419
12 Consensus Drug Design Using IT Microcosm
On the whole, the pharmacologic effects of the extract become manifest as a
result of the complex effect of all 23 components; they are due to its combined immunostimulatory and metabolic action, which is predominantly peripheral.
An experimental verification of the prediction results was performed on 60 newborn Simmental calves on three bred livestock farms [35]. In comparison with the
controls, the groups of calves receiving the agent showed almost no diarrhea morbidity; there were no mortality cases; the rate of liveweight gain was considerably
higher; and the protective properties of the blood were considerably better. All of
the detected differences were statistically significant. The findings obtained indicate
an enhanced natural resistance of the newborn calves’ organisms, which confirms
the results of the in silico prediction that the extract has an ability to enhance protein
synthesis and adaptogenic, immunostimulatory and metabolic effects. A powerful
wound-healing effect of the extract was shown in experiments on dogs. All of the
animals showed a good tolerance for the drug; no local irritation, allergy or deviation in behavioural reactions was noted.
Consequently, the results of the experiments confirmed the estimates of the in
silico prediction of a series of beneficial pharmacological effects of Juglans regia
extracted from the fruits of milky-wax ripeness [35, 97, 105, 119, 120].
12.5.3.2 Synergism of the Active Compounds in Gymnema Sylvestre Extract
The extract of Gymnema sylvestre leaves is an effective hypoglycemic nutritional
supplement; it is widely used as an adjuvant agent in antidiabetic therapy [55]. Our
task was to determine with the help of IT Microcosm how the ratio of the main
substances in the extract affects the extent of its hypoglycemic activity [74, 75, 105,
112]. The normal strategy was chosen for prediction because it makes it possible
to account for nonstandard QSAR regularities, including those associated with the
pharmacologic interaction of several substances, and it achieves this with fewer errors than with the risk strategy.
Gymnema sylvestre extract is composed of seven main components (Fig. 12.7):
gymnemic acids I, II, III, IV (XV-XVIII), gymnemosides A and B (XIX, XX), and
conduritol B (XXI). The structural formulas of six mixtures of these substances
with varying compositions were constructed. A prediction of the presence of hypoglycemic activity in the individual components of Gymnema sylvestre extract
and their mixtures was made with the help of decision rules calculated for a set of
known hypoglycemic substances (see Sect. 3). The expected extent of hypoglycemic activity was estimated according to the membership-function value. The results
are shown in Table 12.19.
According to the results of the predicted hypoglycemic activity of the individual
components of the extract, it was established that gymnemic acid III (XVII) should
be the most active among all of the components; gymnemic acid II (XVI) should
show a high or medium activity; gymnemic acid IV (XVIII) and gymnemoside A
(XIX) should show a moderate activity; and gymnemoside B (XX) and conduritol
B (XXI) should be inactive.
12 Consensus Drug Design Using IT Microcosm
On the whole, the pharmacologic effects of the extract become manifest as a
result of the complex effect of all 23 components; they are due to its combined immunostimulatory and metabolic action, which is predominantly peripheral.
An experimental verification of the prediction results was performed on 60 newborn Simmental calves on three bred livestock farms [35]. In comparison with the
controls, the groups of calves receiving the agent showed almost no diarrhea morbidity; there were no mortality cases; the rate of liveweight gain was considerably
higher; and the protective properties of the blood were considerably better. All of
the detected differences were statistically significant. The findings obtained indicate
an enhanced natural resistance of the newborn calves’ organisms, which confirms
the results of the in silico prediction that the extract has an ability to enhance protein
synthesis and adaptogenic, immunostimulatory and metabolic effects. A powerful
wound-healing effect of the extract was shown in experiments on dogs. All of the
animals showed a good tolerance for the drug; no local irritation, allergy or deviation in behavioural reactions was noted.
Consequently, the results of the experiments confirmed the estimates of the in
silico prediction of a series of beneficial pharmacological effects of Juglans regia
extracted from the fruits of milky-wax ripeness [35, 97, 105, 119, 120].
12.5.3.2 Synergism of the Active Compounds in Gymnema Sylvestre Extract
The extract of Gymnema sylvestre leaves is an effective hypoglycemic nutritional
supplement; it is widely used as an adjuvant agent in antidiabetic therapy [55]. Our
task was to determine with the help of IT Microcosm how the ratio of the main
substances in the extract affects the extent of its hypoglycemic activity [74, 75, 105,
112]. The normal strategy was chosen for prediction because it makes it possible
to account for nonstandard QSAR regularities, including those associated with the
pharmacologic interaction of several substances, and it achieves this with fewer errors than with the risk strategy.
Gymnema sylvestre extract is composed of seven main components (Fig. 12.7):
gymnemic acids I, II, III, IV (XV-XVIII), gymnemosides A and B (XIX, XX), and
conduritol B (XXI). The structural formulas of six mixtures of these substances
with varying compositions were constructed. A prediction of the presence of hypoglycemic activity in the individual components of Gymnema sylvestre extract
and their mixtures was made with the help of decision rules calculated for a set of
known hypoglycemic substances (see Sect. 3). The expected extent of hypoglycemic activity was estimated according to the membership-function value. The results
are shown in Table 12.19.
According to the results of the predicted hypoglycemic activity of the individual
components of the extract, it was established that gymnemic acid III (XVII) should
be the most active among all of the components; gymnemic acid II (XVI) should
show a high or medium activity; gymnemic acid IV (XVIII) and gymnemoside A
(XIX) should show a moderate activity; and gymnemoside B (XX) and conduritol
B (XXI) should be inactive.