2. Academic Validation
  3. Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways

Effects of honokiol protects against chronic kidney disease via BNIP3/NIX and FUNDC1-mediated mitophagy and AMPK pathways

  • Mol Biol Rep. 2023 Jun 20. doi: 10.1007/s11033-023-08592-1.
Xian Wei 1,  Yuzhi Wang 2,  Yunlan Lao 2,  Jiali Weng 2,  Ruyu Deng 3,  Shunmin Li 1,  Jiandong Lu 1,  Shudong Yang 4,  Xinhui Liu 5
Affiliations

Affiliations

  • 1 Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China.
  • 2 The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518000, Guangdong, China.
  • 3 Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, 518000, Guangdong, China.
  • 4 Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China. ysd0870@gzucm.edu.cn.
  • 5 Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China. liuxinhui0317@163.com.
PMID: 37338733 DOI: 10.1007/s11033-023-08592-1
Abstract

Background: Chronic kidney disease (CKD) is a serious health threat worldwide. Defective Mitophagy has been reported to induce mitochondrial dysfunction, which is closely associated with CKD pathogenesis. Honokiol (HKL) is a bioactive component of Magnolia officinalis that has multiple efficacies. Our study aimed to investigate the effect of HKL on a CKD rat model and explore the possible mechanisms of Mitophagy mediated by Bcl-2 interacting protein 3 and BNIP3-like (NIX) (also known as the BNIP3/NIX pathway) and FUN14 domain-containing 1 (the FUNDC1 pathway) and the role of the AMP-activated protein kinase (AMPK) pathway.

Methods: A CKD rat model was established by feeding the Animals dietary adenine (0.75% w/w, 3 weeks). Simultaneously, the treatment group was given HKL (5 mg/kg/day, 4 weeks) by gavage. Renal function was assessed by measuring serum creatinine (Scr) and blood urea nitrogen (BUN) levels. Pathological changes were analyzed by periodic acid-Schiff (PAS) and Masson's trichrome staining. Protein expression was evaluated by Western blotting and immunohistochemistry.

Results: HKL treatment ameliorated the decline in renal function and reduced tubular lesions and interstitial fibrosis in CKD rats. Accordingly, the renal fibrosis markers Col-IV and α-SMA were decreased by HKL. Moreover, HKL suppressed the upregulation of the proapoptotic proteins Bad and Bax and Cleaved Caspase-3 expression in CKD rats. Furthermore, HKL suppressed BNIP3, NIX and FUNDC1 expression, leading to the reduction of excessive Mitophagy in CKD rats. Additionally, AMPK was activated by adenine, and HKL reversed this change and significantly decreased the level of activated AMPK (phosphorylated AMPK, P-AMPK).

Conclusion: HKL exerted a renoprotective effect on CKD rats, which was possibly associated with BNIP3/NIX and FUNDC1-mediated Mitophagy and the AMPK pathway.

Keywords

AMP-activated protein kinase; Bcl-2 interacting protein 3; Chronic kidney disease; FUN14 domain containing 1; Honokiol; Mitophagy; NIX.

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