Evaluation of Hepatoprotective Activity of Coix lacryma-jobi L. Seed Extract for Isoniazid-Induced Hepatotoxicity in Experimental Animal
TL;DR
CLJSE exhibits significant dose-dependent hepatoprotective activity against isoniazid-induced liver injury, primarily through antioxidant, anti-lipid-peroxidative, and membrane-stabilizing mechanisms, supporting its potential as an adjuvant phytotherapeutic agent during antitubercular therapy.
Abstract
Background: Drug-induced liver injury (DILI) is a major cause of hepatic morbidity. Isoniazid (INH), a first-line antitubercular drug, is frequently associated with hepatotoxicity due to the formation of reactive metabolites that deplete hepatic antioxidant defenses. Plant-derived antioxidants may offer protection against such injury. Objective: To evaluate the hepatoprotective potential of the ethanolic seed extract of Coix lacryma-jobi L. (CLJSE) against isoniazid-induced hepatotoxicity using in vitro and in vivo models. Methods: CLJSE was prepared by Soxhlet extraction using 70% ethanol and standardized through pharmacognostic, physicochemical, phytochemical, and FTIR analyses. Antioxidant activity was assessed by the DPPH assay, while hepatoprotective activity was evaluated in HepG2 cells against H₂O₂-induced cytotoxicity using the MTT assay. Acute oral toxicity was conducted according to OECD Guideline 423. For the in vivo study, Wistar rats were divided into normal control, toxic control (INH, 50 mg/kg i.p., twice weekly for 28 days), standard (INH + silymarin 100 mg/kg p.o.), and extract-treated groups (INH + CLJSE 200 or 400 mg/kg p.o.). Serum liver markers, hepatic antioxidant parameters, liver weight, and histopathology were evaluated. Results: CLJSE showed concentration-dependent DPPH radical scavenging activity (IC₅₀ = 74.56 µg/mL) and protected HepG2 cells against oxidative stress, producing 94.46% cell viability at 100 µg/mL. The extract was nontoxic up to 2000 mg/kg. INH significantly increased serum AST, ALT, ALP, total bilirubin, liver weight, and MDA levels, while reducing GSH, SOD, and CAT levels (p < 0.01). CLJSE treatment significantly and dose-dependently reversed these changes, with the 400 mg/kg dose showing effects comparable to silymarin. Histopathological findings confirmed marked protection of hepatic architecture. Conclusion: CLJSE exhibits significant dose-dependent hepatoprotective activity against isoniazid-induced liver injury, primarily through antioxidant, anti-lipid-peroxidative, and membrane-stabilizing mechanisms, supporting its potential as an adjuvant phytotherapeutic agent during antitubercular therapy.