Ginkgo Biloba Leaf Extract may prevent Diabetic Nephropathy, Finds Study
Diabetes is considered a serious threat to human health, and is the most prevalent disease, apart from cardiovascular disease and cancer. In a recent stud researchers have found that Ginkgo Biloba Leaf Extract (GBE) prevented extracellular matrix (ECM) accumulation by suppressing Tissue transglutaminase (tTG) expression in Diabetic Nephropathy (DN). The study findings were published in the journal Experimental and Therapeutic Medicine on February 08, 2021.
Tissue transglutaminase (tTG) is a member of the Ca2+-dependent TG family, which catalyzes the formation of the γ-glutamyl-ε-lysine isopeptide bond and introduces a covalent crosslink between the protein and peptide, thus inducing resistance to enzymatic degradation. In a previous study, researchers have reported that GBE can be used to prevent and treat renal fibrosis in rats, which may inhibit the Angiotensin (Ang) II-induced upregulation of the mRNA expression levels of TGF-β and CTGF. However, the effects of GBE on tTG have not yet been elucidated. Therefore, researchers of the Jilin University, China, conducted a study to evaluate the effects of GBE on tTG expression in the diabetic kidneys of rats and high glucose-treated mesangial cells to determine whether GBE exerts protective mechanisms.
It was a preclinical study in which researchers used a streptozotocin (STZ) induced rat model of diabetic nephropathy (DN) as an invio model. The rats were subsequently administered GBE. For the Invitro model, they used rat glomerular mesangial cells (HBZY-1 cells) cultured with high glucose and treated with GBE. The concentrations of tTG, fibronectin, type IV collagen, transforming growth factor (TGF)-β and connective tissue growth factor (CTGF) were detected via ELISA.
Key findings of the study were:
- Upon invivo analysis, researchers have found that GBE significantly decreased blood glucose, the urine protein excretion rate and ECM accumulation in DN rats.
- They also found that the development of DN significantly induced tissue transglutaminase (tTG) protein expression, which was detected by immunohistochemistry, western blotting and PCR analyses, while GBE administration decreased tTG expression in the diabetic kidney.
- Upon invitro analysis, they found that GBE notably decreased the concentration of tTG, fibronectin, type IV collagen, TGF-β and CTGF proteins, and tTG expression was positively associated with TGF-β.
- They also found that GBE suppressed the tTG expression of high glucose-treated HBZY-1 cells in a concentration-dependent manner. Also, they detected tTG protein expression in high glucose-treated HBZY-1 cells transfected with small interfering RNA (siRNA) oligonucleotides against TGF-β and CTGF to investigate a possible mechanism of GBE-mediated inhibition of tTG.
- It showed that the tTG levels remained unchanged in CTGF siRNA-transfected cells, but were decreased in the GBE + CTGF siRNA group compared with the control siRNA group, suggesting that tTG may not be regulated by CTGF, and the inhibitory effect of GBE on tTG may not be associated with the direct inhibition of CTGF.
The authors concluded, "The results of the present study demonstrated that GBE decreased tTG expression both in DN rats and rat mesangial cells in vitro under high glucose conditions, and GBE may protect rat mesangial cells by inhibiting tTG via modulating TGF-β expression, thus providing a novel strategy for the treatment of DN."
For further information:
https://www.spandidos-publications.com/10.3892/etm.2021.9764
