Biomedical subjects
Publications and source records attributed to R X Tan.
This review covers distribution, structural determination, syntheses and biological activities of the cerebrosides reported so far. Those with absolute stereochemistry assigned are marked herein with '*'. The literature from 1969 to mid-2003 is reviewed and 189 references cited.
In order to purify enough material for establishing the absolute stereochemistry of the new antifungal metabolite 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4H)-one produced by Keissleriella sp., a marine filamentous fungus (strain number: YS 4108), a repeated growth and fractionation of the fungal culture was performed to give instead a new antimicrobial metabolite, keisslone (1), the structure of which was elucidated on the basis of spectral analyses including homo- and hetero-nuclear correlation NMR experiments (HMQC, COSY, NOESY and HMBC). The absolute configuration of metabolite 1 was determined mainly by its CD data and NOESY spectrum. The compound 1 was shown to be inhibitory against the human pathogenic fungi Candida albicans, Trichophyton rubrum and Aspergillus niger with MICs of 50, 70, 40 microg/mL, respectively. In order to purify enough material for establishing the absolute stereochemistry of the new antifungal metabolite 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4 H)-one produced by Keissleriella sp., a marine filamentous fungus (strain number: YS 4108), a repeated growth and fractionation of the fungal culture was performed to give instead a new antimicrobial metabolite, keisslone (1), the structure of which was elucidated on the basis of spectral analyses including homo- and hetero-nuclear correlation NMR experiments (HMQC, COSY, NOESY and HMBC). The absolute configuration of metabolite 1 was determined mainly by its CD data and NOESY spectrum. The compound 1 was shown to be inhibitory against the human pathogenic fungi Candida albicans, Trichophyton rubrum and Aspergillus niger with MICs of 50, 70, 40 microg/mL, respectively.
The structures of two new macrocyclic jatrophane diterpenoid esters from the whole herb of Euphorbia esula, were established as 11,14-epoxy-3beta,5alpha,7beta,8alpha,9alpha,15beta-hexaacetoxy-12-oxo-13alphaH-jatropha-6(17)-ene (1) and 1alpha,3beta-diacetoxy-5alpha,7beta-dibenzoyloxy-9,14-dioxo-11beta,12alpha-epoxy-2alpha,8alpha,15beta-trihydroxy-13betaH-jatropha-6(17)-ene (2) by a combination of 1D- and 2D-NMR techniques as well as UV, IR and mass spectral data. Bioassay evaluation of all isolates against the human tumor cell lines (B16, KB, SMMC and BGC) indicated that ester 2 was cytotoxic to B16 with the IC50 value being 1.81 microg/ml. In addition, the irritant activity assay indicated that both diterpenoids were inactive (ID(24)50 > 100 microg/ear).
In addition to four known metabolites (4-acetyl-6,8-dihydroxy-5-methylisocoumarin, 6,8-dihydroxy-3-methylisocoumarin, 6,8-dihydroxy-3,5,7-trimethylisocoumarin and 3,3'-oxy-(5-methyl)-phenol), bioassay-guided fractionation of the culture of Keissleriella sp., a marine filamentous fungus (strain number: YS 4108), afforded an antifungal metabolite with a new carbon skeleton whose structure was elucidated spectrometrically as 3,6,8-trihydroxy-3-[3,5-dimethyl-2-oxo-3(E)-heptenyl]-2,3-dihydronaphthalen-1(4H)-one. In vitro antifungal assays of all isolates revealed that the new metabolite and 3,3'-oxybis[5-methylphenol] were inhibitory to the growth of the human pathogenic fungi Candida albicans, Tricophyton rubrum and Aspergillus niger with MICs of the former being 40, 20 and 80 microg/ml, and those of the latter 10, 30 and 50 microg/ml, respectively.
Artemisia annua, well recognized for its production of antimalarial drug artemisinin, is seldom attacked by any of phytopathogenic fungi, which could be partially associated with the presence of endophytes. Present investigation is aiming at disclosing whether the endophytes inside A. annua produce antifungal substances. A total of 39 endophytes were isolated and fermented, and the ferment broth was evaluated in vitro for the antifungal activity against crop-threatening fungi Gaeumannomyces graminis var. tritici, Rhizoctonia cerealis, Helminthosporium sativum, Fusarium graminearum, Gerlachia nivalis and Phytophthora capsici. These plant pathogens are still causing wheat take-all, sharp eyespot, common rot, scab, snow mould, and pepper phytophthora blight, respectively. Out of 39 endophytes investigated, 21 can produce in vitro substances that are inhibitory to all or a few of the tested phytopathogens whereas the rest yielded nothing active. Moreover, the most active broth of endophyte IV403 was extracted with EtOAc and n-butanol, and comparisons of the antifungal activity of the extracts indicated that the major active metabolites were EtOAc-extractable.
Fractionation of the xanthine oxidase inhibitory methanol extract of Conyza bonariensis afforded three glycosides, in addition to nine known compounds including amyrin, beta-sitostero1 daucosterol, syringic acid 3-hydroxy-5-methoxybenzoic acid, eugenol 4-O-glucopyranoside, and luteolin, apigenin and takakin 8-O-glucuronide. The structures of the glycosides were established by a combination of spectroscopic methods (IR, MS, 1H and 13C NMR, DEPT, COSY, HMQC and HMBC) as 4-hydroxypyridin-3-carboxylic acid 4-O-glucopyranoside, 8-hydroxy-6,7-dihydrolinalool 8-O-glucopyranoside and bonaroside [viz. 1,3,4,12-tetrahydroxy-2-(9-hexadecenoylamino)octadecane 1-O-glucopyranoside]. The in vitro enzyme assay showed that syringic acid and takakin 8-O-glucuronide displayed weak inhibitory activity against xanthine oxidase with IC50 values of 500+/-41 microM and 170+/-12 microM, respectively.
Three highly oxygenated guaianolides were isolated from the aerial parts of Ajania fruticulosa along with 17 known phytochemicals including a triterpene (alpha-amyrin), two plant sterols (beta-sitosterol, daucosterol), four flavonoids (axillarin, centaureidin, santin and 5,7,4'-trihydroxy-3,3'-dimethoxyflavone), and ten sesquiterpenes [1alpha-hydroperoxy-4beta,8alpha,10alpha,13-tetrahydroxyguaia-2-en-12,6alpha-olide, 1alpha-hydroperoxy-4alpha,10alpha-dihydroxyguaia-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 3beta,4alpha-dihydroxyguaia-11(13),10(14)-dien-12,6alpha-olide, 1alpha,4alpha,10alpha-trihydroxy-9alpha-angeloyloxyguaia-2,11(13)-dien-12,6alpha-olide, 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxy-guaia-11(13)-en-12,6alpha-olide and 2-oxo-8alpha-hydroxyguaia-1(10),3,11(13)-trien-12,6alpha-olide, ketoplenolide B, alantolactone, 9beta-hydroxyeudesma-4,11(13)-dien-12-oic acid and 9beta-acetoxyeudesma-4,11(13)-dien-12-oic acid]. The structures of the three guaianolides were elucidated by a combination of spectroscopic methods (EIMS, HREIMS, COSY, HMQC, HMBC and NOESY) as 1beta,2beta-epoxy-3beta,4alpha,8beta,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (1), 1beta,2beta-epoxy-3beta,4alpha,9alpha,10alpha-tetrahydroxyguaia-11(13)-en-12,6alpha-olide (2) and 1beta,2beta-epoxy-10alpha-hydroperoxy-3beta,4alpha,8beta-trihydroxyguaia-11(13)-en-12,6alpha-olide (3), respectively. Antifungal bioassay of all isolates showed that guaianolides 1, 2, 3, and 1beta,2beta-epoxy-3beta,4alpha,10alpha-trihydroxyguaia-11(13)-en-12,6alpha-olide were inhibitory to the growth of Candida albicans with MICs being 20, 20, 20, and 40 microg/ml, respectively.
Five new (1-5) and one known (6) jatrophane diterpenoid esters were isolated from the ethanol extract of the whole herb of Euphorbia turczaninowii. Their structures were established by extensive spectroscopic methods. The absolute stereochemistry of 3 beta,5 alpha,8 alpha,15 beta-tetraacetoxy-7 beta-benzoyloxyjatropha-6(17),11E-dien-9,14-dione (1) was confirmed by a single-crystal X-ray analysis coupled with the exciton chirality circular dichroism method. Compounds 1-6 were inactive when evaluated both in a mouse ear inflammation assay and for cytotoxicity against the B16 mouse melanoma cell line.
Psoralen and isopsoralen, furocoumarins isolated from the plant Psoralea corylifolia L., were demonstrated to exhibit in vitro inhibitory actions on monoamine oxidase (MAO) activities in rat brain mitochondria, preferentially inhibiting MAO-A activity over MAO-B activity. This inhibition of enzyme activities was found to be dose-dependent and reversible. For MAO-A, the IC50 values are 15.2 +/- 1.3 microM psoralen and 9.0 +/- 0.6 microM isopsoralen. For MAO-B, the IC50 values are 61.8 +/- 4.3 microM psoralen and 12.8 +/- 0.5 microM isopsoralen. Lineweaver-Burk transformation of the inhibition data indicates that inhibition by both psoralen and isopsoralen is non-competitive for MAO-A. The Ki values were calculated to be 14.0 microM for psoralen and 6.5 microM for isopsoralen. On the other hand, inhibition by both psoralen and isopsoralen is competitive for MAO-B. The Ki values were calculated to be 58.1 microM for psoralen and 10.8 microM for isopsoralen. These inhibitory actions of psoralen and isopsoralen on rat brain mitochondrial MAO activities are discussed in relation to their toxicities and their potential applications to treat affective disorders.
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Three protoberberine alkaloids jatrorrhizine, berberine and palmatine were isolated from the monoamine oxidase (MAO) inhibitory fraction of the methanol extract of Coptis chinensis rhizoma. Jatrorrhizine was shown to inhibit non-competitively both MAO-A and -B from rat brain mitochondria with the IC50 values of 4 and 62 microM, respectively. Berberine only competitively inhibited MAO-A with an IC50 values of 126 microM whereas palmatine exhibited, up to 200 microM, no inhibition on any type of the enzyme. The structure-activity relationship was briefly discussed.
The bioassay guided refractionation of the methanol extract of roots and rhizomes of Veratrum taliense (Liliaceae) yielded five stilbenoids: veraphenol, resveratrol, piceid, isorhapontin, and mulberroside E, all inhibiting xanthine oxidase (XO, EC 1.2.3.2.) in vitro in a dose-dependent manner with IC50 values of 11.0, 96.7, 66.1, 70.0, and 78.4 microM, respectively. Veraphenol and mulberroside E were found to be mixed XO inhibitors with the Ki and Ki data of the former being 32.8 and 239.3 microM, and those of latter 32.5 and 13.8 microM, respectively. However, the inhibition on the enzyme by resveratrol, isorhapontin, and piceid was shown to be competitive with their Ki values of 9.7, 19.1, and 14.3 microM, respectively. Among the five stilbenoids, veraphenol and resveratrol were also revealed to inhibit competitively monoamine oxidase A (MAO, EC 1.4.3.4) with IC50 values at 38.0 and 26.6 microM, and Ki data 36.4 and 47.3 microM, respectively. However, none of the stilbenoids was inhibitory on MAO B in our assay. The structure-activity relationship examination showed that glycosylation of the stilbenoids could reduce the inhibition on XO and diminish the activity against MAO A, indicating that the free phenolic hydroxy group of the compounds was most likely essential for these bioactivities.
AIM: To study the effect of fluoxetine on dendrite atrophy of hippocampal neurons in rat depression model. METHODS: CMS (chronic mild stress), mimicking human depression, was used as the animal depression model. The neurons shape and numbers of nitric oxide synthase positive cells in the hippocampal subfields were measured by Nissl staining and histochemical staining of NADPH (nicotinamide adenine dinucleotide phosphate)-diaphorase respectively. RESULTS: CMS deforms neurons in the hippocampal formation, and fluoxetine can renormalize the deformed neurons by inhibiting the nitric oxide synthase catalyzing the over-production of NO, which lead subsequently to the morphological abnormality in the circumscribed area of brain. CONCLUSION: Fluoxetine, an antidepressant, renormalizes dendrite atrophy of hippocampal neurons by inhibiting nitric oxide synthase overexpression in rat chronic mild stress model.
The methanol extract of the stem of Sinofranchetia inhibited the activity of xanthine oxidase in vitro. Bioassay-guided purification led to the isolation ofliquiritigenin and isoliquiritigenin as the main xanthine oxidase inhibitors. This inhibition of enzyme activity was found to be dose dependent, with an IC50 value of approximately 49.3 microM for liquiritigenin and 55.8 microM for isoliquiritigenin. Lineweaver-Burk transformation of the inhibition data indicated that the inhibition was of a mixed type for both liquiritigenin and isoliquiritigenin. For liquiritigenin, the Ki and K(I) were determined to be 14.0 microM and 151.6 microM, respectively. For isoliquiritigenin, the Ki and K(I) were determined to be 17.4 microM and 81.9 microM, respectively. These results suggest that these natural products could be used to treat conditions where the inhibition of xanthine oxidase is warranted.
Two new cyclobutane-type lignans, named moslolignans A and B, together with two known ones, andamanicin and magnosalin, were isolated from the whole plant of Mosla scabra. Their structures were established as 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(3- methoxy-4,5-methylene-dioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cycl obutane and 1beta*,2beta*,3alpha*,4alpha*-1,2-dimethyl-3-(2, 5-dimethoxy-3,4-methylenedioxyphenyl)-4-(2,4,5-trimethoxyphenyl)-cyclobu tane by spectroscopic methods. This is the first report of naturally-occurring cyclobutane-type lignans with asymmetrical substitutions.
Banxia Houpu Decoction, having been used for the treatment of depression-related diseases since ancient times, is a traditional Chinese medicinal empirical formula consisting of Pinellia ternata, Poria cocos, Magnolia officinalis, Perilla frutescens and Zingiber officinale. The effects of the total decoction extract and five fractions therefrom, were evaluated in mice by tail suspension and forced swimming tests. The total 90% ethanol extract of the decoction was shown to possess an antidepressant activity that was close to that of Prozac, an antidepressant agent being applied clinically. Furthermore, the active principles were desmonstrated to be mainly in the aqueous (Bx4) and lipophic (Bx5) parts of the decoction extract while the polyphenol fraction (Bx2) exhibited a moderate action.
The enzyme xanthine oxidase catalyses the oxidation of hypoxanthine to xanthine and then to uric acid, which plays a crucial role in gout. A total of 122 traditional Chinese medicinal plants, selected according to the clinical efficacy and prescription frequency for the treatment of gout and other hyperuricemia-related disorders, have been evaluated for the enzyme inhibitory activity. Among the 122 methanol extracts derived from these species, 69 were shown to be inhibitory at 100 microg/ml, with 29 having greater than 50% inhibition. As to the equal amount of water extracts, 40 were disclosed to be active at 100 microg/ml, with 13 possessing more than 50% inhibition. At 50 microg/ml, 58 methanol and 24 water extracts exhibited inhibitory activity, with 15 of the former and two of the latter showing greater than 50% inhibition. The most active was the methanol extract of the twig of Cinnamomum cassia (Lauraceae) (IC(50), 18 microg/ml), which was followed immediately by those of the flower of Chrysanthemum indicum (Asteraceae) (IC(50), 22 microg/ml) and the leaves of Lycopus europaeus (Lamiatae) (IC(50), 26 microg/ml). Among the water extracts, the strongest inhibition of the enzyme was observed with that of the rhizome of Polygonum cuspidatum (Polygonaceae) (IC(50), 38 microg/ml). The IC(50) value of allopurinol used as a positive control was 1.06 microg/ml. The study demonstrated that the effects for these medicinal plants used for the gout treatment were based, at least in part, on the xanthine oxidase inhibitory action.
A new antimicrobial metabolite, named colletotric acid (1), was isolated from a liquid culture of Colletotrichum gloeosporioides, an endophytic fungus colonized inside the stem of Artemisia mongolica. The structure was determined using spectroscopic methods (EIMS and FABMS,(1)H and (13)C NMR, (1)H-(1)H COSY, HMBC, and HMQC). Compound 1 inhibited the growth of Bacillus subtilis, Staphylococcusaureus, and Sarcina lutea with minimal inhibitory concentrations (MICs) of 25, 50, and 50 microg/mL, respectively, and the crop pathogenic fungus Helminthosporium sativum (MIC: 50 microg/mL).