Abstract
In this study, we measured the antiallergic activities of ginsenosides isolated from the root of Panax ginseng ( Araliaceae), and of their metabolites, as produced by human intestinal bacteria. Compound K, which was identified as a main metabolite, had the most potent inhibitory activity on β-hexosaminidase release from RBL-2H3 cells and on the PCA reaction. The inhibitory activity of compound K was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. This compound demonstrated a membrane stabilizing action on differential scanning calorimetry. However, compound K did not inhibit the activation of hyaluronidase and did not scavenge active oxygen. These results suggest that the antiallergic action of compound K originates from its cell membrane stabilizing activity and that the ginsenosides of ginseng are prodrugs with extensive antiallergic properties.
Abbreviations
compound K:20-O-β-D-glucopyranosyl-20(S)-protopanaxadiol
DNP:dinitrophenol
DSCG:disodium cromoglycate
DPPC:dipalmitoylphosphatidylcholine
DPPH:1,1-diphenyl-2-picrylhydrazyl
HSA:human serum albumin
IC50:50% inhibitory concentration
EC50:50% effective concentration
XOD:xanthine oxidase
ICR:Institute of Cancer Research
PBS:phosphate buffered saline
PCA:passive cutaneous anaphylaxis
RAW264.7:mouse monocyte leukemiaRBL-2H3: rat basophil leukemia
SD:Sprague-Dawley
Key words
Panax ginseng
- Araliaceae - ginsenosides - compound K - antiallergic activity - intestinal bacteria
References
-
1
Tanaka N, Tanaka O, Shibata S.
Chemical studies on the oriental plant drugs. XXVIII. Saponins and sapogenins of ginseng; Stereochemistry of sapogenin of ginsenoside Rb1, Rb2 and Rc.
Chemical and Pharmaceutical Bulletin.
1972;
20
1212-6
-
2
Shibata S, Fujita M, Itokawa H, Tanaka O, Ishii T.
Panaxadiol, a sapongenin of ginseng roots (1).
Chemical and Pharmaceutical Bulletin.
1963;
11
759-64
-
3
Wu J Y, Gardner B H, Murphy C I, Seals J R, Kensil C R, Recchia J, Beltz G A, Newman G W, Newman M J.
Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine.
Journal of Immunology.
1992;
148
1519-25
-
4
Mochizuki M, Yoo C Y, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I.
Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside Rb2, 20(R)- and 20(S)-ginsenoside Rg3, of red ginseng.
Biological and Pharmaceutical Bulletin.
1995;
18
1197-202
-
5
Wakabayashi C, Hasegawa H, Murata J, and Saiki I.
In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration.
Oncology Research.
1998;
9
411-7
-
6
Akao T, Kida H ., Kanaoka M, Hattori M, Kobashi K.
Intestinal bacterial hydrolysis is required for the appearance of compound K in rat plasma after oral administration of ginsenoside Rb1 from Panax ginseng
.
Journal of Pharmacy and Pharmacology.
1988;
50
1155-60
-
7
Hasegawa H, Sung J H, Benno Y.
Role of human intestinal Prevotella oris in hydrolyzing Ginseng saponins.
Planta Medica.
1997;
63
436-40
-
8
Akao T, Kanaoka M, Kobashi K.
Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration - measurement of compound K by enzyme immunoassay.
Biological and Pharmaceutical Bulletin.
1988;
21
245-9
-
9
Bae E A, Park S Y, Kim D H.
Constitutive β-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria.
Biological and Pharmaceutical Bulletin.
2000;
23
1481-5
-
10
Bae E A, Han M J, Choo M K, Park S Y, Kim D H.
Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities.
Biological and Pharmaceutical Bulletin.
2002;
25
58-63
-
11
Lee S J, Sung J H, Lee S J, Moon C K, Lee B H.
Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin.
Cancer Letters.
1999;
144
39-43
-
12
Bae E A, Choo M K, Park E K, Park S Y, Shin H Y, Kim D H.
Metabolism of ginsenoside Rc by human intestinal bacteria and its related antiallergic activity.
Biological and Pharmaceutical Bulletin.
2002;
25
743-7
-
13
Choi O H, Kim J H, Kinet J P.
Calcium mobilization via sphingosine kinase in signaling by the Fc epsilon.
Nature.
1996;
380
634-6
-
14
Ryu S Y, Oak M H, Kim K M.
Yomogin inhibits the degranulation of mast cells and the production of nitric oxide in activated RAW264.7 cells.
Planta Medica.
2000;
66
171-3
-
15
Kakegawa H, Matsumoto H, Satoh T.
Inhibitory effects of some natural products on the activation of hyaluronidase.
Chemical and Pharmaceutical.
Bulletin. 1992;
40
1439-42
-
16
Xiong Q, Kadota S, Tani T, Namba T.
Antioxidative effects of phenylethanoids from Cistanche deserticola
.
Chemical and Pharmaceutical Bulletin.
1996;
19
1580-5
-
17
Tasaka K, Mio M, Okamoto M.
Intracellular calcium release induced by histamine releasers and its inhibition by some antiallergic drugs.
Annals of Allergy.
1986;
56
464-9
-
18
Katayama S, Shionoya H, Ohtake S.
A new method for extraction of extravasated dye in the skin and the influence of fasting stress on passive cutaneous anaphylaxis in guinea pigs and rats.
Microbiology and Immunology.
1978;
22
89-101
-
19
Simons F ER.
The antiallergic effects of antihistamines (H1-receptor antagonists).
Journal of Allergy and Clinical Immunology.
1992;
90
705-15
-
20
Cox J SG.
Disodium cromglycate (FPL-670) (”Intar”): A specific inhibitor of reaginic antibody-antigen mechanism.
Nature.
1967;
216
1326-9
-
21
Ito H, Miyazaki T, Ono M, Sakurai H.
Antiallergic activities of rabdosiin and its related compounds: chemical and biochemical evaluations.
Bioorganic and Medical Chemistry.
1998;
6
1051-6
-
22
Akagi M, Mio M, Tasaka K.
Histamine release inhibition and prevention of the decrease in membrane fluidity induced by certain antiallergic drugs: analysis of the inhibitory mechanism of NCO-650.
Agents Actions.
1983;
13
149-56
-
23
Shibata H, Mio M, Tasaka K.
Analysis of the mechanism of histamine release induced by substance P.
Biochemical and Biophysical Acta.
1985;
846
1-7
Prof. Dr. Dong-Hyun Kim
College of Pharmacy
Kyung-Hee University
1 Hoegi
Dongdaemun-ku
Seoul 130-701
Korea
Email: dhkim@khu.ac.kr
Fax: +82-2-957-5030