Jong-Chol Cyong

Relationship between chemical structure and anti-complementary activity of plant polysaccharides

Abstract Seventeen water-soluble polysaccharides obtained from various plants were tested for anti-complementary activities. Considerable activity was observed for Zizyphus-arabinan [(1→5)-linked α- l -arabinofuranosyl main-chain having (1→2)-linked α- l -arabinofuranosyl side-chains] from the dried fruit of Zizyphus jujuba var. inermis , paniculatan [highly branched, partially O -acetylated, acidic mucous polysaccharide composed of (1→2)-linked α- l -rhamnopyranosyl residues having branches composed of O -(4- O -methyl-α- d -glucopyranosyluronic acid)-(1→4)-β- d -galactopyranose at position 4 and (1→4)-linked α- d -galactopyranosyluronic acid residues having β- d -glucosyluronic acid groups at position 3] from the inner bark of Hydrangea paniculata , and Plantago-mucilage A [highly branched, partially O -acetylated, acidic mucous polysaccharide with a main chain of (1→4)-linked β- d -xylopyranosyl residues having other β- d -xylopyranosyl groups and branches composed of O -(α- d -glucopyranosyluronic acid)-(1→3)-α- l -arabinofuranosyl and O -(α- d -galactopyranosyluronic acid)-(1→3)-α- l -arabinofuranosyl groups at position 3 as side chains] from the seed of Plantago asiatica . The majority of the mucous acidic polysaccharides from the plants belonging to Malvaceae had weak activities. These polysaccharides commonly contained (1→2)-α- l -rhamnopyranosyl-(1→4)-α- d -galactopyranosyluronic acid residues as the main chain. Glucomannans and pectin did not show any significant activity. The results of tests on C4 titration, anti-complementary activity in the absence of Ca 2+ , crossed immunoelectrophoresis, and activity of the alternative complement pathway using rabbit erythrocytes indicated that the mode of complement activation by paniculatan occurred mainly via the classical pathway, whereas activation by Zizyphus-arabinan and Plantago-mucilage A were both via the alternative and classical pathways. The mode of complement activation by paniculatan did not depend on its particulate state.

Structural characterisation of an anti-complementary pectic polysaccharide from the roots of Bupleurum falcatum L.

An anti-complementary pectic polysaccharide (BR-2-IIb), isolated from the roots of Bupleurum falcatum L., has an average molecular weight of 36,000 (gel filtration), and was subjected to methylation analysis before and after carboxyl-reduction, digestion with endo-polygalacturonase, base-catalysed beta-elimination, and partial acid hydrolysis. BR-2-IIb consisted mainly of galacturonic acid, arabinose, rhamnose, and galactose in the molar ratios 13.0:2.1:1.4:1.0 and contained a large enzyme-sensitive polygalacturonan region. The enzyme-resistant region (PG-1) was rich in neutral sugars and contained a backbone of 4-linked GalA and 2-linked Rha to which a highly branched arabinogalactan was attached to position 4 of some 2-linked Rha units. Partial acid hydrolysis of BR-2-IIb gave Ara-(1----3)-Ara, Ara-(1----4)-Arap, Ara-(1----5)-Araf, Ara-(1----6)-Gal, Gal-(1----4)-Gal, GalA-(1----2)-Rha, GalA-(1----4)-Rha, GalA----Rha----Rha, Gal----Rha----Rha, and GlA-(1----6)-Gal in addition to (1----4)linked oligogalacturonides. The anticomplementary activity of BR-2-IIb was enhanced by de-esterification, but carboxyl-reduction decreased the activity.

Structural characterisation of an anti-complementary arabinogalactan from the roots of Angelica acutiloba Kitagawa

An anti-complementary arabinogalactan (AGIIb-1), isolated from the roots of Angelica acutiloba Kitagawa, has been subjected to methylation analysis, digestion with alpha-L-arabinofuranosidase, controlled Smith-degradation, and partial acid hydrolysis. AGIIb-1 consisted of arabinose, galactose, rhamnose, galacturonic acid, and glucuronic acid in the molar ratios 1.8-2.2:1.0:0.2-0.3:0.2-0.4:0.1. AGIIb-1 contained mainly an arabino-3,6-galactan moiety, and most of the Ara was present as alpha-L-arabinofuranosyl residues in the non-reducing terminals and the highly polymerised and branched side-chains which were attached mainly to positions 3 and 6 of (1----6)- and (1----3)-linked Gal, respectively. Some Ara-containing chains were also attached to (1----4)-linked Gal residues. The 13C-n.m.r. data for AGIIb-1 showed that the Galp was beta. Mild acid hydrolysis of AGIIb-1 yielded several linear and highly branched arabino-oligosaccharides, a neutral arabinogalactan, and two acidic arabinogalactans. Some arabino-oligosaccharides contained a (1----4)-linked Arap at the reducing terminal. The neutral arabinogalactan contained (1----3)-, (1----4)-, and (1----6)-linked and 3,6-di-O-substituted Gal, whereas the acidic arabinogalactans contained, in addition, non-reducing terminal GlcA, (1----4)-linked GalA, and 2,4-di-O-substituted Rha. The anti-complementary activity was decreased when AGIIb-1 was partially hydrolysed with mild acid (10mM HCl, 100 degrees, 10 min), but treatment with exo-alpha-L-arabinofuranosidase markedly enhanced the activity.

A Randomized, Double-Blind, Placebo-Controlled Clinical Trial of the Chinese Herbal Medicine “Ba Wei Di Huang Wan” in the Treatment of Dementia

Objectives: To evaluate whether a traditional Chinese herbal medicine, ba wei di huang wan (BDW), improves cognitive and physical functioning in dementia patients.

Structure and anti-complementary activity of pectic polysaccharides isolated from the root of Angelica acutiloba Kitagawa.

Four pectic polysaccharides (AR-2IIa-IId) with anti-complementary activity have been isolated from a hot-water extract of the root of Angelica acutiloba Kitagawa. Each of these polysaccharides contained a large proportion of GalA together with neutral sugars consisting mainly of Rha, Ara, and Gal. Digestion with endo-alpha-(1----4)-polygalacturonase indicated that AR-2IIa-IIc each contained a large proportion of enzyme-sensitive polygalacturonan regions, and that AR-2IId contained a large proportion of enzyme-resistant regions. When AR-2IId was de-esterified, it became sensitive to the enzyme. These polysaccharides also contained small proportions of enzyme-resistant regions (PG-1) which were rich in neutral sugars. Methylation analysis and base-catalysed beta-elimination studies suggested that each PG-1 contained a rhamnogalacturonan moiety in which 2,4-disubstituted Rha was attached to 4-substituted GalA through position 2 of Rha. Carboxyl-reduction and methyl- and de-esterification of these polysaccharides modulated their anti-complementary activities. Digestion with endo-alpha-(1----4)-polygalacturonase decreased the activities of AR-2IIa and -2IIb, but not those of AR-2IIc and -2IId. Although PG-1 fractions from AR-2IIa-IIc were more active than the original polysaccharides, oligogalacturonide fragments obtained by enzymic digestion had weak or negligible activity. AR-2IIa-IIc expressed their anti-complementary activities mainly via the classical pathway, but AR-2IId and each PG-1 expressed their activities via both the classical and alternative pathways.

Clinical and pharmacological studies on liver diseases treated with Kampo herbal medicine.

Hepatitis C virus (HCV) infection frequently causes chronic hepatitis, which is linked to the development of liver cirrhosis and hepatocellular carcinoma. Most physicians who practice Kampo medicine in Japan have observed that Kampo medicine can be as effective as interferon therapy in the treatment of chronic hepatitis C. In the present study, to evaluate the effect of Kampo medicine on chronic hepatitis C, clinical treatment was assessed in short-term and long-term study, and it was shown that ninjin-yoei-to (Formula ginseng compositae: TJ-108) was very effective. Therefore, to find the most active herbal component of TJ-108 in the treatment of HCV, Citrus Unshiu Peel, Schisandra Fruit, and Polygala Root, which are specific to TJ-108, were screened using an in vitro HCV infection model. Among the three herbs, Schisandra Fruit was found to be most active. In the next step, Gomisin A, an active component of Schisandra Fruit, was studied using an in vitro model with MOLT-4 cells and an animal model of immunologically induced acute hepatic failures. It is concluded that the therapeutic effect of TJ-108 on chronic hepatitis C is from the inhibitory effect on HCV infection, and also from the protective effect on immunological hepatopathy of Schisandra Fruit and its lignan component, Gomisin A.

Effects of Astragali root and Hedysari root on the murine B and T cell differentiation.

It has traditionally been known in Asian countries that the Astragali and Hedysari roots have similar beneficial effects. They have been applied in clinical practice for immunological diseases, we investigated their effects on specific antibody production, B cells and T cells in BALB/c mice immunized with ovalbumin (OVA). Both the Astragali and Hedysari roots reduced the production of IgG2a in the primary response to OVA. Hedysari root reduced the production of IgG2a in the secondary response. Both reduced the production of IgM, suppressed IL-6 production in spleen cells. It was presumed that the suppression of IgG2a production was induced by the suppression of IL-6, which is an antibody production inducer. It was found that the Hedysari root increased the B cells and activated them, and the Astragali root also tended to increase them. In addition, Hedysari root decreased the proportions of IFN-gamma-producing cells in splenic CD4(+) T lymphocytes. It was shown that the Astragali and Hedysari roots could act as a growth factor of B cells by increasing the proportion of the total B cells and activated B cells. In conclusion, both the Astragali and Hedysari roots showed the same actions, but the latter was more effective.

Relationship between structure and activity of an anticomplementary arabinogalactan from the roots of Angelica acutiloba kitagawa

An anti-complementary arabinogalactan (AGIIb-1), isolated from the roots of Angelica acutiloba Kitagawa, comprised one neutral (N-I) and two acidic arabinogalactan (A-I and A-II) units and one neutral arabinan unit (N-II). N-I showed the most potent anti-complementary activity. AGIIb-1, A-I, and A-II had similar moderate activities, but N-II had weak activity. The product (AF-AGIIb-1) of digestion of AGIIb-1 with exo-alpha-L-arabinofuranosidase had markedly increased anti-complementary activity, as did that (AF-N-I) of N-I. Degradation of the rhamnogalacturonan core in AGIIb-1 slightly decreased the anti-complementary activity, whereas the high-molecular-weight neutral arabinogalactan and galacto-oligosaccharide side-chains in A-I and A-II showed potent activities. When AF-AGIIb-1 was digested with endo-arabinanase, the activity decreased slightly. Partial elimination of the (1--6)-beta-D-galactosyl side-chains from AF-N-I by digestion with exo-beta-D-galactosidase did not affect the activity. AGIIb-1 reacted weakly with the beta-D-glucosyl-Yariv antigen, but AF-AGIIb-1 and AF-N-1 had increased reactivity with the antigen. The anti-complementary activity of AGIIb-1 was expressed mainly through the classical pathway, whereas AF-AGIIb-1 and AF-N-I had markedly increased activity through the alterative pathway.

The pectic polysaccharide from Bupleurum falcatum L. enhances immune-complexes binding to peritoneal macrophages through Fc receptor expression

Binding of glucose oxidase-anti-glucose oxidase complexes (GAG), a model of immune complexes, to macrophages was enhanced by treatment with an acidic pectic polysaccharide, bupleuran 2IIb, from Bupleurum falcatum L. GAG binding to macrophages by bupleuran 2IIb increased in a dose-dependent fashion, and was abolished when the Pronase-treated macrophages were incubated with bupleuran 2IIb. The GAG binding enhancing activity of bupleuran 2IIb was reduced by periodate oxidation but not Pronase digestion of bupleuran 2IIb. When bupleuran 2IIb was digested with endo-polygalacturonase, the resulting enzyme resistant carbohydrate portion showed potent activity. Scatchard analysis indicated enhanced expression of the Fc receptor (FcR) on the surface by the action of bupleuran 2IIb. The enhancement of GAG binding by bupleuran 2IIb was inhibited by the presence of actinomycin D or cycloheximide. Bupleuran-2IIb-stimulated cells showed enhanced expression of both FcRI and FcRII mRNA, which were measured as PCR products. These results suggested that the endo-polygalacturonase resistant carbohydrate portion of bupleuran 2IIb is important for the expression of the activity, and that the activity of bupleuran 2IIb on GAG binding was mediated by receptors for polysaccharide on the cells. The up-regulation of the Fc receptor by bupleuran 2IIb was also suggested to mediate by de novo synthesis of the receptor protein.

Characterization of anti-complementary neutral polysaccharides from the roots of Bupleurum falcatum

Abstract The anti-complementary neutral polysaccharide, BR-5-I, was purified from the roots of Bupleurum falcatum . It seemed to be a homogeneous polymer from the results of gel filtration, HPLC and electrophoresis. BR-5-I mainly consists of l -arabinose and d -glucose in a molar ratio of 9:10. Its M r was estimated to be 18 500 by gel filtration. From the results of methylation analysis, Smith degradation and NMR studies, it appeared that BR-5-I contained a three-branched (1→5)linked α- l -arabinan moiety and a (1→4)linked α- d -glucan moiety. When BR-5-I was treated with exo-α- l -arabinofuranosidase, a glucan-rich polymer was obtained, but when it was treated with β- and α-amylase, an arabinan-rich polymer was obtained. Both polymers showed reduced anti-complementary activities and had the same M r as BR-5-I. BR-5-I was, however, separated into Con-A unbound arabinan and Con-A bound glucan containing arabinose and glucan by affinity chromatography on Con-A Sepharose. These results indicated that BR-5-I was a mixture of highly 3-branched (1→5)linked α- l -arabinan, (1→4)linked α- d -glucan containing arabinose, and (1→4)linked α- d -glucan. Surprisingly, these polymers have almost the same M r and same electrophoretic mobility. All the polysaccharides showed potent anti-complementary activity but the α- l -arabinan showed the highest activity.