Clerodendranthus spicatus inhibits epithelial-mesenchymal transition of renal tubular cells through the NF-B/Snail signalling pathway in hyperuricaemia nephropathy

Context: Clerodendranthus spicatus Thunb. (Labiatae) (CS), a perennial traditional Chinese medicinal herb that can reduce serum uric acid (sUA) levels and ameliorate renal function is widely used to treat hyperuricaemic nephropathy (HN). Objective: To investigate the molecular mechanism of action of CS in HN treatment using in vivo and in vitro experiments. Materials and methods: Sprague-Dawley rats were randomly divided into control, HN, CS and positive control allopurinol groups. The HN group was intraperitoneally injected with 750mg/kg oxonic acid potassium (OA), whereas the CS group was injected with OA along with a gavage of CS (low dose 3.125 g/kg, high dose 6.25 g/kg) for five weeks. For in vitro studies, uric acid-treated HK2 cells were used to verify the therapeutic mechanism of CS in HN. Results: HN rats exhibit pathological phenotypes of elevated sUA levels and renal injury. CS significantly improved these symptoms and sUA (p < 0.05) and blood urea nitrogen (p < 0.01) levels, and dramatically improved renal tubular injury in HN rats. The IC50 value of UA (uric acid) in HK2 cells was 826.32 +/- 3.55 lg/mL; however, 120 ng/mL CS had no significant cytotoxicity on HK2 cells. In vivo and in vitro studies showed that CS inhibited NF-kappa B phosphorylation and inhibited alpha-smooth muscle actin (alpha-SMA) and vimentin expression while increasing E-cadherin expression, suggesting that CS inhibited the fibrotic process in renal cells, thus protecting renal function. Discussion and conclusions: These findings provide a fundamental understanding of the application of CS in HN treatment to better guide clinical interventions.