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  • Frontiers Media SA  (18)
  • Li, Chen  (18)
  • Pharmacy  (18)
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  • Frontiers Media SA  (18)
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  • Pharmacy  (18)
  • 1
    Online Resource
    Online Resource
    Recent Developments in Pharmacological Effect, Mechanism and Application Prospect of Diazeniumdiolates
    Frontiers Media SA ; 2020
    In:  Frontiers in Pharmacology Vol. 11 ( 2020-6-23)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 11 ( 2020-6-23)
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2020.00923
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2020
    detail.hit.zdb_id: 2587355-6
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  • 2
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    DataSheet9.ZIP
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-3-23)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-3-23)
    Abstract: Bone homeostasis only exists when the physical function of osteoblast and osteoclast stays in the balance between bone formation and resorption. Bone resorption occurs when the two processes are uncoupled, shifting the balance in favour of bone resorption. Excessive activation of osteoclasts leads to a range of osteolytic bone diseases including osteoporosis, aseptic prosthesis loosening, rheumatoid arthritis, and osteoarthritis. Receptor activator of nuclear factor kappa-B ligand (RANKL) and its downstream signaling pathways are recognized as key mediators that drive the formation and activation of osteoclastic function. Hence, osteoclast formation and/or its function remain as dominant targets for research and development of agents reaching the treatment towards osteolytic diseases. Chrysin (CHR) is a flavonoid with a wide range of anti-inflammatory and anti-tumor effects. However, its effect on osteoclasts remains unknown. In this study, we found the effects of CHR on inhibiting osteoclast differentiation which were assessed in terms of the number and size of TRAcP positive multinucleated osteoclasts (OCs). Further, the inhibitory effects of CHR on bone resorption and osteoclast fusion of pre-OC were assessed by hydroxyapatite resorption pit assay and F-actin belts staining; respectively. Western blotting analysis of RANKL-induced signaling pathways and immunofluorescence analysis for p65 nuclear translocation in response to RANKL-induced osteoclasts were used to analyze the mechanism of action of CHR affecting osteoclasts. Lastly, the murine calvarial osteolysis model revealed that CHR could protect against particle-induced bone destruction in vivo . Collectively, our data strongly suggested that CHR with its promising anti-tumor effects would also be a potential therapeutic agent for osteolytic diseases.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.793087
    DOI: 10.3389/fphar.2022.793087.s001
    DOI: 10.3389/fphar.2022.793087.s002
    DOI: 10.3389/fphar.2022.793087.s003
    DOI: 10.3389/fphar.2022.793087.s004
    DOI: 10.3389/fphar.2022.793087.s005
    DOI: 10.3389/fphar.2022.793087.s006
    DOI: 10.3389/fphar.2022.793087.s007
    DOI: 10.3389/fphar.2022.793087.s008
    DOI: 10.3389/fphar.2022.793087.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 3
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    Online Resource
    Table1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-12-5)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-12-5)
    Abstract: The cyclic GMP-AMP synthase-stimulator of interferon genes signal transduction pathway is critical in innate immunity, infection, and inflammation. In response to pathogenic microbial infections and other conditions, cyclic GMP-AMP synthase (cGAS) recognizes abnormal DNA and initiates a downstream type I interferon response. This paper reviews the pathogenic mechanisms of stimulator of interferon genes (STING) in different organs, including changes in fibrosis-related biomarkers, intending to systematically investigate the effect of the cyclic GMP-AMP synthase-stimulator of interferon genes signal transduction in inflammation and fibrosis processes. The effects of stimulator of interferon genes in related auto-inflammatory and neurodegenerative diseases are described in this article, in addition to the application of stimulator of interferon genes-related drugs in treating fibrosis.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.1033982
    DOI: 10.3389/fphar.2022.1033982.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
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  • 4
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    Water decoction of Pericarpium citri reticulatae and Amomi fructus ameliorates alcohol-induced liver disease involved in the modulation of gut microbiota and TLR4/NF-κB pathway
    Frontiers Media SA ; 2024
    In:  Frontiers in Pharmacology Vol. 15 ( 2024-6-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 15 ( 2024-6-20)
    Abstract: Alcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury. Methods C57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury. Results Treatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice. Conclusion Administration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut–liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2024.1392338
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2587355-6
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  • 5
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    Online Resource
    Image1.pdf
    Frontiers Media SA ; 2023
    In:  Frontiers in Pharmacology Vol. 14 ( 2023-3-24)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 14 ( 2023-3-24)
    Abstract: Introduction: Chronic kidney disease (CKD) can lead to significant elevation of 1-deoxysphingolipids (1-deoxySL). The increase of 1-deoxySL in turn can result in mitochondrial damage and oxidative stress, which can cause further progression of CKD. Methods: This study assessed the therapeutic effect of Astragaloside IV (AST) against 1-deoxySL-induced cytotoxicity in vitro and in rats with CKD. HK-2 cells were exposed to 1-deoxysphinganine (doxSA) or doxSA + AST. doxSA-induced mitochondrial dysfunction and oxidative stress were evaluated by immunostaining, real-time PCR, oxidative stress sensor, and transmission electron microscopy. The potential effects of AST on kidney damage were evaluated in a rat 5/6 nephrectomy (5/6 Nx) model of CKD. Results: The findings of in vitro experiments showed that doxSA induced mitochondrial damage, oxidative stress, and apoptosis. AST markedly reduced the level of mitochondrial reactive oxygen species, lowered apoptosis, and improved mitochondrial function. In addition, exposure to AST significantly induced the phosphorylation of p62 and the nuclear translocation of Nrf2 as well as its downstream anti-oxidant genes. p62 knock-down fully abolished Nrf2 nuclear translocation in cells after AST treatment. However, p62 knock-down did not affect TBHQ-induced Nrf2 nuclear translocation, indicating that AST can ameliorate doxSA-induced oxidative stress through modulation of p62 phosphorylation and Nrf2 nuclear translocation. Conclusion: The findings indicate that AST can activate Nrf2 antioxidant pathway in a p62 dependent manner. The anti-oxidative stress effect and the further mitochondrial protective effect of AST represent a promising therapeutic strategy for the progression of CKD.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2023.1092475
    DOI: 10.3389/fphar.2023.1092475.s001
    DOI: 10.3389/fphar.2023.1092475.s002
    DOI: 10.3389/fphar.2023.1092475.s003
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2587355-6
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  • 6
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    Basolateral Amygdala Serotonin 2C Receptor Regulates Emotional Disorder-Related Symptoms Induced by Chronic Methamphetamine Administration
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-2-8)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-2-8)
    Abstract: Globally, methamphetamine (MA) is the second most abused drug, with psychotic symptoms being one of the most common adverse effects. Emotional disorders induced by MA abuse have been widely reported both in human and animal models; however, the mechanisms underlying such disorders have not yet been fully elucidated. In this study, a chronic MA administration mouse model was utilized to elucidate the serotonergic pathway involved in MA-induced emotional disorders. After 4 weeks of MA administration, the animals exhibited significantly increased depressive and anxious symptoms. Molecular and morphological evidence showed that chronic MA administration reduced the expression of the 5-hydroxytryptamine (5-HT) rate-limiting enzyme, tryptophan hydroxylase 2, in the dorsal raphe and the concentrations of 5-HT and its metabolite 5-hydroxyindoleacetic acid in the basolateral amygdala (BLA) nuclei. Alterations in both 5-HT and 5-HT receptor levels occurred simultaneously in BLA; quantitative polymerase chain reaction, western blotting, and fluorescence analysis revealed that the expression of the 5-HT2C receptor (5-HT 2C R) increased. Neuropharmacology and virus-mediated silencing strategies confirmed that targeting 5-HT 2C R reversed the depressive and anxious behaviors induced by chronic MA administration. In the BLA, 5-HT 2C R-positive cells co-localized with GABAergic interneurons. The inactivation of 5-HT 2C R ameliorated impaired GABAergic inhibition and decreased BLA activation. Thus, herein, for the first time, we report that the abnormal regulation of 5-HT 2C R is involved in the manifestation of emotional disorder-like symptoms induced by chronic MA use. Our study suggests that 5-HT 2C R in the BLA is a promising clinical target for the treatment of MA-induced emotional disorders.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.627307
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2587355-6
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  • 7
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    Online Resource
    Saikosaponin D Rescues Deficits in Sexual Behavior and Ameliorates Neurological Dysfunction in Mice Exposed to Chronic Mild Stress
    Frontiers Media SA ; 2021
    In:  Frontiers in Pharmacology Vol. 12 ( 2021-2-16)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 12 ( 2021-2-16)
    Abstract: Often associated with sexual dysfunction (SD), chronic stress is the main contributing risk factor for the pathogenesis of depression. Radix bupleuri had been widely used in traditional Chinese medicine formulation for the regulation of emotion and sexual activity. As the main active component of Radix bupleuri, saikosaponin D (SSD) has a demonstrated antidepressant effect in preclinical studies. Herein, we sought to investigate the effect of SSD to restore sexual functions in chronically stressed mice and elucidate the potential brain mechanisms that might underly these effects. SSD was gavage administered for three weeks during the induction of chronic mild stress (CMS), and its effects on emotional and sexual behaviors in CMS mice were observed. The medial posterodorsal amygdala (MePD) was speculated to be involved in the manifestation of sexual dysfunctions in CMS mice. Our results revealed that SSD not only alleviated CMS-induced depressive-like behaviors but also rescued CMS-induced low sexual motivation and poor sexual performance. CMS destroyed astrocytes and activated microglia in the MePD. SSD treatment reversed the changes in glial pathology and inhibited neuroinflammatory and oxidative stress in the MePD of CMS mice. The neuronal morphological and functional deficits in the MePD were also alleviated by SSD administration. Our results provide insights into the central mechanisms involving the brain associated with sexual dysfunction. These findings deepen our understanding of SSD in light of the psychopharmacology of stress and sexual disorders, providing a theoretical basis for its potential clinical application.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2021.625074
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 8
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    Table1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Pharmacology Vol. 13 ( 2022-6-20)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 13 ( 2022-6-20)
    Abstract: Background: Although major advances have been made in the pathogenesis and management of pulmonary arterial hypertension (PAH), the endothelin system is still considered to play a vital role in the pathology of PAH due to its vasoconstrictive action. Endothelin receptor antagonists (ERAs), either as monotherapy or in combination with other drugs, have attracted much attention in the treatment of this lethal disease, and research is continuing. Methods: A novel ERA, pipersentan 5-(1,3-Benzodioxol-5-yl)-6-[2-(5-bromopyrimidin-2-yl)oxyethoxy]-N-(2-methoxyethylsulfamoyl)pyrimidin-4-amine, was recently synthesized and the physicochemical characterizations and the pharmacology both in vitro and in vivo were studied. Results: This orally administered ERA can both competitively and selectively inhibit the binding of endothelin-1 (ET-1) to its receptors with good physicochemical characteristics. Pipersentan efficaciously antagonized the effects of ET-1 on pulmonary artery smooth muscle cell proliferation, migration and calcium mobilization and effectively improved right ventricular hypertrophy and pulmonary arterial pressure in both monocrotaline- and hypoxia-induced pulmonary hypertension (PH) rat models. Conclusions: This profile identifies pipersentan as a new agent for treating ET-1 system activation-related PH.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2022.920222
    DOI: 10.3389/fphar.2022.920222.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 9
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    N-p-coumaroyloctopamine ameliorates hepatic glucose metabolism and oxidative stress involved in a PI3K/AKT/GSK3β pathway
    Frontiers Media SA ; 2024
    In:  Frontiers in Pharmacology Vol. 15 ( 2024-4-25)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 15 ( 2024-4-25)
    Abstract: Type 2 diabetes mellitus is regarded as a chronic metabolic disease characterized by hyperglycemia. Long-term hyperglycemia may result in oxidative stress, damage pancreatic β-cell function and induce insulin resistance. Herein we explored the anti-hypoglycemic effects and mechanisms of action of N- p -coumaroyloctopamine (N-p-CO) in vitro and in vivo . N-p-CO exhibited high antioxidant activity, as indicated by the increased activity of SOD, GSH and GSH-Px in HL-7702 cells induced by both high glucose (HG) and palmitic acid (PA). N-p-CO treatment significantly augmented glucose uptake and glycogen synthesis in HG/PA-treated HL-7702 cells. Moreover, administration of N-p-CO in diabetic mice induced by both high-fat diet (HFD) and streptozotocin (STZ) not only significantly increased the antioxidant levels of GSH-PX, SOD and GSH, but also dramatically alleviated hyperglycemia and hepatic glucose metabolism in a dose-dependent manner. More importantly, N-p-CO upregulated the expressions of PI3K, AKT and GSK3β proteins in both HG/PA-induced HL-7702 cells and HFD/STZ-induced mice. These findings clearly suggest that N-p-CO exerts anti-hypoglycemic and anti-oxidant effects, most probably via the regulation of a PI3K/AKT/GSK3β signaling pathway. Thus, N-p-CO may have high potentials as a new candidate for the prevention and treatment of diabetes.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    DOI: 10.3389/fphar.2024.1396641
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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  • 10
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    Online Resource
    DataSheet9.PDF
    Frontiers Media SA ; 2024
    In:  Frontiers in Pharmacology Vol. 15 ( 2024-6-26)
    Details
    In: Frontiers in Pharmacology, Frontiers Media SA, Vol. 15 ( 2024-6-26)
    Abstract: Changes in intestinal flora and intestinal barrier in patients with preclinical and diagnosed rheumatoid arthritis (RA) suggest that intestinal flora and intestinal barrier play an important role in the induction and persistence of RA. Huangqin Qingre Chubi Capsule (HQC) is a clinically effective herbal formula for the treatment of RA, but its therapeutic mechanism has not been fully clarified. Materials and methods In this study, real-time qPCR (RT-qPCR), 16SrRNA sequencing, Western blot (WB), immunofluorescence and other methods were used to investigate whether HQC inhibited RA. Results Based on research in collages-induced arthritis (CIA) model in mice, human colon cancer cell line (Caco-2), and fibroblast-like synoviocytes (FLS) from RA patients, we found that intestinal flora was disturbed in CIA model group, intestinal barrier was damaged, and lipolyaccharide (LPS) level was increased, and HQC could regulate intestinal flora and intestinal barrier and reduce LPS translocation into blood. Antibiotic depletion weakened the anti-RA effect of HQC, and HQC fecal microbiota transplantation alleviated RA pathology. In addition, LPS increased the expression of RA pathologic factors MMP3, Fibronectin and inflammatory factors IL-6, TNF-α, IL-1β and IL-8, indicating that elevated peripheral blood level of LPS was related to RA pathology. Conclusion The dysregulation of intestinal flora and the disruption of intestinal barrier are significant factors in the development of RA. HQC improves RA by regulating intestinal flora, intestinal barrier and inhibiting LPS translocation into blood. The study unveiles RA’s new pathogenesis and laid a scientific groundwork for advancing HQC therapy for RA.
    Type of Medium: Online Resource
    ISSN: 1663-9812
    URL: Article
    URL: Article
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    URL: Article
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    URL: Article
    URL: Article
    URL: Article
    URL: Article
    DOI: 10.3389/fphar.2024.1422245
    DOI: 10.3389/fphar.2024.1422245.s001
    DOI: 10.3389/fphar.2024.1422245.s002
    DOI: 10.3389/fphar.2024.1422245.s003
    DOI: 10.3389/fphar.2024.1422245.s004
    DOI: 10.3389/fphar.2024.1422245.s005
    DOI: 10.3389/fphar.2024.1422245.s006
    DOI: 10.3389/fphar.2024.1422245.s007
    DOI: 10.3389/fphar.2024.1422245.s008
    DOI: 10.3389/fphar.2024.1422245.s009
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2024
    detail.hit.zdb_id: 2587355-6
    SSG: 15,3
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