2. Academic Validation
  3. Herb pair of Rhubarb-Astragalus mitigates renal interstitial fibrosis through downregulation of autophagy via p38-MAPK/TGF-β1 and p38-MAPK/smad2/3 pathways

Herb pair of Rhubarb-Astragalus mitigates renal interstitial fibrosis through downregulation of autophagy via p38-MAPK/TGF-β1 and p38-MAPK/smad2/3 pathways

  • Int J Biochem Cell Biol. 2024 Feb 8:169:106549. doi: 10.1016/j.biocel.2024.106549.
Jinxiu Li 1,  Xiping Qin 1,  Weimin Xu 1,  Hongliang Zhang 2,  Songqing Huang 1,  Yufang Yang 3,  Mengyuan Qin 4,  Zhengcheng Mi 1,  Xiaobin Zhong 5
Affiliations

Affiliations

  • 1 Pharmacy Department, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 2 Pharmacy Department, the First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: [email protected].
  • 3 Pharmacy Department, the First Affiliated Hospital of Guangxi Medical University, Nanning, China. Electronic address: [email protected].
  • 4 Student Affairs Department, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
  • 5 Regenerative Medicine Research Center of Guangxi Medical University, Nanning, China.
PMID: 38340950 DOI: 10.1016/j.biocel.2024.106549
Abstract

Background: Chronic kidney disease (CKD) has a high incidence and poor prognosis; however, no effective treatment is currently available. Our previous study found that the improvement effect of the herb pair of Rhubarb-Astragalus on CKD is likely related to the inhibition of the TGF-β1/p38-MAPK pathway. In the present study, a p38-MAPK inhibitor was used to further investigate the inhibitory effect of Rhubarb-Astragalus on the TGF-β1/p38-MAPK pathway and its relationship with Autophagy.

Methods: A rat model of unilateral ureteral obstruction (UUO) was established, and a subgroup of rats was administered Rhubarb-Astragalus. Renal function and renal interstitial fibrosis (RIF) were assessed 21 d after UUO induction. In vitro, HK-2 cells were treated with TGF-β1 and a subset of cells were treated with Rhubarb-Astragalus or p38-MAPK inhibitor. Western blotting, immunohistochemistry, and qRT-PCR analyses were used to detect the relevant protein and mRNA levels. Transmission electron microscopy was used to observe autophagosomes.

Results: Rhubarb-Astragalus treatment markedly decreased the elevated levels of blood urea nitrogen, serum creatinine, and urinary N-acetyl-β-D-glucosaminidase; attenuated renal damage and RIF induced by UUO; and reduced the number of autophagosomes and lysosomes in UUO-induced renal tissues. Additionally, Rhubarb-Astragalus reduced the protein and mRNA levels of α-SMA, collagen I, LC3, Atg3, TGF-β1, p38-MAPK, SMAD2/3, and TAK1 in renal tissues of UUO rats. Rhubarb-Astragalus also reduced protein and mRNA levels of these indicators in vitro. Importantly, the effect of the p38-MAPK inhibitor was similar to that of Rhubarb-Astragalus.

Conclusions: Rhubarb-Astragalus improves CKD possibly by downregulating Autophagy via the p38-MAPK/TGF-β1 and p38-MAPK/SMAD2/3 pathways.

Keywords

Autophagy; Herb pair of Rhubarb-Astragalus; P38-MAPK/TGF-β1; Renal interstitial fibrosis; Unilateral ureteral obstruction.

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