experimental animals. Metabolic studies of 24 and 75 highlighted the rapid
absorption of these compounds into circulation. Glucuronidation, sulfation, and Noxidation were found to be the metabolic reaction involved in the metabolism of 24,
wherein 4 metabolites were characterized in urine, one metabolite in plasma and
feces was characterized. In case of 30, 6 metabolites were identified in urine, 4 in
plasma, and 4 in fecal samples. Hydroxylation, glucuronidation, N-oxidation, and
demethylation were identified as the metabolic pathways. A high amount of 20 in
feces and lower amounts in plasma and urine highlighted the low absorption of
these compounds. 11 metabolites were identified in urine, 2 in plasma, and 9 in
fecal samples. Compound 20 was mainly metabolized into phase I products.
Further, these results conclude that the absorption of these molecules is directly
related to the polarity of the molecules (Sch/Epi > Val > Pic). Thus, a total of 40
compounds were detected in urine, 33 in plasma, and 38 in feces.
Yun-Li Zhao et al. have studied the pharmacokinetic effects of A. scholaris total
alkaloids (TA) in SD rat plasma by a validated LC-MS/MS method (Zhao et al.
2018). After the oral administration of various doses (10, 25, and 50 mg/kg) of total
alkaloids, the plasma concentration of 4 bioactive alkaloids (24, 75, 30, and 20)
fitted an open two-compartment model. T max of 24 and 75 occurred within 10 min
while 30 and 20 occurred in 15 min. These compounds were eliminated from
plasma after 24 h of the administration. A TA dosage proportional increase in the
C max and AUC last was obtained for the four indole alkaloids. Further, a short
elimination half-life (T 1/2a ) was also identified. In the study, 20 and 30 were rapidly
acting while the remaining alkaloids were exhibited faster activity in in vivo conditions. Thus, it has been suggested that three times a day administration of total
alkaloids will produce a best therapeutic effect in humans.
Scholaricine (24)
N
N
H
HO
O
O
OH
19-Epi scholaricine (75)
N
N
H
HO
O
O
OH
Vallesamine (30)
N
N
O
O
O
H
H
Picrinine (20)
N
H
N
O
O
O
Fig. 14.66 Chemical structures of various alkaloids from A. scholaris (20, 24, 30, 75)
Actinophyllic Acid (373)
N
O
N
H
OH
O
HO
Fig. 14.65 Chemical structure of actinophyllic acid (373)
14 Pharmaceutical Application of Bio-actives …
523
absorption of these compounds into circulation. Glucuronidation, sulfation, and Noxidation were found to be the metabolic reaction involved in the metabolism of 24,
wherein 4 metabolites were characterized in urine, one metabolite in plasma and
feces was characterized. In case of 30, 6 metabolites were identified in urine, 4 in
plasma, and 4 in fecal samples. Hydroxylation, glucuronidation, N-oxidation, and
demethylation were identified as the metabolic pathways. A high amount of 20 in
feces and lower amounts in plasma and urine highlighted the low absorption of
these compounds. 11 metabolites were identified in urine, 2 in plasma, and 9 in
fecal samples. Compound 20 was mainly metabolized into phase I products.
Further, these results conclude that the absorption of these molecules is directly
related to the polarity of the molecules (Sch/Epi > Val > Pic). Thus, a total of 40
compounds were detected in urine, 33 in plasma, and 38 in feces.
Yun-Li Zhao et al. have studied the pharmacokinetic effects of A. scholaris total
alkaloids (TA) in SD rat plasma by a validated LC-MS/MS method (Zhao et al.
2018). After the oral administration of various doses (10, 25, and 50 mg/kg) of total
alkaloids, the plasma concentration of 4 bioactive alkaloids (24, 75, 30, and 20)
fitted an open two-compartment model. T max of 24 and 75 occurred within 10 min
while 30 and 20 occurred in 15 min. These compounds were eliminated from
plasma after 24 h of the administration. A TA dosage proportional increase in the
C max and AUC last was obtained for the four indole alkaloids. Further, a short
elimination half-life (T 1/2a ) was also identified. In the study, 20 and 30 were rapidly
acting while the remaining alkaloids were exhibited faster activity in in vivo conditions. Thus, it has been suggested that three times a day administration of total
alkaloids will produce a best therapeutic effect in humans.
Scholaricine (24)
N
N
H
HO
O
O
OH
19-Epi scholaricine (75)
N
N
H
HO
O
O
OH
Vallesamine (30)
N
N
O
O
O
H
H
Picrinine (20)
N
H
N
O
O
O
Fig. 14.66 Chemical structures of various alkaloids from A. scholaris (20, 24, 30, 75)
Actinophyllic Acid (373)
N
O
N
H
OH
O
HO
Fig. 14.65 Chemical structure of actinophyllic acid (373)
14 Pharmaceutical Application of Bio-actives …
523