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1.
Biomed Chromatogr ; 38(7): e5870, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38664069

RESUMEN

Spleen deficiency can lead to various abnormal physiological functions of the spleen. Atractylodis Macrocephalae Rhizoma (AMR) is a traditional Chinese medicine used to invigorate the spleen and tonify qi. The study aimed to identify the primary active components influencing the efficacy of AMR in strengthening the spleen and replenishing qi through spectrum-effect relationship and chemometrics. Network pharmacology was used to investigate the mechanism by which AMR strengthens the spleen and replenishes qi, with molecular docking utilized for validation purposes. The findings indicated that bran-fried AMR exhibited superior efficacy, with atractylenolides and atractylone identified as the primary active constituents. Atractylenolide II emerged as the most influential component impacting the effectiveness of AMR, while the key target was androgen receptor. Furthermore, crucial pathways implicated included the mitogen-activated protein cascade (MAPK) cascade, RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding, and RNA polymerase II sequence-specific DNA-binding transcription factor binding. In summary, our study has identified the primary active components associated with the efficacy of AMR and has provided an initial exploration of its mechanism of action. This offers a theoretical foundation for future investigations into the material basis and molecular mechanisms underlying the pharmacodynamics of AMR.


Asunto(s)
Atractylodes , Medicamentos Herbarios Chinos , Lactonas , Simulación del Acoplamiento Molecular , Farmacología en Red , Sesquiterpenos , Bazo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Animales , Atractylodes/química , Lactonas/química , Lactonas/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Bazo/efectos de los fármacos , Bazo/metabolismo , Rizoma/química , Masculino
2.
Front Immunol ; 15: 1381340, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38633246

RESUMEN

Background: In addition to abnormal liver inflammation, the main symptoms of non-alcoholic steatohepatitis (NASH) are often accompanied by gastrointestinal digestive dysfunction, consistent with the concept of spleen deficiency (SD) in traditional Chinese medicine. As an important metabolic sensor, whether peroxisome proliferator-activated receptor alpha (PPARα) participates in regulating the occurrence and development of NASH with SD (NASH-SD) remains to be explored. Methods: Clinical liver samples were collected for RNA-seq analysis. C57BL/6J mice induced by folium sennae (SE) were used as an SD model. qPCR analysis was conducted to evaluate the inflammation and metabolic levels of mice. PPARα knockout mice (PPARαko) were subjected to SE and methionine-choline-deficient (MCD) diet to establish the NASH-SD model. The phenotype of NASH and the inflammatory indicators were measured using histopathologic analysis and qPCR as well. Results: The abnormal expression of PPARα signaling, coupled with metabolism and inflammation, was found in the results of RNA-seq analysis from clinical samples. SD mice showed a more severe inflammatory response in the liver evidenced by the increases in macrophage biomarkers, inflammatory factors, and fibrotic indicators in the liver. qPCR results also showed differences in PPARα between SD mice and control mice. In PPARαko mice, further evidence was found that the lack of PPARα exacerbated the inflammatory response phenotype as well as the lipid metabolism disorder in NASH-SD mice. Conclusion: The abnormal NR signaling accelerated the vicious cycle between lipotoxicity and inflammatory response in NAFLD with SD. Our results provide new evidence for nuclear receptors as potential therapeutic targets for NAFLD with spleen deficiency.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , PPAR alfa , Animales , Ratones , Inflamación , Ratones Endogámicos C57BL , Ratones Noqueados , Enfermedad del Hígado Graso no Alcohólico/genética , Enfermedad del Hígado Graso no Alcohólico/metabolismo , PPAR alfa/metabolismo , Bazo/metabolismo , Bazo/patología
3.
Int Immunopharmacol ; 130: 111574, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38367461

RESUMEN

Selenium (Se) is a trace element necessary for humans to maintain normal physiological activities, and Se deficiency may lead to splenic injury, while Se supplementation can alleviate splenic injury. However, the mechanism is unclear. In this study, we constructed a Se deficiency animal model by feeding Sprague-Dawley (SD) rats with low Se feed. Meanwhile, we observed the repairing effect of Se supplementation on splenic injury with two doses of novel nano-selenium (Nano-Se) supplement by gavage. We measured the Se content in the spleens of the rats by atomic fluorescence spectroscopy (AFS) method and combined the results of hematoxylin-eosin (HE) and Masson staining to observe the splenic injury, comprehensively evaluating the construction of the animal model of low selenium-induced splenic injury. We measured the mRNA and protein expression levels of p38 mitogen-activated protein kinase (p38 MAPK), nuclear factor kappa-B (NF-κB), and interleukin-6 (IL-6) in the spleen by Real-time quantitative polymerase chain reaction (qPCR), western blot (WB), and immunohistochemistry (IHC). We found that the Se deficiency group exhibited lower Se content, splenic fibrosis, and high expression of p38 MAPK, NF-κB, and IL-6 compared to the normal group. The Se supplement groups exhibited higher Se content, attenuated splenic injury, and down-regulated expression of p38 MAPK, NF-κB, and IL-6 relative to the Se deficiency group. This study suggests that Se deficiency leads to splenic injury in rats, and Se supplementation may attenuate splenic injury by inhibiting the expression of p38 MAPK, NF-κB and IL-6.


Asunto(s)
FN-kappa B , Selenio , Humanos , Ratas , Animales , FN-kappa B/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Bazo/metabolismo , Selenio/uso terapéutico , Selenio/farmacología , Interleucina-6 , Ratas Sprague-Dawley , Suplementos Dietéticos
4.
Dev Comp Immunol ; 151: 105094, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37951325

RESUMEN

In recent years, increasing interest has focused on natural components extracted from plants, among which plant polysaccharides as natural immunomodulators that can promote animal immunity. The present study was performed to investigate the effect of feed supplement Pseudostellaria Heterophylla Polysaccharide (PHP) on serum Immunoglobulins, T lymphocyte subpopulations, Cytokines and Lysozyme (LZM) activity in chicks. In addition, the influence of PHP on splenic gene expression was investigated by transcriptome sequencing. Four hundred 7-day-old Gushi cocks were randomly divided into four groups in a completely randomized design. The chicks were fed with a basal diet supplemented with 0 (CON-A), 100 (PHP-L), 200 (PHP-M) and 400 (PHP-H) mg/kg PHP. Blood and spleen samples were collected from 6 randomly selected chicks in each group at 14, 21, 28, and 35 days of age. The results showed that compared to the CON-A group, the PHP-M group exhibited significant increases in the levels of IgA, IgG, IgM, CD3, and LZM in the serum at 14, 21, 28, and 35 days (P < 0.05), and at 28 d, there was a significant quadratic relationship between the levels of dietary PHP and the levels of IgG, IgM, IFN-γ, IL-2, CD3, and LZM. Furthermore, a total of 470 differentially expressed genes (DEGs) were identified in spleen from PHP-M and CON-A at 28 d. These DEGs were significantly enriched in the Phagosome, Intestinal immune network for IgA production and Cytokine-cytokine receptor interaction pathways. The present investigation highlights the ameliorating effect of dietary PHP on immunological variables and spleen of chicks, the study suggests that PHP supplementation can enhance immunity and positively impact spleen mRNA expression in chicks.


Asunto(s)
Suplementos Dietéticos , Bazo , Animales , Bazo/metabolismo , Dieta , Citocinas/metabolismo , Polisacáridos/metabolismo , Inmunoglobulina G/metabolismo , ARN Mensajero/metabolismo , Inmunoglobulina A/metabolismo , Inmunoglobulina M/metabolismo , Pollos
5.
Int J Mol Sci ; 24(7)2023 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-37047433

RESUMEN

Chronic heat stress (CHS) compromised the immunity and spleen immunological function of pigs, which may associate with antioxidant suppression and splenocyte apoptosis and splenic inflammation. Selenium (Se) exhibited antioxidant function and immunomodulatory through selenoprotein. Thus, this study aimed to investigate the protective effect of dietary hydroxy-selenomethionine (Selisso®, SeO) on chronic heat stress (CHS)-induced porcine splenic oxidative stress, apoptosis and inflammation. Growing pigs were raised in the thermoneutral environment (22 ± 2 °C) with the basal diet (BD), or raised in hyperthermal conditions (33 ± 2 °C) with BD supplied with 0.0, 0.2, 0.4 and 0.6 mg Se/kg SeO for 28 d, respectively. The results showed that dietary SeO supplementation recovered the spleen mass and enhanced the splenic antioxidant capacity of CHS growing pigs. Meanwhile, SeO activated the Nrf2/Keap1 signal, downregulated p38, caspase 3 and Bax, inhibited the activation of NFκb and STAT3, and enhanced the protein expression level of GPX1, GPX3, GPX4, SELENOS and SELENOF. In summary, SeO supplementation mitigates the CHS-induced splenic oxidative damages, apoptosis and inflammation in pigs, and the processes are associated with the activation of Nrf2/Keap1 signal and the suppression of NFκb, p38(MAPK) and STAT signal. It seems that the antioxidant-related selenoproteins (GPXs) and functional selenoproteins (SELENOS and SELENOF) play important roles in the alleviation processes.


Asunto(s)
Selenio , Selenometionina , Animales , Antioxidantes/farmacología , Antioxidantes/metabolismo , Respuesta al Choque Térmico , Inflamación/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Selenio/farmacología , Selenio/metabolismo , Selenometionina/farmacología , Selenoproteínas/metabolismo , Bazo/metabolismo , Porcinos , Factores de Transcripción STAT/metabolismo
6.
Zhen Ci Yan Jiu ; 48(3): 240-6, 2023 Mar 25.
Artículo en Chino | MEDLINE | ID: mdl-36951075

RESUMEN

OBJECTIVE: To observe the therapeutic effect of electroacupuncture(EA) on obese mice, and to explore the underlying mechanism of EA in treating obesity by focusing on the balance of regulatory T cells (Treg) and T helper 17 cells (Th17) and related inflammatory factors. METHODS: C57BL/6J male mice were randomly divided into normal group, model group and EA group, with 10 mice in each group. The obesity model was established by feeding the mice with high-fat diet. Mice in the EA group was treated with EA at "Zhongwan"(CV12), "Guanyuan"(CV4), "Zusanli"(ST36) and "Fenglong"(ST40) for 20 min every time, 3 times every week, for a total of 8 weeks. The food intake and body weight of mice were observed and recorded, and Lee's index was calculated; the contents of interleukin 2(IL-2), IL-4, IL-6, IL-10, IL-17A, gamma interferon (IFN-γ) and tumor necrosis factor(TNF)-α in serum were detected by multiplex liquid chip quantitative technique; the levels of Treg and Th17 cells in mice spleen tissues were detected by flow cytometry; and the expression levels of foxhead box p3(Foxp3) and retinoic acid related orphan receptor γt(ROR-γt) mRNA in spleen were detected by real-time quantitative PCR. RESULTS: Compared with the normal group, the food intake, body weight, Lee's index, the contents of IL-2, IL-6, IL-17A, IFN-γ and TNF-α in the serum, and the percentage of Th17 and expression of ROR-γt mRNA in the spleen tissues were significantly increased (P<0.01, P<0.001), while the contents of IL-4 and IL-10 in the serum, the percentage of Treg and expression of Foxp3 mRNA in the spleen tissues were significantly decreased (P<0.001, P<0.01) in the model group. Compared with the model group, the food intake, body weight, Lee's index, the contents of IL-2, IL-6, IL-17A, IFN-γ, and TNF-α in the serum, the percentage of Th17 and expression of ROR-γt mRNA in the spleen tissues were significantly decreased (P<0.01), while the contents of IL-4 and IL-10 in serum, the percentage of Treg and expression of Foxp3 mRNA in the spleen tissues were significantly increased(P<0.01, P<0.05) in the EA group. CONCLUSION: EA may improve the obese state of mice by regulating the balance of Treg/Th17 in spleen and the expression of inflammatory factors in serum.


Asunto(s)
Electroacupuntura , Bazo , Ratas , Ratones , Masculino , Animales , Ratas Wistar , Bazo/metabolismo , Células Th17/metabolismo , Interleucina-2 , Ratones Obesos , Interleucina-10 , Interleucina-17/genética , Miembro 3 del Grupo F de la Subfamilia 1 de Receptores Nucleares/genética , Factor de Necrosis Tumoral alfa/metabolismo , Linfocitos T Reguladores/metabolismo , Interleucina-6 , Interleucina-4 , Ratones Endogámicos C57BL , Inflamación , Obesidad/genética , Obesidad/terapia , Factores de Transcripción Forkhead/genética
7.
Biol Pharm Bull ; 46(2): 187-193, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36724947

RESUMEN

Endoplasmic reticulum (ER) dysfunction is characterized by ER stress, which can be triggered by sepsis. Recent studies have reported that lessening ER stress is a promising therapeutic approach to improving the outcome of sepsis. Genipin is derived from gardenia fruit, which is a traditional Chinese medicinal herb for anti-inflammation. Here, mice were treated with genipin (2.5 mg/kg) intravenously to assess its biological effects and underlying mechanism against polymicrobial sepsis. Furthermore, the present study focused on detecting the levels of ER stress-related proteins, including protein kinase R-like ER kinase (PERK), glucose-regulated protein of 78 kDa (GRP78), phosphorylated-eukaryotic initiation factor 2α (p-eIF2α), and CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP). The results demonstrated that genipin significantly decreased the serum concentrations of tumor necrosis factor-α and interleukin-6, alleviated histopathological damage to the lungs, livers and spleens, and even improved the survival rates of septic mice. Moreover, sepsis significantly upregulated the protein expression levels of splenic GRP78, PERK, p-eIF2α and CHOP, but their levels were significantly suppressed by genipin. Furthermore, genipin also significantly downregulated cleaved caspase-3 expression levels and reduced sepsis-induced splenocyte apoptosis. In conclusion, genipin potentially improved the survival rate of sepsis and attenuated sepsis-induced organ injury and an excessive inflammatory response in mice. The effects of genipin against sepsis were potentially associated with decreased splenocyte apoptosis via the attenuation of sepsis-induced ER stress to further inhibit ER stress-induced apoptosis.


Asunto(s)
Chaperón BiP del Retículo Endoplásmico , Sepsis , Ratones , Animales , Bazo/metabolismo , Apoptosis , Estrés del Retículo Endoplásmico , Sepsis/complicaciones , Sepsis/tratamiento farmacológico , Factor de Transcripción CHOP/metabolismo
8.
Animal ; 17(3): 100714, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36764015

RESUMEN

The thymus and spleen, the main reservoirs for T lymphocytes, modulate the innate immune response. Oxidative stress, excessive inflammation and abnormal pyroptosis can cause dysfunction of these organs. This study aimed to examine whether tryptophan supplementation can improve growth performance and mitochondrial function via the adenosine 5'-monophosphate-activated protein kinase (AMPK)/sirtuin1 (Sirt1)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signalling pathway and decrease pyroptosis via the nucleotidebinding oligomerisation domain-like receptor protein 3 (NLRP3)/caspase-1/gasderminD (GSDMD) signalling pathway in the spleen and thymus of piglets after lipopolysaccharide (LPS) challenge. Eighteen weaned piglets were allotted to three treatment groups: non-challenged control, LPS-challenged control and LPS + 0.2% tryptophan. On day 35, the pigs in the LPS and LPS + 0.2% tryptophan groups were injected with 100 µg/kg BW LPS, whereas those in the control group were administered with sterile saline. At 4 h postchallenge, the weaned piglets were sacrificed, and their thymuses and spleens were collected. Results showed that tryptophan enhanced growth performance and antioxidant status by increasing catalase, glutathione peroxidase and total superoxide dismutase activities and decreasing malondialdehyde and reactive oxygen species contents. Tryptophan also reduced the mRNA levels of proinflammatory cytokine genes and enhanced mitochondrial function by increasing the mRNA levels of mitochondrial transcription factor A, nuclear respiratory factor-1, mitochondria transcription factor B1, AMPKα1, AMPKα2, Sirt1 and PGC1α and the protein expression of phosphorylated AMPK, Sirt1 and PGC1α. It also reduced pyroptosis by decreasing the mRNA levels of NLRP3, apoptosis-associated speck-like protein containing CARD, caspase-1 and GSDMD and the protein expression of NLRP3, caspase-1 and GSDMD. These results indicate that tryptophan supplementation enhances growth performance and mitochondrial function via the AMPK/Sirt1/PGC1α signalling pathway and decreases pyroptosis via the NLRP3/caspase-1/GSDMD signalling pathway in the spleen and thymus of LPS-challenged piglets.


Asunto(s)
Lipopolisacáridos , Piroptosis , Porcinos , Animales , Lipopolisacáridos/toxicidad , Lipopolisacáridos/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Triptófano/farmacología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Bazo/metabolismo , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Adenosina Monofosfato/metabolismo , Suplementos Dietéticos , Mitocondrias/metabolismo , ARN Mensajero/metabolismo , Caspasas/metabolismo
9.
Biol Trace Elem Res ; 201(11): 5192-5200, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36786964

RESUMEN

The aim of the present study was to investigate the effect of selenium (Se) deficiency on the relationship between the pyroptosis and MAPK signaling pathway in spleen injury. A total of 10 two-month-old Sus scrofa domesticus specimens were allocated to two groups. The control group was fed a basal diet (0.15-mg/kg Se), and the experimental group was fed a 0.03-mg/kg Se-deficient diet for 2 months. The pig-spleen histopathological changes were observed with hematoxylin-eosin staining. Frozen sections were prepared to detect the content of ROS in pig-spleen cells. The oxidation stress related indexes were determined using a spectrophotometer. The levels of pyroptosis- and MAPK signaling pathway-related factors were detected via quantitative real-time polymerase chain reaction (qPCR) and western blotting (WB). The results of sections showed that the lymphocytes decreased in number, the spacing of cells widened, and some cells were necrotic in the spleen tissue of pigs fed a low-selenium diet. The content of ROS, malondialdehyde, nitric oxide, H2O2, and catalase activity in the low-selenium group was significantly higher than that in the control group, and SOD activity was decreased. The protein-ratio-levels of p-Nrf2 to Nrf2 were decreased. The expression levels of nod-like receptor (NLR) family pyrin domain containing 3 (NLRP3), IL-1ß, IL-18, ASC, gasdermin D, and caspase-1, the protein-ratio-levels of p-AKT serine/threonine kinase (p-AKT) to AKT, p-extracellular regulated protein kinases (ERK) to ERK, p-P38 MAPK to p-P38, and p-c-Jun N-terminal kinase (p-JNK) to JNK were significantly increased in the Se-deficient group compared with the control group. These results suggested that Se deficiency can induce oxidant stress, which increases pyroptosis- and inflammation-related factors of pig-spleen injury.


Asunto(s)
Piroptosis , Selenio , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Selenio/farmacología , Bazo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Peróxido de Hidrógeno/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal
10.
Biochem Biophys Res Commun ; 646: 86-95, 2023 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-36706710

RESUMEN

BACKGROUND: Acupuncture has shown the preventive effects on depression in rats with chronic unpredictable mild stress (CUMS). However, the mechanisms of acupuncture for preventing depression still need to be explored. In the study, acupuncture was applied to a rat depression model of CUMS, high-mobility group box 1(HMGB1)/toll-like receptor 4 (TLR4) and brain-spleen axis were assessed. METHODS: Male Sprague Dawley (SD) rats were exposed to CUMS with two stressors per day for 28 days. In the meantime, manual acupuncture (at GV16 and GV23 acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL) were administered daily post CUMS stressors. Behavioral tests and biological detection methods were conducted in sequence to evaluate depression-like phenotypes in rats. RESULTS: The results showed CUMS induced depression-like behaviors, hyper-activation of HMGB1/TLR4 signaling pathway, elevated inflammation in amygdala and peripheral blood, and hyperactivation of hypothalamic-pituitary-adrenal (HPA) axis. These changes could be prevented and reversed by acupuncture to varying extents. CONCLUSION: Acupuncture prevented and ameliorated depression-like symptoms induced by CUMS, possibly via regulating inflammation through brain-spleen axis mediated by HMGB1/TLR4 signaling pathway and HPA axis regulation.


Asunto(s)
Terapia por Acupuntura , Proteína HMGB1 , Ratas , Masculino , Animales , Depresión/etiología , Depresión/prevención & control , Ratas Sprague-Dawley , Antidepresivos/farmacología , Proteína HMGB1/metabolismo , Receptor Toll-Like 4/metabolismo , Sistema Hipotálamo-Hipofisario/metabolismo , Bazo/metabolismo , Sistema Hipófiso-Suprarrenal/metabolismo , Encéfalo/metabolismo , Amígdala del Cerebelo/metabolismo , Inflamación/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/terapia , Estrés Psicológico/metabolismo , Hipocampo/metabolismo
11.
Biol Trace Elem Res ; 201(4): 1748-1760, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35581429

RESUMEN

Ammonia (NH3) is a harmful gas in livestock houses. So far, many researchers have demonstrated that NH3 is detrimental to animal and human organs. Selenium (Se) is one of the essential trace elements in the body and has a good antioxidant effect. However, there was little conclusive evidence that Se alleviated NH3 poisoning. To investigate the toxic mechanism of NH3 on pig spleen and the antagonistic effect of L-selenomethionine, a porcine NH3-poisoning model and an L-selenomethionine intervention model were established in this study. Our results showed that NH3 exposure increased the apoptosis rate, while L-selenomethionine supplementation alleviated the process of excessive apoptosis. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qRT-PCR), and western blot results confirmed that exposure to NH3 changed the expression levels of interleukin family factors, apoptosis, death receptor, and oxidative stress factors. Our study further confirmed that excessive NH3 induced inflammatory response and mediated necroptosis leading to cell apoptosis by activating the Nrf2 signaling pathway. Excessive NH3 could mediate spleen injury through oxidative stress-induced mitochondrial dynamics disorder. L-Selenomethionine could alleviate inflammation and abnormal apoptosis by inhibiting the IL-17/TNF-α/FADD axis. Our study would pave the way for comparative medicine and environmental toxicology.


Asunto(s)
Selenio , Humanos , Animales , Porcinos , Selenio/farmacología , Selenio/metabolismo , Amoníaco/farmacología , Amoníaco/toxicidad , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Selenometionina/farmacología , Selenometionina/metabolismo , Bazo/metabolismo , Pollos/metabolismo , Transducción de Señal , Antioxidantes/metabolismo , Apoptosis , Estrés Oxidativo , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Interleucinas/metabolismo , Interleucinas/farmacología , Receptores de Muerte Celular/metabolismo
12.
Pestic Biochem Physiol ; 187: 105190, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36127050

RESUMEN

Avermectin is one of the most widely used pesticides, but its toxicity to non-target organisms, especially aquatic organisms, has been ignored. Therefore, an acute spleen injury model of avermectin in carp was established to assess the non-target toxicity of avermectin to carp. In this study, 3.005 µg/L and 12.02 µg/L were set as the low and high dose groups of avermectin, respectively, and a four days acute exposure experiment was conducted. Pathological structure observation showed that avermectin damaged spleen tissue structure and produced inflammatory cell infiltration. Biochemical analysis showed that avermectin significantly reduced the activities of antioxidant enzymes CAT, SOD, and GSH-px, but increased the content of MDA, a marker of oxidative damage. Avermectin exposure also significantly increased the transcription levels of inflammatory cytokines such as IL-1ß, IL-6, TNF-α, and INOS, and also significantly enhanced the activity of the inflammatory mediator iNOS, but suppressed the transcription levels of anti-inflammatory factors TGF-ß1 and IL-10. In addition, TUNEL detected that the apoptosis rate increased significantly with the increase of avermectin dosage, and the transcription levels of apoptosis-related genes BAX, P53, and Caspase 3/9 also increased in a dose-dependent manner. This study is preliminary evidence that avermectin induces spleen injury in carp through oxidative stress, inflammation, and apoptosis, which has important implications for subsequent studies on the effects of avermectin on non-target organisms.


Asunto(s)
Carpas , Plaguicidas , Animales , Antioxidantes/metabolismo , Apoptosis , Carpas/metabolismo , Caspasa 3/metabolismo , Inflamación/inducido químicamente , Mediadores de Inflamación/farmacología , Interleucina-10/metabolismo , Interleucina-10/farmacología , Interleucina-6/farmacología , Ivermectina/análogos & derivados , Estrés Oxidativo , Plaguicidas/farmacología , Bazo/metabolismo , Superóxido Dismutasa/metabolismo , Factor de Crecimiento Transformador beta1/farmacología , Factor de Necrosis Tumoral alfa , Proteína p53 Supresora de Tumor , Proteína X Asociada a bcl-2
13.
Food Chem Toxicol ; 168: 113324, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-35917956

RESUMEN

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage.


Asunto(s)
Dietilhexil Ftalato , Contaminantes Ambientales , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Aceite de Maíz/farmacología , Dietilhexil Ftalato/toxicidad , Contaminantes Ambientales/farmacología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Licopeno/farmacología , Ratones , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Ácidos Ftálicos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal , Bazo/metabolismo , Superóxido Dismutasa/metabolismo , Agua
14.
Food Funct ; 13(16): 8500-8508, 2022 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-35876550

RESUMEN

Iron deficiency is a global issue, influencing more than one-third of the population in the world. Ferritin as a natural iron-containing protein is considered a marvelous iron supplement due to its biocompatibility, biodegradability and bioavailability. However, foodstuffs contain plenty of reductants which could induce iron release from the cavity of ferritin and cause oxidative damage. In this study, we aimed to prevent the iron release from donkey spleen ferritin (DSF) by pectin encapsulation driven by the electrostatic interaction and evaluated the iron supplementation of the DSF-pectin complex (DPC). After DSF was purified, we fabricated the DPC and the iron release was decreased by 53.68% after 60 min when DSF : pectin was 1 : 10 (w/w). TEM analysis showed that ferritin in the DPC is clustered in a linear pattern, and the cell viability assay indicated that the DPC has no toxicity towards Caco-2 cells. In the mouse experiment, the DPC increased the content of serum iron and serum ferritin with no significant difference from the control check. Furthermore, the DPC increased the iron content in the liver, suppressed the expression of hepcidin and increased the expression of ferroportin. These results suggested that the DPC could prevent the interactions between food components and ferritin and is a promising iron supplement to ameliorate iron deficiency.


Asunto(s)
Hierro , Bazo , Animales , Células CACO-2 , Suplementos Dietéticos , Equidae/metabolismo , Ferritinas/metabolismo , Hepcidinas/genética , Hepcidinas/metabolismo , Humanos , Hierro/metabolismo , Ratones , Pectinas/metabolismo , Pectinas/farmacología , Bazo/metabolismo
15.
Ecotoxicol Environ Saf ; 242: 113887, 2022 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-35849905

RESUMEN

Ammonia (NH3) is a typical pollutant in the atmosphere and is well known for its harmful effects on plants, animals as well as human health. Previous studies have shown that NH3 exposure can cause damage to immune organs and impaired immune function in animals. Selenomethionine is a kind of organic selenium, which can not only promote the growth and development of the body, but also inhibit the generation of intracellular reactive oxygen species (ROS), and effectively improve the immune function of the body. Therefore, this study evaluated the toxic effect of NH3 exposure on spleen from a new perspective and investigated the protective effect of selenomethionine on ammonia-induced immunotoxicity. Twenty-four Large White*Duroc*Min pigs were randomly assigned to 4 groups: control group, NH3 group, selenium group, and NH3 + selenium group. Our results showed that NH3 inhalation caused autophagy in the pig spleen, a decrease in lymphocytes, and an increase in autophagic vesicles. Also, NH3 exposure led to a decrease in the activity of some antioxidant enzymes (decreased by about 50%) and a significant increase in the expression of genes related to oxidative stress and endoplasmic reticulum stress (ERS). Our results indicated that selenomethionine mitigated ammonia toxicity in pigs (alleviated about 20-55%). In summary, our findings should be of value in providing a theoretical basis for revealing the toxicity of the high-risk gas NH3, and providing a new perspective on the mechanism of Se against toxic substances.


Asunto(s)
Selenio , Selenometionina , Animales , Amoníaco/metabolismo , Amoníaco/toxicidad , Antioxidantes/metabolismo , Autofagia , Pollos/metabolismo , Estrés del Retículo Endoplásmico , Estrés Oxidativo , Selenio/farmacología , Selenometionina/toxicidad , Bazo/metabolismo , Porcinos
16.
J Pharm Biomed Anal ; 217: 114831, 2022 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-35609509

RESUMEN

The effects of Scutellaria baicalensis Georgi. (S. baicalensis Georgi.) on the diversity of intestinal flora in rats with spleen deficiency and damp-heat was explored in the present study. 51 compounds in S. baicalensis Georgi. extract, including 37 flavonoids, 9 dihydroflavone, and 5 flavanols, were identified by ultra-high performance liquid chromatography-Q-Orbitrap-mass spectrometry(UPLC-Q-Orbitrap-MS/MS). Ethanol extract from Scutellariae Radix and fresh feces from rats with spleen deficiency and damp-heat were incubated in vitro for 48 h. At the phylum level, the ethanol extract noticeably increased the relative abundance of Firmicutes in the feces and effectively reduced those of Proteobacteria and Actinobacteria. At the genus level, the extract increased the relative abundance of the Lactobacillus and Bifidobacterium and reduced those of pathogenic bacteria, including Clostridium, Escherichia, Enterococcus, and Streptococcus. The results suggest that S. baicalensis Georgi. can regulate the structure and diversity of intestinal flora in rats with spleen deficiency and damp-heat and balance the body's metabolism.


Asunto(s)
Microbioma Gastrointestinal , Scutellaria baicalensis , Animales , Etanol , Flavonoides , Calor , Extractos Vegetales/química , Ratas , Scutellaria baicalensis/química , Bazo/metabolismo , Espectrometría de Masas en Tándem/métodos
17.
J Tradit Chin Med ; 42(3): 451-457, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35610016

RESUMEN

OBJECTIVE: To investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1 (SAMHD1) expression and T cell activation, furthermore, identifying objective indexes of lung-spleen deficiency symptom pattern. METHODS: We assessed the profile of T lymphocyte subsets, characteristics of SAMHD1 and human leukocyte antigen DR (HLA-DR) expression in lung-spleen deficiency patients. At the same time, people living with human immunodeficiency virus / acquired immune deficiency syndrome (HIV/AIDS) (PLWHA) without obvious clinical symptoms and healthy donors in this area were used as controls. RESULTS: Immunohematologic indexes lower CD4 count, lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen deficiency patients. Furthermore, we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen deficiency syndrome and patients without obvious clinical signs and symptoms groups. CONCLUSIONS: These data indicated the positive relationship between SAMHD1 and T cell activation which further elucidated the role of SAMHD1 in cellular immune response. Furthermore, combination of T lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV / AIDS traditional Chinese medicine syndromes.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Ácido Aspártico , VIH/metabolismo , Infecciones por VIH/complicaciones , Infecciones por VIH/genética , Histidina , Humanos , Pulmón/metabolismo , Proteína 1 que Contiene Dominios SAM y HD/metabolismo , Bazo/metabolismo , Motivo alfa Estéril , Linfocitos T
18.
Int Immunopharmacol ; 107: 108679, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35279514

RESUMEN

PURPOSE: Spleen deficiency diarrhea (SDD) is one of the most common types of diarrhea and is linked to intestinal barrier dysfunction and intestinal flora disorders. Atractyloside-A (AA) is one of the main components of Atractylodes Lancea(Thunb.) DC., which acts on the gastrointestinal tract and has therapeutic effects on diarrhea. Folium sennae is a medicinal plant inducing diarrhea; thus, it is one of the effective methods to obtain a diarrhea model. However, the mechanism of action of AA in the treatment of SDD induced by Folium sennae is unclear. METHODS: The intestinal thrapeutic effect of AA on SDD in mice was evaluated by colon pathology. RNA sequencing (RNA-seq) was used to analyze the colonic transcriptome profiles. In addition, 16S rDNA sequencing and fecal microbiota transplantation (FMT) were carried out to verify the role of AA in the regulation of the intestinal flora. RESULTS: The findings revealed that AA alleviated SDD by ameliorating the pathological symptoms while suppressing intestinal inflammatory responses through the TLR4/MyD88/NF-kB signaling and reversing the impairment of mucin synthesis. Furthermore, AA improved the integrity of the intestinal barrier. RNA-seq identified 436 common DEGs out of 1033 DEGs between SDD and AA, and 1933 DEGs between SDD and Ctrl, which are highly enriched in the NF-κB and TNF pathways. Moreover, AA altered the composition of the intestinal flora and FMT reduced SDD. CONCLUSION: AA exerted a therapeutic effect on SDD through the regulation of the intestinal flora and the inflammation by interfering with the TLR4/MyD88/NF-κB signaling pathway.


Asunto(s)
Microbioma Gastrointestinal , FN-kappa B , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Atractilósido , Diarrea/tratamiento farmacológico , Homeostasis , Ratones , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , FN-kappa B/metabolismo , Transducción de Señal , Bazo/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo
19.
Int J Mol Sci ; 23(4)2022 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-35216146

RESUMEN

Chicoric acid (CA), a polyphenolic acid compound extracted from chicory and echinacea, possesses antiviral, antioxidative and anti-inflammatory activities. Growing evidence supports the pivotal roles of brain-spleen and brain-gut axes in neurodegenerative diseases, including Parkinson's disease (PD), and the immune response of the spleen and colon is always the active participant in the pathogenesis and development of PD. In this study, we observe that CA prevented dopaminergic neuronal lesions, motor deficits and glial activation in PD mice, along with the increment in striatal brain-derived neurotrophic factor (BDNF), dopamine (DA) and 5-hydroxyindoleacetic acid (5-HT). Furthermore, CA reversed the level of interleukin-17(IL-17), interferon-gamma (IFN-γ) and transforming growth factor-beta (TGF-ß) of PD mice, implicating its regulatory effect on the immunological response of spleen and colon. Transcriptome analysis revealed that 22 genes in the spleen (21 upregulated and 1 downregulated) and 306 genes (190 upregulated and 116 downregulated) in the colon were significantly differentially expressed in CA-pretreated mice. These genes were functionally annotated with GSEA, GO and KEGG pathway enrichment, providing the potential target genes and molecular biological mechanisms for the modulation of CA on the spleen and gut in PD. Remarkably, CA restored some gene expressions to normal level. Our results highlighted that the neuroprotection of CA might be associated with the manipulation of CA on brain-spleen and brain-gut axes in PD.


Asunto(s)
Antiinflamatorios/uso terapéutico , Ácidos Cafeicos/uso terapéutico , Intoxicación por MPTP/metabolismo , Fármacos Neuroprotectores/uso terapéutico , Succinatos/uso terapéutico , Transcriptoma , Animales , Antiinflamatorios/farmacología , Ácidos Cafeicos/farmacología , Colon/efectos de los fármacos , Colon/metabolismo , Citocinas/genética , Citocinas/metabolismo , Intoxicación por MPTP/tratamiento farmacológico , Intoxicación por MPTP/prevención & control , Masculino , Ratones , Ratones Endogámicos C57BL , Fármacos Neuroprotectores/farmacología , Bazo/efectos de los fármacos , Bazo/metabolismo , Succinatos/farmacología
20.
Exp Mol Pathol ; 124: 104740, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34998864

RESUMEN

Aloin, an anthraquinone glycoside, is one of other C-glycosides found in the leaf exudate of Aloe plant. Aloin possesses several biologic activities, including antitumor activity in vitro and in vivo. However, aloin treatment has shown iron deficiency anemia and erythropoiesis in vivo. The present study was undertaken to verify if iron supplementation could alleviate these perturbations, compared to doxorubicin, an anthracycline analog. Oral iron supplementation (20.56 mg elemental Fe/kg bw) to aloin-treated rats normalized red blood corpuscles count, hemoglobin concentration, and serum levels of total iron binding capacity and saturated transferrin, as well as hepatic iron content, hepcidin level, and mRNA expression of ferritin heavy chain (Ferr-H) and transferrin receptor-1 (TfR-1) genes. Although, serum hyperferremia, and leukocytosis were maintained, yet the spleen iron overload was substantially modulated. However, combined aloin and iron treatment increased iron storage levels in the heart and bone marrow, compared to aloin treatment per se. On other hand, oral iron supplementation to rats treated with doxorubicin (15 mg/kg bw) lessened the increase in the spleen iron content concomitantly with hepatic hepcidin level, rebound hepatic iron content to normal level, and by contrast augmented serum levels of iron and transferrin saturation. Also, activated Ferr-H mRNA expression and repressed TfR-1 mRNA expression were recorded, compared to doxorubicin treatment per se. Histopathological examination of the major body iron stores in rats supplemented with iron along with aloin or doxorubicin showed an increase in extramedullary hematopoiesis. In conclusion, iron supplementation restores the disturbances in iron homeostasis and erythropoiesis induced by aloin treatment.


Asunto(s)
Anemia Ferropénica , Suplementos Dietéticos , Emodina/análogos & derivados , Hierro , Anemia Ferropénica/tratamiento farmacológico , Anemia Ferropénica/metabolismo , Animales , Emodina/efectos adversos , Emodina/farmacología , Eritropoyesis/efectos de los fármacos , Glicósidos/efectos adversos , Glicósidos/farmacología , Hepcidinas/sangre , Hepcidinas/efectos de los fármacos , Hierro/metabolismo , Hierro/uso terapéutico , Deficiencias de Hierro/tratamiento farmacológico , Deficiencias de Hierro/metabolismo , Hígado/metabolismo , Ratas , Receptores de Transferrina/sangre , Receptores de Transferrina/efectos de los fármacos , Bazo/metabolismo
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