The aim of the study is to investigate chemical constituents of the leaves of Pieris japonica. The isolation and purification of the constituents were performed by various chromatography and spectral analysis. Three new phenolic glucosides, erythro-syringoylglycerol 4-O-beta-D-glucoside (1), 1-(2-beta-D-glucopyranoxyl-4-methoxyl-6-hydroxyphenyl)-3-hydroxyl-l-propanone (3), erythro-l-(4-hydroxyl-3-methoxyphenyl)-2-[4-(3-beta-D-glucopyranoxypropyl)-2 ,6-dimethoxyphenoxy]-1, 3-propanediol (4), along with five known phenolic glucosides, syringoylglycerol 8-O-beta-D-glucoside (2), magnolenin C (5), syringaresinol mono-beta-D-glucoside (6), 3-(4-hydroxyl-3-methyphenyl)-1 -propanol-l-O-beta-D-glucoside (7) and 3, 5-dimethoxyl-4-hydroxybenzyl alcohol 4-O-beta-D-glucoside (8) were isolated and identified from the plant leaves. Compounds 1 and 2 inhibited significantly (P <0.01) the proliferation of murine T and B cells at concentration of 1 x 10(-6) mol L(-1), in vitro.
Ericaceae ; chemistry ; Glucosides ; chemistry ; isolation & purification ; Immunosuppressive Agents ; chemistry ; isolation & purification ; Lignans ; chemistry ; isolation & purification ; Phenols ; chemistry ; isolation & purification ; Plant Leaves ; chemistry ; Plants, Medicinal ; chemistry

Brasilicardin A (BraA) is a natural diterpene glycoside isolated from the pathogenic actinomycete Nocardia brasiliensis IFM 0406 with highly potent immunosuppressive activity (IC₅₀=0.057 μg/mL). BraA potently inhibits the uptake of amino acids that are substrates for amino acid transport system L of T cells, which is different from the existing clinical immunosuppressants. BraA is more potent in a mouse mixed lymphocyte reaction and less toxic against various human cell lines compared with the known clinical immunosuppressants, such as cyclosporin A, ascomycin and tacrolimus. Therefore, BraA attracted more attention as a new promising immunosuppressant. However, the development of this promising immunosuppressant as drug for medical use is so far hindered because BraA has the unusual and synthetically challenging skeleton and shows the low-yield production in the natural pathogenic producer. This review introduces the molecular structure of BraA, its activity, mechanism of action, chemical synthesis of BraA analogs, heterologous expression of gene cluster, and an application of combining microbial and chemical synthesis for production of BraA, with the aim to facilitate the efficient production of BraA and its analogs.
Animals ; Mice ; Humans ; Immunosuppressive Agents/chemistry* ; Aminoglycosides/pharmacology* ; Cyclosporine/pharmacology* ; Diterpenes

Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Humans ; Immunosuppressive Agents ; pharmacology ; Tripterygium ; adverse effects ; chemistry

OBJECTIVETo investigate the chemical constituents with immunosuppressive function from Alisma orientalis.

METHODThe chemical constituents were isolated and purified by kinds of column chromatography and its structures were elucidated by NMR spectra and physicochemical properties. Its immunocompentence of lymphocytes taken from spleen of mouse were examined by MTT assay.

RESULTTwelve compounds were isolated and identified as clovandiol (1), orientalol E (2), alismoxide (3), alismol (4), 4alpha, l0alpha-dihydroxy-5beta-H-guaj-6-en (5), alismorientols A (6), alisol F (7), alisol A (8), 13beta,17beta-epoxy alisol A (9), alisol B 23-acetate (10), 1H-indole-3-carboxylic acid (11) and cuccinic acid (12). Compounds 9, 10 and alisol A 24-acetate showed immunosuppressive function.

CONCLUSIONCompounds 1, 5, 11 and 12 were isolated firstly from this genus,and the NMR spectra data of 1 were corrected firstly, some protostan-type triterpenoids may be developed as new drug with immunosuppressive function.

Alisma ; chemistry ; Animals ; Cells, Cultured ; Cholestenones ; chemistry ; pharmacology ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Immunosuppressive Agents ; chemistry ; pharmacology ; Indoles ; chemistry ; pharmacology ; Magnetic Resonance Spectroscopy ; Mice ; Mice, Inbred C57BL ; Sesquiterpenes ; chemistry ; pharmacology ; T-Lymphocytes ; cytology ; drug effects ; Triterpenes ; chemistry ; pharmacology

The collected information is an attempt to cover the more recent developments in the phytochemistry and pharmacology of this genus. During the past years, alkaloids, flavonoids, volatile oils, organic acids, polysaccharides, tannins and phenolic constituents have been isolated from Ephedra. Pharmacological studies are described according to hypoglycemic effects, anticoagulated blood properties, depressurization, immunosuppressive activity, antioxidation and antivirus activity and so on. The information summarized here is intended to provid a rational foundation for the futher development and utilization of Ephedra which is rich in China.
Alkaloids ; chemistry ; isolation & purification ; Animals ; Ephedra ; chemistry ; classification ; Flavonoids ; chemistry ; isolation & purification ; Hypoglycemic Agents ; pharmacology ; Immunosuppressive Agents ; pharmacology ; Molecular Structure ; Plant Stems ; chemistry ; Plants, Medicinal ; chemistry ; Polysaccharides ; isolation & purification ; pharmacology

AIMTo investigate the chemical constituents of the rhizomes of Beesia calthaefolia native to China in order to obtain a more comprehensive understanding of its effective components.

METHODSCompounds were isolated by column chromatography with silica gel. Their structures were elucidated by spectral analysis and chemical evidence. Compounds identified were subjected to pharmacological evaluation.

RESULTSTwo novel compounds were isolated and identified as (20S, 24S)-15 alpha-acetoxy-16 beta, 24; 20, 24-diepoxy-9, 19-cyclolanostane-3 beta, 25-diol-3-O-beta-D-xylopyranoside (I) and (20S, 24R)-15 alpha-acetoxy-9, 19-cyclolanostane-3 beta, 16 beta, 20, 24, 25-pentaol-3-O-beta-D-xylopyranoside (II), named beesioside O and beesioside P.

CONCLUSIONCompounds I and II are new compounds. Compounds I exhibited immunosuppressive activity and could inhibit angiogenesis as well as inhibit the proliferation of osteoblast. Compound II displayed remarkable inhibition activity against calcium channel receptor.

Angiogenesis Inhibitors ; chemistry ; pharmacology ; Animals ; Calcium Channel Blockers ; chemistry ; pharmacology ; Immunosuppressive Agents ; chemistry ; pharmacology ; Mice ; Molecular Conformation ; Molecular Structure ; Plants, Medicinal ; chemistry ; Ranunculaceae ; chemistry ; Saponins ; chemistry ; isolation & purification ; pharmacology

To investigate me material basis of Mahuang Fuzi Xixin decoction (MFXD) for anti-inflammation and immune-suppression based on the combined method of serum chemical and serum pharmacological. The LC-MS/MS fingerprints of MFXD, drug-containing serum and blank serum were compared to define the components in plasma. Histamine, β-hexosaminidase released from RBL-2H3 cell infulenced by drug-containing serum at different time points were measured by ELISA. The effect of drug-containing serum on lipopolysaccharide-induced splenocyte proliferation at different time points were determined by MTT. A correlation analysis was made on components of MFXD and pharmacological indexes based the stepwise regression method. After the intragastrical administration with MFXD, 32 components were discovered in rat serum, including 27 prototype components (10 from Mahuang, 13 from Fuzi and four from Xixin) and five unknown components. Compared with blank serum, drug-containing serum could reduce the release of histamine from RBL-2H3 induced by antigen at different time points (P < 0.05); except the 4-hour drug-containing serum, all of the remaining drug-containing serums could inhibit the RBL-2H3 mastocyte degranulation induced by antigen at different time points (P < 0.05). Drug-containing serum could significantly lipopolysaccharide-induced mouse splenocyte proliferation at 15 and 30 min (P < 0.05). A regression analysis was made on the chemical data of components absorbed into blood and pharmacological indexes, i. e. release rate of histamine, release rate of β-hexosaminidase and inhibition rate of splenocyte. This suggested the close correlations among methyl pseudo-ephedrine, pseudoephedrine and histamine released from RBL-2H3 induced by antigen; pseudoephedrine, hypaconine, methyl pseudoephedrine and β-hexosaminidase released from RBL-2H3 induced by antigen; as well as benzoyl hypaconine, benzoylaconine, 14-benzoyl-10-OH-mesaconine, mesaconine and lipopolysaccharide-induced mouse splenocyte proliferation. Methylpseudoephedrine, pseudoephedrine, benzoyl hypaconine, benzoylaconine and mesaconine may be part of material basis of MFXD on anti-inflammation and immune suppression.
Animals ; Anti-Inflammatory Agents ; chemistry ; pharmacology ; Cell Degranulation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Female ; Histamine ; immunology ; Immunosuppressive Agents ; chemistry ; pharmacology ; Male ; Mass Spectrometry ; Mast Cells ; drug effects ; immunology ; Mice ; Rats ; Rats, Wistar ; Serum ; chemistry

BACKGROUND: Therapeutic drug monitoring (TDM) of tacrolimus is essential because of narrow therapeutic range and poor correlation of dose to blood concentration. Affinity Column Mediated Immunometric Assay (ACMIA) does not require a pretreatment steps in measurement of tacrolimus. In this study, we evaluated the performance of tacrolimus assay using ACMIA (Dimension RxL Max, Dade Behring). METHODS: The imprecision, the linearity and the detection limits and the interferences by bilirubin and chyle, and correlation with hematocrit for tacrolimus by ACMIA were evaluated according to Clinical and Laboratory Standards Institute guidelines EP5-A2, EP6-A, EP17-A, EP9-A2, and EP7-A2. Method comparison studies with microparticle enzyme immunoassay (MEIA) (IMx Tacrolimus II, Abbott Laboratories) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) (Waters 2795 Quattromicro API, Micromass) were also performed. RESULTS: The total imprecision for low, middle and high level was 12.8%, 9.0% and 6.7%, respectively. The range of tacrolimus from 3.1 ng/mL to 35.4 ng/mL showed a clinically relevant linearity. The limit of detection and the functional sensitivity were 0.24 ng/mL and 0.72 ng/mL, respectively. Tacrolimus concentration measurement (Tac-CM) with ACMIA did not show significant interferences with bile and chyle and also did not show significant correlation with hematocrit. In comparison study for Tac-CM with MEIA and LC-MS/MS, Tac-CM with ACMIA showed a good correlation with MEIA (r=0.950) and LC-MS/MS (r=0.946). CONCLUSIONS: The imprecision, linearity, detection limits, interference and correlation of Tac-CM with ACMIA were suitable for clinical use. Tac-CM with ACMIA could reduce turn around time and help clinicians to manage transplant patients on immunosuppressant therapy.
Bilirubin/chemistry ; Chromatography, Affinity ; Chyle/chemistry ; Drug Monitoring ; Humans ; Immunoassay/*methods ; Immunosuppressive Agents/*blood ; Limit of Detection ; Reagent Kits, Diagnostic ; Reproducibility of Results ; Tacrolimus/*blood

A novel series of fingolimod analogues containing diphenyl ether moiety were designed and synthesized based on the modification of immunosuppressive agent fingolimod used in the treatment of multiple sclerosis. Compounds were evaluated in vivo for lymphopenic activity and heart rate affection. Most compounds showed moderate lymphopenic activity. It is worth noting that compounds 6c, 6d and 14c-14e showed considerable immunosuppressive activities comparable to fingolimod. And compound 14e had no effect on heart rate.
Animals ; Fingolimod Hydrochloride ; chemical synthesis ; pharmacology ; Heart Rate ; drug effects ; Immunosuppressive Agents ; chemistry ; Lymphopenia ; pathology ; Phenyl Ethers ; chemistry ; Structure-Activity Relationship

OBJECTIVETo observe the effects of lipopolysaccharides of Bacterium prodigiosum (BP-LPS) in inhibiting tumor growth and improving immunosuppression in mice.

METHODSIn mice bearing S180 tumor and a mouse model of immunosuppression induced by cyclophosphamide (CTX), the tumor growth, indexes of the immune organs and peripheral white blood cell count were measured after intraperitoneal injection of BP-LPS.

RESULTSInjections of BP-LPS (40 U/kg) for 8 consecutive days resulted in a significant inhibition of the tumor growth in mice bearing S180 tumor (P<0.01), with a dose-dependent increase of the spleen indexes but no obvious changes in the thymus indexes. Intraperitoneal injections of BP-LPS for 7 days inhibited the reduction of peripheral white blood cells and spleen indexes in immunosuppressive mice, but did not produce any significant changes in normal mice.

CONCLUSIONBP-LPS can inhibit the tumor growth in tumor-bearing mice and enhance the immune functions of immunosuppressive mice.

Animals ; Antineoplastic Agents ; pharmacology ; Female ; Immunosuppressive Agents ; pharmacology ; Lipopolysaccharides ; isolation & purification ; pharmacology ; Male ; Mice ; Polysaccharides, Bacterial ; isolation & purification ; pharmacology ; Random Allocation ; Serratia ; chemistry