Cell lines

Normal human lung epithelial cell line BEAS-2B and human lung cancer cell line A549

Preparation Method

Cells were treated with different concentrations of NF-κB inhibitor JSH-23 (5, 10, 20, 30, 40, and 50 µM, respectively) for 24 h.

Reaction Conditions

5, 10, 20, 30, 40, and 50 µM for 24 hours

Applications

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.

Animal models

Male 12-week-old normotensive Wistar rats and Prague hereditary hypertriglyceridemic (HTG) rats

Preparation Method

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).

Dosage form

Intraperitoneal injection, 5, 10, 20 mg/kg

Applications

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).

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].

References:
[1]. Kumar A, Negi G, Sharma S S. JSH(C)\23 targets nuclear factor(C)\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.