Translational Andrology and Urology
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2024
·Vol. 13
·期 9
·1971
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IF 1.9
Jiahao Jiang,Fei Xiao,Lanxin Yang,Yan Zeng,Jing Chen,Hengcheng Zhu,Lingqi Liu
Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common male urological disease characterized by chronic pelvic pain and various discomforts. Astaxanthin (AST) has multiple functions, including anti-inflammatory property, but it is unclear whether AST plays a key role in CP/CPPS and how it works. This study aimed to investigate the protective effect of AST on CP/CPPS in rats and the underlying mechanism. Methods A CP/CPPS rat model was induced by intraprostatic injection of carrageenan and the blood specimens and prostates were harvested for further research after oral administration of AST for 4 weeks. Results Tactile allodynia test showed that AST ameliorated chronic pelvic pain in a dose-depended manner. In addition, histological evaluation indicated that AST alleviated CP/CPPS rat prostate histological inflammation. Meanwhile, AST suppressed the expression of proinflammatory cytokines, including interleukin-1β (IL-1β), IL-6, IL-8, and tumor necrosis factor-α (TNF-α). Besides, AST inhibited the activities of prostaglandin E2 (PGE2) and cyclooxygenase 2 (COX2). Furthermore, AST decreased the activation of the nuclear factor-κB (NF-κB) signaling pathway. Conclusions Our study has shown that AST exerts an anti-inflammatory and protective effect against CP/CPPS and the function is mediated at least through the suppression of NF-κB signaling pathway. These results provide evidence of AST as the potential agents for the treatment of CP/CPPS.
研究领域:
泌尿科
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药理学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
NEUROCHEMICAL RESEARCH
·
2022
·Vol. 48
·期 2
·625-640
·
IF 4.414
Hui Yuzuo,Zhao Han,Shi Lei,Zhang Haitao
8-Methoxypsoralen (8-MOP) has anti-inflammatory, antioxidant and tissue-repairing abilities. Here, we probed the function and mechanism of 8-MOP in traumatic brain injury (TBI). The in - vivo TBI model was constructed in Sprague-Dawley (SD) rats using controlled cortical impact (CCI) surgery. In parallel, BV2 microglia and HT22 neurons were activated by lipopolysaccharide (LPS) to establish an in-vitro model. The modified neurological score (mNSS) and the Morris water maze experiment were employed to evaluate the rats’ neurological functions. The rats’ brain edema was assessed by the dry and wet method, and neuronal apoptosis in damaged brain tissues was monitored by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) and Nissl’s staining. Immunohistochemistry (IHC) was applied to verify Iba1-microglial activation in brain lesions of rats. The expression of inflammatory cytokines in BV2 microglia and HT22 neurons in the injured lesion of TBI rats was examined by the enzyme-linked immunosorbent assay (ELISA). The levels of iNOS, COX2, TLR4, PPARγ, STAT3, and NF-κB in brain lesions, BV2 microglia and HT22 neurons were compared by Western blot. As a result, 8-MOP administration reduced inflammation and LPS-induced neuronal damage in BV2 microglia. In vivo, 8-MOP treatment relieved neurological deficits in TBI rats, improved cognitive, learning and motor functions and mitigated brain edema and neuroinflammation induced by TBI. Furthermore, LPS or TBI activated the NF-κB and STAT3 pathways and repressed the PPARγ expression. However, 8-MOP treatment attenuated NF-κB and STAT3 phosphorylation and elevated PPARγ levels. Hence, 8-MOP exerts neuroprotective and anti-inflammatory effects in TBI rats by modulating the PPARγ/NF-κB pathway.
研究领域:
神经科学
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药理学
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炎症
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神经保护
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DOI
PubMed
高影响因子
CNS Neuroscience & Therapeutics
·
2023
·Vol. 29
·期 4
·1000-1011
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IF 5.5
Di Zhang,Bei Jing,Zhen-ni Chen,Xin Li,Hui-mei Shi,Ya-chun Zheng,Shi-quan Chang,Li Gao,Guo-ping Zhao
Introduction Sciatica causes intense pain. No satisfactory therapeutic drugs exist to treat sciatica. This study aimed to probe the potential mechanism of ferulic acid in sciatica treatment. Methods Thirty-two SD rats were randomly divided into 4 groups: sham operation, chronic constriction injury (CCI), mecobalamin, and ferulic acid. We conducted RNA sequencing, behavioral tests, ELISA, PCR, western blotting, and immunofluorescence analysis. TAK-242 and JSH23 were administered to RSC96 and GMI-R1 cells to explore whether ferulic acid can inhibit apoptosis and alleviate inflammation. Results RNA sequencing showed that TLR4/NF-κB pathway is involved in the mechanism of sciatica. CCI induced cold and mechanical hyperalgesia; destroyed the sciatic nerve structure; increased IL-1β, IL-6, TNF-α, IL-8, and TGF-β protein levels and IL-1β, IL-6, TNF-α, TGF-β, TLR4, and IBA-1 mRNA levels; and decreased IL-10 and INF-γ protein levels and IL-4 mRNA levels. Immunohistochemistry showed that IBA-1, CD32, IL-1β, iNOS, nNOS, COX2, and TLR4 expression was increased while S100β and Arg-1 decreased. CCI increased TLR4, IBA-1, IL-1β, iNOS, Myd88, p-NF-κB, and p-p38MAPK protein levels. Treatment with mecobalamin and ferulic acid reversed these trends. Lipopolysaccharide (LPS) induced RSC96 cell apoptosis by reducing Bcl-2 and Bcl-xl protein and mRNA levels and increasing Bax and Bad mRNA and IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK protein levels, while ferulic acid inhibited cell apoptosis by decreasing IL-1β, TLR4, Myd88, p-NF-κB, and p-p38MAPK levels and increasing Bcl-2 and Bcl-xl levels. In GMI-R1 cells, Ferulic acid attenuated LPS-induced M1 polarization by decreasing the M1 polarization markers IL-1β, IL-6, iNOS, and CD32 and increasing the M2 polarization markers CD206, IL-4, IL-10 and Arg-1. After LPS treatment, IL-1β, iNOS, TLR4, Myd88, p-p38MAPK, and p-NF-κB levels were obviously increased, and Arg-1 expression was reduced, while ferulic acid reversed these changes. Conclusion Ferulic acid can promote injured sciatic nerve repair by reducing neuronal cell apoptosis and inflammatory infiltration though the TLR4/NF-κB pathway.
研究领域:
神经科学
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药理学
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分子生物学
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细胞生物学
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炎症研究
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产品关联
DOI
PubMed
高影响因子
Frontiers in Pharmacology
·
2022
·
IF 5.988
Zijie Wang,Anan Jiang,Hongmei Xiao,Xiaofan Yuan,Shaoru Zhang,Xinyue Qin
Objective: To study the potential targets and molecular mechanisms of Fritiliariae Irrhosae Bulbus (FIB) in the treatment of ischemic strokes based on a network pharmacology strategy, with a combination of molecular docking and animal experiments.Methods: The active components and targets of FIB were screened by TCMSP database and TCMIP database, and the related targets of ischemic strokes were screened by GeneCards, OMIM, CTD, and DrugBank, then the intersection targets of the two were taken. The protein interaction network was constructed by STRING, the PPI network diagram was drawn by using Cytoscape software, and the key targets of FIB treatment of ischemic strokes were analyzed by MCODE. The DAVID database was used for GO and KEGG enrichment analysis, and the potential pathway of FIB against ischemic strokes was obtained. Molecular docking was performed by using AutoDock Tools 1.5.6 software. Finally, a mouse model of ischemic stroke was established, and the results of network pharmacology were verified by in vivo experiments. Realtime Polymerase Chain Reaction was used to detect the expression levels of relevant mRNAs in the mouse brain tissue. Western blot was used to detect the expression levels of related proteins in the mouse brain tissue.Results: 13 kinds of active components of FIB were screened, 31 targets were found in the intersection of FIB and ischemic strokes, 10 key targets were obtained by MCODE analysis, 236 biological processes were involved in GO enrichment analysis, and key targets of KEGG enrichment analysis were mainly concentrated in Neuroactive light receptor interaction, Calcium signaling pathway, Cholinergic synapse, Hepatitis B, Apoptosis—multiple specifications, Pathways in cancer and other significantly related pathways. There was good binding activity between the screened main active components and target proteins when molecular docking was performed. Animal experiments showed that the infarct volume of brain tissue in the FIB treatment group was considerably reduced. RT-qPCR and the results of Western Blot showed that FIB could inhibit the expression of active-Caspase3, HSP90AA1, phosphorylated C-JUN, and COX2.Conclusion: Based on network pharmacology, the effect of FIB in the treatment of ischemic strokes was discussed through the multi-component-multi-target-multi-pathway. The therapeutic effect and potential mechanisms of FIB on ischemic strokes were preliminarily explored, which provided a ground work for further researches on the pharmacodynamic material basis, mechanism of action and clinical application.
研究领域:
药理学
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神经科学
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分子生物学
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生物信息学
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实验医学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2023
·
IF 5.4
Yan Lin,Xing-Jun Chen,Jing-Jing Li,Lei He,Ya-Ru Yang,Fei Zhong,Ming-Hui He,Yi-Tong Shen,Bo Tu,Xu Zhang,Zhu Zeng
Ethnopharmacology relevance Sophora flavescens Aiton, was a crucial source of Traditional Chinese Medicine (TCM) that has benefited human health for hundreds of years. Alkaloids and flavonoids were the major bioactive constituents from S. flavescens , which had been widely used for liver disease treatment in China. However, the liver-protective components of flavonoids from S. flavescens and their mechanism of action were not clear. Aim of the study This work aimed to evaluate the in vitro hepatoprotective activities of 35 flavonoids from S. flavescens and screen active compounds. Furthermore, it was conducted to demonstrate the hepatoprotective effects of a new active compound (kurarinol A, 1 ) was isolated by authors and the ethyl acetate (EtOAc) extract form S. flavescens against carbon tetrachloride (CCl 4 )-induced hepatic injury in Kunming (KM) mice, meanwhile revealed the potential mechanism. Materials and methods The 35 flavonoids from S. flavescens were co-incubated with HepG2 cells and treated with 0.35% CCl 4 for 6 h cell viability was measured by (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt) (MTS) assay. Then, in vivo animal experiments, the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the serum were analyzed, the degree of hepatic injury was examined using hematoxylin-eosin (H&E) staining, the mRNA expression of Superoxide Dismutase 2 (SOD2), Nuclear factor E2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1), Interleukin 6 (IL-6), Tumor Necrosis Factor-α (TNF-α), interleukin-1β (IL-1β), and the protein levels of nuclear factor-kappa B p65/p-p65 (NF-κB p65/p-p65), toll-like receptor 2 (TLR2), IL-1β and cyclooxygenase-2 (COX2) in hepatic tissues were detected. Results The lavandulyl flavonoid (kurarinol A, 1 ) and the EtOAc extract from S. flavescens showed protective effects on CCl 4 -injured HepG2 cells, increasing cell viability from 24.5% to 61.3% and 91.8%, respectively. What’s more, we found that treatment with kurarinol A ( 1 ) and the EtOAc extract lead to a significant reduction in hepatotoxicity in response to acute CCl 4 exposure. Compared with the model group, experimental results exhibited kurarinol A (10 mg/kg, i.p.) and the EtOAc extract (300 mg/kg, i.p.) could decrease the levels of AST, ALT, ALP and tissue damage. Further mechanistic investigations revealed that up-regulated the mRNA expression of SOD2, Nrf2, OH-1 and down-regulated the IL-1β in liver tissues, respectively. Additionally, Western blot analyses elucidated that inhibition of IL-1β, TLR2, COX-2, NF-κB (p65/p-p65) via TLR2/NF-κB signaling pathway by kurarinol A and the EtOAc extract contribute to its hepatoprotective activity. Conclusion These findings demonstrated that the novel compound (kurarinol A, 1 ) possessed notable hepatoprotective activity against CCl 4 . It was confirmed that kurarinol A had a certain effect on mice with liver damage induced by CCl 4 , and its mechanism could be include inhibiting inflammation and reducing of oxidative stress reaction by regulating expression of related genes and proteins. Thus, kurarinol A could as a novel active agent that contributes to the hepatoprotective activity of S. flavescens for the treatment of live injury.
研究领域:
药理学
·
民族药理学
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分子生物学
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细胞生物学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）