L-Borneol ameliorates renal fibrosis induced by unilateral ureteral obstruction in rats.

Abstract

L-Borneol (BO), a naturally occurring bicyclic monoterpene, was investigated for its antifibrotic efficacy in an experimental model of surgically induced renal fibrosis in rats. Renal fibrosis was induced by unilateral ureteral obstruction (UUO). BO was administered at doses of 50, 100, and 200 mg/kg for 14 days post-UUO surgery. On the 15th day, urine and blood samples were collected to determine the status of the renal function. The kidneys were isolated following euthanasia and processed for estimation of oxidative stress, histological alterations (hematoxylin and eosin staining), and collagen deposition (Masson's Trichome staining). The biological targets of BO were explored using network pharmacology analysis. BO treatment improved kidney function and attenuated fibrosis, as evidenced by reduced hydroxyproline (HYP) content and decreased extracellular matrix accumulation in the renal tissues. BO also mitigated the UUO-induced alterations in the oxidative stress markers including reduced glutathione (GSH), superoxide dismutase (SOD), catalase, lipid peroxidation (LPO), and nitric oxide (NO). The effects of 50 and 100 mg/kg dose of BO were dose dependent, with the 100 mg/kg dose providing better renoprotection and reduced fibrosis. However, the 200 mg/kg dose appeared to induce alterations in kidney function. Gene and pathway analysis indicated that BO exerts its effects through interleukin-17 (IL-17), nuclear factor κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K-Akt), tumor necrosis factor (TNF), AMP-activated protein kinase (AMPK), mitogen-activated protein kinase (MAPK), and vascular endothelial growth factor (VEGF) signaling pathways, with NFKB1 and MAPK8 identified as central hub genes. BO may represent a promising therapeutic candidate for RF associated with chronic kidney disease (CKD). Nevertheless, the potential toxicities observed with higher doses warrant further investigation into the underlying molecular mechanisms and clinical efficacy.