Experiments involving human intellectual skills such as telegraphy and proof reading and animal experiments involving negotiation of a spiral maze confirmed improved mental activity and therefore ginseng pretreatment was suggested for tasks requiring speed, accuracy and stamina. Ginseng administered orally was successfully used to counter the decline in learning ability that is normally produced under physiological stress (Bao et al., 1984a,c). In a 12-week doubleblind, placebo-controlled trial involving 16 fit male volunteers (aged 20-24 years) and an oral dosage of 100mg of Ginseng G115 twice a day, D'Angelo et al. (1986) noted statistically significant improvements in attention, information-processing, reaction times and well-being and, in particular, in mental arithmetic.
More recent studies by Petkov and Mosharrof (1987) have offered a more detailed explanation of this improvement of learning, memory and physical capability induced by administration of standardised Ginseng G115 extract. Learning and relearning can be considered in terms of memory. Ginseng was considered particularly useful if the breakdown of mental activity was due either to senescence or to individual specificity. Age is a very important factor especially as one can by 75 years of age lose 25% of the memory capacity held at 20 years of age. Fortunately such loss does vary considerably from person to person. Slowing down of the cerebral processes is accompanied by a decrease in the deposition of biogenic amines and acetylcholine, the compounds essential for nerve ending transmission, and is manifested more obviously by lack of attention, decrease in concentration and lapses in memory.
Memory is associated with the hippocampus, an elongated structure composed of a modified form of cerebral cortex forming ridges on the floor of each lateral ventricle of the brain. The hippocampus is regarded as the brain's critical decision-making neuronal mechanism, determining the importance and type of incoming sensory signals. It has been suggested that the hippocampus acts as the encoding centre for conversion of short term memory into long term memory and facilitates and controls the long term memory storage of data i.e. knowledge.
Benishin et al. (1991) noted that, in rats, ginsenoside Rb1 obtained from P. quinquefolium roots was able to partially prevent the memory deficits caused by the cholinergic agent hyoscine (=scopolamine). Although the ginsenoside Rb1 had no apparent effect on acetylcholinesterase activity, it facilitated the release of acetylcholine from hippocampal slices and thus the uptake of choline into the nerve endings without alteration in calcium influx. Therefore they concluded that the ability of ginsenoside Rb1 to reduce or prevent memory deficits was probably related to facilitation of acetylcholine metabolism in the central nervous system. Other workers confirmed such observations. Thus Ni et al. (1993) used a T-maze delayed alternation task technique and rats whose spatial memories had been disrupted by intraperitoneal injection of hyoscine (0.025-0.1 mg/kg). The hyoscine effect was dose-dependent but the hyoscine (0.1 mg/kg) action could be reversed by physostigmine (0.4 mg/kg) and also by orally administered ginseng extract (0.5-4.0 g/kg dried root). Ginseng extract given orally 60 min before testing improved the maze solving problem in a dose-dependent fashion, opposing the memory deficit induced by hyoscine. Oral ginseng given for 7 days in drinking water (2.0 and 4.0 g/kg/day) also produced dose-dependent reversal of the hyoscine-induced performance disruption and improved spatial working memory. The Japanese team of Yamaguchi et al. (1995) similarly recorded the impaired performance of rats in a radial-arm maze, the apparent deterioration of initially correct performances being induced also by hyoscine treatment. A single intraperitoneal injection of ginsenoside Rg1 but not ginsenosides Rb1 or Rd, prevented the impairment of performance but it was noted that the inhibition of the reduction in initially correct responses was associated with a bell-shaped dose-response curve for ginsenoside Rg1. As ginsenoside Rg1 was unable to counter the spatial learning deficits prompted by a lesion in the medial septum, it was suggested that the cholinergic neurons in the medial septum were involved in the correction of the impaired performance. Later the same group (Yamaguchi et al., 1997) observed that, in young adult rats suffering hyoscine-induced cognitive impairment, the choline acetyltransferase activity increased in the medial septum but not in the diagonal band, caudate and hippocampus 30 min. after injection of the protopanaxatriol ginsenosides Rg1 or Re. Significantly the protopanaxadiol ginsenosides Rb1 and Rd had no effect on choline acetyltransferase activity. Aged rats performed a smaller number of initially correct responses when introduced into the radial arm maze and this was related to a lower level of choline acetyltransferase activity in the medial septum although not in the diagonal band. However in aged rats repeated intraperitoneal injections of ginsenoside Rg1 caused an increase in the number of initially correct responses and an increase in choline acetyltransferase activity in the medial septum although not in the diagonal band. It was therefore suggested that the protopanaxatriol type ginsenosides Rg1 and Re ameliorated the cognitive deficit in aged rats through an increase in choline acetyltransferase activity in the medial septum.
Although brain function is still poorly understood it seems clear that the chemistry of the cholinergic system in the brain reticular formation and hippocampus is critical. In living systems free radicals, strongly active, highly reactive substances, such as singlet oxygen, superoxide anion and hydroxy radical are formed at tissue level in parallel with oxygen consumption for cell respiration and such radicals can affect targetted cells. Naturally occurring endogenous protective systems normally neutralise free radicals but if such systems are inadequate or the production of free radicals is excessive, the brain becomes disturbed. Free radicals are normally produced in small amounts only and are mopped up endogenously by scavenger enzymes e.g. superoxidodismutase, catalase, peroxidase, tocopherols, ascorbic acid, etc. In the event of scavenger enzymes and antioxidants failing to neutralise the free radicals, reaction with unsaturated fatty acids in the various biomembranes yields lipid peroxides. Such peroxides are normally reduced to less reactive hydroxy acids although some may break down to yield malondialdehyde. It remains to be seen whether the naturally occurring antioxidants found in ginseng extracts are major factors in the improvement of memory and intellectual skills experienced by many ginseng users.
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