2. Academic Validation
  3. Bilobetin induces kidney injury by influencing cGMP-mediated AQP-2 trafficking and podocyte cell cycle arrest

Bilobetin induces kidney injury by influencing cGMP-mediated AQP-2 trafficking and podocyte cell cycle arrest

  • Phytomedicine. 2019 Nov:64:153073. doi: 10.1016/j.phymed.2019.153073.
Qun Wang 1,  Zhi Li Wu 2,  Xing Yuan 2,  Hong Yuan Dong 2,  Xin Xu 3,  Hong Xin 4,  Yin Hang Wang 4,  Jian Bing Zhang 5,  Li Chen 5,  Hui Liang Li 6,  Xue Mei Zhang 7,  Wei Dong Zhang 8
Affiliations

Affiliations

  • 1 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; Institute of Interdisciplinary Research Complex, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: [email protected].
  • 2 School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
  • 3 Institute of Interdisciplinary Research Complex, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
  • 4 Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China.
  • 5 WanBangDe Pharmaceutical Group Co.,Ltd. Wenlin, Zhejiang 317500, China.
  • 6 School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: [email protected].
  • 7 Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 201203, China. Electronic address: [email protected].
  • 8 School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 211198, China; School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Institute of Interdisciplinary Research Complex, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: [email protected].
PMID: 31542661 DOI: 10.1016/j.phymed.2019.153073
Abstract

Background: Ginkgo biloba (Gb) extracts have been used as a traditional Chinese medicine. Gb contains Flavonoids, which are considered to be its active ingredients and have been used in the treatment of a variety of diseases. However, few scientific research studies on the side effects of flavonoid in Gb have been reported.

Purpose: The present study aimed to investigate the effect of bilobetin on the kidney of Sprague-Dawley (SD) rats.

Study design and result: In this study, rats were injected with 50 mg/kg of bilobetin, a biflavone isolated from Gb, for 7 days and aristolochic acid was used as positive controls. The results showed that the body weight and urine output of the rats were dramatically decreased, and urinary protein increased after the intraperitoneal injection of bilobetin compared with the control group. Bilobetin treatment showed vacuolar degeneration in the renal tubular epithelium, glomerular atrophy by histostaining, and podocyte fusion by electron microscopy. This study further showed that bilobetin promoted the trafficking of Aquaporin 2 (AQP-2) onto the plasma membrane to achieve the function of urine concentration by in vivo study in rats and in vitro study in IMCD-3 cells. The redistribution of AQP-2 is due to increased expression of cGMP in IMCD-3 cells, which in turn promoted the phosphorylation of AQP-2 at site Ser-256. The proteinuria caused by bilobetin may be attributed to podocyte cell cycle arrest at G2/M transition, which is may associated with Akt and MAPK signaling.

Conclusions: The current study showed that bilobetin has some side effects on kidneys at a dose of 50 mg/kg in SD rats and provides insight into the potential detrimental effects of monomeric ingredients in Gb.

Keywords

Aquaporin 2; Bilobetin; Kidney; Podocytes; Proteinuria.

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