Betulinic Acid: Triterpenoid Derivative Induced NADPH-d Expression in the Urinary System with a Possible Renal Protective Role of Nitric Oxide

The birch tree-derived pentacyclic lupine type-triterpenoid Betulinic acid has demonstrated a variety of biological activities BetA is known for its harmlessness on normal healthy cells. However, recent investigations have indicated that BetA can cause cellular changes in mouse normal embryonic fibroblasts even with a minimal concentration. This report cautioned the use of BetA at the clinical level, which encouraged us to examine whether BetA could produce any key effect on normal healthy cells of any organs in mice. The present study extended its investigation to evaluate whether BetA could induce any changes in the renal system and the expression pattern of NADPH-diaphorase an indirect marker of the enzyme nitric oxide synthase in mice. Our results indicated that BetA exposure induced NADPH-d expression in both organs without causing any significant morphological changes. Moreover, NADPH-d activity patterns in the organs of BetA-treated animals tremendously increased (from day 4 until day 12) when compared to controls. The expression of NADPH-d in both the kidney and bladder implies that NADPH-d-mediated nitric oxide signaling could be a mechanism involved in BetA-induced nephroprotection. These outcomes are of direct clinical importance and could pay the way for the improvement of BetA as an important pharmaceutical product.