Engineered berberine and berberrubine nanobilosomes as a sustainable approach for reversing the toxic metals contamination-induced hepatorenal injuries in rats

Berberine (BB) is recognized for its medicinal properties; however, its clinical application is limited by its poor bioavailability. This study prepared ecologically friendly albumin-modified nanobilosomes (ABL) to enhance and compare the therapeutic efficacies of BB and berberrubine (BR) in managing hepatic and renal damages. Hepatic and renal injuries were induced in rats through their daily consumption of toxic metal-contaminated water portion (TM/W) containing lead (20 mg/kg), aluminum (10 mg/kg), and cadmium (5 mg/kg) for 90 days. Rats were subsequently treated with free BB, BR, or BB-ABL/BR-ABL (25 mg/kg/day) for 45 days. Biochemical parameters, oxidative stress, inflammation, and autophagy markers were evaluated. The optimized formulations possessed high drug entrapment efficiencies of 83.2 ± 1.35% for BB-ABL and 84.5 ± 0.06% for BR-ABL. BB-ABL and BR-ABL exhibited significantly greater therapeutic efficacy than free drugs in attenuating TM/W-induced hepatic and renal injuries as evidenced by significant reductions in nitric oxide (NO), microtubule-associated protein light chain 3-II (LC3-II), interleukins (IL-1β and IL-6), and AMP-activated protein kinase (AMPK) protein levels (p < 0.05). Hepatic mTOR levels were significantly elevated by 32.4% and 37.5% in the TM/BB-ABL and TM/BB-ABL treated groups, respectively, while renal mTOR levels increased by 39.6% and 42.8% compared with the TM/W group. Likewise, hepatic PI3K levels increased by 37.9% and 47.4%, whereas renal PI3K levels increased by 33.1% and 37.8% in the TM/BB-ABL and TM/BR-ABL-treated groups, respectively, relative to the TM/W group. Engineered albumin-modified nanobilosomes enhanced the antioxidant, anti-inflammatory, anti-apoptotic, and autophagy-modulatory properties of BB and BR for the treatment of toxic metal-induced hepatorenal damage.