Nephroprotective mechanisms of Rhizoma Chuanxiong and Radix et Rhizoma Rhei against acute renal injury and renal fibrosis based on network pharmacology and experimental validation

Jun Li; Tonglu Li; Zongping Li; Zhiyong Song; Xuezhong Gong

doi:10.3389/fphar.2023.1154743

Nephroprotective mechanisms of Rhizoma Chuanxiong and Radix et Rhizoma Rhei against acute renal injury and renal fibrosis based on network pharmacology and experimental validation

Front Pharmacol. 2023 May 9:14:1154743. doi: 10.3389/fphar.2023.1154743. eCollection 2023.

Authors

Jun Li¹, Tonglu Li¹, Zongping Li¹, Zhiyong Song¹, Xuezhong Gong¹

Affiliation

¹ Department of Nephrology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

Abstract

The molecular mechanisms of Rhizoma Chuanxiong (Chuanxiong, CX) and Rhei Radix et Rhizoma (Dahuang, DH) in treating acute kidney injury (AKI) and subsequent renal fibrosis (RF) were investigated in this study by applying network pharmacology and experimental validation. The results showed that aloe-emodin, (-)-catechin, beta-sitosterol, and folic acid were the core active ingredients, and TP53, AKT1, CSF1R, and TGFBR1 were the core target genes. Enrichment analyses showed that the key signaling pathways were the MAPK and IL-17 signaling pathways. In vivo experiments confirmed that Chuanxiong and Dahuang pretreatments significantly inhibited the levels of SCr, BUN, UNAG, and UGGT in contrast media-induced acute kidney injury (CIAKI) rats (p < 0.001). The results of Western blotting showed that compared with the control group, the protein levels of p-p38/p38 MAPK, p53, and Bax in the contrast media-induced acute kidney injury group were significantly increased, and the levels of Bcl-2 were significantly reduced (p < 0.001). Chuanxiong and Dahuang interventions significantly reversed the expression levels of these proteins (p < 0.01). The localization and quantification of p-p53 expression in immunohistochemistry technology also support the aforementioned results. In conclusion, our data also suggest that Chuanxiong and Dahuang may inhibit tubular epithelial cell apoptosis and improve acute kidney injury and renal fibrosis by inhibiting p38 MAPK/p53 signaling.

Keywords: Chuanxiong–Dahuang herb pair; acute kidney injury; experimental validation; network pharmacology; p53 regulation; renal fibrosis.

Grants and funding

This project was supported by the National Natural Science Foundation of China (Nos 82074387 and 81873280), Shanghai Municipal Science and Technology Commission Project (No. 20Y21902200) and Shanghai Municipal Health Commission Project ZY (2021-2023)-0207-01.