ABSTRACT
Ocotillol (OT)-type ginsenosides, one subtype of ginsenosides, consist of a dammarane skeleton and a tetrahydrofuran ring. Most naturally-occurring OT-type ginsenosides exist in Panax species, particularly in Panax quinquefolius, which may be attributed to the warm and humid climate of its native areas. Till now, merely 28 types of naturally-occurring OT-type ginsenosides have been isolated. In contrast, semi-synthesized OT-type ginsenosides are attracted considerable attentions. These ginsenosides can be obtained through oxidation and cyclization of side chains of dammarane-type ginsenosides, and other methods, which may change their physical and chemical properties and further improve their bioavailabilities. It is also notable that the pharmacological activities of ginsenosides are closely related to the stereoisomers caused by the configuration at C-20. Semi-synthesis of OT-type ginsenosides can facilitate our understanding of the biosynthesis, transformation and metabolism of OT-type ginsenosides in the body. This review will systematically summarize the research progress on naturally-occurring and semi-synthetic OT-type ginsenosides, which provides a theoretical basis for their bioactivity-guided research.
ABSTRACT
OBJECTIVE: To develop an LC-MS /MS method for the quantitative analysis of ocotillol in rat plasma, and study the pharmacokinetic characteristics of ocotillol in rats after oral administration. METHODS: Ocotillol was extracted from plasma sample by protein precipitation. The concentration of ocotillol in plasma was determined by LC-MS/MS and the plasma concentration-time curve and main pharmacokinetic parameters were calculated after a single oral administration of ocotillol at 40 mg•kg-1 to SD rats. RESULTS: Excellent linearity was found between 10 - 240 ng•mL-1. Intra-and inter-day precision values (RSDs) of QC samples were both below 15% and the extraction recoveries of ocotillol from plasma were higher than 84.14%. Double peaks were observed in the mean plasma concentration versus time profile of ocotillol after oral administration. The main pharmacokinetic parameters of ocotillol were as follows: the mean maximum plasma concentration (ρmax) was (156.60 ± 51.84) ng•mL-1 occurring at (0.83 ± 0.26) h post dose, the mean elimination half-time (t1/2) was (8.82 ± 7.56) h, and the mean area under the plasma concentration versus time curve (AUC0-t) was (687.15 ± 144.08) ng•h•mL-1. CONCLUSION: The current data shows that ocotillol is rapidly absorbed in rats after oral administration and slowly eliminated from circulatory blood system, with low plasma exposure. Enterohepatic circulation may contribute to the atypical drug absorption profiles.
ABSTRACT
@#Ocotillol(3)and its epimer(4)have been synthesized from 20(S)-protopanaxatriol ［20(S)-PPT］ via two routes, and their formation mechanism has been speculated. Route 1: Compounds 3 and 4 were obtained from 20(S)-PPT by oxidation with m-CPBA at the yield of 44. 1% and 28. 6%, respectively. Route 2: Compounds 3 and 4 were prepared from 20(S)-PPT by acetylation, oxidation and saponification at the yield of 16. 4% and 16. 2%, respectively. The formation mechanism of compounds 3 and 4 is speculated as below: 1)The chemical environments of both sides of C24(25)double bond in 20(S)-PPT are different due to the existence of intramolecular hydrogen bond, which led to the different oxidation ratio of the two sides, and the different yields of compounds 3 and 4. 2)There is not intramolecular hydrogen bond in acetylated 20(S)-PPT, and the chemical environments of both sides of C24(25)double bond are similar, which resulted in almost equal yields of compounds 3 and 4 synthesized through oxidation with m-CPBA, intramolecular SN2 and saponification.
ABSTRACT
Objective To explore the excretion of the 20 (S)-protopanaxatriol (PPT) and its metabolites ocotillol type epimers (M1 and M2) in urine, feces samples and the excretion of Ml and M2 in bile samples. Methods The concentration of PPT, Ml and M2 in urine, feces samples and the concentration of Ml and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization by β-glucuronidase. Results After intragastric(ig) administration of PPT, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.88%, 1.34% and 0.084%, respectively. With the hydrolization by β-glucuronidase, the cumulative excretion rate for 72 h of PPT, Ml and M2 in feces were 14.77%, 1.36% and 0.085%, respectively. However, the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2, the accumulation excretion rate were 4.41% for M1 and 47.2% for M2 in feces, while both epimers were hardly detected in urine. After ig administration of M1 or M2, the 36 h cumulative biliary excretion rate was 3.01% for M1, and only 0.068% for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80% after intravenous administration, while only 1.24% for M2. Conclusion After ig administration of PPT, a small amount of PPT and its metabolites (Ml, M2) are excreted by the feces but little via urine, and there are stereoselectivity differences in biliary excretion between M1 and M2.
ABSTRACT
Objective To explore the excretion of the 20(S)-protopanaxatriol(PPT)and its metabolites ocotillol type epi?mers(M1 and M2)in urine,feces samples and the excretion of M1 and M2 in bile samples. Methods The concentration of PPT,M1 and M2 in urine,feces samples and the concentration of M1 and M2 in bile samples were determined by the LC-MS/MS methods with or without the hydrolization byβ-glucuronidase. Results After intragastric(ig)administration of PPT,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.88%,1.34%and 0.084%,respectively. With the hydrolization byβ-glucuronidase,the cumulative excretion rate for 72 h of PPT,M1 and M2 in feces were 14.77%,1.36%and 0.085%,respectively. However,the epimers and PPT were hardly detected in urine. After ig administration of M1 or M2,the accumulation excretion rate were 4.41%for M1 and 47.2%for M2 in feces,while both epimers were hardly detected in urine. After ig administration of M1 or M2,the 36 h cumulative bili?ary excretion rate was 3.01%for M1,and only 0.068%for M2. The 36 h cumulative biliary excretion rate of M1 was 8.80%after intra?venous administration ,while only 1.24%for M2. Conclusion After ig administration of PPT,a small amount of PPT and its metabo?lites(M1,M2)are excreted by the feces but little via urine ,and there are stereoselectivity differences in biliary excretion between M1 and M2.