Sphaeranthus indicus flower derived constituents exhibits synergistic effect against acetylcholinesterase and possess potential antiamnestic activity.

OBJECTIVE: The present investigation was aimed at discovery of novel acetylcholinesterase (AChE) inhibitors. METHODS: In vitro AchE inhibitory activity of various extracts of Sphaeranthus indicus flower heads was carried out. The petroleum ether fraction of S. indicus flowers (SIPE) exhibited significant activity. The fraction was found to be rich in sesquiterpene lactone content possibly responsible for in vitro AChE inhibition. In further study, the antiamnesic activities of SIPE in mice on the learning and memory impairments induced by scopolamine (1.0 mg/kg, i.p.) were examined. RESULTS: SIPE (10 mg/kg, p.o.) administration significantly reversed cognitive impairments in mice by passive avoidance test (P < 0.05). It also reduced escape latencies in training trials and prolonged swimming times in the target quadrant during the probe trial in the water maze task (P < 0.05). These results indicated that S. indicus due to its sesquiterpene lactones have anti-cholinesterase activity. A major sesquiterpene lactone, 7-hydroxy frullanolide along with other constituents were isolated from SIPE and evaluated for AchE inhibitory activity. Negative results were obtained in case of isolated compounds. CONCLUSION: Synergistic effect between constituents of SIPE was confirmed to have anti-amnesic activities that may be useful for cognitive impairment treatment.

Isoquinoline alkaloids from Tinospora cordifolia inhibit rat lens aldose reductase.

The inhibitory activity of Tinospora cordifolia stem-derived alkaloids was evaluated against lens aldose reductase (AR) isolated from male Wistar rats. Anticataract potential of the alkaloids of T. cordifolia was evaluated in vitro in rat lenses, considering the activity of normal rat lenses as 100%. The biologically active constituents of T. cordifolia extract were characterized as the isoquinoline alkaloids, jatrorrhizine, palmatine and magnoflorine, by spectral analysis. The inhibitory effects varied with all chemicals and concentrations used. The inhibitory concentration (IC50) values of jatrorrhizine, palmatine and magnoflorine are 3.23, 3.45 and 1.25 µg/mL respectively. The concentration of maximum activity was selected for its effect on galactose-induced polyol accumulation in vitro. The percentage inhibition of galactose-induced polyol accumulation was 62.6, 58.8 and 27.7% in the presence of jatrorrhizine, palmatine and magnoflorine, respectively. Magnoflorine may be useful as lead compounds and new agents for AR inhibition.

Hypoglycemic activity of alkaloidal fraction of Tinospora cordifolia.

The stem of Tinospora cordifolia (TC) is widely used in the therapy of diabetes in traditional folk medicine of India. In the present study, isoquinoline alkaloid rich fraction (AFTC) derived from stem of TC and three alkaloids viz., palmatine, jatrorrhizine and magnoflorine were evaluated for insulin-mimicking and insulin-releasing effect in vitro and in vivo. Their effect on hepatic gluconeogenesis was examined in rat hepatocytes. Insulin releasing effect was detected in vitro using rat pancreatic ß-cell line, RINm5F. Furthermore, effects of AFTC and isolated alkaloids on serum glucose and insulin level were studied in fasted and glucose challenged normal rats. AFTC significantly decreased gluconeogenesis in rat hepatocytes as insulin did and it increases insulin secretion in RINm5F cells similar to tolbutamide. In acute 30 min test in vitro, AFTC, palmatine, jatrorrhizine and magnoflorine stimulated insulin secretion from the RINm5F cell line. As in vivo results, administration of AFTC (50, 100, and 200 mg/kg), palmatine, jatrorrhizine and magnoflorine (10, 20 and 40 mg/kg each) orally significantly decreased fasting serum glucose, and suppressed the increase of blood glucose levels after 2 g/kg glucose loading in normal rats. In vivo study further justified their insulin secreting potential by raising the serum insulin level in glucose fed rats. These results demonstrate the alkaloid present in TC contributed for antihyperglycemic activity. AFTC may have hypoglycemic effects via mechanisms of insulin releasing and insulin-mimicking activity and thus improves postprandial hyperglycemia.