Background Anxiety and depressive disorders are increasingly associated with oxidative stress and neurotransmitter imbalance. Limitations of current pharmacotherapies have intensified interest in plant-derived agents with multi-target activity. Objective This study investigated the phytochemical composition, antioxidant capacity, and anxiolytic- and antidepressant-like effects of the n-butanol fraction of Caralluma dalzielii (BUF), alongside exploratory in silico analysis of potential molecular interactions. Methods Phytochemical profiling was performed using HPLC. Antioxidant activity was evaluated using DPPH radical scavenging, ferric reducing antioxidant power (FRAP), hydrogen peroxide scavenging, total antioxidant capacity (TAC), and total phenolic content (TPC) assays. Behavioural effects of BUF (10, 50, and 100 mg/kg, p.o.) were assessed in naïve mice using the elevated plus maze (EPM), open field test (OFT), tail suspension test (TST), and forced swim test (FST). Post-behavioural biochemical analyses included modulation of oxidative stress markers, triacylglycerol levels, and acetylcholinesterase activity. Molecular docking was conducted against selected neurobiological targets. Results BUF exhibited strong antioxidant capacity (DPPH IC 50 < 0.2 mg/mL; TPC 537.75 ± 3.06 mg GAE/g extract). In the EPM, 100 mg/kg significantly increased open-arm entries and time spent in open arms (p < 0.0001), while in the OFT, central crossings were significantly elevated (p < 0.0001), indicating anxiolytic-like activity. In behavioural despair paradigms, immobility time was significantly reduced at 100 mg/kg in both the TST (p < 0.001) and FST (p < 0.001). Biochemically, BUF significantly reduced malondialdehyde levels (p < 0.001), increased catalase and superoxide dismutase activities (p < 0.0001), reduced triacylglycerol levels (p < 0.0001), and inhibited acetylcholinesterase activity (p < 0.0001). Docking analyses indicated favourable binding of key flavonoids, particularly naringenin, to serotonergic, monoaminergic, and GABAergic targets. Conclusion These findings provide experimental evidence that the BUF exerts significant anxiolytic- and antidepressant-like effects in validated behavioural models, likely mediated through integrated antioxidant, monoaminergic, and cholinergic mechanisms.
Song et al. (Sun,) studied this question.