Background Age-related cognitive disorders like amnesia and Alzheimer’s disease impair productivity and quality of life, prompting exploration of phytomedicine as a safer alternative to nootropic agents. Objective This study compared the neuropharmacological effects of Unani classical sugar-based Majoon-e-Falasafa (MF) with redesigned sugar-free tablets: powder-based tablets (TP), aqueous extract-based tablets (TAE), and hydroalcoholic extract-based tablets (THAE) in rats, and aimed to relate these effects to their HPLC chromatographic characteristics. Methods Three sugar-free tablet formulations were prepared by omitting sugar from the traditional pharmacopoeial formula of MF and incorporating approved additives, followed by compression to produce TP, TAE, and THAE. Each 20 µL sample of the four tablet formulations was subjected to HPLC analysis on a Shimadzu LC-20 AD system with a detection wavelength of 254 nm. Wistar rats were randomly assigned to treatment groups receiving oral doses of MF (1166.67 mg/kg), TP (303.33 mg/kg), TAE (291.35 mg/kg), THAE (303.27 mg/kg), or 0.3% carboxymethyl cellulose as vehicle control, administered twice daily for 7 consecutive days. Neuropharmacological parameters assessed included gross behavioural observation, phenobarbitone-induced narcosis potentiation, spontaneous motor activity, neuromuscular coordination, central analgesic effect, anticonvulsant activity, conditioned avoidance response, and three validated maze models evaluating learning acquisition, working memory, and spatial working memory. Results HPLC analysis revealed distinct compositional differences: TP was dominated by early-eluting polar constituents, TAE showed enrichment of mid-retention peaks, while THAE exhibited a broad distribution of peaks spanning early, mid, and late retention times, indicating the presence of diverse phytoconstituents. All formulations exhibited a favorable safety profile (LD₅₀ > 2000 mg/kg), without mortality or abnormal behavioural changes observed during the 14-day acute toxicity test. THAE consistently exhibited the most pronounced pharmacological effects across all paradigms tested: it significantly increased spontaneous locomotor activity ( P < 0.01), prolonged phenobarbitone-induced sleep duration ( P < 0.01), reduced the extensor phase of maximal electroshock-induced convulsions ( P < 0.01), and exerted the most potent central analgesic effect with reaction times of 9.67 ± 0.67 s at 60 min and 9.83 ± 1.37 s at 80 min ( P < 0.01). THAE also showed the greatest suppression of the conditioned avoidance response (66.6%) and superior cognitive-enhancing effects, significantly attenuating scopolamine-induced memory impairment: it reduced transfer latency in the elevated plus maze ( P < 0.001), achieved a 79.8% success rate in the radial arm maze, and increased the spontaneous alternation percentage to 74.14% in the Y-maze ( P < 0.01). Conclusion The findings suggest that THAE possesses superior CNS activity, likely attributable to its enriched and diverse phytochemical profile. The observed effects may involve modulation of central neurotransmission and neuroprotective mechanisms; however, these remain hypothesis-generating. This study highlights the importance of extraction methodology in optimizing the therapeutic potential of polyherbal formulations and supports further mechanistic and clinical investigations.
Tajuddin et al. (Mon,) studied this question.
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