Cyclophosphamide-induced Immunosuppression Research Articles

Modulation of cyclophosphamide-induced immunosuppression and intestinal flora in broiler by deep eutectic solvent extracted polysaccharides of Acanthopanax senticosus

IntroductionThe aim of this experiment was to investigate the modulation effect of Acanthopanax senticosus polysaccharide (ASPS-PD) extracted with deep eutectic solvent on cyclophosphamide-induced immunosuppression in broilers and its modulation of the gut microbiota of broilers.MethodsThe 108 one-day-old broilers were divided into six groups, including the control group, the Cyclophosphamide (CY) model group, the ASPS-PD control group, the ASPA-PD high and low dose groups and the Astragalus polysaccharide group. Body weight, feed intake, feed conversion ratio, and immune organ index of broilers at 7, 14, and 21 days were determined; IL-2, IFN-γ, and lgG1 levels were determined by enzyme-linked immunosorbent assay (ELISA); Broiler caeca feces were analyzed by amplification and 16S rRNA sequencing.ResultsThe results showed that ASPS-PD can restore growth performance, increase immune organ index and improve serum cytokine levels of IL-2 and IFN-γ and immunoglobulin lgG1 levels in CY-treated broilers. The analysis of cecum flora showed that ASPS-PD can promote the proliferation of beneficial bacteria and reduce the number of harmful bacteria, regulating intestinal flora.DiscussionTherefore, ASPA-PD may be a potential novel immunomodulator to ameliorate CY-induced immunosuppression and intestinal flora dysregulation in broiler.

Immunostimulatory Effects of Korean Mineral-Rich Seawaters on Cyclophosphamide-Induced Immunosuppression in Mice

Immunostimulatory Effects of Korean Mineral-Rich Seawaters on Cyclophosphamide-Induced Immunosuppression in Mice

Effect of Flavonols of Aronia melanocarpa Fruits on Morphofunctional State of Immunocompetent Organs of Rats under Cyclophosphamide-Induced Immunosuppression.

Aronia melanocarpa berries contain many compounds with potential benefits for human health. The food flavonoids quercetin and rutin, found in significant amounts in the fruits of A. melanocarpa, are known to have favourable effects on animal and human organisms. However, data on the effect of flavonols isolated from black chokeberry on immune functions during immunosuppression are not available in the literature. Thus, the aim of this study was to evaluate the effect of flavonol fraction isolated from A. melanocarpa fruits, in comparison with pure quercetin and rutin substances, on the dysfunctional state of rat thymus and spleen in immunodeficiency. The study was performed on Wistar rats. The animals were orally administered solutions of the investigated substances for 7 days: water, a mixture of quercetin and rutin and flavonol fraction of A. melanocarpa. For induction of immunosuppression, the animals were injected once intraperitoneally with cyclophosphamide. Substance administration was then continued for another 7 days. The results showed that under the influence of flavonols, there was a decrease in cyclophosphamide-mediated reaction of lipid peroxidation enhancement and stimulation of proliferation of lymphocytes of thymus and spleen in rats. At that, the effect of the flavonol fraction of aronia was more pronounced.

Yogurt Alleviates Cyclophosphamide-Induced Immunosuppression in Mice through D-Lactate.

Numerous studies have investigated the immunomodulatory effects of yogurt, but the underlying mechanism remained elusive. This study aimed to elucidate the alleviating properties of yogurt on immunosuppression and proposed the underlying mechanism was related to the metabolite D-lactate. In the healthy mice, we validated the safety of daily yogurt consumption (600 μL) or D-lactate (300 mg/kg). In immunosuppressed mice induced by cyclophosphamide (CTX), we evaluated the immune regulation of yogurt and D-lactate. The result showed that yogurt restored body weight, boosted immune organ index, repaired splenic tissue, recovered the severity of delayed-type hypersensitivity reactions and increased serum cytokines (IgA, IgG, IL-6, IFN-γ). Additionally, yogurt enhanced intestinal immune function by restoring the intestinal barrier and upregulating the abundance of Bifidobacterium and Lactobacillus. Further studies showed that D-lactate alleviated immunosuppression in mice mainly by promoting cellular immunity. D-lactate recovered body weight and organ development, elevated serum cytokines (IgA, IgG, IL-6, IFN-γ), enhanced splenic lymphocyte proliferation and increased the mRNA level of T-bet in splenic lymphocyte to bolster Th1 differentiation. Finally, CTX is a chemotherapeutic drug, thus, the application of yogurt and D-lactate in the tumor-bearing mouse model was initially explored. The results showed that both yogurt (600 μL) and D-lactate (300 mg/kg) reduced cyclophosphamide-induced immunosuppression without promoting tumor growth. Overall, this study evaluated the safety, immune efficacy and applicability of yogurt and D-lactate in regulating immunosuppression. It emphasized the potential of yogurt as a functional food for immune regulation, with D-lactate playing a crucial role in its immunomodulatory effects.

Protective effects of oyster polypeptide on cyclophosphamide-induced immunosuppressed rats.

Oyster polypeptide (OP) is a mixture of oligopeptides extracted from oysters through enzyme lysis, separation, and purification. It is associated with immunomodulatory effects, but the underlying mechanisms are not known. This study therefore combined proton nuclear magnetic resonance (1H-NMR) urinary metabolomics and 16S rRNA gene sequencing of the gut microbiome to determine the immunoprotective mechanisms of OP in rats subjected to cyclophosphamide-induced immunosuppression. Oyster polypeptide restored the body weight and the structure of spleen and thymus in rats with cyclophosphamide-induced immunosuppression. It upregulated the levels of white blood cells (WBCs), hemoglobin (HGB), platelets (PLT), red blood cells (RBCs), immunoglobulin G (IgG), immunoglobulin M (IgM), cytokines such as interleukin‑6 (IL-6) and tumor necrosis factor-α (TNF-α), and increased the numbers of CD3+ and CD4+ T cells in the immunosuppressed rats. The 1H-NMR metabolomics results showed that OP significantly reversed the levels of ten metabolites in urine, including 2-oxoglutarate, citrate, dimethylamine, taurine, N-phenylacetylglycine, alanine, betaine, creatinine, uracil, and benzoate. The 16S rRNA gene sequencing results showed that OP restored the gut microbiome homeostasis by increasing the abundance of beneficial bacteria and reducing the abundance of pathogenic bacteria. Finally, a combination of metabolomics and microbiomics found that the metabolism of taurine and hypotaurine, and the metabolism of alanine, aspartate, and glutamate were disturbed, but these metabolic pathways were restored by OP. This study demonstrated that OP had immunoprotective effects in rats with cyclophosphamide-induced immunosuppression by restoring key metabolic pathways and the gut microbiome homeostasis. Our findings provide a framework for further research into the immunoregulatory mechanisms of OP and its potential use in drugs and nutritional supplements. © 2024 Society of Chemical Industry.

Poria cocos polysaccharides alleviate cyclophosphamide-induced immunosuppression effects in silkworm and their metabolic profiling analysis

The present study investigated the immune regulatory mechanisms of Poria cocos polysaccharides (PS) in a cyclophosphamide (CTX)-induced immunosuppression silkworm model. We found that PS increased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) activities, as well as reactive oxygen species (ROS) levels in the fat body or haemocytes of CTX-treated silkworms. PS also strongly stimulated the immunity of silkworms by increasing haemocyte counts and PO activity and upregulating the mRNA expression of immune-related genes. We further investigated the metabolic profile of the fat body after PS treatment using liquid chromatography–massspectrometry/mass spectrometry (LC–MS/MS) and identified 236 differentially expressed metabolites. Among them, nine metabolites related to amino acid metabolism were present at high levels in the PS-treated group, whereas the contents of metabolites involved in sphingolipid metabolism and alpha-linolenic acid metabolism were significantly decreased after PS treatment. The amino acid metabolism pathways and lipid metabolism pathways were found to be significantly altered in the PS-treated group, which indicates that PS may regulate the immune system of silkworms by reprogramming lipid and amino acid metabolism. This study provides new insight into the immune regulatory effect of PS in animals.

Polygonatum sibiricum Saponin Prevents Immune Dysfunction and Strengthens Intestinal Mucosal Barrier Function in Cyclophosphamide-Induced Immunosuppressed BALB/c Mice.

The aim of this study was to explore the immunomodulatory effect of Polygonatum sibiricum saponin (PS) in a cyclophosphamide-induced (Cy) immunosuppression mice model. Oral administration of PS by gavage effectively alleviated weight loss caused by Cy and increased the index of immune organs. PS promoted the proliferation of splenic lymphocytes and T cell subsets (CD3+, CD355+, CD4+/CD8+) and relieved the xylene-induced inflammatory response and Cy-induced increase of serum hemolysin. Moreover, PS increased serum levels of lactate dehydrogenase and acid phosphatase. PS elevated serum level of cytokines and immunoglobulins (TNF-α, IFN-γ, IL-4, IL-6, IL-β, SIgA, and IgG) and the expression of mRNA of IL-10, TNF-α, and IL-6 in the spleen. Increased mRNA expression of tight junction protein (ZO-1, Mucin2, Occludin) expression and protein expression of IL-6/MyD88/TLR4 in the small intestine showed that PS exhibited a restorative effect on intestinal mucosal injury caused by cyclophosphamide. Oral PS prevented Cy-induced decline in leukocytes, red blood cells, lymphocytes, hemoglobin concentrations, and neutrophils, providing evidence for alleviating hematopoietic disorders. In addition, PS increased SOD and NO levels, reduced MDA levels, and improved oxidative damage in the liver. These findings demonstrate that PS has the potential to be developed as a supplemental agent for alleviating immunosuppression caused by chemotherapeutic agents.

Immunoenhancement effect of cinobufagin on macrophages and the cyclophosphamide-induced immunosuppression mouse model

Cinobufagin (CBG) is a natural active substance. Although its various pharmacological activities have been explored, the immunomodulatory activity of CBG remains unexplored. Therefore, this study aimed to investigate the anti-inflammatory and immunomodulatory activities of CBG ex vivo and in vivo. The immunomodulatory activity of CBG was investigated in RAW 264.7 cells. CBG showed no significant toxicity to cells. Additionally, 0.5–8 μg/mL CBG significantly increased the phagocytosis ability of macrophages and the secretion levels of IL-1β and TNF-α. Thus, it exerted immunomodulatory effects. We established the immunosuppressive model induced by cyclophosphamide (CTX) in mice and studied the immunomodulatory activity of CBG in vivo. The experimental results showed that the intervention of CBG alleviated the CTX-induced weight loss, restored the lymphocyte nuclear cell number, and promoted the secretion and mRNA expression of cytokines IFN-γ, IL-4, IL-6, and IL-12. Moreover, CBG increased the immune organ index, protected the growth of the spleen and thymus, and improved the pathological changes in immunosuppressed mice. Western blot results showed that different concentrations of CBG upregulated the phosphorylation level of PI3K/Akt/mTOR in the spleen of CTX-induced immunosuppressed mice. This suggests that the immunomodulatory effect of CBG may be related to the regulation of PI3K/Akt/mTOR signaling pathway. This study provides a theoretical basis for developing CBG immune enhancers and opens up new ideas for the comprehensive utilization and development of CBG in factories.

Phyllanthus emblica polysaccharide (PEP) attenuates cyclophosphamide-induced immunosuppression through microbiota-dependent or –independent regulation of immune responses

The aim of this study was to investigate the effects of Phyllanthus Emblica polysaccharide (PEP) on immunomodulation and intestinal flora in cyclophosphamide (CTX)-treated female mice. The results showed that PEP could directly modulate the immune activity of cyclophosphamide (CTX) in mice by attenuating its damage to spleen, thymus and intestinal tissues. Meanwhile, our study revealed that PEP could activate TLR4-mediated MAPK and NF-κB pathways and promote the expression of cytokines such as IL-2 and TNF-α, thus modulating the immune function of immunosuppressed mice. In addition, PEP was positively correlated with immune properties, with the strongest correlation with spleen index, and PEP could also regulate the immune function of mice by modulating the intestinal flora, such as increasing the content of Lactobacillus and Bifidobacterium. Therefore, PEP may be a potential novel immunomodulator to ameliorate CTX-induced immunosuppression and intestinal flora dysregulation.

Sciadonic acid ameliorates cyclophosphamide-induced immunosuppression by modulating the immune response and altering the gut microbiota.

Cyclophosphamide (Cy) is a frequently used chemotherapeutic drug, but long-term Cy treatment can cause immunosuppression and intestinal mucosal damage. The intestinal mucosal barrier and gut flora play important roles in regulating host metabolism, maintaining physiological functions and protecting immune homeostasis. Dysbiosis of the intestinal flora affects the development of the intestinal microenvironment, as well as the development of various external systemic diseases and metabolic syndrome. The present study investigated the influence of sciadonic acid (SA) on Cy-induced immunosuppression in mice. The results showed that SA gavage significantly alleviated Cy-induced immune damage by improving the immune system organ index, immune response and oxidative stress. Moreover, SA restored intestinal morphology, improved villus integrity and activated the nuclear factor κB signaling pathway, stimulated cytokine production, and reduced serum lipopolysaccharide (LPS) levels. Furthermore, gut microbiota analysis indicated that SA increased t beneficial bacteria (Alistipes, Lachnospiraceae_NK4A136_group, Rikenella and Odoribacter) and decreased pathogenic bacteria (norank-f-Oscillospiraceae, Ruminococcus and Desulfovibrio) to maintain intestinal homeostasis. The present study provided new insights into the SA regulation of intestinal flora to enhance immune responses. © 2024 Society of Chemical Industry.

Effects of mealworm hydrolysates on improving immune function and gut microbiota in cyclophosphamide-induced mice

Abstract The immune system plays a crucial role in protecting the host from infections and other diseases. Dysregulation of immune function is a risk factor for various noninfectious diseases, including obesity, cardiovascular disease, diabetes, and cancer. Tenebrio molitor larvae, also known as mealworms, are edible insects that are a protein-rich food source. This study investigated the effects of mealworm hydrolysate (MH) on immune enhancement and gut microbiota changes in a cyclophosphamide-induced immunosuppression mouse model. The findings revealed that MH administration increased natural killer (NK) cell activity and cytokine levels. The MH treatment group demonstrated significantly elevated serum cytokine levels and splenic cytokine mRNA expression compared to the model group. MH also increased the phosphorylation of nuclear factor-kappa B (NF-κB) and NF-κB inhibitor alpha (IκBα). Additionally, MH treatment altered the composition of the gut microbiota, increasing the relative abundance of Akkermansia and Corynebacterium, which are linked to immune function. Collectively, this study shows that MH improves immune-related markers and modulates the gut microbiota, implying that it could be used as a functional food for immune enhancement.

Immune-boosting effect of Yookgong-dan against cyclophosphamide-induced immunosuppression in mice

Immune responses must be strictly regulated to prevent autoimmune and infectious diseases and to protect against infectious agents. As people age, their immunity wanes, leading to a decrease in lymphocyte production in bone marrow and thymus and a decline in the efficacy of mature lymphocytes in secondary lymphoid organs. This study explores the immune-boosting potential of Yookgong-dan (YGD) in enhancing the immune system by activating immune cells. In our in vitro experiments, cyclophosphamide (Cy) treatment led to a significant decrease in primary splenocyte viability. However, subsequent treatment with YGD significantly improved cell viability, with doses ranging between 1 and 25 μg/mL in Cy-treated splenocytes. Flow cytometry analysis demonstrated that the Cy group exhibited reduced positivity of CD3+ T cells and CD45+ leukocytes compared to the blank group. In contrast, treatment with YGD led to a notable, dose-responsive increase in these immune cell types. In our in vivo experiments, YGD was orally administered to Cy-induced immunosuppressed mice at 20 and 100 mg/kg doses for 10 days. The results indicated a dose-dependent elevation in immunoglobulin (Ig)G and IgM levels in the serum, emphasizing the immunostimulatory effect of YGD. Furthermore, the Cy-treated group showed decreased T cells, B (CD19+) cells, and leukocytes in the total splenocyte population. Yet, YGD treatment resulted in a dose-dependent reversal of this pattern, suggesting its ability to counter immunosuppression. Notably, YGD was found to effectively stimulate T (CD4+ and CD8+) lymphocyte subsets and natural killer cells, along with enhancing Th1/Th2 cytokines in immunosuppressed conditions. These outcomes correlated with the modulation of BCL-2 and BAX expression, which are critical for apoptosis. In conclusion, YGD has the potential to bolster immune functionality through the activation of immune cells, thereby enhancing the immune system's capacity to combat diseases and improve overall health and wellness.

Oat protein isolate-Pleurotus ostreatus β-glucan conjugate nanoparticles bound to β-carotene effectively alleviate immunosuppression by regulating gut microbiota.

Individuals with immune disorders cannot establish an adequate defense to pathogens, leading to gut microbiota dysbiosis. β-Carotene can regulate immune response, but its bioavailability in vivo is very low. Herein, we developed a glycosylated oat protein-based nanoparticle to improve the application of β-carotene for mitigating cyclophosphamide-induced immunosuppression and gut microbiota imbalance in mice. The results showed that the nanoparticles facilitated a conversion of β-carotene to retinol or retinyl palmitate into the systemic circulation, leading to an increased bioavailability of β-carotene. The encapsulated β-carotene bolstered humoral immunity by elevating immunoglobulin levels, augmenting splenic T lymphocyte subpopulations, and increasing splenic cytokine concentrations in immunosuppressed mice. This effect was accompanied by the alleviation of pathological features observed in the spleen. In addition, the encapsulated β-carotene restored the abnormal gut microbiota associated with immunosuppression, including Erysipelotrichaceae, Akkermansia, Bifidobacterium and Roseburia. This study suggested that nanoparticles loaded with β-carotene have great potential for therapeutic intervention in human immune disorders by specifically targeting the gut microbiota.

Investigation of immunomodulatory activity of hericium erinaceus on cyclophosphamide-induced immunosuppression in mice

The study was conducted to assess the immunostimulatory effect of Hericium Erinaceus on cyclophosphamide-induced immunodeficient mice. Animals were administered Hericium Erinaceus orally at 0.72 g/kg b.w and 1.44 g/kg b.w for seven consecutive days. On the 4th day, CP (200 mg/kg) was intraperitoneally injected into mice. The results illustrated that Hericium Erinaceus at 0.72 g/kg b.w only posed an immunostimulating potency in the cyclophosphamide-induced immunosuppression model. Besides, Hericium Erinaceus at 1.44 g/kg b.w ameliorated the effects of CP on delayed-type hypersensitivity (DTH) response, relative spleen weight, serum IL-2, TNF-α concentration, and micro-histological images of spleen and thymus substantially. This suggested the potential of Hericium Erinaceus to treat immunosuppression diseases in clinical practice.

Immunomodulation by extracellular vesicle-like nanoparticles from marine macroalgae Sargassum fusiforme: Enhancing Type 1 T helper and cytotoxic T lymphocyte-mediated immune responses

This study investigated the immunological features and therapeutic potential of extracellular vesicle-like nanoparticles isolated from the marine macroalgae Sargassum fusiforme (SF-NPs). SF-NPs were approximately 266.4 nm in size, and comprehensive metabolomic analysis revealed 38 metabolites. SF-NPs can upregulate dendritic cell (DC) maturation markers, increase pro-inflammatory cytokine production, and enhance antigen presentation capacity. DC maturation is regulated by the mitogen-activated protein kinase and nuclear factor-kappa B pathways. Notably, SF-NPs-primed DCs orchestrated robust CD4+ and CD8+ T-cell proliferation, fostering potent Type 1 T-helper(Th1) responses and cytotoxic T lymphocyte (CTL) activity. In a cyclophosphamide-induced immunosuppression mouse model, SF-NPs restored and activated immune cell populations, including DCs, natural killer, CD4+ T, and CD8+ T cells. SF-NPs reversed cyclophosphamide-induced Type 2 T-helperand regulatory T cell-biased responses, favoring Th1 and CTL responses, including multifunctional T cell responses. This study highlighted the potential of SF-NPs as therapeutic candidates for diseases requiring Th1 and CTL responses.

Structural characterization and immunomodulatory effect of a starch-like Grifola frondosa polysaccharides on cyclophosphamide-induced immunosuppression in mice

In this study, a pure Grifola frondosa polysaccharide (GFP-1) was extracted and purified from Grifola frondosa. By HPLC, GC-MS, FT-IR, and NMR analysis, GFP-1 was determined to be a starch-like polysaccharide with an average molecular weight of 3370 kDa. It included three monosaccharides, i.e., glucose, galactose, and mannose. The backbone of GFP-1 consisted of →4)-α-Glcp-(1→ and →4,6)-α-Glcp-(1 → . The side branches were composed of →6)-α-Galp-(1→, α-Glcp-(1→, and a small amount of α-Manp-(1 → . By using a cyclophosphamide (CTX)-induced immunosuppressed mice model, we evaluated the immunomodulatory activity of GFP-1. The results showed that GFP-1 increased the thymic and spleen indices, promoted the level of IgG and IgA in serum, and activated the mitogen-activated protein kinase (MAPK) pathway in CTX-induced mice. Also, GFP-1 significantly promoted the mRNA expression of intestinal barrier factors and protected intestinal structural integrity in immunosuppressed mice. In conclusion, the data presented here suggested that GFP-1 might be a potential immune-enhancing supplement.

The Mechanism of Mori Folium and Eucommiae Cortex against Cyclophosphamide-Induced Immunosuppression Integrating Network Pharmacology, Molecular Docking, Molecular Dynamics Simulations, and Experimental Validation.

It has been reported that Mori Folium (MF) and Eucommiae Cortex (EC) exhibit pharmacological effects in the treatment of immunosuppression. However, the mechanism of MF and EC against immunosuppression remains unclear. This study aims to explore the mechanism of action of MF and EC for the treatment of immunosuppression through network pharmacology, molecular docking, molecular dynamics simulations and animal experiments. As a result, 11 critical components, 9 hub targets, and related signaling pathways in the treatment of immunosuppression were obtained based on network pharmacology. The molecular docking suggested that 11 critical components exhibited great binding affinity to 9 hub targets of immunosuppression. The molecular dynamics simulations results showed that (-)-tabernemontanine-AR, beta-sitosterol-AR and Dehydrodieugenol-HSP90AA1 complexes are stably bound. Additionally, in the animal experiments, the treated group results compared to the control group suggest that MF and EC have a significant effect on the treatment of immunosuppression. Therefore, MF and EC treatment for immunosuppression may take effects in a multi-component, multi-target, and multi-pathway manner. The results herein may provide novel insights into the treatment of immunosuppression in humans.

Green tea extract improves cyclophosphamide-induced immunosuppression in mouse spleen and enhances the immune activity of RAW 264.7 cells

Cyclophosphamide (CP) is mainly used to treat autoimmune diseases and cancer; however, it damages normal immune cells. Therefore, the effects of chemotherapy on CP are limited. Notably, green tea has been reported to effectively modulate immune function. Here, given the pharmacological properties of green tea, we evaluated the ability of green tea extract (GTE) to restore immunity suppressed by CP in vivo and to activate macrophages in vitro. GTE significantly improved the suppressed immune function, including spleen index and proliferation of spleen T lymphocytes, as revealed by histopathological examination and flow cytometry analysis. Moreover, GTE effectively activated RAW 264.7, as represented by the induction of nitric oxide, reactive oxygen species, and cytokine levels. GTE also increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B in RAW 264.7 cells. In conclusion, GTE ameliorated CP-induced immunosuppression in mice and stimulated immune activity in RAW 264.7 cells, possibly by activating the MAPK signaling pathway. These findings suggest that GTE has the potential to be used as a supplementary agent in chemotherapy for CP.

Rhodotorula mucilaginosa ZTHY2 Attenuates Cyclophosphamide-Induced Immunosuppression in Mice.

Rhodotorula mucilaginosa (R. mucilaginosa) can enhance the immune and antioxidant function of the body. However, whether R. mucilaginosa has an immunoregulatory effect on cyclophosphamide (CTX)-induced immunosuppressed animals remains to be clarified. In this study, the R. mucilaginosa ZTHY2 that we isolated from the coastal waters of the South China Sea previously was prepared in order to investigate its immunoprotective effect on CTX-induced immunosuppression in mice, and the effects were compared to those of Lactobacillus acidophilus (LA) (a well-known probiotic). Seventy-two male SPF mice were divided into six groups: The C group (control); IM group (immunosuppressive model group) (+CTX); Rl, Rm, and Rh groups (+CTX+low, medium, and high concentration of R. mucilaginosa, respectively); and PC (positive control) group (+CTX+LA). After a 28-day feeding trial, blood samples were taken for biochemical and serum immunological analysis, and the thymus and spleen were collected to analyze the organ index, lymphocyte proliferation and differentiation, and antioxidant capacity. The findings showed that R. mucilaginosa ZTHY2 improved the spleen and thymus indices, effectively attenuated immune organ atrophy caused by CTX, and enhanced the proliferation of T and B lymphocytes induced by ConA and LPS. R. mucilaginosa ZTHY2 promoted the secretion of cytokines and immunoglobulins and significantly increased the contents of IL-2, IL-4, IL-6, TNF-α, IFN-γ, IgA, IgG, IgM, CD4, CD8, CD19, and CD20 in serum. The proportion of CD4+, CD8+, CD19+, and CD20+ lymphocytes in spleen, thymus, and mesenteric lymph nodes were increased. In addition, R. mucilaginosa ZTHY2 reduced the reactive oxygen species (ROS) and malondialdehyde (MDA) levels and increased glutathione (GSH), total superoxide dismutase (SOD), and catalase (CAT) levels. Our results indicated that R. mucilaginosa ZTHY2 can significantly enhance the immune function of immunosuppressed mice, and improving antioxidant capacity thus attenuates CTX-induced immunosuppression and immune organ atrophy.

Improvement of Cyclophosphamide-Induced Immunosuppression by Miaoyao Fanggan Sachet Extract

Chemotherapy drugs, such as cyclophosphamide, often produce side effects of immunosuppression in the treatment of tumors. This study investigated whether the Miaoyao Fanggan sachet extracts—diammonium glycyrrhizinate and magnesium isoglycyrrhizinate—can regulate respiratory immunity in mice. A cyclophosphamide-induced immunosuppressive mice model was treated with diammonium glycyrrhizinate and magnesium isoglycyrrhizinate. Interferon (IFN)-α, interferon-β, interleukin (IL)-6, and interleukin-18 levels in the bronchoalveolar lavage fluid and lung tissue were detected using enzyme-linked immunosorbent assay and quantitative reverse transcription-polymerase chain reaction, respectively. The p-(phospho) transforming growth factor beta-activated kinase 1 (TAK1)/TAK1 and p-IkappaB (IκB)/IκB in the lung tissue and bronchial mucosa were detected by Western blot. Compared with the control group, the IFN-α and IL-6 levels decreased, while IFN-βand IL-18 levels increased in the mice model. However, these changes were reversed with the treatment with diammonium glycyrrhizinate and magnesium isoglycyrrhizinate; p-TAK1/TAK1 and p-IκB/IκB in the model group decreased significantly and increased with the increasing treatment dose of diammonium glycyrrhizinate and magnesium isoglycyrrhizinate. Diammonium glycyrrhizinate and magnesium isoglycyrrhizinate had a certain effect on cyclophosphamide-induced immunosuppression in mice, likely mediated through the phosphorylation of TAK1 and IκB, activating nuclear factor kappa-B and subsequently stimulating the Janus kinase/signal transducer and activator of transcription/mitogen-activated protein kinase pathway.