FITOTERAPIA
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2019
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IF 2.431
Chen-Jun Ye,Sheng-An Li,Yun Zhang,Wen-Hui Lee
Naturally occurring monoterpenes are known for their various pharmacological activities including anti-inflammation. K V 1.3 ion channel is a voltage-gated potassium channel and has been validated as a drug target for autoimmune and chronic inflammatory diseases like psoriasis . Here we experimentally test the direct interaction between monoterpenes and K V 1.3 ion channel. Our electrophysiological analysis determined that monoterpenes (geraniol, nerol , β-citronellol, citral and linalool) have inhibitory effects on K V 1.3 ion channel. Representatively, geraniol reversibly blocked K V 1.3 currents in a voltage-dependent manner with an IC 50 of 490.50 ± 1.04 μM at +40 mV in HEK293T cells. At the effective concentrations, geraniol also inhibited cytokine secretion of activated human T cells, including IL-2, TNF-α and IFN-γ. In an imiquimod-induced psoriasis-like animal model, geraniol administration significantly reduced psoriasis area and severity index scores, ameliorated the deteriorating histopathology and decreased the degree of splenomegaly . Together, our findings not only suggest that monoterpenes may serve as lead molecules for the development of K V 1.3 inhibitors, but also indicate that geraniol could be considered as a promising therapeutic candidate to treat autoimmune diseases.
研究领域:
药理学
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免疫学
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炎症研究
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药物开发
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产品关联
DOI
PubMed
高影响因子
BRITISH JOURNAL OF HAEMATOLOGY
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2021
·Vol. 195
·期 2
·267-275
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IF 6.998
Zaoke He,Xiaoqin Sun,Shixiang Wang,Dongsheng Bai,Xiangyu Zhao,Ying Han,Piliang Hao,Xue-Song Liu
Summary The expression of GGCT (γ-glutamyl cyclotransferase) is upregulated in various human cancers. γ-glutamyl cyclotransferase enzyme activity was originally purified from human red blood cells (RBCs), but the physiological function of GGCT in RBCs is still not clear. Here we reported that Ggct deletion in mice leads to splenomegaly and progressive anaemia phenotypes, due to elevated oxidative damage and the shortened life span of Ggct −/− RBCs. Ggct −/− RBCs have increased reactive oxygen species (ROS), and are more sensitive to H 2 O 2 -induced damage compared to control RBCs. Glutathione (GSH) and GSH synthesis precursor l -cysteine are decreased in Ggct −/− RBCs. Our study suggests a critical function of Ggct in RBC redox balance and life span maintenance through regulating GSH metabolism.
研究领域:
血液学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2021
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IF 4.36
Li-na Ji,Shan Wu,Dan-qing Fu,Si-jia Fang,Guan-qun Xie,Yong-sheng Fan,Jie Bao
Ethnopharmacological relevance Jieduquyuziyin prescription (JP) is a traditional Chinese medicine (TCM) formula. According to both TCM theory and more than a decade of clinical practice, JP has been testified to be effective for systemic lupus erythematosus (SLE) treatment as an approved hospital prescription in China. Aim of the study To determine the effect of JP on the treatment of SLE by glucocorticoid (GC) and to further examine the molecular mechanisms. Materials and methods We conducted in vivo experiments to estimate the effect of JP on hepatic gluconeogenesis in MRL/lpr mice treated with GC. Additionally, isoproterenol (ISO) induced hepatic gluconeogenesis model and GC-treated MRL/lpr mouse hepatocytes were carried out in vitro experiments to verify the effect of JP on gluconeogenesis. Results The results showed that JP combined with GC could effectively alleviate the lupus symptoms in MRL/lpr mice and improve the pathological changes of the kidney and liver. And the combination of JP reduced the side effects caused by GC, which was related to the inhibition of GC-induced hepatic gluconeogenesis in MRL/lpr mice. Specifically, JP up-regulated the expression of glucocorticoid receptor (GR) α, phosphoinositide-3-kinase (PI3K) and Akt restrained by GC to reduce the production of forkhead box O1 (FoxO1), peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α), and the gluconeogenic genes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). In viv o, the use of JP either alone or with GC could reduce spleen enlargement , high levels of serum antibodies, aggravated urine protein and renal pathological damage in MRL/lpr mice. Furthermore, the glucose content was reduced in the liver of MRL/lpr mice treated with JP, and the liver damage and steatosis were also alleviated. In vitro , the expressions of PI3K and Akt increased and the expressions of FoxO1, PGC-1α, PEPCK and G6Pase decreased after JP treatment in ISO-treated hepatocytes. Compared with MRL/MP mice, we found that JP could significantly inhibit the expression of gluconeogenesis in the hepatocytes of MRL/lpr mice induced by GC to a greater extent. Conclusions The therapeutic effect of JP on GC-induced is likely related to hepatic gluconeogenesis, which provides a new perspective to reveal the positive role of JP in SLE.
研究领域:
药理学
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免疫学
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分子生物学
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中医
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产品关联
DOI
PubMed
高影响因子
Advanced Healthcare Materials
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2024
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IF 10
Shuang Xie,Yu Li,Wenxiong Cao,Jiawen Peng,Kun Huang,Jie Meng,Xiaohong Li
Intracellular bacteria are the major cause of serious infections including sepsis and peritonitis, but face great challenges in fighting against the stubborn intracellular small colony variants (SCVs). Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHA G ) are inoculated into ε-polylysine NGs to obtain NG@G1-mHA G2 through crosslinking with phenylboronic acid and tannic acid. The H 2 O 2 consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose-mediated uptake into macrophages, the acid-triggered degradation of mHA G NPs generates Ca 2+ to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1-mHA G2 treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.
研究领域:
纳米技术
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药学
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传染病学
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生物医学工程
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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