A potent anti-diabetic agent fromKalopanax pictus

Park, Hee-Juhn; Kim, Dong-Hyun; Choi, Jongwon; Park, Jong-Hee; Han, Yong-Nam

doi:10.1007/bf03216748

Cited by 64 publications

(40 citation statements)

References 13 publications

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“…15) Since 1996, we also have elucidated a potent hypoglycemic, 4) cytotoxic, 5) antimutagenic 5) and hepatotoxic 16) effects of hederagenin monodesmosides. Because the active component of this crude drug has never been reported on anti-inflammatory effect, we examined the effects of the various hederagenin monodesmodies on release of two inflammatory mediators (NO and PGE 2 ), TNF-a, and the expression level of iNOS and COX-2 of the macrophages activated by LPS.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous reports on anti-diabetic, 4) cytotoxic 5) and antifungal assays 6) have shown that the active components should be hederagenin monodesmosides. In addition, we also demonstrated that hederagenin bisdesmoside could be converted to its monodesmosides and its serial saponins by human intestinal bacteria and that these metabolites showed anti-diabetic activity.…”

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confidence: 99%

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In Vitro Antiinflammatory Activity of Kalopanaxsaponin A Isolated from Kalopanax pictus in Murine Macrophage RAW 264.7 Cells.

Kim

Park

et al. 2002

Biological & Pharmaceutical Bulletin

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The stem bark of Kalopanax pictus NAKAI (Araliaceae), a deciduous tree growing in East Asian countries, 1) has been traditionally used for the treatment of rheumatoidal arthritis, neurotic pain and diabetes mellitus. The constituents such as hederagenin glycosides, syringin, liriodendrin and coniferylaldehyde glucosides have been isolated from this plant. 2,3)Our previous reports on anti-diabetic, 4) cytotoxic 5) and antifungal assays 6) have shown that the active components should be hederagenin monodesmosides. In addition, we also demonstrated that hederagenin bisdesmoside could be converted to its monodesmosides and its serial saponins by human intestinal bacteria and that these metabolites showed anti-diabetic activity. 7) Although several pharmacological effects of hederagenin monodesmosides as well as its serial saponins are reported, there have been very few reports on the effects of hederagenin monodesmosides on the antiinflammatory role. During inflammatory processes, large amounts of pro-inflammatory mediators, nitric oxide (NO) and prostaglandin E 2 (PGE 2 ) are generated by the inducible isoforms of NO synthase (iNOS) and cyclooxygenase (COX-2), respectively. 8) In mammailian cells, three isoforms of NOS, types I, II, and III, have been identified on the basis of physical and biochemical characteristics of the purified enzymes. Type I (neuronal NOS, nNOS) and type III (endothelial NOS, eNOS) have been classified as constitutive NOS (cNOS) because these are continuously present in the cells, whereas type II, an iNOS, is expressed only after exposure to specific stimulants such as cytokines, bacterial endotoxic lipopolysaccharide (LPS), and calcium ionophore in some cells.9-11) Cyclooxygenase (COX) is the enzyme which converts arachidonic acid to prostaglandins (PGs). Like NOS, COX has been found in two isoforms, and COX-2 is an inducible form responsible for the production of large amounts of proinflammatory PGs at the inflammatory site. 12)Our previous investigation concerning kalopanaxsaponin A demonstrated their anti-inflammatory syndromes in the rat induced by Freund's complete adjuvant reagent.13) Thus, as a prelude to reveal the underlying mechanisms for the anti-inflammatory effect of kalopanaxsaponin A, we evaluated and compared the effects of various hederagenin monodesmosides ( Fig. 1) isolated from stem bark of Kalopanax pictus NAKAI on LPS-induced NO, PGE 2 and tumor necrosis factora (TNF-a) release by the macrophage cell line RAW 264.7 in the present study. Moreover, we also examined if these hederagenin monodesmosides reduced iNOS and COX-2 enzyme expression. Wonju 220-702, Korea. Received October 30, 2001; accepted January 16, 2002 In the present study, effects of various hederagenin monodesmosides isolated from the stem bark of Kalopanax pictus NAKAI, such as hederagenin, d d-hederin, kalopanaxsaponin A, kalopanaxsaponin I, and sapindoside C, have been evaluated on lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E 2 (PGE 2 ) and tumor necrosis factor-a a (TNF-a a...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In Vitro Antiinflammatory Activity of Kalopanaxsaponin A Isolated from Kalopanax pictus in Murine Macrophage RAW 264.7 Cells.

Kim

Park

et al. 2002

Biological & Pharmaceutical Bulletin

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“…KPA and KPI reduced the vascular permeability, and KPA was more effective than KPI. When the biological activities of kalopanaxsaponins were investigated in hyperglycemia, 4,7) cytotoxicity, 5) mutagenicity, 13) and hepatotoxicity model, 14) KPA was found to be the most active compound. In this FCA-induced rat rheumatoid arthritis model, KPA was also effective.…”

Section: Time Course Of Metabolism Of Kpk and Kpj By Human Intestinalmentioning

confidence: 99%

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

Kim

Bae

Han

et al. 2002

Biological & Pharmaceutical Bulletin

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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.

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“…1 Phytochemical studies on the stem bark have demonstrated the presence of hederagenin glycosides, syringin, liriodendrin, and coniferylaldehyde glucosides, 2,3 and the methanol extract of the stem bark of K. pictus has been reported to possess cytotoxic, 4 antidiabetic, 5 and anti-inflammatory activities. 6 In this report, a new compound (3) and 11 known compounds (1, 2 and 4-12) were isolated from the methanol extract of the stem bark of K. pictus.…”

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Anti-inflammatory and PPAR Subtypes Transactivational Activities of Phenolics and Lignans from the Stem Bark of Kalopanax pictus

Quang¹,

Ngân²,

Minh³

et al. 2011

Bulletin of the Korean Chemical Society

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A new compound, kalopanaxin F (3), and 11 known compounds (1, 2, 4-12), were isolated from the stem bark of Kalopanax pictus. Their structures were elucidated on the basis of chemical and spectroscopic methods. Five of the compounds (2, 3, 5, 6, and 12) significantly inhibited TNFα-induced NF-κB transcriptional activity in HepG2 cells in a dose-dependent manner, with IC 50 values ranging from 6.2 to 9.1 µM. Furthermore, the transcriptional inhibitory function of these compounds was confirmed based on decreases in COX-2 and iNOS gene expression in HepG2 cells. Compounds 3-7, 9, and 12 significantly activated the transcriptional activity of PPARs dose-dependently, with EC 50 values ranging from 4.1-12.7 µM. Compounds 4 and 5 exhibited PPARα, PPARγ, and PPARβ(δ) transactivational activities in a dose-dependent manner, with EC 50 values of 16.0 and 17.0, 8.7 and 16.5, 26.2 and 26.3 µM, respectively.

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A potent anti-diabetic agent fromKalopanax pictus

Cited by 64 publications

References 13 publications

In Vitro Antiinflammatory Activity of Kalopanaxsaponin A Isolated from Kalopanax pictus in Murine Macrophage RAW 264.7 Cells.

In Vitro Antiinflammatory Activity of Kalopanaxsaponin A Isolated from Kalopanax pictus in Murine Macrophage RAW 264.7 Cells.

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

Anti-inflammatory and PPAR Subtypes Transactivational Activities of Phenolics and Lignans from the Stem Bark of Kalopanax pictus

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