2. Academic Validation
  3. Baicalin ameliorates renal fibrosis by upregulating CPT1α-mediated fatty acid oxidation in diabetic kidney disease

Baicalin ameliorates renal fibrosis by upregulating CPT1α-mediated fatty acid oxidation in diabetic kidney disease

  • Phytomedicine. 2024 Jan:122:155162. doi: 10.1016/j.phymed.2023.155162.
Hongtu Hu 1,  Weiwei Li 2,  Yiqun Hao 3,  Zhuan Peng 3,  Zhengping Zou 4,  Wei Liang 5
Affiliations

Affiliations

  • 1 Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China; Key Clinical Research Center of Kidney Disease in Hubei, 238 Jiefang Rd, Wuhan, Hubei 430060, China; Central Laboratory, Renmin Hospital of Wuhan University, Wuhan, China.
  • 2 Division of Nephrology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, No.158 Wuyang Avenue, Enshi City, Hubei Province, China.
  • 3 Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China; Key Clinical Research Center of Kidney Disease in Hubei, 238 Jiefang Rd, Wuhan, Hubei 430060, China.
  • 4 Division of Nephrology, Qianjiang Hospital Affiliated to Renmin Hospital of Wuhan University, No. 22, Zhanghua Zhong Road, Qianjiang, Hubei 433100, China; Qianjiang Clinical Medical College, Health Science Center, Yangtze University, China. Electronic address: [email protected].
  • 5 Division of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan, Hubei 430060, China; Key Clinical Research Center of Kidney Disease in Hubei, 238 Jiefang Rd, Wuhan, Hubei 430060, China. Electronic address: [email protected].
PMID: 37922789 DOI: 10.1016/j.phymed.2023.155162
Abstract

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD). The progression of DKD is often marked by heightened renal fibrosis due to hindered fatty acid oxidation within renal tubules. Baicalin (BA), a naturally derived compound, has exhibited the potential to mitigate the advancement of DKD. Delving deeper into the precise targets and mechanisms of BA's effect on DKD is crucial.

Purpose: This study sought to elucidate the specific mechanism through which BA moderates the progression of DKD.

Methods: Renal tubular tissues from diabetic (db/db) and control (db/m) mice were subjected to mRNA Sequencing to discern BA's influence on DKD. Immunohistochemical staining and Western blot were employed to assess the expression of CPT1α in DKD patients and db/db and db/m mice administered with either BA (50 mg/kg/day) or a vehicle for 12 weeks. In vitro, human proximal renal tubule cells (HK-2) were treated with 40 mM high glucose or 50 μM BA. The potential inhibitory mechanism of BA on renal fibrosis in DKD was evaluated using Oil Red O staining and oxygen consumption rate (OCR) measurements.

Results: The results demonstrated that BA notably reduced lipid accumulation and renal fibrosis in db/db mice. Moreover, mRNA Sequencing pinpointed a significant downregulation of CPT1α in DKD. In vitro assays revealed that both the overexpression of CPT1α and treatment with BA exerted similar influences on mitochondrial respiration, fatty acid oxidation, and renal fibrosis levels. Given the pronounced downregulation of CPT1α in DKD patients and its substantial correlation with clinical indicators, it was evident that CPT1α could serve as a therapeutic target for BA in addressing DKD.

Conclusion: Our findings demonstrated that BA potentially enhances FAO by augmenting the expression of CPT1α, subsequently diminishing renal fibrosis in DKD. As such, CPT1α emerges as a promising therapeutic target for DKD intervention.

Keywords

Baicalin; CPT1α; Diabetic kidney disease; Fatty acid oxidation; Renal fibrosis.

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