Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway

Lan Yao; Renjie Zhao; Shiyang He; Qi Feng; Yingjin Qiao; Pei Wang; Jun Li

doi:10.1016/j.phymed.2022.154414

Effects of salvianolic acid A and salvianolic acid B in renal interstitial fibrosis via PDGF-C/PDGFR-α signaling pathway

Phytomedicine. 2022 Nov:106:154414. doi: 10.1016/j.phymed.2022.154414. Epub 2022 Aug 27.

Authors

Lan Yao¹, Renjie Zhao², Shiyang He³, Qi Feng⁴, Yingjin Qiao⁵, Pei Wang⁶, Jun Li⁷

Affiliations

¹ Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, China; Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China.
² Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China; Department of Nephrology, the Affiliated Hospital of Chengdu University, Chengdu 610081, China.
³ Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China.
⁴ Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, China.
⁵ Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, China.
⁶ Blood Purification Center, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China; Research Institute of Nephrology, Zhengzhou University, Zhengzhou 450052, China. Electronic address: wangpei146@hotmail.com.
⁷ Basic and Applied Laboratory of Traditional Chinese Medicine, the Fifth Affiliated Hospital of Zunyi Medical University, Zhuhai 519000, China; Key Laboratory of Pharmacology, Zunyi Medical University, Zunyi 563000, China. Electronic address: lijun69-1214@163.com.

PMID: 36057144
DOI: 10.1016/j.phymed.2022.154414

Abstract

Background: Renal interstitial fibrosis (RIF) is the main pathological feature of end-stage renal disease (ESRD) caused by various chronic kidney diseases (CKD), and is closely related to renal dysfunction and patient prognosis. Salvianolic acid A (Sal A) and salvianolic acid B (Sal B), isolated from traditional Chinese medicine Salviae miltiorrhizae, have been confirmed to have anti-fibrotic effects on liver, cardiac and kidney. However, the precise molecular mechanism underlying the nephroprotective effects of Sal A and Sal B, and whether there is a difference between the two in RIF are still unclear.

Purpose: This study investigated the pharmacological effects of Sal A and Sal B in RIF and explore the underlying mechanisms by in vivo and in vitro experiments.

Methods: The nephroprotective effects of Sal A, Sal B and Sal A+B were evaluated by assessing the parameters related to kidney function such as renal histology, renal function, urinary protein NAG, urinary β2 microglobulin. In addition, RIF-related markers such as CTCF and Par3 were also detected. Thereafter, the related protein or gene levels of PDGF-C/PDGFR-α signaling pathways, apoptosis and endoplasmic reticulum stress (ERS) were determined by western blot, real-time PCR, flow cytometry or immunofluorescence staining.

Results: In vivo, the results showed that Sal A, Sal B and Sal A+B partially improved kidney dysfunction, increased the expression of Par-3 and reduced the expression of CTGF, PDGF-C and PDGFR-α. In vitro, the results also showed that Sal A, Sal B and Sal A+B reversed apoptosis and ERS in HSA-induced HK-2 cells via regulating PDGF-C/PDGFR-α signaling pathway.

Conclusion: This article revealed a novel mechanism linking PDGF-C/PDGFR-α signaling pathway to RIF and suggested that Sal A, Sal B and Sal A+B were considered as potential therapeutic agents for the amelioration of RIF.

Keywords: Apoptosis; Endoplasmic reticulum stress; PDGF-C/PDGFR-α signaling pathway; Renal interstitial fibrosis; Salvianolic acid A; Salvianolic acid B.

MeSH terms

Benzofurans
Caffeic Acids
Depsides
Fibrosis
Humans
Kidney Diseases* / drug therapy
Lactates
Lymphokines
Platelet-Derived Growth Factor
Signal Transduction*

Substances

Benzofurans
Caffeic Acids
Depsides
Lactates
Lymphokines
Platelet-Derived Growth Factor
platelet-derived growth factor C
salvianolic acid A
salvianolic acid B