Three naphthalenes from root bark of Hibiscus syriacus

Three new naphthalenes, designated as syriacusins A-C, were isolated from the root bark of Hibiscus syriacus. These compounds were identified as 2,7-dihydroxy-6-methyl-8-methoxy-1-naphthalenecarbaldehyde, 2-hydroxy-6-hydroxymethyl-7,8-dimethoxy-1-naphthalenecarbaldehyde, 1-carboxy-2,8-dihydroxy-6-methyl-7-methoxynaphthalenecarbolactone (1-->8), respectively, on the basis of various spectral studies. The compounds inhibited lipid peroxidation with IC50s of 0.54, 5.90 and 1.02 micrograms ml-1, respectively. The first compound also showed cytotoxicity against some human cancer cell lines with an ED50 of 1.5-2.4 micrograms ml-1.     

An experimental study of the anti-ulcer properties of an extract of poplar bark

Marked antiulcerative properties of a Populus tremula bark extract were demonstrated in experiments on mice and rats with stress-, reserpine-induced, and acetylsalicylic ulcers. The gastroprotective activity of the extract was expressed in decrease in the number of animals with mucosal ulcers and in marked decrease in the number of ulcers. It exceeded similar parameters of alanton, plantaglucide, and Hippopheae oil.     

Isolation and molecular cloning of a novel type 2 ribosome-inactivating protein with an inactive B chain from elderberry (Sambucus nigra) bark

One of the predominant proteins in the bark of elderberry (Sambucus nigra) has been identified as a novel type 2 ribosome-inactivating protein that exhibits a normal RNA N-glycosidase activity, but is devoid of carbohydrate binding activity. Sequence analysis of the corresponding cDNA clones revealed a striking homology to the previously cloned bark lectins from elderberry, suggesting that the new protein is a lectin-related protein. Molecular modeling of the protein confirmed that its A chain is fully active, whereas its B chain contains two functionally inactive carbohydrate-binding sites. These findings not only demonstrate for the first time the occurrence of a type 2 ribosome-inactivating protein with an inactive B chain, but also offer interesting perspectives for the synthesis of immunotoxins with an improved selectivity.     

New antifungal and cytotoxic steroidal saponins from the bulbs of an elephant garlic mutant

Saponins in bulbs of a mutant of elephant garlic were investigated, and three new steroidal saponins named yayoisaponins A-C were obtained together with the known dioscin and aginoside. Their structures, including the relative stereochemistry, were elucidated by spectral data interpretation, while the absolute stereochemistry of the sugar moieties was assigned on the basis of a chiral gas chromatographic analysis of the acid hydrolysates. Yayoisaponins A-C and aginoside exhibited not only in vitro cytotoxicity against P388 cells at 2.1 micrograms/ml, but also antifungal activity against Mortierella ramanniana at 10 micrograms/disk.     

Asterlingulatosides C and D, cytotoxic triterpenoid saponins from Aster lingulatus

Over the last few decades, European courses in which 'classical' tropical medicine (i.e. parasitology, entomology, and clinical aspects of tropical diseases) is taught have largely become anachronisms. Most countries in the tropics have their own medical schools and few have much need of expatriate doctors. There do, however, appear to be other ways in which Europeans may still help improve health in the tropics. One is to control the quality of the expatriate nurses who are still in demand in the tropics (often as cheaper, generally less demanding substitutes for doctors). This may be achieved by only training the best, insisting they spend some time after graduation gaining maturity before they leave for the tropics, ensuring they realise that their clinical skills will probably be inferior to their local counterparts in the tropics, and encouraging them to continue studying once abroad. The second way Europeans may help is to change the bias of their courses from teaching to training. There seems little doubt that the intellectual personalities of the brightest young men and women in the tropics often develop far better when they spend a period in a foreign environment, especially when they are allowed to function within a team, with trainees and trainers from other countries. Some 'international' courses may offer such benefits, especially if closely tailored to the needs of the trainees and their home countries.     

Inactivation of cytochrome P450s 2B1, 2B4, 2B6, and 2B11 by arylalkynes

The time-dependent loss of the 7-ethoxy-4-trifluoromethylcoumarin (EFC) O-deethylase activity of rat P450 2B1, rabbit P450 2B4, or dog P450 2B11 by 1-ethynylnaphthalene (1EN), 2-ethynylnaphthalene (2EN), 2-(1-propynyl)naphthalene (2PN), 1-ethynylanthracene (1EA), 2-ethynylanthracene, 2-ethynylphenanthrene, 3-ethynylphenanthrene, 9-ethynylphenanthrene (9EPh), 9-(1-propynyl)phenanthrene (9PPh), 4-ethynylpyrene (4EP), and 4-(1-propynyl)biphenyl (4PbP) was investigated. The rate constants for inactivation by the arylalkynes in descending order of effectiveness for the top five compounds were 9EPh>9PPh>1EN, 2EN, 2PN for 2B1, 9EPh>2EN>4EP>1EN, 1EA for 2B4, and 9EPh>1EA>4EP, 9PPh>2EN for 2B11. The size and the shape of the aromatic ring system and the placement of the alkyne functional group were important for inactivation. The most effective inactivator with all the isozymes was 9EPh. This compound also inactivated the EFC activity in microsomes from human lymphoblastoid cells expressing human P450 2B6. The specificity of 9EPh for the inhibition or inactivation of different P450 activities in microsomes from rats treated with various inducing agents was determined by measuring lidocaine, testosterone, p-nitrophenol, or erythromycin metabolism. The greatest effect was observed with the 2B-specific products from lidocaine and testosterone, whereas no effect was seen with p-nitrophenol or erythromycin. When the covalent binding of [3H]2EN to microsomal protein was analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography, a radiolabeled protein band that corresponds to 2B1 was observed in the lanes containing microsomes from rats treated with phenobarbital and, to a lesser extent, pyridine and isosafrole after incubation with NADPH. When these microsomes were incubated with [3H]9EPh or [3H]1EP, two NADPH-dependent bands were radiolabeled. One corresponded to 2B1/2 and the other to a protein of approximately 59 kDa, which was observed in the lanes from phenobarbital-treated male and female rats and pyridine-treated male rats. No radiolabeled bands were observed with [3H,14C]4PbP with any of the microsomes.     

The potential use of an extract of aspen bark for enhancing the efficacy of specific treatment methods in experimental malignant neoplasms

The effect of liquid aspen bark extract on the effectiveness of cytostatic and surgical methods of treatment of experimental tumors in mice was studied. The extract was found to raise the antitumorous and antimetastatic effects of the above indicated methods of treatment on the tumor process.     

New diterpenoids, isodoternifolins A and B, from Isodon ternifolius

Two new diterpenoids, named isodoternifolin A and B, together with seven known compounds were isolated from the ethanol extract of dried stems and leaves of Isodon ternifolius (D. Don) Kudo. Their structures were determined as 7 beta-hydroxy-6 beta, 11 alpha, 15 beta-triacetoxy-7 alpha, 20-epoxyentkaur-16-ene (1) and 6 beta, 7 beta, 15 beta-trihydroxy-11 alpha-acetoxy-7 alpha, 20-epoxy-entkaur-16-ene (2) by chemical and spectral evidence.     

Synthesis and intestinal metabolism of ursodeoxycholic acid conjugate with an antiinflammatory agent, 5-aminosalicylic acid

5-Aminosalicylic acid conjugate of ursodeoxycholic acid was synthesized in above 90% yield by adding a basic solution of 5-aminosalicylic acid into the mixed anhydride formed with ursodeoxycholic acid and ethyl chloroformate. The 5-aminosalicylic acid conjugate of ursodeoxycholic acid was poorly secreted into the bile and was deconjugated with cholylglycine hydrolase and Clostridium perfringens, that deconjugate naturally occurring glycine and taurine conjugates of bile acids. However, ursodeoxycholic acid 5-aminosalicylic acid conjugate was not absorbed from the duodenum but was concentrated in the colon where it was partially hydrolyzed by the intestinal bacteria to ursodeoxycholic acid and 5-aminosalicylic acid. We believe that this unique conjugation of ursodeoxycholic acid with 5-aminosalicylic acid may facilitate the transport of both 5-aminosalicylic acid and ursodeoxycholic acid to the colon and may be useful for the treatment of colonic inflammatory bowel diseases, ulcerative colitis and Crohn's disease.     

A garlic extract protects from ultraviolet B (280-320 nm) radiation-induced suppression of contact hypersensitivity

Lyophilized aged garlic extract has been incorporated at concentrations of 0.1%, 1% and 4% by weight into semipurified powdered diets and fed to hairless mice. Under moderate UVB exposure conditions resulting in 58% suppression of the systemic contact hypersensitivity response in control-fed mice, a dose-responsive protection was observed in the garlic-fed mice; contact hypersensitivity in the UVB-exposed mice fed 4% garlic extract was suppressed by only 19%. If the UVB exposure was replaced by topical application of one of a series of lotions containing increasing concentrations of cis-urocanic acid, a dose-responsive suppression of contact hypersensitivity was demonstrated in control-fed mice (urocanic acid at 25, 50, 100 and 200 micrograms per mouse resulting in 22-46% suppression). Mice fed a diet containing 1% aged garlic extract were partially protected from cis-urocanic acid-induced suppression of contact hypersensitivity, with greater protection from the lower concentrations of urocanic acid. Mice fed a diet containing 4% aged garlic extract were protected from all concentrations of urocanic acid. The results indicate that aged garlic extract contains ingredient(s) that protect from UVB-induced suppression of contact hypersensitivity and suggest that the mechanism of protection is by antagonism of the cis-urocanic acid mediation of this form of immunosuppression.     

Thyrotropin-releasing activity of histone H2A, H2B and peptide MB35

Histones possess multiple hormone-like activities. We studied the specificity and signal transduction pathways involved in the thyrotrophin (TSH)-releasing activity of histones H2A, H2B and peptide MB35, a H2A fragment, using perifused and incubated dispersed rat pituitary cells and measuring TSH release by a specific R1A. Histones released TSH in a dose- and time-dependent fashion while peptide MB35 behaved as a weaker secretagogue. Trifluoperazine and EGTA blocked histone-stimulated TSH release while forskolin and other cAMP enhancers did not. We conclude that the TSH-releasing activity of histones H2A and H2B is mediated by calcium- and diacylglycerol-associated pathways.     

Betulinans A and B, two benzoquinone compounds from Lenzites betulina

Two lipid peroxidation inhibitors, designated as betulinans A (1) and B (2), were isolated from the MeOH extract of Lenzites betulina. The structures of these compounds have been determined to be 2,5-diphenyl-3,6-dimethoxy-p-benzoquinone and 2-phenyl-3-methoxy-[1H-2-benzopyran][4,3-e][p]benzoquinone, respectively, on the basis of various spectral data. Betulinans A and B inhibited lipid peroxidation with IC50 values of 0.46 and 2.88 micrograms/mL, respectively.     

Glabracins A and B, two new acetogenins from Annona glabra

Two new bioactive bis-THF Annonaceous acetogenins, glabracins A (1) and B (2), and two previously known acetogenins, javoricin (3) and bullatanocin (4), have been isolated from the leaves of Annona glabra by activity-directed fractionation using the brine shrimp lethality test (BST). The structures of 1 and 2 were elucidated based on spectroscopic and chemical methods, and the absolute stereochemistries were partially determined by the advanced Mosher ester method. 1 and 2 showed selective cytotoxicities to certain human tumor cell lines, and 1 was significantly more potent although 1 and 2 differ only in the stereochemistry of their vicinal diols at C-23/24.     

NF00659A1, A2, A3, B1 and B2, novel antitumor antibiotics produced by Aspergillus sp. NF 00659. II. Structural elucidation

NF00659A1, A2, A3, B1 and B2, having insecticidal and antitumor activities, were isolated from a culture mycelium of Aspergillus sp. NF 00659. The novel structure of NF00659s were determined mainly by spectroscopic studies including various NMR measurements. NF00659s have a common structure which consists of acyl, alpha-pyrone and 4,5-seco-tricyclic diterpene moieties.     

Hydroxycinnamoyl ester glycosides and saponins from flowers of Verbascum phlomoides

A new iridoid ester glycoside acylated with p-coumaric acid was isolated from the flowers of Verbascum phlomoides, together with one known one, specioside. Caffeic acid esters, verbascoside and forsythoside B were found as minor constituents. A new saponin was also obtained and identified as desrhamnosylverbascosaponin.