Metabolism of Kalopanaxsaponin K by Human Intestinal Bacteria and Antirheumatoid Arthritis Activity of Their Metabolites.

Abstract

The stem bark of Kalopanax pictus belonging to the family Araliaceae has been used in Korea as a tonic, analgesic, antiinflammatory and antidiabetic medicine. From this plant, hederagenin glycosides, syringin, liriodendrin, and coniferylaldehyde glucosides have been isolated. [1][2][3] Related to biological activities of K. pictus, it was reported that the active components on antidiabetic, 4) cytotoxic, 5) and antifungal assays 6) may be hederagenin monodesmosides. We also reported that kalopanaxsaponin B (KPB) and H (KPH) were easily metabolized by human intestinal bacteria to kalopanaxsaponin A (KPA) and kalopanaxsaponin I (KPI), resepectively.7) However, these metabolites were slowly transformed to hederagenin. KPI was slowly transformed to hederagenin via KPA. Among these compounds, the most antidiabetic compound was KPA. However, studies related to the metabolic pathway of KPI to hederagenin in the intestine, the biotransfromation of kalopanaxsaponin K (KPK) to KPA, which is an antitumor compound, 5) and their biological activities, such as antirheumatoid arthritis, are incomplete.Therefore we isolated the main components KPB, KPH, and KPK from the stem bark of K. pictus, investigated the metabolic pathway of these kalopanaxsaponins by human intestinal bacteria, and measured the antirheumatoid arthritis activity of the main metabolites. We also screened the biotransforming bacteria of KPK to the bioactive compound KPA from human intestinal bacteria. MATERIALS AND METHODSInstrument Melting points were determined on an electrothermal digital melting point apparatus.1 H-and 13 C-NMR spectra were recorded on a Brucker-AM 500 with tetramethylsilane (TMS) as an internal standard. The TLC chromatogram of metabolites was quantitatively analyzed with a Shimadzu CS-920 TLC-scanner.

19.ALPHA.-Hydroxyursane-Type Triterpenoids: Antinociceptive Anti-inflammatory Principles of the Roots of Rosa rugosa

“…Furthermore, as we previously reported, triterpenoid glycosides exhibit bioactivity via the enzymatic hydrolysis of glycosidic sugar chains by human intestinal bacteria. 16) In conclusion, the present results suggest that the four triterpenoids of the root of R. rugosa are responsible for the antiinflammatory activity. In particular, euscaphic acid and tormentic acid had more potent antinociceptive/antiinflammatory effects than the corresponding 28-O-glycosides, kaji-ichigoside F 1 and rosamultin.…”

“…We previously reported that the compounds obtained from the hydrolysis of the triterpenoid glycosides (kalopanaxsaponins B and K) exert significant bioactivities. 15,16) Four compounds were tested for antiinflammatory and antinociceptive activity in rats and mice. As shown in Table 3, the antinociceptive effects of the triterpene glycosides (1, 2) was mild to significant at oral dosages of 20 and 30 mg/kg, whereas euscaphic acid (3) and tormentic acid (4) had a pronounced effect.…”

The Stem Bark ofKalopanax pictusExhibits Anti-inflammatory Effect through Heme Oxygenase-1 Induction and NF-κB Suppression

“…The other constituent of KP, α-hederin methyl ester, showed anticarrageenan activity in rats and anti-arthritic activity in rats and mice (15). Kalopanaxsaponin A was reported to have anti-rheumatoidal (16-19), anti-tumor (20), anti-diabetic (21), antifungal (22) activities. Kalopanaxsaponins A inhibits the production of NO, prostaglandin E2 (PGE2) and TNF-α in macrophage cell line RAW 264.7 (1).…”

Antinociceptive and Antiinflammatory Effects of Niga-ichigoside F1 and 23-Hydroxytormentic Acid Obtained from Rubus coreanus

“…administration. 7) Since the triterpenoids are usually more active than the corresponding glycosides, 8,9) we hydrolyzed the active niga-ichigoside F 1 (1) to produce a 23-hydroxytormentic acid (1a). Unlike the experimental design undertaken by Niero et al, 7) we orally administered niga-ichigoside F 1 obtained from R. coreanus and the aglycone 23-hydroxytormentic acid in the present study and compared their antinociceptive and antiinflammatory activities.…”