Protective potential of mokko lactone from Cheilocostus speciosus (J. Koenig) CDSpecht (Costaceae) rhizomes against fulminant hepatic failure

Cheilocostus speciosus (Syn: Costus speciosus) (Crepe or spiral ginger) is one of the species of the family Costaceae that is widely used in various traditional medicines for treating various ailments. Mokko lactone (ML) belongs to the guaianolide family of sesquiterpenes, which has been separated from C. speciosus. It showed noticeable antiinflammation and antioxidative capacities. The current study explored the ML hepatoprotective potential against FHF (fulminant hepatic failure) in mice. FHF was successfully estab-lished using intraperitoneal injection of ?-galactosamine (?-GalN, 700 mg/kg)/lipopolysaccharide (LPS, 10 & mu;g/kg) in male Swiss-albino mice. The mice were pretreated with ML (20 or 40 mg/kg, orally) daily for five days before ?-GalN/LPS challenge. Eight hours after D-GalN/LPS injection, serum and hepatic tissue were harvested for different biochemical, histologic grading, immunohistochemical, and ELISA analyses. The results have shown that D-GalN/LPS-induced massive hepatic damage that was evident through the tremendous increase in serum biochemical parameters: transaminases, & gamma;-GT, and ALP, as well as deteriorated histopathological architecture of the liver. D-GalN/LPS created a state of oxidative damage in the hepatocytes as there was a significant rise in MDA level concurrently with depressed antioxidants as GSH (reduced glutathione), SOD (superoxide dismutase) activity, and TAC (total antioxidant capacity). Ad-ditionally, D-GalN/LPS activated NF-& kappa;B (nuclear factor kappa-B), resulting in an increase in the production of TNF-& alpha;, IL-6, and IL-1 & beta;. Interestingly, all these changes were amended by ML pretreatment, indicating the potent hepatoprotective, antioxidant, and antiinflam-matory efficacy of ML against D-GalN/LPS-induced FHF. These effects could be mediated through inhibition of NF-& kappa;B/downstream cytokine signaling. Hence, ML is suggested as new candidate for the treatment of FHF.