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ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.
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Colitis Ulcerosa , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Ratas Sprague-Dawley , Deficiencia Yang , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Colitis Ulcerosa/inducido químicamente , Deficiencia Yang/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Ratas , Metabolómica , ARN Ribosómico 16S/genética , Bazo/efectos de los fármacos , Bazo/metabolismo , Riñón/efectos de los fármacos , Riñón/metabolismo , Metaboloma/efectos de los fármacos , Modelos Animales de EnfermedadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Panax ginseng (P. ginseng) C.A. Meyer. Has been studied for decades for its various biological activities, especially in terms of immune-regulatory properties. Traditionally, it has been known that root, leaves, and fruits of P. ginseng were eaten for improving body's Qi and homeostasis. Also, these were used to protect body from various types of infectious diseases. However, molecular mechanisms of immunomodulatory activities of ginseng berries have not been systemically studied as often as other parts of the plant. AIM OF THE STUDY: The aim of this research is to discover the regulatory effects of P. ginseng berries, more importantly, their ginsenosides, on innate immune responses and to elucidate the molecular mechanism. MATERIALS AND METHODS: Ginseng berry concentrate (GBC) was orally injected into BALB/c mice for 30 days, and spleens were extracted for evaluation of immune-regulatory effects. Murine macrophage RAW264.7 cells were used for detailed molecular mechanism studies. Splenic natural killer (NK) cells were isolated using the magnetic-activated cell sorting (MACS) system, and the cytotoxic activity of isolated NK cells was measured using a lactate dehydrogenase (LDH) release assay. The splenic immune cell population was determined by flow-cytometry. NF-κB promoter activity was assessed by in vitro luciferase assay. Expression of inflammatory proteins and cytokines of the spleen and RAW264.7 cells were evaluated using western blotting and real-time PCR, respectively. RESULTS: The GBC enhanced cytotoxic activity of NK cells and the immune-regulation-related splenic cell population. Moreover, GBC promoted NF-κB promoter activity and stimulated the NF-κB signaling cascade. In spleen and RAW264.7 cells, expression of pro-inflammatory cytokines was increased upon GBC application, while expression of anti-inflammatory cytokines decreased. CONCLUSIONS: These results suggest that P. ginseng berry can stimulate innate immune responses and help maintain a balanced immune condition, mostly due to the action of its key ginsenoside Re, along with other protopanaxadiol- and protopanaxatriol-type ginsenosides. Such finding will provide a new insight into the field of well-being diet research as well as non-chemical immune modulator, by providing nature-derived and plant-based bioactive materials.
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Citocinas , Frutas , Ginsenósidos , Células Asesinas Naturales , Macrófagos , Ratones Endogámicos BALB C , FN-kappa B , Panax , Regulación hacia Arriba , Animales , Panax/química , Ginsenósidos/farmacología , FN-kappa B/metabolismo , Ratones , Células RAW 264.7 , Citocinas/metabolismo , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/metabolismo , Células Asesinas Naturales/inmunología , Regulación hacia Arriba/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Macrófagos/inmunología , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/citología , Bazo/inmunología , Extractos Vegetales/farmacología , MasculinoRESUMEN
Purpose: To investigate the preparation of inclusion complexes of diphenylcyclopropenone (DPCP)/ß-cyclodextrin (ß-CD) derivatives using a three-dimensional (3D) ball mill, and verify the inclusion behavior of the solid dispersion. Additionally, we aimed to investigate the effect of DPCP/ß-CDs complex formation on the spleens of male C57BL/6 mice in terms of anti-inflammatory effects. Methods: The inclusion complexes of DPCP with ß-CD and hydroxypropyl-ß-cyclodextrin (HPßCD) were prepared using a 3D ball mill. Powder X-ray diffraction (PXRD) and Fourier-transform infrared spectroscopy (FT-IR) were used to evaluate the solid-state properties. The solubility of the prepared DPCP/ß-CD and HPßCD complexes and the intermolecular interaction between DPCP and ß-CD derivatives in solution were assessed using 1H nuclear magnetic resonance (NMR). Furthermore, the anti-inflammatory effects of DPCPs in the prepared DPCP/CD complexes were investigated using spleens from male C57BL/6 mice, with measurement of interferon gamma (IFN-γ) secretion as an endpoint. Additionally, the protective effects of each drug on NIH-3T3 cells exposed to ultraviolet (UV) irradiation were examined. Results: Solid-state characterization confirmed the formation of inclusion complexes in the 3D ground mixture (3DGM) (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) complexes through PXRD and IR analysis. The solubility of 3DGM (DPCP/ß-CD = 1/1) and 3DGM (DPCP/HPßCD = 1/1) was 17.5 µg/mL and 58.4 µg/mL, respectively, indicating higher solubility than that of DPCP alone. NMR analysis of 3DGM samples suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. Regarding the anti-inflammatory activity of DPCP, 3DGM (DPCP/HPß-CD) showed anti-inflammatory effects at lower doses compared to 3DGM (DPCP/ß-CD) in terms of IFN-γ and NIH-3T3 cells injured by UV irradiation. Conclusion: We successfully formed inclusion complexes of DPCP/ß-CD and DPCP/HPßCD using the 3D ground mixture method. NMR analysis suggested that DPCP/ß-CD and DPCP/HPßCD form inclusion complexes at a molar ratio of 1/1 but with different inclusion modes. The anti-inflammatory activity of DPCP was more pronounced in 3DGM (DPCP/HPßCD) at lower doses compared to that in 3DGM (DPCP/ß-CD), indicating that the HPßCD derivatives were more effective in enhancing the anti-inflammatory properties of DPCP.
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Alopecia Areata , Antiinflamatorios , Ciclopropanos , Ratones Endogámicos C57BL , Solubilidad , beta-Ciclodextrinas , Animales , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacología , Masculino , Ratones , Ciclopropanos/farmacología , Ciclopropanos/química , Ciclopropanos/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Alopecia Areata/tratamiento farmacológico , Bazo/efectos de los fármacos , 2-Hidroxipropil-beta-Ciclodextrina/química , 2-Hidroxipropil-beta-Ciclodextrina/farmacologíaRESUMEN
While Resolvin D1 (RvD1) shows promise in resolving inflammation in experimental autoimmune encephalomyelitis (EAE), its pro-resolving roles on dendritic cells (DCs) remain unknown, and the chemical instability of RvD1 poses significant challenges to its drug development. This study aims to investigate whether 4-(2'-methoxyphenyl)-1-[2'-[N-(2â³-pyridinyl)-p-fluorobenzamido]ethyl]piperazine (p-MPPF), a novel chemically stable analogue of RvD1, can play a pro-resolving role in EAE, particularly on DCs, and if p-MPPF could serve as a potential substitute for RvD1. We showed that both RvD1 and p-MPPF mediated the resolution of inflammation in EAE, as evidenced by ameliorated EAE progression, attenuated pathological changes in the spinal cord, altered cytokine expression profile in serum, and reduced proportion of pro-inflammatory immune cells in the spleen. Utilizing DCs derived from both the spleen and bone marrow of EAE, our investigation showed that RvD1 and p-MPPF prevented DC maturation, decreased pro-inflammatory cytokine secretion, shifted DCs away from a pro-inflammatory phenotype, increased the phagocytosis capacity of DCs, and suppressed their ability to induce differentiation of CD4+ T cells into Th1 and Th17 subsets. For underlying intracellular mechanisms, we found that RvD1 and p-MPPF down-regulated the lactate dehydrogenase A signaling pathways. Comparisons between RvD1 and p-MPPF showed that they exerted overlapped pro-resolving effects to a large extent. This study demonstrates that both RvD1 and p-MPPF exert therapeutic effects on EAE by mediating inflammation resolution, which is closely associated with modulating DC immune function towards a tolerogenic phenotype. SPM mimetics may serve as a more promising therapeutic drug.
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Citocinas , Células Dendríticas , Ácidos Docosahexaenoicos , Encefalomielitis Autoinmune Experimental , Ratones Endogámicos C57BL , Encefalomielitis Autoinmune Experimental/tratamiento farmacológico , Encefalomielitis Autoinmune Experimental/inmunología , Animales , Células Dendríticas/efectos de los fármacos , Células Dendríticas/inmunología , Ácidos Docosahexaenoicos/uso terapéutico , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/química , Femenino , Ratones , Citocinas/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Médula Espinal/efectos de los fármacos , Médula Espinal/inmunología , Médula Espinal/patología , Médula Espinal/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/inmunología , Piperazinas/farmacología , Piperazinas/uso terapéutico , Piperazinas/química , Células Cultivadas , Bazo/efectos de los fármacos , Bazo/inmunología , Células Th17/inmunología , Células Th17/efectos de los fármacosRESUMEN
Side effects and low efficacy of current anti-toxoplasmosis therapeutics against encysted bradyzoites necessitate research into alternative safe therapeutic options. The safety, immunostimulatory, and antimicrobial properties of alginate nanoparticle formulation (Alg-NP) highlight its potential as an oral therapy against acute toxoplasmosis. In the current study, Alg-NP was formulated and characterized and then assessed for its anti-Toxoplasma effects using parasitological, ultrastructural, immunological, and histopathological studies. Treatment with Alg-NP significantly prolonged mice survival and reduced the parasite burden in both peritoneal fluid and tissue impression smears. In addition, it altered parasite viability and caused severe tachyzoite deformities as evidenced by ultrastructural studies. Alg-NP induced high levels of serum IFN-γ in infected mice with significant amelioration in histopathological changes in both hepatic and splenic tissue sections. In conclusion, Alg-NP could be considered a promising therapeutic agent against acute murine toxoplasmosis, and owing to its safety, it could potentially be enlisted for human use.
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Alginatos , Modelos Animales de Enfermedad , Nanopartículas , Toxoplasma , Toxoplasmosis Animal , Animales , Alginatos/química , Ratones , Administración Oral , Toxoplasma/efectos de los fármacos , Toxoplasmosis Animal/tratamiento farmacológico , Antiprotozoarios/farmacología , Antiprotozoarios/administración & dosificación , Antiprotozoarios/uso terapéutico , Ácido Glucurónico , Femenino , Ácidos Hexurónicos , Hígado/parasitología , Hígado/patología , Hígado/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/parasitología , Líquido Ascítico/parasitología , Carga de Parásitos , Análisis de Supervivencia , Interferón gamma/sangre , Ratones Endogámicos BALB C , Resultado del TratamientoRESUMEN
Perfluorohexane sulfonate (PFHxS) is a member of the per- and polyfluoroalkyls (PFAS) superfamily of molecules, characterized by their fluorinated carbon chains and use in a wide range of industrial applications. PFHxS and perfluorooctane sulfonate are able to accumulate in the environment and in humans with the approximated serum elimination half-life in the range of several years. More recently, some PFAS compounds have also been suggested as potential immunosuppressants. In this study, we analyze immune cell numbers in mice following 28-d repeated oral exposure to potassium PFHxS at 12, 120, 1,200, and 12,000 ng/kg/d, with resulting serum levels ranging up to â¼1,600 ng/ml, approximating ranges found in the general population and at higher levels in PFAS workers. The immunosuppressant cyclophosphamide was analyzed as a positive control. B cells, T cells, and granulocytes from the bone marrow, liver, spleen, lymph nodes, and thymus were evaluated. We found that at these exposures, there was no effect of PFHxS on major T or B cell populations, macrophages, dendritic cells, basophils, mast cells, eosinophils, neutrophils, or circulating Ab isotypes. By contrast, mice exposed to cyclophosphamide exhibited depletion of several granulocyte and T and B cell populations in the thymus, bone marrow, and spleen, as well as reductions in IgG1, IgG2b, IgG2c, IgG3, IgE, and IgM. These data indicate that exposures of up to 12,000 ng/kg of PFHxS for 28 d do not affect immune cell numbers in naive mice, which provides valuable information for assessing the risks and health influences of exposures to this compound.
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Fluorocarburos , Animales , Ratones , Linfocitos B/inmunología , Linfocitos B/efectos de los fármacos , Ácidos Sulfónicos , Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Femenino , Bazo/inmunología , Bazo/efectos de los fármacos , Bazo/citología , Timo/efectos de los fármacos , Timo/inmunología , Granulocitos/efectos de los fármacos , Granulocitos/inmunología , MasculinoRESUMEN
As a replacement for bisphenol A (BPA), bisphenol AF (BPAF) showed stronger maternal transfer and higher fetal accumulation than BPA. Therefore, concerns should be raised about the health risks of maternal exposure to BPAF during gestation on the offspring. In this study, SD rats were exposed to BPAF (0, 50, and 100 mg/kg/day) during gestation to investigate the bioaccumulation and adverse effects in liver, spleen, and kidney tissues of the offspring at weaning period. Bioaccumulation of BPAF in these tissues with concentrations ranging from 1.56 ng/mg (in spleen of males) to 55.44 ng/mg (in liver of females) led to adverse effects at different biological levels, including increased relative weights of spleen and kidneys, histopathological damage in liver, spleen, and kidney, organ functional damage in liver, spleen, and kidney, upregulated expression of genes related to lipid metabolism (in liver), oxidative stress response (in kidney), immunity and inflammatory (in spleen). Furthermore, dysregulated metabolomics was identified in spleen, with 217 differential metabolites screened and 9 KEGG pathways significantly enriched. This study provides a comprehensive insight into the systemic toxicities of prenatal exposure to BPAF in SD rats. Given the broad applications and widespread occurrence of BPAF, its safety should be re-considered.
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Compuestos de Bencidrilo , Riñón , Hígado , Fenoles , Efectos Tardíos de la Exposición Prenatal , Ratas Sprague-Dawley , Bazo , Animales , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Femenino , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Embarazo , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Masculino , Ratas , Exposición Materna/efectos adversos , FluorocarburosRESUMEN
PURPOSE: Type 1 diabetes (T1DM) is a chronic metabolic disorder that can cause damage to multiple organs including the spleen. Sole insulin therapy is not satisfactory. This study aims to investigate the effects and mechanisms of combined treatment with insulin and N-acetylcysteine (NAC) on spleen damage in T1DM canines, in order to identify drugs that may better assist patients in the management of diabetes and its complications. METHODS: The canine model of T1DM was established by intravenous injection of alloxan (ALX) and streptozotocin (STZ). The therapeutic effects of insulin and NAC were evaluated by clinical manifestations, spleen protein and mRNA expression. RESULTS: The results indicate that the combined treatment of insulin and NAC can alleviate hyperglycemia and hematologic abnormalities, improve splenic histopathological changes, prevent fibrous tissue proliferation, and glycogen deposition. In addition, we observed that this combination treatment significantly suppressed the protein expression of p-P65/P65 (17.6 %, P < 0.05), NLRP3 (46.8 %, P < 0.05), and p-P38/P38 (37.1 %, P < 0.05) induced by T1DM when compared to insulin treatment alone. Moreover, it also significantly decreased the mRNA expression of TLR4 (45.0 %, P < 0.01), TNF-α (30.3 %, P < 0.05), and NLRP3 (43.3 %, P < 0.05). CONCLUSIONS: This combination has the potential to mitigate splenic inflammatory injury in T1DM canines by suppressing the activation of MAPKs-NF-κB pathway and pyroptosis. These findings provide a reference for the treatment strategies of diabetes and its complications.
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Acetilcisteína , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Quimioterapia Combinada , Insulina , FN-kappa B , Piroptosis , Transducción de Señal , Bazo , Animales , Perros , Acetilcisteína/farmacología , Acetilcisteína/uso terapéutico , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/tratamiento farmacológico , FN-kappa B/metabolismo , Piroptosis/efectos de los fármacos , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Masculino , Bazo/efectos de los fármacos , Bazo/patología , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Enfermedades del Bazo/tratamiento farmacológico , Enfermedades del Bazo/etiología , Enfermedades del Bazo/complicaciones , Sistema de Señalización de MAP Quinasas/efectos de los fármacosRESUMEN
In recent years, the immunomodulatory efficacy of Dendrobium officinale leaf polysaccharide (DOLP) has attracted much attention, but its potential immunomodulatory mechanism remains unclear. Therefore, we investigated the molecular mechanism of DOLP to ameliorate cyclophosphamide-induced immunosuppressed mice based on transcriptome profiling technology. The results indicated that DOLP significantly mitigated damage to immune organs, regulated the expression levels of inflammatory factors and immunoglobulins, and restored the balance of gut microbiota. Furthermore, it modulated metabolic pathways associated with the immune system, including antigen processing and presentation, hematopoietic cell line development, and natural killer cell-mediated cytotoxicity. DOLP might promote host hematopoietic function to enhance immune cell proliferation and differentiation by up-regulating Cd19, Cr2 and Il7r but down-regulating Dntt. DOLP also up-regulated the expression of MHC-1 (Gm11127, H2-K1, H2-Q10, H2-Q6, and H2-Q7), thus promoting antigen recognition by NK cells to enhance the innate immunity and helping T cells to deliver antigen and secrete immune factors so that enhancing the adaptive immunity.
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Dendrobium , Microbioma Gastrointestinal , Hojas de la Planta , Polisacáridos , Bazo , Transcriptoma , Animales , Dendrobium/química , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Polisacáridos/farmacología , Hojas de la Planta/química , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismo , Transcriptoma/efectos de los fármacos , Perfilación de la Expresión Génica , Agentes Inmunomoduladores/farmacología , MasculinoRESUMEN
The widespread use of microplastics and their harmful effects on the environment have emerged as serious concerns. However, the effect of microplastics on the immune system of mammals, particularly their offspring, has received little attention. In this study, polystyrene microplastics (PS-MPs) were orally administered to male mice during lactation. Flow cytometry was used to assess the immune cells in the spleens of both adult male mice and their offspring. The results showed that mice exposed to PS-MPs exhibited an increase in spleen weight and an elevated number of B and regulatory T cells (Tregs), irrespective of dosage. Furthermore, the F1 male offspring of the PS-MPs-exposed group had enlarged spleens; an increased number of B cells, T helper cells (Th cells), and Tregs; and an elevated ratio of T helper cells 17 (Th17 cells) to Tregs and T helper cells 1 (Th1 cells) to T helper cells 2 (Th2 cells). These results suggested a pro-inflammatory state in the spleen. In contrast, in the F1 female offspring exposed to PS-MPs, the changes in splenic immune cells were less pronounced. In the F2 generation of mice with exposed to PS-MPs, minimal alterations were observed in spleen immune cells and morphology. In conclusion, our study demonstrated that exposure to real human doses of PS-MPs during lactation in male mice altered the immune status, which can be passed on to F1 offspring but is not inherited across generations.
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Lactancia , Microplásticos , Poliestirenos , Animales , Poliestirenos/toxicidad , Microplásticos/toxicidad , Ratones , Femenino , Masculino , Bazo/efectos de los fármacos , Linfocitos T Reguladores/efectos de los fármacos , Linfocitos T Reguladores/inmunologíaRESUMEN
Aging is associated with systemic, non-resolving inflammation and the accumulation of senescent cells. The resolution of inflammation (or inflammation-resolution) is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory leukotrienes (LTs). Aged mice (i.e. 2 years of age) exhibit a significant decrease in the SPM:LT ratio in specific organs including the spleen, which suggests that this organ may exhibit heightened inflammation and may be particularly amenable to SPM therapy. Previous studies have shown that resolvin D1 (RvD1) is decreased in spleens of aged mice compared with young controls. Therefore, we asked whether treatment of RvD1 in aged mice would impact markers of cellular senescence in splenic macrophages, and downstream effects on splenic fibrosis, a hallmark of splenic aging. We found that in aged mice, both zymosan-elicited and splenic macrophages showed an increase in mRNA expression of inflammatory and eicosanoid biosynthesis genes and a dysregulation of genes involved in the cell cycle. Injections with RvD1 reversed these changes. Importantly, RvD1 also decreased splenic fibrosis, a hallmark of splenic aging. Our findings suggest that RvD1 treatment may limit several features of aging, including senescence and fibrosis in spleens from aged mice. Summary Aging is associated with systemic, low grade, non-resolving inflammation. The resolution of inflammation is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory lipid mediators, like leukotrienes (LTs). A hallmark of aging is the accumulation of senescent cells that promote low grade inflammation by secreting pro-inflammatory cytokines and lipid mediators. Splenic macrophages contribute to systemic aging, and spleens of aged mice demonstrate decreased levels of the SPM called resolvin D1 (RvD1). Whether addition of RvD1 is protective in spleens of aged mice is unknown and is focus of this study. RvD1 treatment to aged mice led to decreased mRNA expression of markers of cellular senescence and inflammation in splenic macrophages compared with age-matched vehicle controls. Moreover, RvD1 decreased splenic fibrosis, which occurs due to persistent low-grade inflammation in aging. Promoting inflammation resolution with RvD1 thus limits macrophage senescence, pro-inflammatory signals and established splenic fibrosis in aging.
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Envejecimiento , Senescencia Celular , Ácidos Docosahexaenoicos , Fibrosis , Macrófagos , Bazo , Animales , Bazo/efectos de los fármacos , Bazo/metabolismo , Bazo/patología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Ratones , Ácidos Docosahexaenoicos/farmacología , Senescencia Celular/efectos de los fármacos , Envejecimiento/efectos de los fármacos , Ratones Endogámicos C57BL , Masculino , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patologíaRESUMEN
OBJECTIVE: To investigate the impact of the glucagon-like peptide-1 (GLP-1) receptor agonist Exendin-4 on the proportion of myeloid-derived suppressor cells (MDSCs) in male ApoE-/- mice, and investigate alterations in the concentrations of inflammatory factors in plasma and spleen tissues and assess their correlation with MDSCs. METHODS: Thirty male ApoE-/- mice were randomly divided into five groups (n = 6 per group): control group (CON), model group (MOD), Exendin-4 intervention group (MOD/Ex-4), Exendin-9-39 intervention group (MOD/Ex-9-39), and Exendin-4 + Exendin-9-39 combined intervention group (MOD/Ex-4 + Ex-9-39). After 4 weeks of drug intervention, changes in aortic plaque were observed using Oil Red O staining and H&E staining. Flow cytometry was employed to detect the content of myeloid-derived suppressor cells (MDSCs) in bone marrow and peripheral blood. ELISA was utilized to measure the concentrations of inflammatory factors in mouse peripheral blood plasma, while RT-qPCR was employed to quantify the expression levels of inflammatory factors in the spleen. Pearson correlation analysis was conducted to assess the relationship between MDSCs and inflammatory factors. RESULTS: Mice in the MOD group had significantly higher body weight compared to the CON group, with a statistically significant difference (P<0.05). Following Exendin-4 intervention, body weight was reduced compared to the MOD group (P<0.05). Additionally, Exendin-4 treatment led to a significant reduction in atherosclerotic plaque compared to the MOD group (P<0.001). After Exendin-4 intervention, the proportion of MDSCs in the bone marrow was higher than in the MOD group (P<0.001), and the proportion of MDSCs in peripheral blood was significantly higher than in the MOD group (P<0.05). Further investigation revealed that Exendin-4 could regulate lipid levels in mice, decreasing concentrations of TG (P<0.01), TC (P<0.0001), and LDL-C (P<0.0001), while increasing HDL-C concentrations (P<0.01). Moreover, after Exendin-4 treatment, the level of the cytokine IL-6 in peripheral plasma was significantly lower compared to the MOD group (P<0.0001), while levels of IL-10 and TGF-ß were significantly higher compared to the MOD group (P<0.0001). In the spleen, levels of the cytokines IL-10 (P<0.0001) and TGF-ß (P<0.001) were significantly increased compared to the MOD group. Pearson correlation analysis showed that the proportion of MDSCs in peripheral blood was positively correlated with IL-10 and TGF-ß levels in both the spleen and peripheral blood. Additionally, the proportion of MDSCs in the bone marrow was positively correlated with IL-10 and TGF-ß levels in the spleen and peripheral blood. CONCLUSION: Exendin-4 alleviates the severity of atherosclerosis. This process may be achieved by promoting the secretion of myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood of atherosclerotic ApoE-/- mice, regulating the ratio of inflammatory factors in the body, reducing mouse body weight, and lowering blood lipids.
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Apolipoproteínas E , Aterosclerosis , Citocinas , Exenatida , Células Supresoras de Origen Mieloide , Animales , Exenatida/farmacología , Exenatida/uso terapéutico , Células Supresoras de Origen Mieloide/inmunología , Células Supresoras de Origen Mieloide/efectos de los fármacos , Células Supresoras de Origen Mieloide/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/inmunología , Masculino , Citocinas/metabolismo , Citocinas/sangre , Ratones , Apolipoproteínas E/genética , Bazo/inmunología , Bazo/efectos de los fármacos , Placa Aterosclerótica/tratamiento farmacológico , Ratones Endogámicos C57BL , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Ratones Noqueados , Modelos Animales de Enfermedad , Mediadores de Inflamación/metabolismo , Fragmentos de PéptidosRESUMEN
In the context of the potential immunomodulatory properties of curcumin in counteracting the detrimental effects of concurrent exposure to Deoxynivalenol (DON) and Aflatoxin B1 (AFB1), a comprehensive 28-days trial was conducted utilizing 60 randomly allocated mice divided into four groups. Administration of curcumin at a dosage of 5 mg/kg body weight in conjunction with DON at 0.1 mg/kg and AFB1 at 0.01 mg/kg body weight was undertaken to assess its efficacy. Results indicated that curcumin intervention demonstrated mitigation of splenic structural damage, augmentation of serum immunoglobulin A (IgA) and immunoglobulin G (IgG) levels, elevation in T lymphocyte subset levels, and enhancement in the mRNA expression levels of pro-inflammatory cytokines TNF-α, IFN-γ, IL-2, and IL-6. Furthermore, curcumin exhibited a suppressive effect on apoptosis in mice, as evidenced by decreased activity of caspase-3 and caspase-9, reduced expression levels of pro-apoptotic markers Bax and Cytochrome-c (Cyt-c) at both the protein and mRNA levels, and the maintenance of a balanced expression ratio of mitochondrial apoptotic regulators Bax and Bcl-2. Collectively, these findings offer novel insights into the therapeutic promise of curcumin in mitigating immunosuppression and apoptotic events triggered by mycotoxin co-exposure.
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Aflatoxina B1 , Apoptosis , Curcumina , Citocinas , Bazo , Tricotecenos , Animales , Tricotecenos/toxicidad , Curcumina/farmacología , Aflatoxina B1/toxicidad , Apoptosis/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunología , Ratones , Citocinas/metabolismo , Citocinas/genética , MasculinoRESUMEN
INTRODUCTION: Cyclophosphamide (CP), which is a commonly used chemotherapy drug, can lead to a range of side effects such as immunosuppression, bone marrow suppression, leukopenia, and oxidative stress. This study aims to explore the effects of Auraptene (AUR), which has immunomodulatory and antioxidant properties, on immune function in mice that are experiencing suppression induced by CP. MATERIALS AND METHODS: The experiment involved 60 male BALB/c mice that underwent a 10-day treatment. On days 1, 3, and 9, CP was given at 80 mg/kg IP doses to induce immunosuppression. The mice were divided into five groups: Control group, CP group, CP + liposomal AUR 0.2 mg/kg (AUR 0.2), CP + liposomal AUR 0.25 mg/kg (AUR 0.25), and liposomal vehicle group. Various parameters were measured, including mouse weight, immune organ weight index (spleen and thymus), spleen and thymus histopathology, levels of inflammatory cytokines (IL2, IL10, IL4, IFN-γ), TH1/TH2 balance ratio, IgG and IgM immunoglobulin levels, white blood cell count, platelets, neutrophils, lymphocytes, and oxidative activity measured by MDA, SOD, and Total Antioxidant. RESULTS: In the group treated with CP, the mice showed a significant decrease in weight compared to the control group. In contrast, the group treated with AUR maintained their weight and did not show a significant difference from the control group. AUR 0.25 reduced the damage to the spleen and thymus caused by CP. Additionally, AUR 0.25 demonstrated a significant decrease in IL4 and IL10 levels compared to the CP group (p = 0.04), approaching the levels of the control group. Furthermore, IL2 and IFN-γ levels in the AUR 0.25 group significantly increased (p = 0.04) compared to the CP group, reaching levels similar to the control group. AUR also increased serum IgM and IgG levels two to three times compared to the CP group, approaching the levels of the control group. MDA levels in the AUR 0.25 group decreased to normal and control levels. AUR 0.25 also showed increased SOD and Total Antioxidant levels. Additionally, white blood cells, platelets, neutrophils, and lymphocytes in the AUR group significantly increased compared to the CP group, reaching normal levels similar to the control group. The TH1/TH2 ratio in the AUR group exhibited a significant increase of two and a half times (p = 0.002) compared to the CP group. CONCLUSION: These results show that AUR protects against the side effects of CP by increasing the function of the humoral and cellular immune system through the balance of TH1/TH2 and increasing the level of immunoglobulins, as well as increasing the antioxidant activity and the protective role of cytotoxicity.
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Antioxidantes , Cumarinas , Ciclofosfamida , Citocinas , Liposomas , Ratones Endogámicos BALB C , Animales , Ciclofosfamida/farmacología , Antioxidantes/farmacología , Masculino , Ratones , Citocinas/metabolismo , Cumarinas/farmacología , Estrés Oxidativo/efectos de los fármacos , Bazo/efectos de los fármacos , Factores Inmunológicos/farmacología , Timo/efectos de los fármacos , Terapia de Inmunosupresión , Inmunosupresores/farmacologíaRESUMEN
Methods: A total of 392 patients with seasonal allergic rhinitis were selected from the population of the epidemiological investigation project of allergic diseases in Hohhot, Inner Mongolia. The project was led by Department of Allergy, Beijing Shijitan Hospital, Capital Medical University, and assisted by Hohhot First Hospital from April to May 2023. The patients were randomly divided into a spleen aminopeptide group (296 cases) and control group (96 cases) at a ratio of 3â¶1, and the enrollment period was from June 1 to 14, 2023. The treatment group was treated with spleen aminopeptide oral solution for 12 weeks starting from 4-6 weeks (±7 days) before the pollen dispersal period, while the control group was treated with a simulated agent of spleen aminopeptide oral solution. Both the treatment group and the control group were treated with oral antihistamines and/or nasal glucocorticoids as needed during the pollen dispersal period. Evaluate the therapeutic effect by comparing the symptom scores, drug scores and quality of life scores of the two groups, and detect the expression levels of cytokines in serum. Symptom scores, quality of life scores, drug scores and laboratory results were compared by independent sample t test/Kruskal-Wallis test and χ2 test/Fisher's exact test. Results: Compared with the control group, spleen aminopeptide treatment for 12 weeks significantly improved symptoms of nasal congestion [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=6.308, P<0.05], nasal itching [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=4.966, P<0.05], sneezing [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=5.245, P<0.05], runny nose [M(Q1,Q3):2(1, 2) vs. 2(1, 3), H=5.41, P<0.05] and tearing [M(Q1,Q3):1(0, 2) vs. 1(0, 3), H=4.664, P<0.05]. At 12 weeks of treatment, the scores of nasal symptoms and ocular symptoms in control group and experimental group were significantly increased compared with baseline (P<0.05). In experimental group, nasal congestion [M(Q1,Q3):1(0, 1) vs. 1(0, 2), H=4.042, P<0.05], eye itching/foreign body sensation/redness symptom scores [M(Q1,Q3):1(0, 2) vs. 1(0, 2), H=5.302, P<0.05] and total scores [M(Q1,Q3):4(-1, 9) vs. 5(0, 12.5), H=3.958, P<0.05] were significantly increased. The antihistamine drug score of the splenic peptide treatment group at 6 weeks were lower than that of the control group (H=4.232, P<0.05). After 12 weeks of treatment, the antihistamine drug score [M(Q1,Q3):10(0, 24) vs. 19(2, 36.5), H=6.67, P<0.05] and the total drug score [M(Q1,Q3):28.5(5, 77.5) vs. 46(6, 155.5), H=3.995, P<0.05] were significantly lower than those of the control group. The serum IL-17A levels of the treatment group were significantly lower than those of the control group after 6 weeks (0.7±1.77 vs. 0.85±1.67,H=10.08, P<0.05) and 12 weeks (0.81±1.63 vs. 0.94±1.73,H=5.196, P<0.05) of splenic aminopeptide treatment. Conclusions: Early treatment with spleen aminopeptide oral solution can significantly improve nasal and ocular symptoms of patients with seasonal allergic rhinitis, reduce the use of drugs during the onset period, and improve the quality of life. It may exert an immunomodulatory effect by reducing the expression level of IL-17A in the serum of patients. Objects: To conduct a study on the prevention and treatment of seasonal allergic rhinitis in Hohhot, Inner Mongolia, evaluate the preventive and therapeutic effects of spleen aminopeptide oral solution on seasonal allergic rhinitis, and explore its related mechanisms.
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Rinitis Alérgica Estacional , Humanos , Rinitis Alérgica Estacional/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Adulto Joven , Bazo/efectos de los fármacosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Shenlin Baizhu Decoction (SLBZD), which comes from 'Taiping Huimin Heji Ju Fang', belongs to a classical prescription for treating spleen deficiency and dampness obstruction (SQDDS)-type ulcerative colitis (UC) in traditional Chinese medicine. However, the mechanism of SLBZD in treating UC with SQDDS remains unclear. AIM OF THE STUDY: This study aims to investigate the mechanism of SLBZD against SQDDS-type UC of based on the "gut microbiota and metabolism - bone marrow" axis to induce endogenous bone marrow mesenchymal stem cells (BMSCs) homing. MATERIALS AND METHODS: Ultra-performance liquid chromatography-mass spectrometry was used to analysis of SLBZD qualitatively. The efficacy of SLBZD in SQDDS-type UC was evaluated based on the following indicators: the body weight, colon length, disease activity index (DAI) score, Haemotoxylin and Eosin (H&E) pathological sections, and intestinal permeability proteins (occluding and ZO-1). 16S rRNA gene sequencing and non-target metabolomics were performed to identify gut microbiota changes and its metabolites in feces, respectively. BMSCs in each group was collected, cultured, and analyzed. Optimal passaged BMSCs were injected by tail vein into UC rats of SQDDS types. BMSCs homing to the colonic mucosal tissue was observed by immunofluorescent. Finally, the repairing effect of BMSCs homing to the colonic mucosal tissue after SLBZD treatment was analyzed by transmission electron microscopy, qRT-PCR, and immunohistochemistry. RESULTS: SLBZD effectively improved the colonic length and the body weight, reduced DAI and H&E scores, and increased the expression of the intestinal permeability proteins, including occluding and ZO-1, to treat SQDDS-type UC. After SLBZD treatment, the α-diversity and ß-diversity of the gut microbiota were improved. The differential microbiota was screened as Aeromonadaceae, Lactobacillaceae, and Clostridiaceae at the family level, and Aeromonas, Lactobacillus, Clostridium_sensu_stricto_1 at the genus level. Meanwhile, the main metabolic pathway was the galactose metabolism pathway. SLBZD treatment timely corrected the aberrant levels of ß-galactose in peripheral blood and bone marrow, senescence-associate-ß-galactosidase in BMSCs, and galactose kinase-2, galactose mutase, and galactosidase beta-1 in peripheral blood to further elevate the expression levels of senescence-associated (SA) proteins (p16, p53, p21, and p27) in BMSCs. The Spearman's correlation analysis demonstrated the relationship between microbiota and metabolism, and the relationship between the galactose metabolism pathway and SA proteins. After BMSCs in each group injection via the tail vein, the pharmacodynamic effects were consistent with those of SLBZD in SQDDS-type UC rats. Furthermore, BMSCs have been homing to colonic mucosal tissue. BMSCs from the SLBZD treatment group had stronger restorative effects on intestinal permeability function due to increasing protein and mRNA expressions of occludin and ZO-1, and decreasing the proteins and mRNA expressions of SDF-1 and CXCR4 in colon. CONCLUSIONS: SLBZD alleviated the damaged structure of gut microbiota and regulated their metabolism, specifically the galactose metabolism, to treat UC of SDDOS types. SLBZD treatment promotes endogenous BMSCs homing to colonic mucosal tissue to repaire the intestinal permeability. The current exploration revealed an underlying mechanism wherein SLBZD activates endogenous BMSCs by targeting 'the gut microbiota and its metabolism-bone marrow' axis and repairs colonic mucosal damage to treat SDDOS-type UC.
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Colitis Ulcerosa , Medicamentos Herbarios Chinos , Galactosa , Microbioma Gastrointestinal , Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/microbiología , Medicamentos Herbarios Chinos/farmacología , Masculino , Ratas , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Proteína de la Zonula Occludens-1/metabolismo , Colon/efectos de los fármacos , Colon/metabolismo , Colon/microbiología , Colon/patología , Ocludina/metabolismo , Médula Ósea/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/metabolismo , Modelos Animales de EnfermedadRESUMEN
This study compared the effects of polyethylene glycol (PEG) shielding and mannose-conjugated ligands density on lipid nanoparticles (LNPs) for intracellular uptake to macrophages in vitro and accumulation in spleens in vivo. Fabricated phosphatidyl serine-incorporated LNPs (sLNPs) was physically decorated with mannose-conjugated DSPE-PEG (DPM) at different DPM/LNP molar ratios achieving the DPM density from 0 to 0.6 PEGs/nm2. We demonstrated that low PEG shielding sLNPs with mannose ligands (sLNP-DPMs) displayed superior uptake to macrophages (RAW 264.7 cells) compared with high PEG shielding sLNP-DPMs in vitro. However, high PEG shielding sLNP-DPMs showed significant spleen accumulation compared with low PEG shielding sLNP-DPMs in vivo after intravenous injection. In particular, high PEG shielding sLNPs coated with DSPE-methoxyPEG (DP) and DPM mixture at DP/DPM molar ratios of 5/5 exhibited greater accumulation in red pulp of spleens than naked sLNPs by 2.7-folds in vivo. These results suggested that the optimal PEG shielding and mannose densities per a particle might be different between in vitro cellular uptake to macrophages and in vivo spleen accumulation after systemic administration. Taken together, precision-tailored LNP-surface modifications achieved through optimization of PEG shielding and mannose density can greatly enhance accumulation of LNPs in red pulp of spleens, which could be applied for the delivery of nucleic acid-based drugs and vaccines to spleens in vivo.
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Macrófagos , Manosa , Nanopartículas , Polietilenglicoles , Bazo , Animales , Manosa/química , Polietilenglicoles/química , Ratones , Bazo/metabolismo , Bazo/efectos de los fármacos , Células RAW 264.7 , Nanopartículas/química , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Lípidos/química , Masculino , Portadores de Fármacos/química , Fosfatidiletanolaminas/química , Distribución Tisular , LiposomasRESUMEN
Host-directed therapy (HDT) with vitamin D in tuberculosis (TB) is beneficial only if the subject is deficient in vitamin D. We investigated pulmonary delivery of 1,25-dihydroxy vitamin D3 (calcitriol) in mice infected with Mycobacterium tuberculosis (Mtb). We made two kinds of dry powder inhalations (DPI)- soluble particles or poly(lactide) (PLA) particles. We compared treatment outcomes when infected mice were dosed with a DPI alone or as an adjunct to standard oral anti-TB therapy (ATT). Mice infected on Day 0 were treated between Days 28-56 and followed up on Days 57, 71, and 85. Neither DPI significantly reduced Mtb colony forming units (CFU) in the lungs. Combining DPI with ATT did not significantly augment bactericidal activity in the lungs, but CFU were 2-log lower in the spleen. CFU showed a rising trend on stopping treatment, sharper in groups that did not receive calcitriol. Lung morphology and histology improved markedly in animals that received PLA DPI; with or without concomitant ATT. Groups receiving soluble DPI had high mortality. DPI elicited cathelicidin, interleukin (IL)-1 and induced autophagy on days 57, 71, and 85. Macrophage-targeted calcitriol is therefore bacteriostatic, evokes innate microbicidal mechanisms, and mitigates pathology arising from the host response to Mtb.
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Antituberculosos , Calcitriol , Modelos Animales de Enfermedad , Pulmón , Macrófagos , Mycobacterium tuberculosis , Animales , Calcitriol/farmacología , Mycobacterium tuberculosis/efectos de los fármacos , Pulmón/microbiología , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/inmunología , Pulmón/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Macrófagos/inmunología , Antituberculosos/farmacología , Antituberculosos/uso terapéutico , Femenino , Administración por Inhalación , Catelicidinas , Tuberculosis Pulmonar/tratamiento farmacológico , Tuberculosis Pulmonar/microbiología , Tuberculosis Pulmonar/patología , Tuberculosis Pulmonar/inmunología , Poliésteres , Interacciones Huésped-Patógeno , Factores de Tiempo , Ratones Endogámicos C57BL , Bazo/efectos de los fármacos , Bazo/microbiología , Bazo/patología , Bazo/inmunología , Quimioterapia Combinada , Péptidos Catiónicos Antimicrobianos/farmacología , RatonesRESUMEN
High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.
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Ciclofosfamida , Citocinas , Microbioma Gastrointestinal , FN-kappa B , Polisacáridos , Animales , Polisacáridos/farmacología , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Células RAW 264.7 , Masculino , FN-kappa B/metabolismo , Ratas , Citocinas/metabolismo , Terapia de Inmunosupresión , Undaria/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Óxido Nítrico/metabolismo , Ratas Sprague-Dawley , Peso Molecular , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rheum palmatum (RP) is a widely used traditional herb, which possesses antioxidant properties, inhibits ROS production and reduces fever. AIM OF THE STUDY: The aim of this study was to examine the antioxidative properties of the water extract of RP on oxidative-stressed mice. MATERIALS & METHODS: Forty mice were administered with DL-homocysteine (DL-Hcy) to induce oxidative stress and were divided into four groups: 1) CK: NaCl and water; 2) DL-Hcy: DL-Hcy and water; 3) DL-Hcy+50RP: DL-Hcy with 50 mg kg-1 body weight (BW) d-1 RP; and 4) DL-Hcy+150RP: DL-Hcy with 150 mg kg-1 BW d-1 RP. Rhein (0.3 mg g-1 dry matter) was the main active ingredient in RP. RESULTS: When compared with Dl-Hcy mice, the mice with supplementary RP mitigated oxidative stress by reducing the liver concentrations of superoxide dismutase (SOD) by 27% and glutathione peroxidase (GSH-Px) by 32%, and the reactive oxygen species (ROS) in the kidney and spleen. These responses were more pronounced in DL-Hcy+150RP than DL-Hcy+50RP mice. RP also exhibited therapeutic effects on liver steatosis, chronic kidney nephritis and intestinal villus width shortening caused by oxidative stress, and concomitantly decreased the serum glucose concentration (RP vs. DL-HCY, 2.3 vs. 4.1 mmol L-1). CONCLUSION: It was concluded that RP possesses antioxidant and therapeutic properties that can mitigate lesions on organs and prevent diabetes in oxidative-stressed mice. This study highlights the potential of RP as a medicinal supplement for animals in the future.