The Amelioration of Toxin-Induced Hepatic Fibrosis and Acute Necrosis via Modulation of Oxidative Stress and Pro-inflammatory Cytokines by Belosynapsis vivipara Extract and a Novel Zinc-Quercetin Complex

BYLAPPA & HANDRAL: HEPATOPROTECTION BY ZN-QUERCETIN AND B. VIVIPARA

Abstract

Liver fibrosis and drug-induced liver injury represent significant global health challenges with limited therapeutic options. This study evaluated the hepatoprotective, antioxidant, and anti-inflammatory potential of the ethanolic leaf extract of Belosynapsis vivipara (EBL) and a novel synthesized Zinc-Quercetin (ZQ) complex CCl₄-induced chronic fibrosis and paracetamol (APAP)-induced acute hepatotoxicity in Wistar rats. EBL (500 mg/kg) and ZQ (60 mg/kg) evaluated alongside standard Silymarin and pure Quercetin treatments. In the CCl₄ model, treatment with ZQ and EBL significantly (P < 0.0001) attenuated the elevation of serum marker enzymes (ALT, AST, ALP), total bilirubin, and CRP. Specifically,
the ZQ complex drastically reduced ALT levels to 76.4 ± 1.3 U/L, outperforming pure quercetin (96.4 ± 1.3 U/L) and showcasing marked recovery compared to the toxic control (187.6 ± 2.9 U/L). Both treatments better restored hepatic antioxidant status, significantly increasing SOD and GSH levels while suppressing lipid peroxidation (MDA). In the APAP model, ZQ and EBL effectively prevented hepatic necrosis and preserved hepatic synthetic functions by restoring total protein and albumin levels. Furthermore, the ZQ complex potently downregulated severe inflammatory surges, reducing TNF-α from 145.8 ± 6.2 pg/mL to 62.5 ± 3.1 pg/mL, alongside significant reductions in IL-6. Histopathological analysis confirmed the striking preservation of hepatic architecture and the prevention of steatohepatitis and cellular ballooning in the treated groups. The study demonstrates that the ZQ complex exhibits superior hepatoprotective, antioxidant, and
anti-inflammatory efficacy at a substantially lower dose indicate that zinc-complexation is a highly effective structural strategy for overcoming the bioavailability limitations of therapeutic flavonoids.