Protective effect of Ceiba pentandra (L) Gaertn on CCl4-induced oxidative stress and liver damage in rats

•EECP-BK has no toxicity up to 2000 mg/kg in rats.•EECP-BK shows good protection against CCl4 in both in-vitro and in-vivo models.•EECP-BK also lowered the TNFα levels in CCl4 induced hepatotoxicity in rats.•EECP-BK showed good protection by inhibiting TACE.•Ceiba pentandra (L) Gaertn in claims for its efficacy in traditional medicine. Ceiba pentandra (L.) Gaertn, popularly known as the white silk-cotton tree and popularly used in Chinese and Indian traditional medicine. The bark is used to treat diarrhea, pain, fever, cardiac problems, asthma, and gastrointestinal problems. The present study aimed to evaluate the hepatoprotective and antioxidant effects of ethanol extract of C. pentandra bark (EECP-BK) against CCl4-induced hepatic damage in rats. Preliminary phytochemical analysis was performed to identify the bioactive compounds. CCl4 (40 mM) induced enzymatic changes at HepG2 cells were adopted for the in-vitro model. HepG2 cells were pretreated with EECP-BK (25, 50, 100, and 200 µg/ml) and standard (silymarin 12.5 µg/ml) respectively. Rat model of CCl4-induced liver damage for adopted for the in-vivo model. Rats were pretreated orally with EECP-BK 200 & 400 mg/kg and standard (silymarin 100 mg/kg) for 7 days. Rats were injected with 1 ml/kg of 50% CCl4 on day 8 to induce hepatic damage and were observed for antioxidant levels and serum biomarkers. In addition, in-silico studies have been performed to explore the binding properties of compounds from EECP-BK with tumor necrosis factor-alpha converting enzyme (TACE) targeting hepatic inflammation The phytochemical analysis confirmed the presence of glycoside, steroids, phenols, tannins, and saponins. EECP-BK 200 µg/ml showed the highest protection against CCl4 in HepG2 cells. Similarly, silymarin 12.5 µg/ml showed good protection against CCl4. In rats, EECP-BK up to 2000 mg/kg did produce any toxic signs or mortality. CCl4 injection in rats showed elevated liver enzymatic and bilirubin levels and causes liver damage. It also decreased the SOD, CAT, and GSH levels. Pre-treatment with EECP-BK 400 mg/kg showed a significant reduction in SGPT, SGOT, ALP, and total bilirubin levels and increased SOD, CAT, and GSH levels. Similar results were observed with, silymarin treatment also. Furthermore, EECP-BK showed protection over hepatocyte necrosis induced by CCl4 in rats which is evident by histopathology. Molecular docking studies revealed that acacetin 7-rutinoside binds favorably with the active site of TACE w