scholarly journals Gancao Nurish-Yin Decoction Ameliorates Imiquimod-Induced Psoriasis-Like Skin Lesions and Inflammation in Mice

Author(s):  
Chen Yong ◽  
Wu Huimei ◽  
Xiao Changhong ◽  
Kutty Selva Nandakumar

Abstract BackgroundPsoriasis is an autoimmune skin disease with a high clinical prevalence, which is often poses treatment difficulties. In this study, we tested whether Gancao nurish-Yin (GNY) decoction is effective for treating mice with imiquimod (IMQ)-induced psoriasis-like skin lesions. MethodsMice were divided into 4 groups including healthy control group, model group (IMQ-induced psoriasis mice), and two psoriasis induced groups of mice treated with GNY-2.5g/kg and GNY-5g/kg given in the drinking water (n = 8/group). Psoriasis area and severity index (PASI) was used to monitor psoriatic symptoms. H&E staining of dermis and baker’s scores were used to evaluate disease severity. Inflammatory cells positive for Gr-1, CD11c, RORγt and TGF-β were counted by using immunohistochemistry or immunofluorescence staining methods. Flow cytometry was used to analyse CD4+CD17+ Th17 cells, and CD25+Foxp3+ Tregs within splenocyte cell population. Relative mRNA expression of IL-6, IL-10, IL-17A, IL-22, IL-23, TNF-ɑ, TGF-β and AMPKɑ1 in the dermis was was semi-quatified using qPCR. ResultsCompared to model group, GNY decoction treated mice, at both the concentrations, improved morphological features, as demonstrated by PASI scores and decreased levels of hyperproliferating keratinocytes. GNY decoction at a higher concentration significantly decreased Gr-1, CD11c, RORγt and TGF-β positive cells in the dermis as well as the differentiated CD4+CD17+ Th17 cells, whereas, CD25+Foxp3+ Tregs were increased in the spleen, mainly with low dose GNY decoction. Furthermore, relative mRNA expression of IL-6, IL-10, IL-17A, IL-22, IL-23, TNF-ɑ, TGF-β and AMPKɑ1 within dermis were elevated in mice from IMQ model group, which were significantly recduced in mice treated with GNY decoction at GNY-5g/kg concentration.ConclusionHere we demonstrate disease ameliorating effects of GNY decoction in IMQ-induced psoriasis-like skin lesions in mice, which could form basis for considering GNY decoction for treatment of psoriasis patients.

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259211
Author(s):  
A. Adhipatria P. Kartamihardja ◽  
Syahla Nisaa Amalia ◽  
Akiko Sekiguchi ◽  
Anu Bhattarai ◽  
Ayako Taketomi-Takahashi ◽  
...  

Although neutrophil elastase (NE) may play a role in lung fibrosis and liver fibrosis, NE involvement in the development of nephrogenic systemic fibrosis has been unclear. We investigated the involvement of NE in the development of nephrogenic systemic fibrosis-like skin lesions post-injections of linear gadolinium-based contrast agents in renal failure mouse models. Renal failure mouse models were randomly divided into three groups: control group (saline), gadodiamide group, and gadopentetate group. Each solution was intravenously administered three times per week for three weeks. The mice were observed daily for skin lesions. Quantification of skin lesions, infiltrating inflammatory cells, and profibrotic cytokines in the affected skin was performed by immunostaining and reverse-transcription polymerase chain reaction (RT-PCR). Blood samples were collected from the facial vein to quantify NE enzymatic activity. The 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry (ICP-MS). In the gadodiamide group, the mRNA expression of fibrotic markers was increased in the skin lesions compared to the control group. In the gadopentetate group, only collagen 1α and TGF-β mRNA expression were higher than in the control group. The expression of CD3+, CD68+, NE cells and the NE activity in the blood serum were significantly higher in the gadodiamide and gadopentetate groups compared to the control group. Gadolinium concentration in the skin of the gadodiamide group was significantly higher than the gadopentetate group, while almost no traces of gadolinium were found in the control group. Although gadopentetate and gadodiamide affected the fibrotic markers in the skin differently, NE may be involved in the development of fibrosis linked to the GBCAs injections in renal failure mouse models.


2021 ◽  
Vol 7 ◽  
Author(s):  
Yan Lu ◽  
Yi Xiao ◽  
Ming-Zhu Yin ◽  
Xing-Chen Zhou ◽  
Li-Sha Wu ◽  
...  

Objective: To explore the possible mechanism of improving the imiquimod (IMQ)-induced psoriasis-like inflammation by using polyethylene glycol (PEG) ointment.Methods: We evaluated the appearance of psoriasis lesions by Psoriasis Area and Severity Index (PASI), observed the epidermal proliferation by histopathological staining and immunohistochemical staining, and explored the key molecules and signaling pathways of improving psoriasis-like inflammation treated with PEG ointment by RNA sequencing. Finally, we verified the expression of inflammatory cells and inflammatory factors by flow cytometry, immunohistochemical staining, and Q-PCR.Results: PEG ointment could improve the appearance of psoriasis lesions and the epidermis thickness of psoriasis mouse, inhibit the proliferation of keratinocytes, and down-regulate the relative mRNA levels of IL-23, IL-22, IL-6, IL-17C, IL-17F, S100A7, S100A8, S100A9, CXCL1, CXCL2, and IL-1β in the skin lesions of psoriasis mouse by down-regulating the numbers of myeloid-derived suppressor cells (MDSCs) and T helper 17 (Th17) cells.Conclusion: PEG ointment could improve the IMQ-induced psoriasis-like inflammation by down-regulating the functions of Th17 cells and MDSCs.


2021 ◽  
Vol 19 ◽  
pp. 205873922110008
Author(s):  
Meng Chen ◽  
Xinyan Song ◽  
Jifang Jiang ◽  
Lei Xing ◽  
Pengfei Wang

To investigate the protective effects of galangin on liver toxicity induced by carbon tetrachloride (CCl4) in mice. Mouse hepatotoxicity model was established by intraperitoneal injection (i.p.) of 10 ml/kg body weight CCl4 that diluted with corn oil to a proportion of 1:500 on Kunming mice. The mice were randomly divided into five groups named control group, model group, and 1, 5, and 10 mg/kg galangin group. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were analyzed by ELISA. Liver histopathological examination was observed via optical microscopy. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and glutathion (GSSG) were analyzed to assess oxidative stress. Finally, western blot assay was carried out to analyse the expression levels of total AMP-activated protein kinase (AMPK), phospho-AMPK (p-AMPK), total liver kinase B1 (LKB1), and phospho-LKB1 (p-LKB1). Compared with the control group, in the model group, the levels of AST, ALT, MDA, and GSSG increased significantly ( p < 0.01); the activity of SOD and GSH decreased significantly ( p < 0.01); and the histopathological examination revealed liver necrosis. However, treatment with galangin (5 and 10 mg/kg) significantly reversed these CCl4-induced liver damage indicators. Furthermore, treatment with galangin (10 mg/kg) significantly increased the p-AMPK and p-LKB1 expression levels ( p < 0.01). This study supports the hepatoprotective effect of galangin against hepatotoxicity, perhaps occurring mainly through the LKB1/AMPK-mediated pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Zhigang Wang ◽  
Xueting Cai ◽  
Zhonghua Pang ◽  
Dawei Wang ◽  
Juan Ye ◽  
...  

Background. Yupingfeng Pulvis (HFBP) had played an active role in many diseases, especially respiratory tract infections. Exploring the possible prevention mechanism of HFBP may provide new ideas in clinical applications for this well-known herbal formula.Purpose. To study the possible mechanisms of therapy effect of HFBP on asthma mice via regulating the balance of Tregs and Th17 cells.Method. The female BALB/c mice were divided into five groups: control group, model group, prednisone (5.5 mg/kg) group, and 22 g/kg HFBP and 44 g/kg HFBP groups. Ovalbumin was used to make the asthma model of mice; the drug was ig administered daily after atomization for consecutive 15 d. The mice were killed after the last administration. The paraffin-embedded tissue sections of the lungs were stained by H&E. Tregs and Th17 cells in bronchoalveolar lavage fluid were detected by flow cytometry. IL-4, TGF-β, and TNF-αin the serum were detected by ELISA assay.Results. HFBP could alleviate the inflammation in the lung tissue of mice, decrease the proportion of Th17 cells, and increase the proportion of Treg cells in bronchoalveolar lavage fluid. HFBP could decrease IL-4 and TNF-αlevel and increase TGF-βlevel in blood.Conclusion. HFBP could treat the asthma through impacting the balance of Th17 cells and Treg cells as well as the levels of related inflammatory cytokines in asthma mice.


2014 ◽  
Vol 912-914 ◽  
pp. 1940-1943
Author(s):  
Yan Li ◽  
Xiao Ou Li ◽  
Feng Hao ◽  
Lei Zhang ◽  
Lei Liu ◽  
...  

To evaluate the control effect of Oviductus ranae on liver fibrosis in rats, and the change of TGF-β and α-SMA in liver of. To explore the mechanism of Oviductus ranae decoction on liver fibrosis. Methods Wistar female rats were randomly divided into a blank control group, model control group, colchicines group, Oviductus ranae group. Using the CCl4composite approach to make the rat modle. The course of treat-mart was 12 weeks.After treatment,All the rats was killed,and the materials and blood was taken,and to detect biochemical test of liver function after eight weeks. Investigating the variation of liver histology. Meanwhile detecting protein expression of TGF-β and α-SMA and by immunehistochemical method.Result The general condition of rats in all treatment groups are worse than the blank group,but better than the model group. And the rats in the model group were all occurred in liver fibrosis,and liver fibrosis is the most serious.In a normal rat liver tissue of TGF-β and α-SMA were significantly lower in model group and each treatment group, and there were significant differences, and the TGF-β and α-SMA in expression of liver tissue in model rats of TGF-β and α-SMA the highest. Conclusion: Oviductus ranae can effectively improve liver fibrosis rats induced by CC14liver function.Oviductus ranae can reduce the expression of TGF-β1in liver tissue of hepatic fibrosis rats induced by CCl4in. This may be one of the mechanisms of Oviductus ranae in prevention and treatment of liver fibrosis. Even though both increased expression of TGF-β and α-SMA expression, is able to determine TGF-β and α-SMA for the intervention of liver TGF-β signal transduction pathway in liver fibrosis.


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


2018 ◽  
Vol 16 (1) ◽  
pp. 956-962 ◽  
Author(s):  
Yingying Niu ◽  
Junya Wang ◽  
Pengyu Wang ◽  
Xiuchun Guo ◽  
Jinmei Wang ◽  
...  

AbstractThe effects of Malus halliana Koehne polysaccharides on functional constipation was investigated in this study. The rats were divided into six groups: normal group, model group, positive control group, M. halliana polysaccharides high dose groups 1200 mg/ kg, medium dose groups 1000 mg/ kg and low dose groups 800 mg/kg. The model of constipation was established by loperamide hydrochloride. Feces weight at 6 and 24 hours after treatment, Colon moisture content, in addition the levels of motilin (MTL), gastrin (Gas), somatostatin (SS), substance P (SP) in serum were used to evaluate the preventive effects of M. halliana polysaccharides on constipation. Compared with the model group, the positive control group, M. halliana polysaccharide high, medium and low dose group 6 h weight of feces, colon moisture content, the levels of motilin (MTL), gastrin (GAS) and substance P(SP) significantly (p <0.01) increased, the levels of somatostatin (SS) significantly decreased. The results indicated that the high, middle and low dosage of M. halliana polysaccharide could effectively improve functional constipation. Amongst these doses, the low dose group was better than others.


2021 ◽  
Author(s):  
Ziqiang Zhang ◽  
Yingying Sun ◽  
Haojie Wang ◽  
Yuxiang Yang ◽  
Ruiqi Dong ◽  
...  

Abstract Background and PurposeIn this study, the therapeutic effect of Mel-incubated ADSCs on CCl4-induced hepatic fibrosis was investigated. MethodsThe experiment was arranged into ADSCS group, ADSCS + Mel group, Model group and Control group with 10 mice in each group. The other three groups of mice were intraperitoneally injected with 8% CCl4, and the control group was injected with the same dose of PBS twice a week for 4 weeks. From the fifth week, ADSCs group and ADSCs + Mel group mice were injected with 1×106 cells/1 ml PBS dose of ADSCs and 50 μM Mel pretreated ADSCs into tail vein, respectively, twice a week for 2 weeks, and mice in the control and model groups were injected with the same dose of PBS. Samples were tested after six weeks. ResultsIn model group, severe histomathological changes were observed in liver, including severe vacuolation, nuclear fragmentation and liver fibrosis, and these changes were ameliorated by Mel pretreated ADSCs. At the same time, RT-qPCR results showed that Mel-induced ADSCs significantly inhibited the expression of pro-apoptotic genes (Caspase-8, Bax and Caspase-3), and promoted the expression of anti-apoptotic gene (Bcl-2). Immunohistochemical results showed that a large number of MMP-9, TGF-β, MMP-2 yellow-stained positive cells were found in the liver tissues of the model group, while the expression of positive cells was blocked by Mel-induced ADSCs. Conclusion and ImplicationsADSCs pretreated with Mel significantly improved CCl4-induced liver fibrosis, which provides a reference for clinical treatment of liver injury with mesenchymal stem cells.


Author(s):  
Raghad A. Khaleel ◽  
Munaf H. Zalzala

Psoriasis is a common chronic skin condition characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. In this work, psoriasis was induced by an imiquimod 5% cream, an immune response modifier that can induce psoriasis-like skin inflammation when applied topically in mice. Guggulsterone prepared as a suspension and has been orally given to mice before imiquimod application. The results of the current study showed that guggulsterone suspension can significantly reduce psoriasis area and severity index in (guggul suspension+imiquimod group as compared with both control group and (vehicle suspension+imiquimod ) group.  


2019 ◽  
Vol 17 ◽  
pp. 205873921983248
Author(s):  
Shengchuan Huang ◽  
Nina Qu ◽  
Yanming Men ◽  
Zhen Liu

The study was aimed to explore the possible function of thermal ablation treatment on T helper 17 (Th17) cells and regulatory T (Treg) cells in transplantation of hepatocellular carcinoma in mice. In total, 60 male C57BL/6 mice were divided into control group, model group, and treat group. Flow cytometry was used to detect the frequency of Th17 and Treg cells in peripheral blood. The levels of interleukin (IL)-17, IL-23, IL-10, and transforming growth factor beta (TGF-β) in serum were detected by enzyme-linked immunosorbent assay (ELISA).The levels of IL-17, RORγt, Foxp3, and TGF-β mRNA in tumor tissues were detected by real-time fluorescence quantitative PCR (qRT-PCR). Compared with the model group, tumor size was significantly decreased after thermal ablation treatment. After treatment, the frequency of Th17 cells in peripheral blood was significantly decreased, while the frequency of Treg cells was profoundly increased ( P < 0.05). The levels of IL-17 and IL-23 were significantly downregulated, while IL-10 and TGF-β levels were upregulated ( P < 0.05). IL-17 and RORγt mRNA levels in tumor tissues were significantly decreased ( P < 0.05), and Foxp3 and TGF-β mRNA levels were significantly increased ( P < 0.05). Thermal ablation treatment plays a positive role in the treatment of hepatoma in mice through affecting the imbalance of Th17/Treg cells.


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