Triptolide attenuates renal damage by limiting inflammatory responses in DOCA-salt hypertension.

Abstract Background Triptolide (TP), a principal bioactive component of traditional Chinese medicine Tripterygium wilfordii Hook. F., has been shown to have immunosuppressive/anti-inflammatory actions in vitro. Moreover, it is well established that inflammatory mechanisms contribute to the progression of hypertension-induced renal injury. Therefore, this study was performed to determine the protective effects of TP on renal injury in salt-sensitive hypertension and to identify the possible mechanisms for TP-induced protection. Methods Ten-week-old male C57BL/6 mice were subjected to uninephrectomy and deoxycorticosterone acetate (DOCA)-salt treatment with or without intraperitoneal administration of various concentrations of TP. Results Five weeks after the treatment, systolic blood pressure measured by tail-cuff plethysmography increased in DOCA-salt-treated mice, but no difference was found between DOCA-salt-treated mice with or without TP treatment. Treatment with TP dose-dependently attenuated increments in urinary albumin and 8-isoprostane excretion, and glomerulosclerosis and tubulointerstitial injury and fibrosis in DOCA-salt-treated mice. Moreover, our data showed that treatment with TP dose-dependently inhibited DOCA-salt-induced interstitial monocyte/macrophage infiltration associated with decreases in renal levels of proinflammatory cytokine/chemokine and adhesion molecule, as well as renal activated NF-κB concentrations. Our results also demonstrated that suppression of inflammatory responses with dexamethasone, an immunosuppressive agent, alleviated DOCA-salt hypertension-induced renal injury. Conclusions TP treatment induced renal protection associated with inhibition of monocyte/macrophage-mediated inflammatory responses without lowering blood pressure. Thus, our data for the first time indicate that TP treatment ameliorates renal injury possibly via attenuating inflammatory responses in salt-sensitive hypertension.