Experimental and computational elucidation of the diuretic action of tribulus terrestris An integrated in vivo and in silico approach

Abstract

In conclusion, our study suggests that the use of the crude aqueous extract of Tribulus terrestris dried fruits indicates that acute exposure to 2000 mg/kg body weight leads to no toxicologically significant signs or symptoms and can be considered safe and nontoxic up to a dose of 2000 mg/kg body weight in rats, and the median lethal dose (LD50) of the crude aqueous extract of Tribulus terrestris dried fruits in Wistar rats via the oral route is estimated to be more than 2000 mg/kg. The crude aqueous extract of Tribulus terrestris dried fruits is rich in bioactive phytoconstituents and has promising therapeutic effects through diuresis. These benefits can be attributed to the multitarget, multifaceted pathways, such as NOS3, HIF1A, MTOR, and ESR1, by which the extract might have produced diuretic effects similar to those of hydrochlorothiazide and spironolactone. The ability of phytochemicals to successfully bind to both the large sodium chloride cotransporter cavity and the constrained PDZ domain groove illustrates the potential of polyol-based compounds in multitarget therapeutic applications. The distinct interaction patterns observed with each protein target provide valuable insights for rational drug design efforts targeting similar binding sites while highlighting the importance of considering binding site architecture and native ligand characteristics in structure-based design campaigns.