Hepatoprotective role of Pueraria tuberosa water extract (PTWE) in CCl4-induced liver injury through different signaling pathways

Liver damage is one of the leading diseases, resulting in high morbidity. It is more relevant in the context of bad food habits, environmental pollution, and biohazards. The present study aimed to investigate the role of semi-purified water extract of Pueraria tuberosa on carbon tetrachloride (CCl4)-induced liver injury and also its mechanism of action regarding transcriptomic status in liver tissue about inflammation, hypoxia, and apoptosis. Liver injury was induced in Charles foster rats via intraperitoneal injection (IP) of CCl4, 0.1 mg/100gm body weight, diluted with olive oil (30%) twice a week for 20 days. PTWE was given via oral route daily simultaneously with CCl4 at the dose of 50 mg/100 g and 100 mg/100 g body weight. On 21st day all rats were sacrificed. Biochemical tests and histological studies were done. mRNA expression of bcl-2, caspase-3, bax, and GAPDH and protein expression of iNOS, BCL-2, HIF-1 alpha, VEGF, beta-Tubulin was done. Simultaneous treatment of PTWE with CCl4 decreased the level of NO, PC, SGOT, SGPT, ALP, LPO, and iNOS, HIF-1 alpha, VEGF, bax, and caspase-3 expression. In addition, PTWE increased the SOD, Catalase, GSH level, and bcl-2 expression as well as normalized the architecture of hepatic tissue. Immunohistochemical staining showed the decreased accumulation of CD45, VEGF, alpha-SMA, collagen, and desmin after PTWE treatment. This study suggests that PTWE inhibits fibrosis by reducing the accumulation of alpha-SMA, collagen, and desmin in CCl4-induced toxicity. The mechanism of protective action is through its anti-inflammatory (iNOS, NO, CD45), anti-apoptotic (bcl-2, bax, caspase-3), anti-hypoxic (HIF-1 alpha, VEGF), and anti-fibrotic (alpha-SMA, collagen, desmin) potentials.