scholarly journals Lipidomics study of the therapeutic mechanism of Plantaginis Semen in potassium oxonate-induced hyperuricemia rat

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Yang ◽  
Wenjun Shi ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  

Abstract Background Plantaginis Semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but its pharmacological mechanism remains unclear. This study investigated the therapeutic mechanism of Plantaginis Semen extract on potassium oxonate -induced HUA rats based on a lipidomics approach. Methods A model of HUA was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis Semen groups (n = 7). The Plantaginis Semen groups were treated orally with Plantaginis Semen, 0.9375, 1.875  or 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were  measured using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used for the serum lipidomics analysis, multivariate statistical analysis and independent samples t-test were carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors were determined by quantitative real-time polymerase chain reaction (RT-qPCR). Results Compared with the model group, the levels of serum UA, Cr, TG and TNF-α were significantly (p < 0.05) decreased in benzbromarone and three Plantaginis Semen groups. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was  most affected. These perturbations  were partially restored via treatment of benzbromarone and Plantaginis Semen. Additionally, the mRNA expression levels of urate anion transporter 1 (URAT1) and phosphatidylinositol 3-kinase/protein kinases B (PI3K/Akt) were significantly decreased (p < 0.01) after treatment with benzbromarone and high dose of Plantaginis Semen. Conclusions Plantaginis Semen had significant effects on anti-HUA, anti-inflammatory and renal protection. It attenuated potassium oxonate-induced HUA through regulation of lipid metabolism disorder.

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable


Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.


2016 ◽  
Vol 2016 ◽  
pp. 1-4
Author(s):  
Fagen Li ◽  
Shaodan Li ◽  
Yi Liu ◽  
Ke Cao ◽  
Minghui Yang

Objective. To study the effect of Heweianshen decoction (HAD) on orexin-A and cholecystokinin-8 (CCK-8) expression in rat models of insomnia caused by injecting parachlorophenylalanine (PCPA) intraperitoneally.Methods. Fifty male Wistar rats were randomly divided into five groups (10 rats in each group): blank group, model group, and low-, medium-, and high-dose HAD-treated groups. A rat model of insomnia was established by injecting intraperitoneally with PCPA (300 mg/kg body weight). Rats were given normal saline (10 mL/kg) or 5.25, 10.5, and 21 g/kg HAD by intragastric administration once a day for 6 days. After that, the rats were sacrificed to collect the hypothalamus for tests, using radioimmunoassay to detect the expression of orexin-A and CCK-8.Results. Heweianshen decoction reduced the expression of orexin-A and increased the expression of CCK-8 in the hypothalamus of rat model of insomnia.Conclusion. The therapeutic effect of HAD on insomnia is partially attributed to the decreased expression of orexin-A and increased expression of CCK-8.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Tri Yudani Mardining Raras ◽  
Nurul Hidayati ◽  
Shinta Oktya Wardhani

Background: Bleomycin-induced pneumonitis (BIP) is a common consequence of bleomycin (BLE) use during chemotherapy. Kefir is a probiotic with many health benefits. Many cancer patients in Indonesia consume kefir as a complementary traditional medicine alongside standard chemotherapy. Objectives: This study aimed to investigate the effects of high-dose kefir consumption on BIP in a rat model. Methods: Wistar male rats were given 0.3 mg of BLE via intranasal inhalation for 6 days with a daily intragastric administration of either phosphate buffered saline (PBS) or kefir at dosages of 2.5 mL, 3.5 mL, and 4.5 mL per day for 30 days. On day 30, lung sections were obtained and stained with hematoxylin and eosin for histological examinations. Immunohistochemistry tests were carried out to determine the activity levels of matrix metalloproteinase (MMP)-1, signal transducer, and activator of transcription (STAT)-3. TNF-α and IL-6 concentrations in plasma were also evaluated. Results: Histological results showed damage to the lung structure by inflammation with diffuse infiltrate, with some areas exhibiting slight fibrosis. The number of alveolar epithelial cells expressing MMP-1 significantly increased with the kefir dosage. Interestingly, only the highest dose of kefir raised IL-6 levels, while TNF-α levels increased at all kefir doses. STAT-3 showed a slight increase in activity level. As MMP-1 works to degrade fibrosis while both TNF-α and Il-6 are correlated with inflammation, these findings might explain the observed histological changes in lung structure in the BLE and kefir groups. Conclusions: The administration of high doses of kefir in rats increased the expression of pro-inflammatory cytokines, which worsened BIP.


2020 ◽  
Vol 19 (7) ◽  
pp. 1429-1433
Author(s):  
Jihong Shu ◽  
Zhenjiao Fang ◽  
Xinjun Xiong

Purpose: To investigate the effect of penehyclidine hydrochloride (PHC) on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), hypoxia inducible factor-1α (HIF-1α), and oxidative stress levels in lung tissues of acute lung injury (ALI) neonatal rats.Methods: 40 male Sprague-Dawley (SD) rats were assigned to model, low-dose PHC, high-dose PHC, and control groups (n = 10). Levels of IL-6, TNF-α and HIF-1α were evaluated by enzyme-linked immunosorbent assay (ELISA). Pulmonary lesions were determined histologically using H&E staining.Results: The lung tissue levels of IL-6, TNF-α and HIF-1α were significantly higher in model rats than in control rats, and significantly lower in PHC-treated rats than in model group, with decrease in levels as PHC dose increased (p < 0.05). The lung tissue activity of MPO and level of MDA in model rats were significantly higher than those in control rats, but significantly lower in the lung tissues of the two PHC groups than in the model group; decrease in levels occurred as PHC dose increased (p < 0.05).Conclusion: PHC decreases the lung and serum levels of IL-6, TNF-α and HIF-1α in a rat model of ALI, and mitigates pulmonary oxidative stress and lung tissue damage. Thus, penehyclidine hydrochloride may be useful to mitigate ALI-induced damage in patients. However, further studies and clinical trials are required to ascertain this Keywords: Penehyclidine hydrochloride, Alveolar septum, Acute lung injury, Inflammatory cells, IL-6, TNF-α, HIF-1α, Oxidative stress


2019 ◽  
Vol 17 ◽  
pp. 205873921984015
Author(s):  
Liu Shi ◽  
Qing Liu ◽  
Jian-hua Tang ◽  
Jian-jun Wen ◽  
Chen Li

Our study aimed to investigate the protective effects and potential mechanisms of pterostilbene on rats with ulcerative colitis (UC). We established 2,4,6-trinitrobenzenesulfonic acid (TNBS) induced colitis rat model. Rats were randomly divided into three groups, including control group, model group, and pterostilbene group (30 mg/kg). Disease activity index (DAI) including body weight, stool consistency, and gross bleeding was measured. The concentration of superoxide dismutases (SODs), glutathione superoxide (GSH-px), malondialdehyde (MDA), and methylpropanediol (MPO) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The levels of interleukin-1 beta (IL-1β), IL-17, IL-6, and tumor necrosis factor–alpha (TNF-α) in serum were also analyzed by ELISA kits. Histological evaluations of colons were conducted. The levels of peroxisome-proliferator-activated receptor–γ (PPAR-γ), nuclear factor-κB (NF-κB), ZO-1, and Occludin were analyzed by immunohistochemistry. Compared with model group, pterostilbene notably suppressed the production of TNF-α, IL-17, IL-1β, IL-6, MDA and MPO in serum, and markedly increased the SOD and GSH-Px activity in serum. Pterostilbene significantly attenuated macroscopic damage and histological injury, when compared with model rats. Furthermore, pterostilbene also markedly activated the expression of PPAR-γ, ZO-1, and Occludin, and suppressed the expression of NF-κB. The protective effects of pterostilbene might be associated with suppression of NF-κB and activation of PPAR-γ. Pterostilbene might be a promising therapeutic agent for colitis treatment.


2018 ◽  
Vol 16 ◽  
pp. 205873921879453
Author(s):  
Haisheng Hu ◽  
Haiyan Jin ◽  
Longli Yu ◽  
Shiping Qu

The purpose of this study was to explore the role and possible mechanism of inhibiting extracellular signal-regulated kinase (ERK) pathway on rheumatoid arthritis synovial hyperplasia and angiogenesis. Thirty six Sprague–Dawley rats were randomly assigned into normal group, model group, and intervention group, 12 rats in each group. The measures of enzyme-linked immunosorbent assay (ELISA), RT-PCR, Western blot, and HE immunohistochemical staining were used to examine specific indicators in this study. The levels of interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), and angiopoietin-1 (Ang-1) in the serum of model group were significantly increased ( P < 0.05) compared to the normal groups. In contrast with the model group rats, the levels of IL-1β, TNF-α, and Ang-1 in the intervention group were all significantly decreased ( P < 0.05). In addition, the mRNA expression of IL-1β, TNF-α, vascular endothelial growth factor (VEGF), and Ang-1 in the synovial tissue of the model group was distinctly higher than those in the normal group ( P < 0.05). Simultaneously, the levels of cytokines in the intervention group were obviously decreased compared to the model group ( P < 0.05). The expression of phosphorylated state of ERK1/2 (p-ERK1/2), p-JNK, and p-38 in model group rats were significantly higher than those in normal group ( P < 0.05), while the expression of p-ERK1/2 in intervention group rats was evidently decreased compared to model groups ( P < 0.05). Finally, the arthritis index and arthritis volume in intervention group were decreased obviously ( P < 0.05). Inhibition of ERK pathway could suppress the levels of inflammatory cytokines in synovial tissue and also inhibit the proliferation of synovial tissue, and reduce angiogenesis and pannus formation in synovial membrane.


2021 ◽  
Author(s):  
Zhixian He ◽  
Xinyv Wang ◽  
Xing Wang ◽  
Jinyue Wang

Abstract Background: The outbreak of the Coronavirus Disease-2019 (COVID-19) has threatened the public health of the world, and may eventually lead to acute respiratory impoverishment syndrome (ARDS). ARDS is a clinical syndrome caused by intrapulmonary or extrapulmonary reasons, which has complex pathogenesis and high mortality rate, it’s also one of the important factors in death from the 2019 novel coronavirus (2019-nCoV) epidemic. It has been reported that traditional Chinese medicine (TCM) can exert a good effect in the process of treatment. The present study aimed to observe the protective effects of TCM formula Qingfei Paidu Decoction (QFPD) on ARDS rats and explore the pharmacodynamic mechanism of the compound. Methods: 24 male rats were randomly divided into 4 groups (n=6), blank control group, model group, QFPD group (18.6g·kg-1·d-1) and dexamethasone group (2mg·kg-1·d-1). Blank control group rats were given saline, whereas other groups were injected with oleic acid (OA) and lipopolysaccharide (LPS) successively to establish ARDS model, and observed the behavioral performance of rats after model building. The morphological changes of lung tissue under optical microscope were observed; rat lung index (LI) and lung permeability index (LPI) were measured; blood PH, partial arterial oxygen pressure (PaO2, mmHg), partial arterial carbon dioxide pressure (PaCO2, mmHg), arterial oxygen saturation (SaO2) were measured by blood gas analyzer; the levels of tumor necrosis factor-α (TNF-α), interleukin (IL-1β, IL-6, IL-8, IL-10), thromboxane B2 (TXB2), 6-keto-prostaglandin F1α (6-keto-PGF1α), kerbs von lungren 6 antigen (KL-6), C-reactive protein (CRP), and the expression of superoxide dismutase (SOD) were measured via test kit.Results: Compared with the model group, the two treatment groups could improve the respiratory and lung injury in rats, and could restore the expression levels of thromboxane, various cytokines and protein to varying degrees.Conclusions: QFPD and dexamethasone have protective effects on ARDS rats induced by jointly injecting OA and LPS, and QFPD has the better effect in between. These may be related to reducing the expression levels of IL-1β, IL-6, IL-8, TNF-α, CRP, TXB2, KL-6, and increasing the contents of IL-10, 6Keto-PGF1a and SOD vitality in the body.


2020 ◽  
Vol 2 (4) ◽  
pp. 10-15
Author(s):  
Zhiqiang Wang ◽  
Liping Zhu ◽  
Zhenyu Mu ◽  
Xiaogang Wang

Objective To observe the effect of Xiaochaihu Decoction on cytokines and MAO in model rats with experimental autoimmune prostatitis (EAP) to provide an experimental basis for the use of Chinese herbal prescriptions in the treatment of chronic prostatitis. Methods Thirty male Wistar rats were randomly divided into blank Group, model group and treatment group (Xiaochaihu Decoction). Except the blank group, rats in model and treatment groups were injected subcutaneously in multiple points on days 0 and 30 with prostatic protein extractive solution (60 mg/mL), and intraperitoneally injected with diph-theria-pertussis and tetanus vaccine (DPT vaccine) to establish the EAP model. Model rats were administrated Xiaochaihu Decoction and were sacrificed after 4 weeks. Pathological changes in the prostate gland were observed with HE staining and changes in serum interleukin-6 (IL-6), interleukin-8 (IL-8), and Tumor necrosis factor-α (TNF-α) levels were detected with enzyme-linked immunosorbent assay (ELISA). Quantitative PCR to observe the expression of IL-17, CCL2 and MAOA/B. Results After treatment with Xiaochaihu Decoction, the serum IL-6, IL-8, and TNF-α levels all significantly lower in the treatment group as compared with the model group (P < 0.05). The intervention of Xiaochaihu Decoction can change the state of abnormally elevated IL-17, CCL2 and MAOA expression levels. Conclusions The therapeutic efficacy remarkable from the theory of heating into the sperm chamber to experimental autoimmune prostatitis rats.


Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 784
Author(s):  
Sandra Minic ◽  
Marion Florimond ◽  
Jérémy Sadoine ◽  
Anne Valot-Salengro ◽  
Catherine Chaussain ◽  
...  

Dental pulp is a dynamic tissue able to heal after injury under moderate inflammatory conditions. Our study aimed to evaluate pulp repair under inflammatory conditions in rats. For this purpose, we developed a rat model of controlled pulpitis followed by pulpotomy with a tricalcium silicate-based cement. Fifty-four cavities were prepared on the occlusal face of the maxillary upper first molar of 27 eight-week-old male rats. E. coli lipopolysaccharides at 10 mg/mL or phosphate-buffered saline PBS was injected after pulp injury. Non-inflamed molars were used as controls. Levels of inflammation-related molecules were measured 6 and 24 h after induction by enzyme-linked immunosorbent assay of coronal pulp samples. Pulp capping and coronal obturation after pulpotomy were performed with tricalcium silicate-based cement. Four and fifteen days after pulpotomy, histological and immunohistochemical analysis was performed to assess pulp inflammation and repair processes. Our results showed significantly higher levels of innate inflammatory proteins (IL-1β, IL-6, TNF-α and CXCL-1) compared with those in controls. Moderate residual inflammation near the capping material was demonstrated by histology and immunohistochemistry, with the presence of few CD68-positive cells. We showed that, in this model of controlled pulpitis, pulpotomy with BiodentineTM allowed the synthesis at the injury site of a mineralized bridge formed from mineralized tissue secreted by cells displaying odontoblastic characteristics. Analysis of these data suggests overall that, with the limitations inherent to findings in animal models, pulpotomy with a silicate-based cement is a good treatment for controlling inflammation and enhancing repair in cases of controlled pulpitis.


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