Background
JSH-23, exhibited inhibitory effect on nuclear translocation and NF-κB transcriptional activity with an IC50 value of 7.1 μM in lipopolysaccharide (LPS)-stimulated macrophages RAW 264.7 [1].
JSH-23 (1 μM) monotherapy significantly reduced the chemotactic sensitivity of the cells to SDF1. The co-treatment with cordycepin (10 μM) and JSH-23 (1 μM) significantly inhibited the expression of CXCR4 [2].
JSH-23 (1 and 3 mg/kg) treatment significantly reversed the nerve conduction and nerve blood flow deficits seen in diabetic animals [1]. Protein expression studies showed that nuclear translocation of p65/p50 subunit was inhibited by JSH-23 treatment in the sciatic nerve. The treatment also lowered the elevated IL-6, TNF-α, cyclo-oxygenase (COX-2) and inducible nitric oxide synthase (iNOS) levels/expression [1]. Mice were treated with JSH-23 (20 or 40 mg/kg) which directly affects NF-κB transcriptional activity. Kidney function, tubular injury (ATN, serum neutrophil gelatinase-associated lipocalin [NGAL], but not apoptosis) and myeloperoxidase (MPO) activity were significantly improved by JSH-23 (40 mg/kg) [3].
参考文献:
[1]. Kumar A, Negi G, Sharma S S. JSH?\23 targets nuclear factor?\kappa B and reverses various deficits in experimental diabetic neuropathy: effect on neuroinflammation and antioxidant defence[J]. Diabetes, Obesity and Metabolism, 2011, 13(8): 750-758.
[2]. Guo Z, Chen W, Dai G, et al. Cordycepin suppresses the migration and invasion of human liver cancer cells by downregulating the expression of CXCR4[J]. International journal of molecular medicine, 2020, 45(1): 141-150.
[3]. Ozkok A, Ravichandran K, Wang Q, et al. NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI)[J]. Toxicology letters, 2016, 240(1): 105-113.
JSH-23 对核转位和 NF-κB 转录活性具有抑制作用，在脂多糖 (LPS) 刺激的巨噬细胞中 IC50 值为 7.1 μM RAW 264.7 [1]。
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JSH-23 (1 μM) 单一疗法显着降低了细胞对 SDF1 的趋化敏感性。虫草素（10 μM）和JSH-23（1 μM）联合处理显着抑制了CXCR4[2]的表达。
JSH-23（1 和 3 mg/kg）治疗可显着逆转糖尿病动物中观察到的神经传导和神经血流缺陷[1]。蛋白质表达研究表明，坐骨神经中的 JSH-23 处理可抑制 p65/p50 亚基的核转位。该治疗还降低了升高的 IL-6、TNF-α、环氧合酶 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 水平/表达 [1]。用直接影响 NF-κB 转录活性的 JSH-23（20 或 40 mg/kg）处理小鼠。 JSH-23 (40 mg/kg) 显着改善肾功能、肾小管损伤（ATN、血清中性粒细胞明胶酶相关脂质运载蛋白 [NGAL]，但不影响细胞凋亡）和髓过氧化物酶 (MPO) 活性[3].
Protocol
| Cell experiment [1]: |
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Cell lines
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Normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549
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Preparation Method
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Cells were treated with different concentrations of NF-κB inhibitor JSH-23 (5, 10, 20, 30, 40, and 50 μM, respectively) for 24 h.
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Reaction Conditions
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5, 10, 20, 30, 40, and 50 μM for 24 hours
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Applications
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With the increase in JSH-23 concentration, the inhibition rate for cell viability was gradually increased, and significant differences existed when the JSH-23 concentration was greater than 20 μM.
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| Animal experiment [2]: |
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Animal models
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Male 12-week-old normotensive Wistar rats and Prague hereditary hypertriglyceridemic (HTG) rats
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Preparation Method
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Mice were given a total dose of either 20 mg/kg of JSH-23 (10 mg/kg 8 h prior to cisplatin injection and 5 mg/kg on days 1 and 2 after cisplatin injection) or a total dose of 40 mg/kg body weight of JSH-23 (20 mg/kg 8 h prior to cisplatin injection and 20 mg/kg on day 1 after cisplatin injection) or vehicle (DMSO).
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Dosage form
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Intraperitoneal injection, 5, 10, 20 mg/kg
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Applications
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JSH-23 (total dose of 40 mg/kg) resulted in a significant decrease in BUN, serum creatinine and serum NGAL. NGAL is an early diagnostic biomarker of cisplatin-induced AKI. JSH-23 had no effect on BUN and serum creatinine in vehicle-treated mice (Fig. 2).
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参考文献:
[1]: Huang L, Li F, Deng P, et al. MicroRNA-223 promotes tumor progression in lung cancer A549 cells via activation of the NF-κB signaling pathway[J]. Oncology research, 2016, 24(6): 405.
[2]: Ozkok A, Ravichandran K, Wang Q, et al. NF-κB transcriptional inhibition ameliorates cisplatin-induced acute kidney injury (AKI)[J]. Toxicology letters, 2016, 240(1): 105-113.
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