Influence of Methanol Extract of Dennettia tripetala on Hepatic Redox Homeostasis and Detoxification Pathways in Carbon Tetrachloride–Intoxicated Wistar Rats

Abstract

Background: Therapeutic plants are rich sources of bioactive compounds useful in combating various human diseases. This study investigated the in vitro antioxidant activity, gas chromatography–mass spectrometry (GC-MS) profile, and in vivo protective effects of the methanolic leaf extract of Dennettia tripetala in a carbon tetrachloride (CCl₄)-intoxicated rat model. Methods: Twenty-five male Wistar rats (6–8 weeks old, 150–190 g) were randomly allocated into six groups (n = 5 per group). Group A (normal control) received liquid paraffin (1 mL/kg); Group B (intoxicated control) received 30% CCl₄ in liquid paraffin (1 mL/kg); Group C received silymarin (100 mg/kg) plus CCl₄; Groups D, E and F received the methanolic leaf extract at 100, 200 and 300 mg/kg, respectively, plus CCl₄. Extract or silymarin was administered orally for six consecutive days; CCl₄ was given from day 2 to day 6. Liver function indices (ALT, AST, ALP, total protein, total bilirubin) and antioxidant markers (SOD, CAT, GSH, MDA) were measured. Data were analysed by one-way ANOVA followed by Bonferroni multiple-comparison test (GraphPad Prism 8.0.1) after confirmation that the assumptions of normality and homogeneity of variance were met; p < 0.05 was considered significant. Values are presented as mean ± standard error of the mean (SEM). Results: The extract exhibited strong free-radical scavenging activity (IC₅₀ = 4.12 µg/mL against DPPH versus 3.33 µg/mL for ascorbic acid; IC₅₀ = 5.00 µg/mL against ABTS versus 3.87 µg/mL for ascorbic acid). GC-MS analysis identified 37 compounds accounting for 99.7% of the total peak area. The major constituents (≥ 2%) were linoleic acid (36.10%), palmitic acid (18.96%), vitamin E (7.15%), stearic acid (6.06%), caryophyllene (4.24%), γ-sitosterol (3.98%), squalene (3.75%), phytol (2.28%) and α-amyrin (2.12%). These compounds are candidate contributors to the observed antioxidant activity. In vivo, CCl₄ significantly elevated serum ALT, AST, ALP and total bilirubin and reduced total protein relative to the normal control (p < 0.05). Concurrent administration of the extract (100–300 mg/kg) significantly attenuated these elevations and restored total protein toward control values (p < 0.05 versus Group B). The extract also significantly increased hepatic SOD, CAT and GSH while decreasing MDA levels compared with the intoxicated control (p < 0.05). Acute oral toxicity testing indicated an LD₅₀ > 3000 mg/kg. Conclusions: The methanolic leaf extract of D. tripetala demonstrates preclinical hepatoprotective activity against CCl₄-induced oxidative liver injury in rats, consistent with its in vitro antioxidant capacity and the presence of candidate phytochemicals. These findings provide experimental support for further mechanistic and dose–response studies; they do not constitute justification for therapeutic use in humans.