Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen, 518000, China.
The Fourth Clinical Medical College, Guangzhou University of Chinese Medicine, Shenzhen, 518000, Guangdong, China.
Mol Biol Rep. 2023 Aug;50(8):6557-6568. doi: 10.1007/s11033-023-08592-1. Epub 2023 Jun 20.
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.
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.
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).
HKL exerted a renoprotective effect on CKD rats, which was possibly associated with BNIP3/NIX and FUNDC1-mediated mitophagy and the AMPK pathway.
慢性肾脏病（CKD）是全球范围内的严重健康威胁。已有研究报道，缺陷型线粒体自噬可诱导线粒体功能障碍，而后者与 CKD 的发病机制密切相关。厚朴酚（HKL）是厚朴的一种生物活性成分，具有多种功效。本研究旨在探讨 HKL 对 CKD 大鼠模型的影响，并探讨 Bcl-2 相互作用蛋白 3 和 BNIP3 样（NIX）（也称为 BNIP3/NIX 途径）和 FUN14 结构域包含蛋白 1（FUNDC1 途径）介导的线粒体自噬以及 AMP 激活的蛋白激酶（AMPK）途径的可能机制。
通过给予动物含腺嘌呤的饮食（0.75%w/w，3 周）建立 CKD 大鼠模型。同时，治疗组给予 HKL（5mg/kg/天，4 周）灌胃。通过测量血清肌酐（Scr）和血尿素氮（BUN）水平评估肾功能。通过过碘酸-Schiff（PAS）和 Masson 三色染色分析病理变化。通过 Western 印迹和免疫组化评估蛋白表达。
HKL 治疗改善了 CKD 大鼠肾功能下降，并减少了肾小管病变和间质纤维化。相应地，HKL 降低了 CKD 大鼠的肾纤维化标志物 Col-IV 和 α-SMA。此外，HKL 抑制了 CKD 大鼠促凋亡蛋白 Bad 和 Bax 以及 Cleaved caspase-3 的表达上调。此外，HKL 抑制了 BNIP3、NIX 和 FUNDC1 的表达，从而减少了 CKD 大鼠过度的线粒体自噬。此外，AMPK 被腺嘌呤激活，而 HKL 逆转了这一变化，并显著降低了激活的 AMPK（磷酸化 AMPK，P-AMPK）的水平。
HKL 对 CKD 大鼠具有肾脏保护作用，这可能与 BNIP3/NIX 和 FUNDC1 介导的线粒体自噬和 AMPK 途径有关。
