Metabolism and Pharmacokinetics of Orally Administered Saikosaponin b1 in Conventional, Germ-Free and Eubacterium sp. A-44-Infected Gnotobiote Rats

• Published in: Biological & pharmaceutical bulletin Vol. 21; no. 6; pp. 588 - 593
• Main Authors: KIDA, Hiroaki, AKAO, Teruaki, MESELHY, Meselhy Ragab, HATTORI, Masao
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1998; Maruzen; Japan Science and Technology Agency
• Subjects: Animals; Anti-Allergic Agents - administration & dosage; Anti-Allergic Agents - blood; Anti-Allergic Agents - metabolism; Anti-Allergic Agents - pharmacokinetics; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - blood; Antineoplastic Agents, Phytogenic - metabolism; Antineoplastic Agents, Phytogenic - pharmacokinetics; Biological and medical sciences; Eubacterium - metabolism; Eubacterium sp. A-44; Feces - chemistry; Feces - enzymology; Feces - microbiology; Gastrointestinal Contents - chemistry; Gastrointestinal Contents - enzymology; Gastrointestinal Contents - microbiology; General pharmacology; germ-free rat; gnotobiote rat; Intestinal Absorption; intestinal bacteria; Intestinal Mucosa - metabolism; Intestines - microbiology; Male; Medical sciences; Oleanolic Acid - analogs & derivatives; Oleanolic Acid - blood; Permeability; Pharmacognosy. Homeopathy. Health food; Pharmacology. Drug treatments; Rats; Rats, Wistar; saikosaponin b1; Sapogenins - administration & dosage; Sapogenins - blood; Sapogenins - metabolism; Sapogenins - pharmacokinetics; Saponins; Eubacteriales; Rat; Metabolite; Rodentia; Gut; Oral administration; Metabolism; Eubacterium; Blood; Blood plasma; Saponin; Hydrolysis; Vertebrata; Chinese medicine; Mammalia; Folk medicine; Animal; Plant origin; Bacteria; Feces; Pharmacokinetics
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.21.588

The metabolic fate of saikosaponin b1 (1) was investigated using conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats. After the oral administration of 1 to germ-free rats at a dose of 50mg/kg, no metabolite was detected in the plasma, the cecal contents or the cumulative feces through the experiment. On the other hand, when 1 was orally given to the Eubacterium sp. A-44-infected gnotobiote rats, considerable amounts of its metabolites, prosaikogenin A (2) and saikogenin A (3), were detected in the rat plasma with the respective AUC0-10h values of 17 424 and 22 260pmol·min/ml, similar to the case of its oral administration to conventional rats (AUC0-10h values of 9 936 and 12 414pmol·min/ml for 2 and 3, respectively). Furthermore, significant amounts of both metabolites were detected in the cecal contents and the cumulative feces of the gnotobiote and conventional rats, but not in those of the germ-free rats, within 10h after the administration.Fecal and cecal activities of hydrolyzing 1 and 2 were found in the gnotobiote and conventional rats, though there were no detectable activities in the germ-free rats. Accordingly, both hydrolyzing activities in the intestinal bacteria, such as Eubacterium sp. A-44, are essential for the appearance of 2 and 3 in the rat plasma and cumulative feces, since orally administered 1 was poorly absorbed from the gastrointestinal tract.