Hepatoprotective potential of Ceiba chodatii Hassl. Against carbon tetrachloride-induced chronic liver damage supported with phytochemical investigation.

Hepatic fibrosis is a major health concern that can develop into other life-threatening pathologies, with no fully effective treatments are available to date. Ceiba is a genus of multipurpose trees with diverse therapeutic applications, including liver ailments. Prior research has also unveiled the protecting role of Ceiba plants in chemical liver injuries via a number of in vitro and in vivo tests. Due to the crucial need for alternative therapies to prevent liver damage and stop its progress, the present work evaluates the protective effects of the total extract of Ceiba chodatii Hassl. flowers and its derived fractions (I-IV) against CCl4-induced chronic liver damage for the first time. The obtained results indicated the ability of C. chodatii flowers, particularly their chloroform- and ethyl acetate-soluble fractions (II and III), to alleviate liver damage in CCl4-intoxicated rats via normalizing high liver injury hallmarks (e.g., ALT, AST, albumin, and total bilirubin), preventing the build-up of malondialdehyde, enhancing the antioxidant capacity of hepatocytes, mitigating aberrant histopathological changes, and reducing extracellular matrix accumulation. Further mechanistic studies showed the aptitude of C. chodatii flowers to attenuate inflammatory, fibrotic, and apoptotic responses via counteracting the production of inflammatory cytokines (e.g., IL-6 and TNF-α), reducing the levels of cleaved caspase-3, and inhibiting JAK2/STAT3 and TGF-β/Smad signaling pathways. Interestingly, the liver-protecting actions of fractions II and III were also comparable to those of silymarin (50 mg/kg). Moreover, phytochemical investigation of C. chodatii flowers led to the isolation and identification of a group of flavonoid glycosides (1-10), with good antioxidant and liver supporting properties, suggesting their potential contribution to the anti-fibrotic properties of C. chodatii. These data highlight the multi-target hepatoprotective effects of C. chodatii and its potential as an alternative source to develop natural therapeutic agents against liver fibrosis.