacity) value was 1931.63 µM TE/g. In RAW 264.7 cells, SEP extract increased the nitric oxide production by 30.76- and 39.07-fold at 200 and 400 µg/mL, respectively, compared to the untreated cells. SEP extract significantly increased phagocytosis and cytokine release (TNF-α, IL-6, and IL-1β) in the cells. Further, the extract improved immune organ indices, lymphocyte proliferation and serum cytokine levels in CTX-induced mice. The extract at 200 mg/kg significantly increased the natural killer cell activity (24.6%) and phagocytic index (28.03%) of CTX mice. Conclusion Our results strongly support SEP extract with 4% chicoric acid as a functional ingredient for immunomodulation.

Ginsenosides and Polysaccharides from Ginseng Co-Fermented with Multi-Enzyme-Coupling Probiotics Improve In Vivo Immunomodulatory Effects.

The active components of ginseng, such as ginsenosides and polysaccharides, have high therapeutic value in treating cancer, decreasing obesity, and enhancing immunity. However, simple primary ginseng treatment cannot maximize this medicinal potential. Therefore, in this study, Panax ginseng was co-fermented with multi-enzyme-coupling probiotics to obtain a fermentation broth with higher levels of ginsenosides, polysaccharides, and probiotics. When compared to other treatment methods for cyclophosphamide-induced immunosuppression in mice, the results reveal that the P. ginseng fermentation broth treated with multi-enzyme-coupling probiotics could significantly improve the immune function of immunosuppressive mice and restore intestinal flora stability. Overall, this processing method will provide a novel strategy for promoting the application of ginseng and the relief of immunosuppression.

Polysaccharide from Abelmoschus esculentus L. flower ameliorates cyclophosphamide-induced immunosuppression via the TLR4/endocytosis and MAPK-NF-κB signaling pathways in mice

The present study was designed to investigate the immunomodulatory effects and mechanisms of a Abelmoschus esculentus L. flower polysaccharide (AEFP22) in the CTX-induced immunosuppressed mice. After intragastric gavage of AEFP22 for two weeks, nonspecific immunity, humoral immunity, cellular immunity and the status of immune organs were improved significantly in immunosuppressed mice. The immunoglobulins, cytokines and nitric oxide (NO) in serum also increased notably. Transcriptome analysis of the spleen showed that most immune-related differentially expressed genes (DEGs) were regulated inversely in the AEFP22-treated group and model group. Based on gene ontology (GO) analysis and Kyoto Encyclopedia of genes and genomes (KEGG) enrichment analysis of the transcriptome, the expression of key proteins in the toll-like receptor (TLR)4/endocytosis and mitogen-activated protein kinase (MAPK)-nuclear factor kappa B (NF-κB) signaling pathways were evaluated. The results showed that AEFP22 could ameliorate CTX-induced immunosuppression by increasing the expression of TLR4, myeloid differentiation primary response (MyD)88, TNF receptor associated factor (TRAF) 6 and major histocompatibility complex (MHC) class Ⅱ, enhance the phosphorylation of MAPKs and promote the nuclear translocation of NF-κB. This study indicated the immunoregulatory activity and potential mechanisms of AEFP22, which suggested the potential role of AEFP22 as an effective immunomodulator.

Immunostimulant potential of Moringa Oleifera leaves alcoholic extract versus Oregano Essential Oil (OEO) against cyclophosphamide-induced immunosuppression in broilers chicks

The current study was conducted to evaluate the immunoenhancement effect of Moringa oleifera leaves alcoholic extract (MOLE) versus Oregano essential oil (OEO) against cyclophosphamide induced immunosuppression in broilers chicks. A total of a three hundred one-day-old chicks were assigned randomly into three main dietary groups, control, MOLE, and OEO for 14 days. After 14 days the three main experimental groups were subdivided into six groups, control, cyclophosphamide, MOLE, MOLE and Cyclophosphamide, OEO, and OEO and cyclophosphamide. Each group of these six groups was subdivided into three subgroups. Supplementation of broiler chicks with MOLE and OEO for 14 days significantly increased body weight compared to the control group. However, injection of broiler chicks with cyclophosphamide significantly induced body weight loss, impaired immunological response represented by decreasing total leukocytic count, differential leukocytic count, phagocytic activity, phagocytic index, and hemagglutinin inhibition titer for New Castle disease virus, lymphoid organs depletion, and increased the mortality rate. In contrast, supplementation of cyclophosphamide treated chicks with MOLE and OEO significantly reduced cyclophosphamide induced body weight loss and impaired immunological responses, as it showed significant increase in body weight, total leukocytic count, differential leukocytic count, phagocytic activity, phagocytic index, and hemagglutinin inhibition titer for New Castle disease virus, lymphoid organs proliferation, and reduced the mortality rate. This study indicated that MOLE and OEO supplementation ameliorated cyclophosphamide induced body weight loss and impaired immunological responses.

Protective Effect of Anoectochilus formosanus Polysaccharide against Cyclophosphamide-Induced Immunosuppression in BALB/c Mice.

In this study, Anoectochilus formosanus polysaccharide (AFP) was acquired a via water extraction and alcohol precipitation method. The immunoregulatory activity of AFP was first evaluated on cyclophosphamide (Cy)-treated mice. Galacturonic acid, glucose and galactose were confirmed to be the main components of AFP. AFP demonstrated the ability to stimulate the production of TNF-α and IL-6 in RAW 264.7 macrophages. Not surprisingly, the activation of the NF-κB signaling pathway by AFP was validated via Western blot analysis. Furthermore, AFP could alleviate Cy-induced immunosuppression, and significantly enhance the immunity of mice via increasing the thymus index and body weight, stimulating the production of cytokines (IgA, IgG, SIgA, IL-2, IL-6 and IFN-γ). The improvement in the intestinal morphology of immunosuppressed mice showed that AFP could alleviate Cy-induced immune toxicity. These results have raised the possibility that AFP may act as a natural immunomodulator. Overall, the study of AFP was innovative and of great significance for AFP's further application and utilization.

Prevention effect of total ginsenosides and ginseng extract from Panax ginseng on cyclophosphamide-induced immunosuppression in mice.

Oral decoction is widely applied in traditional Chinese medicines. The polysaccharides of decoction promote the exposure of small molecules and increase their bioavailability. This study mainly compared the component and activities of total ginsenosides (TGS) and ginseng extract (GE) on immunosuppressed mice induced by cyclophosphamide. Thirty-two mice were randomly divided into control, model, TGS, and GE groups. The mice were orally administered for 28 days and then injected with cyclophosphamide on the last four days. The results of component analysis showed the total content of 12 ginsenosides in TGS (67.21%) was higher than GE (2.04%); the total content of 17 amino acids in TGS (1.41%) was lower than GE (5.36%); the total content of 10 monosaccharides was similar in TGS (74.12%) and GE (76.36%). The animal results showed that both TGS and GE protected the hematopoietic function of bone marrow by inhibiting cell apoptosis, and recovering the normal cell cycle of BM; maintained the dynamic balance between the Th1 and Th2 cells; also protected the spleen, thymus, and liver. Meanwhile, TGS and GE protected the intestinal bacteria of immunosuppressed mice by increasing the abundance of lactobacillus and decreasing the abundance of the odoribacter and clostridia_UCG-014. The prevention effect of GE was superior to TGS in some parameters. In conclusion, TGS and GE protected the immune function of immunosuppressed mice induced by cyclophosphamide. Meanwhile, GE showed higher bioavailability and bioactivity compared with TGS, because the synergistic effect of polysaccharides and ginsenosides plays an important role in protecting the immune function.

Korean Ginseng Berry Polysaccharide Enhances Immunomodulation Activities of Peritoneal Macrophages in Mice with Cyclophosphamide-Induced Immunosuppression.

Korean ginseng (Panax ginseng C. A. Meyer), a member of the Araliaceae family, is known as a traditional medicinal plant to have a wide range of health properties. Polysaccharides constitute a major component of Korean ginseng, and its berries exhibit immune-modulating properties. The purpose of this study was to investigate the immune effects of crude polysaccharide (GBPC) extracted from Korean ginseng berry on peritoneal macrophages in mice with cyclophosphamide (CY)- induced immunosuppression. BALB/c mice were divided into eight groups: normal control, normal control + CY, levamisole + CY, ginseng + CY, and four concentrations of 50, 100, 250, and 500mg/kg BW/day of GBPC + CY. Mice were orally administered with samples for 10 days. Immunosuppression was established by treating mice with CY (80 mg/kg BW/day) through intraperitoneal injection on days 4 to 6. The immune function of peritoneal macrophages was then evaluated. Oral administration of 500mg/kg BW/day GBPC resulted in proliferation, NO production, and phagocytosis at 100%, 88%, and 91%, respectively, close to the levels of the normal group (100%) of peritoneal macrophages. In CY-treated mice, GBPC of 50-500 mg/kg BW/day also dose-dependently stimulated the proliferation, NO production, and phagocytosis at 56-100%, 47-88%, and 53-91%, respectively, with expression levels of immune-associated genes, such as iNOS, COX-2, IL-1β, IL-6, and TNF-α, of about 0.32 to 2.87-fold, compared to those in the CY group. GBPC could be a potential immunomodulatory material to control peritoneal macrophages under an immunosuppressive condition.

The protective effect and antitumor activity of Aconiti Lateralis Radix Praeparata (Fuzi) polysaccharide on cyclophosphamide-induced immunosuppression in H22 tumor-bearing mice.

Background: Aconiti Lateralis Radix Praeparata, also known as Fuzi in Chinese, has been used in Traditional Chinese Medicine for more than 2,000years. In recent years, some traditional herbal compounds containing Fuzi have achieved positive clinical results in tumor treatment. And the polysaccharide isolated from Fuzi has attracted much attention as a potential immunomodulator. However, its immunomodulatory mechanism remains to be further studied. Aim of the study. Fuzi neutral polysaccharide (FNPS) and cyclophosphamide (CTX) were combined to treat Hepatoma 22 (H22) tumor-bearing mice, and its mechanism of ameliorating immunosuppression caused by CTX was studied. Methods: FNPS was isolated and purified. The molecular weight, functional groups, monosaccharide composition, and apparent morphology were characterized by gel permeation chromatography, Fourier transform infrared spectrometer, ion chromatography and scanning electron microscope, respectively. Through the analysis of tumor, immune organs, and serum cytokine levels of H22 tumor-bearing mice, the immunomodulatory effect and the protective effect on immunosuppressive mice induced by CTX was evaluated. And the immunomodulatory activity of FNPS was further verified by macrophage functional experiments. Results: FNPS was composed of rhamnose, arabinose, galactose, glucose, and mannose in a molar ratio of 0.008:0.017:0.018:0.908:0.048. Its molecular weight was 94kDa. In vivo experiments showed that 200mgmL-1 FNPS could alleviate the suppression of immune organs and immune cells caused by CTX treatment, enhance the antitumor effect of CTX, increase the serum levels of Th1 immune-related pro-inflammatory cytokines (IL-1β and IL-6), and decrease Th2 immune-related anti-inflammatory cytokine (IL-10) and tumor-related pro-inflammatory cytokine (TNF-α) in the chemotherapy mice. Functional experiments revealed that 25μgmL-1 FNPS could promote phagocytosis and proliferation of macrophages. When the concentration reached 50μgmL-1, it enhanced the migration activity. Conclusion: FNPS has the potential to alleviate the immunosuppressive effect of CTX by activating immune cells and promoting inflammation. It could be used as a potential auxiliary medication for liver cancer treatment.

Lactiplantibacillus plantarum DLPT4 Protects Against Cyclophosphamide-Induced Immunosuppression in Mice by Regulating Immune Response and Intestinal Flora.

In this study, the strain Lactiplantibacillus plantarum DLPT4 was investigated for the immunostimulatory activity in cyclophosphamide (CTX)-induced immunosuppressed BALB/c mice. L. plantarum DLPT4 was administered to BALB/c mice by oral gavage for 30days, and CTX was injected intraperitoneally from the 25th to the 27th days. Intraperitoneal injection of CTX caused damage to the thymic cortex and intestines, and the immune dysfunction of the BALB/c mice. L. plantarum DLPT4 oral administration exerted immunoregulating effects evidenced by increasing serum immunoglobulin (IgA, IgG, and IgM) levels and reducing the genes expression of pro-inflammatory factors (IL-6, IL-1β, and TNF-α) of the CTX-induced immunosuppressed mice. The results of the metagenome-sequencing analysis showed that oral administration of L. plantarum DLPT4 could regulate the intestinal microbial community of the immunosuppressed mice by changing the ratio of Lactiplantibacillus and Bifidobacterium. Meanwhile, the abundance of carbohydrate enzyme (CAZyme), immune diseases metabolic pathways, and AP-1/MAPK signaling pathways were enriched in the mice administrated with L. plantarum DLPT4. In conclusion, oral administration of L. plantarum DLPT4 ameliorated symptoms of CTX-induced immunosuppressed mice by regulating gut microbiota, influencing the abundance of carbohydrate esterase in the intestinal flora, and enhancing immune metabolic activity. L. plantarum DLPT4 could be a potential probiotic to regulate the immune response.

Evaluation of the Effects of Euglena gracilis on Enhancing Immune Responses in RAW264.7 Cells and a Cyclophosphamide-Induced Mouse Model.

In this study we evaluated the immune-enhancing effects of β-glucan, the main component of Euglena gracilis (Euglena), and Euglena on inflammatory factor expression in RAW264.7 macrophages and ICR mice with cyclophosphamide-induced immunosuppression. Macrophages were treated with β-glucan or Euglena for 48 h. The β-glucan and Euglena groups exhibited higher levels of inducible nitric oxide synthase, nitric oxide, and tumor necrosis factor (TNF)-α than the control (vehicle alone) group. Animals were fed saline and β-glucan (400 mg/kg body weight (B.W.)) or Euglena (400 or 800 mg/kg B.W.) for 19 days, and on days 17-19, cyclophosphamide (CCP, 80 mg/kg B.W.) was administered to induce immunosuppression in the ICR mouse model. CCP reduced the body weight, spleen index, and cytokine expression of the mice. To measure cytokine and receptor expression, splenocytes were treated with concanavalin A (ConA) or lipopolysaccharide (LPS) as a mitogen for 24 h. In vivo, ConA stimulation significantly upregulated the expression of interferon (IFN)-γ, interleukin (IL)-10, IL-12 receptor β1, IL-1β, and IL-2 in splenocytes from the β-glucan- or Euglena-treated groups compared with those in the splenocytes from the CCP-treated group; LPS stimulation increased the levels of the cytokines TNF-α, IL-1β, and IL-6 in splenocytes from the β-glucan- or Euglena-treated groups compared with those from the CCP-treated group, but most of these differences were not significant. These results demonstrate the effect of Euglena in ameliorating macrophages and immunosuppression in CCP-treated mice. Thus, Euglena has the potential to enhance macrophage- and splenocyte-mediated immune-stimulating responses.

In Vivo Antifungal Activity and Computational Studies of Some Azole Derivatives against Candida Albicans

Resistance of Candida species is a major problem in the management of Candida infection. This study investigated in vivo antifungal activities of several new imidazole and triazole derivatives in a C. albicans systemic infection. The efficacy of derivatives was determined against systemic infection by C. albicans in mice with cyclophosphamide-induced immunosuppression, and the antifungal activities of the synthesized compounds were evaluated in comparison with fluconazole. Compounds 3 and 8 had the highest efficacy with minimum inhibitory concentration (MIC) values of 0.5–1 μM against the C. albicans pathogen. In vivo activities in immunosuppressed mice were also greater than fluconazole. Furthermore, docking analysis was carried out to know the binding mode of imidazole and triazole derivatives to the CYP51 active site of C. albicans and dihydrofolate reductase as a valid antifungal target. The docking study found that the antifungal results are well correlated with docking results. ADMET and in silico physicochemical parameters were also performed. This study demonstrates that compounds 3 and 8 are potential antifungal candidates against the C. albicans pathogen.

Characteristics of the cyclophosphamide-induced immunosuppression model in Balb/c mice

Characteristics of the cyclophosphamide-induced immunosuppression model in Balb/c mice

Effect of Paecilomyces cicadae polysaccharide Pc0-1 on cyclophosphamide-induced immunosuppression and regulation of intestinal flora in mice

Paecilomyces cicadae are rich in resources and have promising research value and applications. A neutral branched heteropolysaccharide Pc0-1 has been extracted from it in our laboratory previously, the structural features and in vitro activity were also characterized. On this basis, the present research intended to investigate the potential mechanism by which Pc0-1 ameliorated cyclophosphamide (Cy)-induced immunosuppression in mice. The results demonstrated that Pc0-1 could alleviate the atrophy of immune organs and restore the tissue structure of the ileum. Pc0-1 could also alleviate oxidative stress and inflammatory response through reducing the level of lipid peroxidation in serum and maintaining the balance of Th1 and Th2. Meanwhile, Pc0-1 was also able to activate the Nrf2- Keap1 signaling pathway and stabilize Nrf2 by decreasing Keap1 activity, thus promoting the role of NQO1 in maintaining redox stability and HO-1 in preventing inflammation. Furthermore, gut microbial sequencing indicated that Pc0-1 prevented the differential expansion of flora, increased the abundance of beneficial bacteria Lactobacillus and Lachnospiraceae_NK4A136_group, decreased the abundance of harmful bacteria Desulfovibrio and Alistipes, and promoted the production of short-chain fatty acids (SCFAs). All these results demonstrated that Pc0-1 could regulate Cy-induced immunosuppression and improve the structure of intestinal flora, providing some theoretical basis for the in-depth development and application of Pc0-1 as an immunomodulator.

Studies on immunostimulatory effect of efcovida powder on Cyclophosphamide-induced immunosuppression in mice

To evaluate the immunostimulatory activity of Efcovida powder, we induced immunosuppression in Swiss mice by cyclophosphamide (CP). Efcovida powder at two doses of 60 mg/kg b.w and 120 mg/kg b.w were administered orally for seven consecutive days to animals. CP (200 mg/kg i.p.) was injected on the 4th day. The result showed that Efcovida powder at the dose of 60 mg/kg b.w only posed an immunostimulating potency in the cyclophosphamide-induced immunosuppression model while Efcovida powder at the dose of 120 mg/kg b.w significantly ameliorated the effects of CP on delayed-type hypersensitivity (DTH) response, leukocyte quantity, relative thymus weight, serum IL-4, IL-6 concentration, and micro-histological images of spleen and thymus. This suggested the potential of Efcovida powder to treat immunosuppression diseases in clinical practice.