Renal protective effects of aspalathin and nothofagin from rooibos (Aspalathus linearis) in a mouse model of sepsis

Background: Aspalathin (Aspt) and nothofagin (Not) were reported to have antioxidant activity and are the two major active dihydrochalcones in green rooibos. This study was conducted to determine whether Asp and Not can modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. Methods: The potential of Aspt and Not treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessing blood urea nitrogen (BUN), serum creatinine, total urine protein, levels of lactate dehydrogenase (LDH), nitric oxide (NO), tumour necrosis factor (TNF)-α, interleukin (IL)-6, and myeloperoxidase (MPO), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Results: Treatment with Aspt and Not decreased plasma levels of BUN, creatinine, urine protein, and LDH in mice with CLP-induced renal damage. Moreover, Aspt and Not inhibited nuclear factor (NF)-κB activation and reduced the induction of NO synthase and excessive production of nitric acid. Aspt and Not treatment also reduced the plasma levels of NO, TNF-α, IL-6, and MPO and reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defence system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in the kidney tissues. Conclusion: Our results suggest that Aspt and Not protect mice against sepsis-triggered renal injury.