Pretreatment of antioxidative Hodgsonia macrocarpa leaves attenuates anxiety, depression, inflammation, and pain: an in vitro, in vivo, and in silico study.

Ethnopharmacological relevance: Hodgsonia macrocarpa (Blume) Cogn., known locally in Southeast Asia as bonyo kumra, is a climber traditionally used to treat a wide range of ailments, including headache, body pain, inflammation, fever, wounds, and ulcers. However, experimental assessments of these bioactivities are scarce.

Aim of the study: This work uses a variety of in vitro, in vivo, and in silico techniques to examine the antioxidant, anti-inflammatory, neuropharmacological, and analgesic capabilities of H. macrocarpa leaf methanol extract.

Materials and methods: The methanolic extract of H. macrocarpa leaves (MEHML) was obtained by extracting H. macrocarpa leaf powder with methanol. GC-MS analysis was performed to determine potential bioactive compounds. Following qualitative and quantitative phytochemical profiling through standard methods, commonly used in vitro assays were employed to detect anti-inflammatory activity. Anxiolytic, antidepressant, and pain-attenuating potential were investigated on Swiss albino mice. Finally, GC-MS-identified compounds were submitted to an in silico study.

Results: Phytochemical profiling suggested the presence of a variety of constituents, including alkaloids, phenols, tannins, carbohydrates, and flavonoids. Significant antioxidant activity was observed in MEHML due to significant amounts of phenolics, flavonoids, beta-carotene, and lycopene, with promising radical scavenging activity (IC₅₀ 7.762 ± 0.14 μg/mL). Moreover, substantial dose-dependent anxiolytic and anti-depressive effects were detected in behavioral assays (p < 0.01-0.001). Noteworthy anti-inflammatory and analgesic (p < 0.001) activities were displayed in in vitro and in vivo assays, respectively. The in-silico study corroborated the biological activities, revealing strong binding interactions of GC-MS-identified compounds, including (E, E)-pyrrolidine 1-(1-oxo-10,12-octadecadienyl) and 5-hydroxymethylfurfural, with target proteins, thereby supporting the experimental findings.

Conclusions: MEHML holds significant analgesic and neuropharmacological potential, as well as promising antioxidant and anti-inflammatory properties, validated by in silico investigations.