Geniposidic Acid Attenuates Chronic Tubulointerstitial Nephropathy Through Regulation of the NF‐ƙB/Nrf2 Pathway Via Aryl Hydrocarbon Receptor Signaling
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引用次数: 0
Abstract
Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti‐fibrotic and anti‐inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine‐induced chronic tubulointerstitial nephropathy (TIN) and in idole‐3‐acetic acid (IAA)–stimulated NRK‐52E cells. Acetate and n‐butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF‐ƙB) and its target gene products as well as activated antioxidative nuclear factor‐erythroid‐2‐related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA‐stimulated NRK‐52E cells. The inhibitory effect of GPA on AHR, NF‐Ƙb, and Nrf2 signaling were partially abolished in IAA‐stimulated NRK‐52E cells treated with CH223191 compared with untreated IAA‐stimulated NRK‐52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.
期刊介绍:
Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field.
Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters.
By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.