1. Protective Effects of Total Flavonoids from Lysimachia christinae on Calcium Oxalate-Induced Oxidative Stress in a Renal Cell Line and Renal Tissue
- Author
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Wenjie Huang, Jia-Jian Chen, Jia-Hao Huang, Xiao-Jun Huang, Jian Wang, Qing Hu, Ting-Ting Tao, Bo-Dong Lv, and Jun Fu
- Subjects
Antioxidant ,biology ,Article Subject ,Chemistry ,medicine.medical_treatment ,Calcium oxalate ,chemistry.chemical_element ,Calcium ,Pharmacology ,medicine.disease_cause ,Malondialdehyde ,Superoxide dismutase ,Heme oxygenase ,chemistry.chemical_compound ,Other systems of medicine ,Complementary and alternative medicine ,medicine ,biology.protein ,NAD+ kinase ,Oxidative stress ,RZ201-999 - Abstract
Background: Flavonoids are compounds with 2-phenylchromone as the basic mother nucleus and are natural antioxidant components of Lysimachia christinae. We previously demonstrated that total flavonoids from L. christinae (TFL) reduce calcium and oxalic acid concentrations in urine and can reduce oxidative stress (OS) in renal tissue, thus, inhibiting calcium oxalate (CaOx) stone formation. The aim of this study was to investigate whether TFL reduced OS in renal tissue, thereby inhibiting CaOx stone formation through the nuclear factor-E2 related factor 2 (Nrf2)/antioxidant response element (ARE) pathway.Methods: The rat model of CaOx stone was established by providing rats with drinking water containing 0.5% glycol and 2% ammonium chloride. After 4 weeks of treatment with different doses of TFL (62.5, 125, and 250 mg/kg/d), body and kidney weights of the rats were measured. CaOx crystal formation was observed under the microscope and the renal tissue contents of superoxide dismutase (SOD) and malondialdehyde (MDA) were analyzed. HK-2 cells were divided into two groups: treatment with CaOx crystals or CaOx crystals + TFL. Other HK-2 cells were treated with small interfering RNA targeting nuclear factor-E2 related factor 2 (Nrf2) and divided into the same two groups. The activities of SOD and content of MDA were measured. The expression of Nrf2, heme oxygenase (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO-1) were detected using western blot.Results: In the in vitro study, TFL significantly increased nuclear Nrf2 and expression of the downstream antioxidant genes, HO-1 and NQO-1. Furthermore, TFL increased superoxide dismutase activity and decreased the malondialdehyde content, thereby alleviating OS in renal tubular epithelial cells. Moreover, silencing the expression of Nrf2 blocked the protective effect of TFL on CaOx-induced OS. In the in vivo study TFL protected the renal cell line and renal tissue against injury, reduced CaOx-induced OS in renal tissue, and reduced CaOx crystal formation.Conclusions: TFL reduces CaOx-induced OS in renal tissue by activating the nuclear Nrf2/antioxidant response element (ARE) pathway.
- Published
- 2021