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1.
Food Funct ; 15(9): 4818-4831, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38606579

RESUMEN

Gamma-aminobutyric acid (GABA) is the predominant amino acid in litchi pulp, known for its neuroregulatory effects and anti-inflammatory properties. Although previous research has highlighted the pro-inflammatory characteristics of litchi thaumatin-like protein (LcTLP), interplay between GABA and LcTLP in relation to inflammation remains unclear. This study aims to explore the hepatoprotective effects of the litchi pulp-derived GABA extract (LGE) against LcTLP-induced liver inflammation in mice and LO2 cells. In vivo experiments demonstrated that LGE significantly reduced the levels of aspartate transaminase and alanine transaminase, and protected the liver against infiltration of CD4+ and CD8+ T cells and histological injury induced by LcTLP. Pro-inflammatory cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α were also diminished by LGE. The LGE appeared to modulate the mitogen-activated protein kinase (MAPK) signaling pathway to exert its anti-inflammatory effects, as evidenced by a reduction of 47%, 35%, and 31% in phosphorylated p38, JNK, and ERK expressions, respectively, in the liver of the high-dose LGE group. Additionally, LGE effectively improved the translocation of gut microbiota by modulating its microbiological composition and abundance. In vitro studies have shown that LGE effectively counteracts the increase in reactive oxygen species, calcium ions, and pro-inflammatory cytokines induced by LcTLP. These findings may offer new perspectives on the health benefits and safety of litchi consumption.


Asunto(s)
Litchi , Extractos Vegetales , Ácido gamma-Aminobutírico , Animales , Ratones , Litchi/química , Extractos Vegetales/farmacología , Masculino , Ácido gamma-Aminobutírico/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Citocinas/metabolismo , Antiinflamatorios/farmacología , Proteínas de Plantas/farmacología , Inflamación/tratamiento farmacológico , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Ratones Endogámicos C57BL , Frutas/química , Aspartato Aminotransferasas
3.
Environ Res ; 252(Pt 1): 118826, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38579999

RESUMEN

Nitration of allergenic proteins caused by atmospheric pollutants O3 and NO2 may enhance their allergenic potential. In the study, the influence of nitration was investigated on the allergenicity of Der p 2, which is a main allergen from house dust mites and plays an important role in allergenic rhinitis and asthma. The results reveal that nitrated Der p 2 enhanced the IgE-binding capacity, upregulated the mRNA expression and release of IL-6 and IL-8 from bronchial epithelial cells, and induced higher levels of specific-IgE, TH2 cytokines and white blood cells in mice. Besides, nitrated Der p 2 caused more severe oxidative stress and allergenic symptoms in mice. It is concluded that nitration enhanced the allergenicity of Der p 2 through not only directly inducing higher amount of specific-IgE and stronger responses of TH2 cytokines, but also indirectly aggravating allergic symptoms by oxidative stress and adjuvant-like activation airway epithelial cells. The study suggests that the contribution of nitration to the promotion in allergenicity should not be ignored when precisely assessing the risk of house dust mite allergens in real environment.


Asunto(s)
Antígenos Dermatofagoides , Proteínas de Artrópodos , Animales , Antígenos Dermatofagoides/inmunología , Proteínas de Artrópodos/inmunología , Proteínas de Artrópodos/química , Ratones , Tirosina , Cisteína Endopeptidasas/inmunología , Ratones Endogámicos BALB C , Humanos , Inmunoglobulina E/inmunología , Alérgenos/inmunología , Femenino , Citocinas/inmunología , Citocinas/metabolismo , Estrés Oxidativo
4.
Trop Anim Health Prod ; 56(4): 142, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662082

RESUMEN

Incorporating Curcumin into animal diets holds significant promise for enhancing both animal health and productivity, with demonstrated positive impacts on antioxidant activity, anti-microbial responses. Therefore, this study aimed to determine whether adding Curcumin to the diet of dairy calves would influence ruminal fermentation, hematologic, immunological, oxidative, and metabolism variables. Fourteen Jersey calves were divided into a control group (GCON) and a treatment group (GTRA). The animals in the GTRA received a diet containing 65.1 mg/kg of dry matter (DM) Curcumin (74% purity) for an experimental period of 90 days. Blood samples were collected on days 0, 15, 45, and 90. Serum levels of total protein and globulins were higher in the GTRA group (P < 0.05) than the GCON group. In the GTRA group, there was a reduction in pro-inflammatory cytokines (IL-1ß and IL-6) (P < 0.05) and an increase in IL-10 (which acts on anti-inflammatory responses) (P < 0.05) when compared to the GCON. There was a significantly higher (P < 0.05) concentration of immunoglobulin A (IgA) in the serum of the GTRA than the GCON. A Treatment × Day interaction was observed for haptoglobin levels, which were higher on day 90 in animals that consumed Curcumin than the GCON (P < 0.05). The catalase and superoxide dismutase activities were significantly higher (P < 0.05) in GTRA, reducing lipid peroxidation when compared to the GCONT. Hematologic variables did not differ significantly between groups. Among the metabolic variables, only urea was higher in the GTRA group when compared to the GCON. Body weight and feed efficiency did not differ between groups (meaning the percentage of apparent digestibility of dry matter, crude protein, and acid detergent fiber (ADF) and neutral detergent fiber (NDF). There was a tendency (P = 0.09) for treatment effect and a treatment x day interaction (P = 0.05) for levels of short-chain fatty acids in rumen fluid, being lower in animals that consumed curcumin. There was a treatment vs. day interaction (P < 0.05) for the concentration of acetate in the rumen fluid (i.e., on day 45, had a reduction in acetate; on day 90, values were higher in the GTRA group when compared to the GCON). We conclude that there was no evidence in the results from this preliminary trial that Curcumin in the diet of dairy calves interfered with feed digestibility. Curcumin may have potential antioxidant, anti-inflammatory, and immune effects that may be desirable for the production system of dairy calves.


Asunto(s)
Alimentación Animal , Curcumina , Dieta , Suplementos Dietéticos , Fermentación , Rumen , Animales , Curcumina/administración & dosificación , Curcumina/farmacología , Rumen/metabolismo , Rumen/efectos de los fármacos , Bovinos , Alimentación Animal/análisis , Dieta/veterinaria , Suplementos Dietéticos/análisis , Estrés Oxidativo/efectos de los fármacos , Masculino , Citocinas/metabolismo , Destete , Antioxidantes/metabolismo , Fenómenos Fisiológicos Nutricionales de los Animales/efectos de los fármacos , Femenino
5.
Food Funct ; 15(8): 4109-4121, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38597225

RESUMEN

While there have been advancements in understanding the direct and indirect impact of riboflavin (B2) on intestinal inflammation, the precise mechanisms are still unknown. This study focuses on evaluating the effects of riboflavin (B2) supplementation on a colitis mouse model induced with 3% dextran sodium sulphate (DSS). We administered three different doses of oral B2 (VB2L, VB2M, and VB2H) and assessed its impact on various physiological and biochemical parameters associated with colitis. Mice given any of the three doses exhibited relative improvement in the symptoms and intestinal damage. This was evidenced by the inhibition of the pro-inflammatory cytokines TNF-α, IL-1ß, and CALP, along with an increase in the anti-inflammatory cytokine IL-10. B2 supplementation also led to a restoration of oxidative homeostasis, as indicated by a decrease in myeloperoxidase (MPO) and malondialdehyde (MDA) levels and an increase in reduced glutathione (GSH) and catalase (CAT) activities. B2 intervention showed positive effects on intestinal barrier function, confirmed by increased expression of tight junction proteins (occludin and ZO-1). B2 was linked to an elevated relative abundance of Actinobacteriota, Desulfobacterota, and Verrucomicrobiota. Notably, Verrucomicrobiota showed a significant increase in the VB2H group, reaching 15.03% relative abundance. Akkermansia exhibited a negative correlation with colitis and might be linked to anti-inflammatory function. Additionally, a remarkable increase in n-butyric acid, i-butyric acid, and i-valeric acid was reported in the VB2H group. The ameliorating role of B2 in gut inflammation can be attributed to immune system modulation as well as alterations in the gut microbiota composition, along with elevated levels of fecal SCFAs.


Asunto(s)
Colitis , Sulfato de Dextran , Microbioma Gastrointestinal , Homeostasis , Ratones Endogámicos C57BL , Riboflavina , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Colitis/tratamiento farmacológico , Colitis/inducido químicamente , Sulfato de Dextran/efectos adversos , Riboflavina/farmacología , Homeostasis/efectos de los fármacos , Masculino , Modelos Animales de Enfermedad , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo
6.
Zhongguo Zhong Yao Za Zhi ; 49(3): 779-788, 2024 Feb.
Artículo en Chino | MEDLINE | ID: mdl-38621882

RESUMEN

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.


Asunto(s)
Cinnamomum camphora , Aceites Volátiles , Femenino , Ratones , Animales , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa , Interleucina-6 , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Depresión/tratamiento farmacológico , Aceites Volátiles/farmacología , Lipopolisacáridos/farmacología
7.
Int Immunopharmacol ; 132: 112027, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38603860

RESUMEN

BACKGROUND AND PURPOSE: Osteoporosis (OP) is a frequent clinical problem for the elderly. Traditional Chinese Medicine (TCM) has achieved beneficial results in the treatment of OP. Ziyuglycoside II (ZGS II) is a major active compound of Sanguisorba officinalis L. that has shown anti-inflammation and antioxidation properties, but little information concerning its anti-OP potential is available. Our research aims to investigate the mechanism of ZGS II in ameliorating bone loss by inflammatory responses and regulation of gut microbiota and short chain fatty acids (SCFAs) in ovariectomized (OVX) mice. METHODS: We predicted the mode of ZGS II action on OP through network pharmacology and molecular docking, and an OVX mouse model was employed to validate its anti-OP efficacy. Then we analyzed its impact on bone microstructure, the levels of inflammatory cytokines and pain mediators in serum, inflammation in colon, intestinal barrier, gut microbiota composition and SCFAs in feces. RESULTS: Network pharmacology identified 55 intersecting targets of ZGS II related to OP. Of these, we predicted IGF1 may be the core target, which was successfully docked with ZGS II and showed excellent binding ability. Our in vivo results showed that ZGS II alleviated bone loss in OVX mice, attenuated systemic inflammation, enhanced intestinal barrier, reduced the pain threshold, modulated the abundance of gut microbiota involving norank_f__Muribaculaceae and Dubosiella, and increased the content of acetic acid and propanoic acid in SCFAs. CONCLUSIONS: Our data indicated that ZGS II attenuated bone loss in OVX mice by relieving inflammation and regulating gut microbiota and SCFAs.


Asunto(s)
Ácidos Grasos Volátiles , Microbioma Gastrointestinal , Simulación del Acoplamiento Molecular , Osteoporosis , Ovariectomía , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Ácidos Grasos Volátiles/metabolismo , Femenino , Ratones , Osteoporosis/tratamiento farmacológico , Osteoporosis/inmunología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Saponinas/farmacología , Saponinas/uso terapéutico , Humanos , Citocinas/metabolismo , Farmacología en Red , Inflamación/tratamiento farmacológico
8.
Phytomedicine ; 128: 155394, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38569294

RESUMEN

BACKGROUND: Current therapeutic agents for AD have limited efficacy and often induce undesirable side effects. Gegen Qinlian tablets (GGQLT) are a well-known clearingheat formula used in clinical treatment of inflammatory diseases. Based on traditional Chinese medicine (TCM) theory, the strategy of clearing-heat is then compatible with the treatment of AD. However, it remains unknown whether GGQLT can exert neuroprotective effects and alleviate neuroinflammation in AD. PURPOSE: This study aimed to evaluate the anti-AD effects of GGQLT and to decipher its intricate mechanism using integrative analyses of network pharmacology, transcriptomic RNA sequencing, and gut microbiota. METHODS: The ingredients of GGQLT were analyzed using HPLC-ESI-Q/TOF-MS. The AD model was established by bilateral injection of Aß1-42 into the intracerebroventricular space of rats. The Morris water maze was used to evaluate the cognitive function of the AD rats. The long-term toxicity of GGQLT in rats was assessed by monitoring their body weights and pathological alterations in the liver and kidney. Reactive astrocytes and microglia were assessed by immunohistochemistry by labeling GFAP and Iba-1. The levels of inflammatory cytokines in the hippocampus were evaluated using ELISA kits, RT-PCR, and Western blot, respectively. The potential anti-AD mechanism was predicted by analyses of RNA-sequencing and network pharmacology. Western blot and immunohistochemistry were utilized to detect the phosphorylation levels of IκBα, NF-κB p65, p38, ERK and JNK. The richness and composition of gut bacterial and fungal microflora were investigated via 16S rRNA and ITS sequencing. RESULTS: Typical ingredients of GGQLT were identified using HPLC-ESI-Q/TOF-MS. GGQLT significantly improved the cognitive function of AD rats by suppressing the activation of microglia and astrocytes, improving glial morphology, and reducing the neuroinflammatory reactions in the hippocampus. RNA-sequencing, network and experimental pharmacological studies demonstrated that GGQLT inhibited the activation of NF-κB/MAPK signaling pathways in the hippocampus. GGQLT could also restore abnormal gut bacterial and fungal homeostasis and no longer-term toxicity of GGQLT was observed. CONCLUSIONS: Our findings, for the first time, demonstrate GGQLT exhibit anti-AD effects and is worthy of further exploration and development.


Asunto(s)
Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Enfermedad de Alzheimer/tratamiento farmacológico , Masculino , Ratas , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Homeostasis/efectos de los fármacos , Comprimidos , Péptidos beta-Amiloides/metabolismo , Neuroglía/efectos de los fármacos , Farmacología en Red , Progresión de la Enfermedad , Citocinas/metabolismo
9.
Clin Respir J ; 18(4): e13742, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38664220

RESUMEN

BACKGROUND: Allergic asthma is an important respiratory system problem characterized by airway inflammation, breathlessness, and bronchoconstriction. Allergic asthma and its outcomes are triggered by type 2 allergic immune responses. Tectorigenin is a methoxy-isoflavone with anti-inflammatory effects. In this study, we investigated the effects of tectorigenin on the pathophysiology of allergic asthma in an animal model. METHODS: Asthmatic mice were treated with tectorigenin. Then airway hyperresponsiveness (AHR), eosinophil percentage, levels of interleukin (IL)-33, IL-25, IL-13, IL-5, IL-4, total and ovalbumin (OVA)-specific immunoglobulin (Ig)E, and lung histopathology were evaluated. RESULT: Tectorigenin significantly (P 〈 0.05) reduced eosinophil infiltration (41 ± 7%) in the broncho-alveolar lavage fluid (BALF), serum IL-5 level (41 ± 5, pg/mL), and bronchial and vascular inflammation (scores of 1.3 ± 0.2 and 1.1 ± 0.3, respectively) but had no significant effects on AHR, serum levels of IL-33, -25, -13, and -4 (403 ± 24, 56 ± 7, 154 ± 11, and 89 ± 6 pg/mL, respectively), total and OVA-specific IgE (2684 ± 265 and 264 ± 19 ng/mL, respectively), goblet cell hyperplasia, and mucus production. CONCLUSION: Tectorigenin could control inflammation and the secretion of inflammatory mediators of asthma, so it can be regarded as a potential antiasthma treatment with the ability to control eosinophilia-related problems.


Asunto(s)
Antiinflamatorios , Antioxidantes , Asma , Modelos Animales de Enfermedad , Isoflavonas , Ratones Endogámicos BALB C , Ovalbúmina , Animales , Asma/tratamiento farmacológico , Asma/inducido químicamente , Asma/metabolismo , Asma/inmunología , Asma/patología , Ratones , Ovalbúmina/toxicidad , Ovalbúmina/efectos adversos , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Antioxidantes/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Inmunoglobulina E/sangre , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/inmunología , Femenino , Pulmón/patología , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/inmunología , Citocinas/metabolismo
10.
Mar Drugs ; 22(4)2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38667792

RESUMEN

Ulcerative colitis (UC) is a kind of inflammatory bowel condition characterized by inflammation within the mucous membrane, rectal bleeding, diarrhea, and pain experienced in the abdominal region. Existing medications for UC have limited treatment efficacy and primarily focus on symptom relief. Limonium bicolor (LB), an aquatic traditional Chinese medicine (TCM), exerts multi-targeted therapeutic effects with few side effects and is used to treat anemia and hemostasis. Nevertheless, the impact of LB on UC and its mechanism of action remain unclear. Therefore, the objective of this study was to investigate the anti-inflammatory effects and mechanism of action of ethanol extract of LB (LBE) in lipopolysaccharide-induced RAW 264.7 macrophages and dextran sulfate sodium (DSS)-induced UC. The results showed that LBE suppressed the secretion of cytokines in LPS-stimulated RAW 264.7 cells in a dose-dependent manner. LBE had protective effects against DSS-induced colitis in mice, decreased the disease activity index (DAI) score, alleviated symptoms, increased colon length, and improved histological characteristics, thus having protective effects against DSS-induced colitis in mice. In addition, it reversed disturbances in the abundance of proteobacteria and probiotics such as Lactobacillus and Blautia in mice with DSS-induced UC. Based on the results of network pharmacology analysis, we identified four main compounds in LBE that are associated with five inflammatory genes (Ptgs2, Plg, Ppar-γ, F2, and Gpr35). These results improve comprehension of the biological activity and functionality of LB and may facilitate the development of LB-based compounds for the treatment of UC.


Asunto(s)
Colitis Ulcerosa , Sulfato de Dextran , Disbiosis , Etanol , Microbioma Gastrointestinal , Plumbaginaceae , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Ratones , Células RAW 264.7 , Microbioma Gastrointestinal/efectos de los fármacos , Disbiosis/tratamiento farmacológico , Plumbaginaceae/química , Etanol/química , Masculino , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Lipopolisacáridos , Ratones Endogámicos C57BL , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo
11.
Chin J Nat Med ; 22(4): 293-306, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38658093

RESUMEN

Icariin, a flavonoid glycoside, is extracted from Epimedium. This study aimed to investigate the vascular protective effects of icariin in type 1 diabetic rats by inhibiting high-mobility group box 1 (HMGB1)-related inflammation and exploring its potential mechanisms. The impact of icariin on vascular dysfunction was assessed in streptozotocin (STZ)-induced diabetic rats through vascular reactivity studies. Western blotting and immunofluorescence assays were performed to measure the expressions of target proteins. The release of HMGB1 and pro-inflammation cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results revealed that icariin administration enhanced acetylcholine-induced vasodilation in the aortas of diabetic rats. It also notably reduced the release of pro-inflammatory cytokines, including interleukin-8 (IL-8), IL-6, IL-1ß, and tumor necrosis factor-alpha (TNF-α) in diabetic rats and high glucose (HG)-induced human umbilical vein endothelial cells (HUVECs). The results also unveiled that the pro-inflammatory cytokines in the culture medium of HUVECs could be increased by rHMGB1. The increased release of HMGB1 and upregulated expressions of HMGB1-related inflammatory factors, including advanced glycation end products (RAGE), Toll-like receptor 4 (TLR4), and phosphorylated p65 (p-p65) in diabetic rats and HG-induced HUVECs, were remarkably suppressed by icariin. Notably, HMGB1 translocation from the nucleus to the cytoplasm in HUVECs under HG was inhibited by icariin. Meanwhile, icariin could activate G protein-coupled estrogen receptor (GPER) and sirt1. To explore the role of GPER and Sirt1 in the inhibitory effect of icariin on HMGB1 release and HMGB-induced inflammation, GPER inhibitor and Sirt1 inhibitor were used in this study. These inhibitors diminished the effects of icariin on HMGB1 release and HMGB1-induced inflammation. Specifically, the GPER inhibitor also negated the activation of Sirt1 by icariin. These findings suggest that icariin activates GPER and increases the expression of Sirt1, which in turn reduces HMGB1 translocation and release, thereby improving vascular endothelial function in type 1 diabetic rats by inhibiting inflammation.


Asunto(s)
Diabetes Mellitus Experimental , Flavonoides , Proteína HMGB1 , Ratas Sprague-Dawley , Receptores de Cannabinoides , Receptores Acoplados a Proteínas G , Transducción de Señal , Sirtuina 1 , Animales , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Sirtuina 1/metabolismo , Sirtuina 1/genética , Flavonoides/farmacología , Transducción de Señal/efectos de los fármacos , Ratas , Masculino , Humanos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/metabolismo , Citocinas/metabolismo , Epimedium/química
12.
Pharm Biol ; 62(1): 326-340, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38584568

RESUMEN

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.


Asunto(s)
Asma , Cebollas , Humanos , Masculino , Animales , Ratones , Modelos Animales de Enfermedad , Asma/tratamiento farmacológico , Asma/prevención & control , Inflamación/tratamiento farmacológico , Inflamación/prevención & control , Inflamación/metabolismo , Citocinas/metabolismo , Pyroglyphidae/metabolismo , Inmunoglobulina E , Ratones Endogámicos BALB C , Pulmón
13.
Iran J Kidney Dis ; 18(2): 87-98, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38660700

RESUMEN

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the  TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing  serum. In in vivo assays, serum creatinine (SCr) and blood urea  nitrogen (BUN) content were measured, kidney histopathology  was evaluated., and α-smooth muscle actin (α-SMA) expression  was detected by immunohistochemistry. Interleukin-1ß (IL-1ß),  interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content,  inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were  assessed. Meanwhile, cell viability, inflammatory cytokines content,  α-SMA expression, IKBα and P65 phosphorylation were detected  in vitro experiment.  Results. SQP exhibited reno-protective effect by decreasing SCr  and BUN content, improving renal interstitial damage, blunting  fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after  the treatment with SQP-containing serum, viability and α-SMA  expression were remarkably decreased in TGFß1-stimulated HK-2  cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and  TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro.  Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa  B (NF-κB) pathway related inflammatory response, which indicates  that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Fibrosis , Riñón , FN-kappa B , Animales , Humanos , Ratas , Actinas/metabolismo , Nitrógeno de la Urea Sanguínea , Línea Celular , Creatinina/sangre , Citocinas/metabolismo , Medicamentos Herbarios Chinos/farmacología , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Fibrosis/patología , Riñón/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , FN-kappa B/efectos de los fármacos , FN-kappa B/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , Ratas Sprague-Dawley , Insuficiencia Renal Crónica/metabolismo , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/tratamiento farmacológico , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/patología , Obstrucción Ureteral/complicaciones , Obstrucción Ureteral/tratamiento farmacológico
14.
J Ethnopharmacol ; 329: 118153, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38604513

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Shengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. AIM OF THE STUDY: This study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. MATERIALS AND METHODS: Fifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1ß, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. RESULTS: SXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. CONCLUSION: Bleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.


Asunto(s)
Bleomicina , Medicamentos Herbarios Chinos , Fibrosis Pulmonar Idiopática , Pulmón , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/inducido químicamente , Fibrosis Pulmonar Idiopática/fisiopatología , Masculino , Pulmón/efectos de los fármacos , Pulmón/patología , Ratas , Citocinas/metabolismo , Apoptosis/efectos de los fármacos , Piridonas/farmacología , Piroptosis/efectos de los fármacos , Modelos Animales de Enfermedad
15.
Vet Microbiol ; 293: 110090, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38636177

RESUMEN

Macleaya cordata was a kind of traditional herbal medicine, which may a potential substitute for antibiotics. However, the effects of Macleaya cordata on neonatal piglets have rarely been reported. In this study, three groups were designed, including normal saline (Control group, CON), 8 mg/mL Macleaya cordata extract (MCE group, MCE) and 5 mg/mL Chlortetracycline Hydrochloride (CCH group, CCH), to investigate the effects of MCE on growth performance, blood parameters, inflammatory cytokines, regenerating islet-derived 3 gamma (REG3γ) expression and the transcriptomes of neonatal piglets. The results showed that, compared with the control group, MCE significantly increased the average daily gain (p < 0.01); spleen index (p < 0.05) contents of IL-10, TGF-ß, IgG in serum and sIgA in the ileum mucus of neonatal piglets at 7 d and 21 d (p < 0.01). The diarrhoea incidence and serum TNF-α and IFN-γ contents of neonatal piglets at 7 d and 21 d were significantly decreased (p < 0.01). In addition, MCE significantly increased the mRNA expression of TGF-ß, IL-10, and REG3γ (p < 0.01) and significantly decreased the mRNA expression of IL-33, TNF-α and IFN-γ in the ileal mucosa of neonatal piglets at 21 d (p < 0.01). The differentially expressed genes and the signal pathways, related to cytokine generation and regulation, immunoregulation and inflammation were identified. In conclusion, MCE can significantly improve growth performance, reduce diarrhoea incidence, relieve inflammation, improve immune function, and improve disease resistance in neonatal piglets. MCE can be used as a potential substitute for antibiotics in neonatal piglets.


Asunto(s)
Animales Recién Nacidos , Antiinflamatorios , Citocinas , Extractos Vegetales , Animales , Porcinos , Extractos Vegetales/farmacología , Antiinflamatorios/farmacología , Citocinas/genética , Citocinas/metabolismo , Papaveraceae/química , Enfermedades de los Porcinos/inmunología , Diarrea/veterinaria , Diarrea/tratamiento farmacológico
16.
Virol J ; 21(1): 95, 2024 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-38664855

RESUMEN

BACKGROUND: African swine fever virus (ASFV) is a major threat to pig production and the lack of effective vaccines underscores the need to develop robust antiviral countermeasures. Pathologically, a significant elevation in pro-inflammatory cytokine production is associated with ASFV infection in pigs and there is high interest in identifying dual-acting natural compounds that exhibit antiviral and anti-inflammatory activities. METHODS: Using the laboratory-adapted ASFV BA71V strain, we screened a library of 297 natural, anti-inflammatory compounds to identify promising candidates that protected Vero cells against virus-induced cytopathic effect (CPE). Virus yield reduction, virucidal, and cell cytotoxicity experiments were performed on positive hits and two lead compounds were further characterized in dose-dependent assays along with time-of-addition, time-of-removal, virus entry, and viral protein synthesis assays. The antiviral effects of the two lead compounds on mitigating virulent ASFV infection in porcine macrophages (PAMs) were also tested using similar methods, and the ability to inhibit pro-inflammatory cytokine production during virulent ASFV infection was assessed by enzyme-linked immunosorbent assay (ELISA). RESULTS: The screen identified five compounds that inhibited ASFV-induced CPE by greater than 50% and virus yield reduction experiments showed that two of these compounds, tetrandrine and berbamine, exhibited particularly high levels of anti-ASFV activity. Mechanistic analysis confirmed that both compounds potently inhibited early stages of ASFV infection and that the compounds also inhibited infection of PAMs by the virulent ASFV Arm/07 isolate. Importantly, during ASFV infection in PAM cells, both compounds markedly reduced the production of pro-inflammatory cytokines involved in disease pathogenesis while tetrandrine had a greater and more sustained anti-inflammatory effect than berbamine. CONCLUSIONS: Together, these findings support that dual-acting natural compounds with antiviral and anti-inflammatory properties hold promise as preventative and therapeutic agents to combat ASFV infection by simultaneously inhibiting viral replication and reducing virus-induced cytokine production.


Asunto(s)
Virus de la Fiebre Porcina Africana , Antiinflamatorios , Antivirales , Animales , Virus de la Fiebre Porcina Africana/efectos de los fármacos , Virus de la Fiebre Porcina Africana/fisiología , Antivirales/farmacología , Porcinos , Antiinflamatorios/farmacología , Chlorocebus aethiops , Células Vero , Macrófagos/efectos de los fármacos , Macrófagos/virología , Macrófagos/inmunología , Fiebre Porcina Africana/virología , Replicación Viral/efectos de los fármacos , Productos Biológicos/farmacología , Evaluación Preclínica de Medicamentos , Efecto Citopatogénico Viral/efectos de los fármacos , Citocinas/metabolismo , Internalización del Virus/efectos de los fármacos
17.
Fitoterapia ; 175: 105939, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38570096

RESUMEN

Sesquiterpenes are a class of metabolites derived from plant species with immunomodulatory activity. In this study, we evaluated the effects of treatment with costic acid on inflammation, angiogenesis, and fibrosis induced by subcutaneous sponge implants in mice. One sponge disc per animal was aseptically implanted in the dorsal region of the mice and treated daily with costic acid (at concentrations of 0.1, 1, and 10 µg diluted in 10 µL of 0.5% DMSO) or 0.5% DMSO (control group). After 9 days of treatment, the animals were euthanized, and the implants collected for further analysis. Treatment with costic acid resulted in the reduction of the inflammatory parameters evaluated compared to the control group, with a decrease in the levels of inflammatory cytokines and chemokines (TNF, CXCL-1, and CCL2) and in the activity of MPO and NAG enzymes. Costic acid administration altered the process of mast cell degranulation. We also observed a reduction in angiogenic parameters, such as a decrease in the number of blood vessels, the hemoglobin content, and the levels of VEGF and FGF cytokines. Finally, when assessing implant-induced fibrogenesis, we observed a reduction in the levels of the pro-fibrogenic cytokine TGF-ß1, and lower collagen deposition. The results of this study demonstrate, for the first time, the anti-inflammatory, anti-angiogenic, and anti-fibrotic effects of costic acid in an in vivo model of chronic inflammation and reinforce the therapeutic potential of costic acid.


Asunto(s)
Colágeno , Citocinas , Inflamación , Sesquiterpenos , Animales , Ratones , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Colágeno/metabolismo , Inflamación/tratamiento farmacológico , Citocinas/metabolismo , Masculino , Fibrosis , Poríferos , Antiinflamatorios/farmacología , Antiinflamatorios/aislamiento & purificación , Neovascularización Patológica/tratamiento farmacológico , Angiogénesis
18.
Fitoterapia ; 175: 105935, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38580032

RESUMEN

Buyang Huanwu Decoction (BHD) has been effective in treating ischemic stroke (IS). However, its mechanism of action remains unclear. The study intended to explore the potential mechanism of BHD against IS using systems pharmacology, proteomics, and animal experiments. The active components of BHD were identified from UPLC-Q-TOF-MS and literature mining. Systems pharmacology and proteomics were employed to investigate the underlying mechanism of BHD against IS. The AutoDock tool was used for molecular docking. A middle cerebral artery occlusion (MCAO) model rat was utilized to explore the therapeutic benefits of BHD. The rats were divided into sham, model, BHD (5, 10, 20 g/kg, ig) groups. The neurological scores, pathological section characteristics, brain infarct volumes, inflammatory cytokines, and signaling pathways were investigated in vivo experiments. The results of systems pharmacology showed that 13 active compounds and 112 common targets were screened in BHD. The docking results suggested that the active compounds in BHD had a high affinity for the key targets. In vivo experiments demonstrated that BHD exhibited neuroprotective benefits by lowering the neurological score, the volume of the cerebral infarct, the release of inflammatory cytokines, and reducing neuroinflammatory damage in MCAO rats. Furthermore, BHD decreased TNF-α and CD38 levels while increasing ATP2B2, PDE1A, CaMK4, p-PI3K, and p-AKT. Combined with systems pharmacology and proteomic studies, we confirmed that PI3K-Akt and calcium signaling pathways are the key mechanisms for BHD against IS. Furthermore, this study demonstrated the feasibility of combining proteomics with systems pharmacology to study the mechanism of herbal medicine.


Asunto(s)
Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos , Infarto de la Arteria Cerebral Media , Accidente Cerebrovascular Isquémico , Simulación del Acoplamiento Molecular , Farmacología en Red , Fármacos Neuroprotectores , Proteómica , Ratas Sprague-Dawley , Animales , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratas , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Masculino , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Citocinas/metabolismo
19.
J Vet Intern Med ; 38(3): 1425-1436, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38613431

RESUMEN

BACKGROUND: Fecal microbiota transplantation (FMT) is increasingly used for gastrointestinal and extra-gastrointestinal diseases in veterinary medicine. However, its effects on immune responses and possible adverse events have not been systematically investigated. HYPOTHESIS/OBJECTIVES: Determine the short-term safety profile and changes in the peripheral immune system after a single FMT administration in healthy dogs. ANIMALS: Ten client-owned, clinically healthy dogs as FMT recipients, and 2 client-owned clinically healthy dogs as FMT donors. METHODS: Prospective non-randomized clinical trial. A single rectal enema of 5 g/kg was given to clinically healthy canine recipients. During the 28 days after FMT administration, owners self-reported adverse events and fecal scores. On Days 0 (baseline), 1, 4, 10, and 28 after FMT, fecal and blood samples were collected. The canine fecal dysbiosis index (DI) was calculated using qPCR. RESULTS: No significant changes were found in the following variables: CBC, serum biochemistry, C-reactive protein, serum cytokines (interleukins [IL]-2, -6, -8, tumor necrosis factor [TNF]-α), peripheral leukocytes (B cells, T cells, cluster of differentiation [CD]4+ T cells, CD8+ T cells, T regulatory cells), and the canine DI. Mild vomiting (n = 3), diarrhea (n = 4), decreased activity (n = 2), and inappetence (n = 1) were reported, and resolved without intervention. CONCLUSIONS AND CLINICAL IMPORTANCE: Fecal microbiota transplantation did not significantly alter the evaluated variables and recipients experienced minimal adverse events associated with FMT administration. Fecal microbiota transplantation was not associated with serious adverse events, changes in peripheral immunologic variables, or the canine DI in the short-term.


Asunto(s)
Trasplante de Microbiota Fecal , Animales , Perros , Trasplante de Microbiota Fecal/veterinaria , Trasplante de Microbiota Fecal/efectos adversos , Femenino , Masculino , Heces/microbiología , Estudios Prospectivos , Citocinas/sangre , Citocinas/metabolismo , Disbiosis/veterinaria , Disbiosis/terapia , Microbioma Gastrointestinal
20.
Transpl Immunol ; 84: 102044, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663757

RESUMEN

BACKGROUND: Glutamine is crucial for the activation and efficacy of T cells, and may play a role in regulating the immune environment. This study aimed to investigate the potential role of glutamine in the activation and proliferation of induced regulatory T cells (iTregs). METHODS: CD4+CD45RA+T cells were sorted from peripheral blood mononuclear cells and cultured to analyze iTreg differentiation. Glutamine was then added to the culture system to evaluate the effects of glutamine on iTregs by determining oxidative phosphorylation (OXPHOS), apoptosis, and cytokine secretion. Additionally, a humanized murine graft-versus-host disease (GVHD) model was constructed to confirm the efficacy of glutamine-treated iTregs in vivo. RESULTS: After being cultured in vitro, glutamine significantly enhanced the levels of Foxp3, CTLA-4, CD39, CD69, IL-10, TGF-ß, and Ki67 (CTLA-4, IL-10, TGF-ß are immunosuppressive markers of iTregs) compared with that of the control iTregs (P < 0.05). Furthermore, the growth curve showed that the proliferative ability of glutamine-treated iTregs was better than that of the control iTregs (P < 0.01). Compared with the control iTregs, glutamine supplementation significantly increased oxygen consumption rates and ATP production (P < 0.05), significantly downregulated Annexin V and Caspase 3, and upregulated BCL2 (P < 0.05). However, GPNA significantly reversed the effects of glutamine (P < 0.05). Finally, a xeno-GVHD mouse model was successfully established to confirm that glutamine-treated iTregs increased the mice survival rate, delayed weight loss, and alleviated colon injury. CONCLUSION: Glutamine supplementation can improve the activity and immunosuppressive action of iTregs, and the possible mechanisms by which this occurs are related to cell proliferation, apoptosis, and OXPHOS.


Asunto(s)
Glutamina , Enfermedad Injerto contra Huésped , Linfocitos T Reguladores , Glutamina/farmacología , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/efectos de los fármacos , Animales , Ratones , Humanos , Células Cultivadas , Enfermedad Injerto contra Huésped/inmunología , Proliferación Celular/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Modelos Animales de Enfermedad , Apoptosis/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Terapia de Inmunosupresión , Citocinas/metabolismo
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