Limits...
Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods.

Han SY, You BH, Kim YC, Chin YW, Choi YH - PLoS ONE (2015)

Bottom Line: Also dose range and administration route are critical factors to determine the ADME profiles.The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine.With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and BK21 PLUS R-FIND Team, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang, Gyeonggi-do, 410-820, South Korea.

ABSTRACT
The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice.

No MeSH data available.


Related in: MedlinePlus

Mean values for the disappearance of α-MG after spiking 1 (■) or 20 (□) μg/mL of α-MG into S9 fractions of various tissues from mice.Bars represent SDs.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4503439&req=5

pone.0131587.g003: Mean values for the disappearance of α-MG after spiking 1 (■) or 20 (□) μg/mL of α-MG into S9 fractions of various tissues from mice.Bars represent SDs.

Mentions: The values for the disappearance of α-MG at 1 or 20 μg/mL in S9 fractions from various mouse tissues are listed in Fig 3. In the S9 fractions of the liver and small intestine, 57.3 and 34.8% of the spiked 1 μg/mL of α-MG had disappeared (mainly metabolized), respectively. The corresponding values at 20 μg/mL of α-MG were 51.4 and 36.2% in liver and small intestine, respectively. However, other tissues studied had almost negligible metabolic activities for both spiked 1 and 20 μg/mL of α-MG.


Dose-Independent ADME Properties and Tentative Identification of Metabolites of α-Mangostin from Garcinia mangostana in Mice by Automated Microsampling and UPLC-MS/MS Methods.

Han SY, You BH, Kim YC, Chin YW, Choi YH - PLoS ONE (2015)

Mean values for the disappearance of α-MG after spiking 1 (■) or 20 (□) μg/mL of α-MG into S9 fractions of various tissues from mice.Bars represent SDs.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4503439&req=5

pone.0131587.g003: Mean values for the disappearance of α-MG after spiking 1 (■) or 20 (□) μg/mL of α-MG into S9 fractions of various tissues from mice.Bars represent SDs.
Mentions: The values for the disappearance of α-MG at 1 or 20 μg/mL in S9 fractions from various mouse tissues are listed in Fig 3. In the S9 fractions of the liver and small intestine, 57.3 and 34.8% of the spiked 1 μg/mL of α-MG had disappeared (mainly metabolized), respectively. The corresponding values at 20 μg/mL of α-MG were 51.4 and 36.2% in liver and small intestine, respectively. However, other tissues studied had almost negligible metabolic activities for both spiked 1 and 20 μg/mL of α-MG.

Bottom Line: Also dose range and administration route are critical factors to determine the ADME profiles.The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine.With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and BK21 PLUS R-FIND Team, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang, Gyeonggi-do, 410-820, South Korea.

ABSTRACT
The information about a marker compound's pharmacokinetics in herbal products including the characteristics of absorption, distribution, metabolism, excretion (ADME) is closely related to the efficacy/toxicity. Also dose range and administration route are critical factors to determine the ADME profiles. Since the supply of a sufficient amount of a marker compound in in vivo study is still difficult, pharmacokinetic investigations which overcome the limit of blood collection in mice are desirable. Thus, we have attempted to investigate concurrently the ADME and proposed metabolite identification of α-mangostin, a major constituent of mangosteen, Garcinia mangostana L, in mice with a wide dose range using an in vitro as well as in vivo automated micro-sampling system together. α-mangostin showed dose-proportional pharmacokinetics at intravenous doses of 5-20 mg/kg and oral doses of 10-100 mg/kg. The gastrointestinal absorption of α-mangostin was poor and the distribution of α-mangostin was relatively high in the liver, intestine, kidney, fat, and lung. α-mangostin was extensively metabolized in the liver and intestine. With regards to the formation of metabolites, the glucuronidated, bis-glucuronidated, dehydrogenated, hydrogenated, oxidized, and methylated α-mangostins were tentatively identified. We suggest that these dose-independent pharmacokinetic characteristics of α-mangostin in mice provide an important basis for preclinical applications of α-mangostin as well as mangosteen. In addition, these experimental methods can be applied to evaluate the pharmacokinetics of natural products in mice.

No MeSH data available.


Related in: MedlinePlus