Quanzhen Yiqi decoction attenuates inflammation in mice with smoking-induced COPD by activating the Nrf2/HO-1 pathway and inhibiting the NLRP3 inflammasome.

OBJECTIVE: Quanzhen Yiqi decoction (QZYQ) is a traditional Chinese medicine for treating chronic obstructive pulmonary disease. METHODS: Mice were exposed to cigarette smoke (CS) 6 days/week (40 cigarettes/day) for 24 weeks and then intragastrically administered QZYQ (4.72, 9.45, or 18.89 g/kg) or dexamethasone (DEX, 0.6 mg/kg) for 6 weeks. We examined the lung function and collected bronchoalveolar lavage fluid for inflammatory cell and cytokine quantification. The pathological lung changes, ROS and oxidative biomarkers were measured. We used immunohistochemistry and western blotting to evaluate the levels of Nrf2/HO-1, NLRP3/ASC/Caspase1/IL-1ß/IL-18. RESULTS: The CS group showed significant increases in the forced vital capacity, lung resistance, and chord compliance and a lower FEV50/FVC compared with the control, and QZYQ improved these changes. In addition, QZYQ effectively reduced emphysema, immune cell infiltration, and airway remodeling. QZYQ stimulated HO-1 expression and reduced oxidative stress through the Nrf2 pathway. QZYQ inhibited the production of NLRP3/ASC/Caspase-1 to inhibit IL-1ß and IL-18. CONCLUSION: Our study suggested that QZYQ can improve the function and histology of the lungs and reduce inflammatory cell recruitment. QZYQ inhibits ROS production and NLRP3 inflammasome activation by upregulating Nrf2 to reduce lung injury. The anti-inflammatory effects of QZYQ are similar to those of DEX.

Polysaccharide of Atractylodes macrocephala Koidz alleviates LPS-induced proliferation, differentiation inhibition and excessive apoptosis in chicken embryonic myogenic cells.

BACKGROUND: Lipopolysaccharide (LPS) can induce systemic inflammation and affect the growth and development of poultry. As a kind of traditional Chinese medicine, polysaccharide of Atractylodes macrocephala Koidz (PAMK) can effectively improve the growth performance of animals and improve the immunity of animal bodies. OBJECTIVES: The purpose of this study was to investigate the effects of PAMK on LPS-induced inflammatory response, proliferation, differentiation and apoptosis of chicken embryonic myogenic cells. METHODS: We used chicken embryonic myogenic cells as a model by detecting EdU/MYHC immunofluorescence, the expression of inflammation, proliferation, differentiation-related genes and proteins and the number of apoptotic cells in the condition of adding LPS, PAMK, belnacasan (an inhibitor of Caspase1) or their combinations. RESULTS: The results showed that LPS stimulation increased the expression of inflammatory factors, inhibited proliferation and differentiation, and excessive apoptosis in chicken embryonic myogenic cells, and PAMK alleviated these adverse effects induced by LPS. After the addition of belnacasan (inhibitor of Caspase1), apoptosis in myogenic cells was inhibited, and therefore, the number of apoptotic cells and the expression of pro-apoptotic genes Caspase1 and Caspase3 were increased. In addition, belnacasan inhibited the increased expression of inflammatory factors, inhibited proliferation, differentiation and excessive apoptosis in chicken embryonic myogenic cells induced by LPS. CONCLUSIONS: This study provides a theoretical basis for further exploring the mechanism of action of PAMK and exogenous LPS on chicken embryonic myogenic cells and lays the foundation for the development and application of green feed additives in animal husbandry industry.

PAMK Relieves LPS-Induced Enteritis and Improves Intestinal Flora Disorder in Goslings.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) is a biologically active component of Atractylodes macrocephala, which has the effect of maintaining the immune homeostasis of the body. Therefore, this study constructed a model of PAMK to relieve LPS-induced gosling enteritis and observed the morphological changes of the small intestine after HE staining. ELISA was used to detect serum CRP, IL-1ß, IL-6, and TNF-α levels; immunohistochemistry was used to detect the positive rate of IgA in the small intestine; TLR4, occludin, ZO-1, cytokines, and immunoglobulin mRNA expression in the small intestine were detected by qPCR; and intestinal flora of gosling excrement was analyzed by 16S rDNA sequencing to analyze the protective effect of PAMK on goslings enteritis and the impact on intestinal flora. The results showed that PAMK relieves LPS-induced gosling enteritis by maintaining the small intestine morphology, cytokine, tight junctions, and immunoglobulin relatively stable and improving the disorder of intestinal flora.

Selenium-Alleviated Hepatocyte Necrosis and DNA Damage in Cyclophosphamide-Treated Geese by Mitigating Oxidative Stress.

Selenium (Se) has been well recognized as an immune-enhancing agent with antioxidant and anti-tumor properties. The commonly used chemotherapy drug, cyclophosphamide (CTX), induces liver injury by increasing the reactive oxygen species (ROS) level. However, little is known about how Se alleviates CTX-induced liver injury in geese. In this study, 90 male Magang geese (3 days old) were randomly allocated into three groups (control, CTX, and Se + CTX group) with three replicates per group and ten geese per replicate. The control and CTX groups were fed a basal diet (Se content was 0.03 mg/kg). The Se + CTX group was fed a basal diet containing 0.44 mg/kg sodium selenite (Se content was 0.2 + 0.03 mg/kg). The control group was injected with 0.5 mL saline, while the CTX and Se + CTX groups were injected with CTX at 40 mg/kg body weight per day on days 21-23. The liver index, liver histology, and ultra-micromorphology detected antioxidant enzyme activity in the liver and serum. In addition, we detected the liver marker enzymes and protein levels in serum, and hepatocyte DNA damage. Se could alleviate liver development dysregulation, hepatocyte structural damage, the disturbances in antioxidant enzyme (GPx, CAT, and SOD) activity, and malondialdehyde (MDA) levels in the serum and liver. Besides, Se could alleviate the dysregulation of liver marker enzyme (ALT and AST) activity and protein (ALB and TP) levels in the serum, and DNA migration induced by CTX. In conclusion, Se may inhibit hepatocyte necrosis and DNA damage by inhibiting CTX-induced oxidative stress.

Polysaccharide of Atractylodes macrocephala Koidz Enhances Cytokine Secretion by Stimulating the TLR4-MyD88-NF-κB Signaling Pathway in the Mouse Spleen.

Polysaccharide of Atractylodes macrocephala Koidz (PAMK) has been reported to have beneficial effects on regulation of immune responses in mammals and poultry. Nonetheless, the immunoregulatory mechanism of action of PAMK remains unclear. The Toll-like receptor 4 (TLR4) signaling cascade has been proved as a classic polysaccharide-regulated pathway. The aim of this study was to explore the effects of PAMK on the TLR4 signaling pathway in the regulation of spleen function in mice. Ninety-six 5-week-old BALB/c female mice were randomly allocated into four groups with three replicates per group and eight mice per replicate in a single-factor completely randomized experimental design. The control group was fed a basic diet (PAMK free); the other three groups were fed 100, 200, or 400 mg/kg PAMK for 28 days. The spleen index, concentrations of cytokines, and mRNA and protein expression levels of genes related to TLR4 signaling were determined in spleen tissue. Compared with the control group, the spleen index significantly increased in all treatment groups. Concentrations of interleukin 2 (IL-2), IL-4, interferon γ (IFN-γ), and tumor necrosis factor α (TNF-α) in the medium-PAMK group also increased significantly. PAMK in the medium-PAMK group significantly increased both mRNA and protein expression of TLR4, myeloid differentiation factor 88 (MyD88), TNFR-associated factor 6 (TRAF6), TRAF3, and nuclear factor kappa B (NF-κB) in the spleen. In conclusion, PAMK may increase immune-response capacity of the spleen in mice via TLR4-MyD88-NF-κB signaling.

Effect of Selenium on Ion Profiles and Antioxidant Defense in Mice Livers.

Se entering the mammalian body from diverse sources shows different liver accumulation patterns. However, the effects of Se from diverse sources on the body's I on spectrum and the relationship between the changes in the ion spectrum and antioxidant function are not clear. In this study, 80 3-week-old female mice were randomly divided into four groups: a control group, sodium selenite group, yeast Se group, and seaweed Se group. The estimated Se contents were 0.03, 0.23, 0.23, and 0.23 mg/kg, respectively. The liver was collected from mice on day 60. The results showed that, compared with the control group, sodium selenite significantly reduced Na and Li contents and significantly increased Cr, Ni, Se, and Sb contents (P < 0.05); yeast Se significantly increased Mg, Ca, Si, Cr, Fe, Co, Cu, Se, Sb, and Al contents, and significantly reduced Tl, As, and Hg contents (P < 0.05); seaweed Se significantly increased B, Si, Cr, Fe, Se, As, and Hg contents, and significantly reduced Zn and Tl contents (P < 0.05). The results of antioxidant parameter analysis showed that Se from three sources increased total superoxide dismutase content and significantly reduced malondialdehyde content (P < 0.05), whereas no clear effect was observed on total antioxidant capacity (P > 0.05). Combined with the ion spectrum and antioxidant test results, yeast Se was found to most effectively promote the accumulation of beneficial elements, enhance antioxidant capacity, and reduce the concentration of toxic elements. The variety of ion spectrum antioxidants followed a similar trend, which indicated that the ion spectrum might be related to antioxidant activity.

Transcriptome profiling reveals the immune response of goose T cells under selenium stimuli.

The goose is an economically important poultry species and a principal natural host of avian viruses. This study aimed to determine the effects of selenium on the immune response of geese. Under selenium stimulation, gene expression profiling was investigated using transcriptome sequencing. The selenoproteins were promoted by selenium stimulation, while the heat shock proteins, interleukin and interferons were mainly down-regulated. After comparison, 2228 differentially expressed genes were primarily involved in immune and environmental response, and infectious disease and genetic information processing related pathways were identified. Specifically, the enzymes of the lysosomes which acted as a safeguard in preventing pathogens were mostly up-regulated and six randomly selected differentially expressed genes were validated by quantitative polymerase chain reaction. In addition, the most proportional increased transcription factor family basic helix-loop-helix (bHLH) located in the 5' flank of selenoprotein P-like protein for selenium metabolism was identified by response to the selenium stimulation in this study. These analyses show that selenium can promote immune function by activating selenoproteins, transcript factors and lysosome pathway related genes, while weakening cytokine content genes in geese.

Effect of Dietary Selenium Deficiency on the Cell Apoptosis and the Level of Thyroid Hormones in Chicken.

This study assessed the effect of dietary selenium (Se) deficiency on male reproductive function in chicken. A total of 180 Hy-line laying cocks (1 day old; Weiwei) were randomly divided into 2 groups (n = 90) of Se-deficient chickens and control chickens. The control group was fed a basic diet (containing 0.15 mg of Se/kg). The Se-deficient group was fed a Se-deficient corn-soy basal diet (containing 0.033 mg of Se/kg). Fifteen chickens were killed in each group on days 30, 60, and 90, respectively. Then, serum and testes were collected and used in the detection of experimental index. Results indicated that GSH-Px activity and Bcl-2 mRNA level in the testes and thyroidal triiodothyronine (T3) and free triiodothyronine (FT3) levels in serum by dietary Se deficiency were significantly decreased compared to the corresponding control groups. Se deficiency-treated group showed a significant increase in MDA concent, TUNEL-positive cells, and mRNA level of Bax, Caspase3, and p53 in the testes and thyroidal thyroxine (T4), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) levels in serum. Histopathologically, Se deficiency caused impairments in the testes. These results suggested that dietary Se deficiency exerts significant harmful effects on male reproductive organ and that the intrinsic and extrinsic pathways and the upstream regulators such as p53, Bax, and Bcl-2 were all involved in Se deficiency-induced testicular apoptosis.

The effect of selenium and polysaccharide of Atractylodes macrocephala Koidz. (PAMK) on immune response in chicken spleen under heat stress.

The aim of the present study was to investigate the effect of selenium (Se), polysaccharide of Atractylodes macrocephala Koidz. (PAMK), and the combination of Se and PAMK on the immune response, heat shock protein (HSP) levels under heat stress (HS) condition in chicken spleen. Two hundred chickens were randomly divided into two groups, the HS group and the control (Con) group. Then these chickens were treated with Se (0.3 mg/kg), PAMK (200 mg/kg) alone, and the combination of Se (0.3 mg/kg) and PAMK (200 mg/kg). The antioxidative enzymes, cytokines contents, and expression levels of HSP27 and HSP70 were examined in chicken spleen. The results indicated that HS induced higher levels of TNF-α, IL-4, HSP27, HSP70, and MDA levels but lower level of IFN-γ, IL-2, Gpx, and SOD in spleen (P < 0.05). These responses were ameliorated by the treatment of Se, PAMK alone, and the combination of Se and PAMK (P < 0.05 or not) The results showed that under common condition, Se and PAMK could improve the immune response by enhancing the levels of some cytokines to proper levels; however, under HS condition, Se and PAMK could change the abnormal levels of cytokines and oxidative damages to ameliorate the injury induced by HS. In addition, there existed synergistic effect on the modulation of these biomarkers in chicken spleen between Se and PAMK. So both Se and PAMK play important roles in regulating the immune function in chicken. Considering the synergistic effect on immune regulation of PAMK, this herb deserves further investigation to evaluate its role in improving the effect of traditional immune regulators.