Reconstituted mother tinctures of Gelsemium sempervirens L. improve memory and cognitive impairment in mice scopolamine-induced dementia model.

ETHNOPHARMACOLOGICAL RELEVANCE: Gelsemium sempervirens (L.) J.St.-Hil is a herb used for the treatment of various neuroses in both homeopathic and Ayurvedic systems. The present study examines whether Gelsemium reconstituted tincture can protect against scopolamine induced cognitive discrepancies in amnesic mouse model. In order to investigate the protective mechanism of Gelsemium against dementia, in vitro acetyl cholinesterase and ß-secretase enzyme inhibition and estimation of glutathione level in mouse brain were carried out. MATERIALS AND METHODS: The inhibition study on acetyl cholinesterase and ß-secretase enzyme was conducted on brain homogenate supernatant spectrophotometrically using specific substrate. Cognitive enhancement activity was assessed by elevated plus maze and passive avoidance study in scopolamine induced dementia mouse model. Glutathione, an anti-oxidant, was measured spectrophotometrically from scopolamine induced amnesic mice brain supernatant using 5,5'-dithiobis 2-nitrobenzoic acid in the presence and absence of Gelsemium tincture. RESULTS: Significant inhibition was found with Gelsemium on AChE and ß-secretase enzyme with an IC50 of 9.25 and 16.25 µg/ml, respectively, followed by increasing glutathione levels in comparison to the untreated dementia group. The effect of Gelsemium of scopolamine-induced cognitive deficits was determined by measuring the behavioral parameters and the antioxidant status of the brain after scopolamine (1mg/kg i.p.) injected amnesic mice. Gelsemium significantly demonstrated in vivo anti-dementia activity (60% protection) and increased exploratory behavior. CONCLUSION: Our investigations indicated that alkaloid, iridoids and coumarin enriched reconstituted Gelsemium tincture extract displays promising cognitive enhancement in adult mice after short-term oral treatment. Hence, Gelsemium can be a promising anti-dementia agent, mediating the protection against amnesia, attention disorders and learning dysfunctions through dual inhibition of both acetyl cholinesterases (no false positive effect was shown), ß-secretase and antioxidant activity.

Effects of neostigmine and edrophonium on human erythrocyte acetylcholinesterase activity.

Erythrocyte acetylcholinesterase (AChE) activities in vivo were measured over 60 min using a spectrophotometric method after administration of neostigmine or edrophonium for antagonism of pancuronium-induced neuromuscular block in 31 patients. Erythrocyte AChE activities decreased to 11.3 (SD 1.2)% and 11.4 (0.8)% of baseline values (P less than 0.001) within 2 min, then recovered slowly and were 43.2 (6.2)% and 27.9 (2.9)% (P less than 0.001) 60 min after administration of neostigmine 0.036 mg kg-1 and 0.071 mg kg-1, respectively. However, the enzyme activity after edrophonium 1.43 mg kg-1 did not change significantly over 60 min. The results suggest that mechanisms other than AChE inhibition may be responsible for the anti-curare effect of edrophonium.

A quantitative study of the pancuronium antagonism at the motor endplate in human organophosphorus intoxication.

Nine patients with organophosphorus (OP) intoxication developing neuromuscular transmission defects were given pancuronium 1, 2, or 4 mg intravenously (IV). Thirteen patient controls with hypoxic encephalopathy received similar dosages. The responses were monitored electrophysiologically using single and repetitive nerve stimulation (20 and 50 Hz). In OP patients, pancuronium did not alter the amplitude of the single CMAP, whereas its repetitive discharges were reduced. Severe neuromuscular blocks were reversed only partially by pancuronium 4 mg. In less severe blocks, 1 and 2 mg resulted in marked improvement. In the patient controls, pancuronium 4 mg induced a severe neuromuscular block but not with 1 and 2 mg. Pancuronium dosages necessary to reverse severe OP-induced neuromuscular blockade produce a neuromuscular block when AChE activity is normal. Low dosages have little effect on normal neuromuscular transmission, but improve the block to a mild degree and may be useful as part of treatment in OP intoxications.