Anxiolytic activity and active principles of Piper amalago (Piperaceae), a medicinal plant used by the Q'eqchi' Maya to treat susto, a culture-bound illness.

ETHNOPHARMACOLOGICAL RELEVANCE: The medicinal plant, Piper amalago L. (Piperaceae), is used traditionally by Q'eqchi' Maya healers for the treatment of "susto" a culture-bound syndrome. Previous research suggests that susto symptoms may be a manifestation of anxiety. The objectives were to characterize the effect of ethanolic extract of P. amalago in behavioral assays of anxiety at doses representative of traditional use and to isolate active principles. MATERIALS AND METHODS: Rats treated orally with low dose ethanolic extracts of P. amalago leaves (8-75mg/kg) were tested in several behavioral paradigms including the elevated plus maze (EPM), social interaction (SI), and conditioned emotional response (CER) tests, and compared to diazepam, a positive control. The active anxiolytic principle was isolated by bioassay guided isolation using an in vitro GABAA competitive binding assay. RESULTS: Extracts had significant anxiolytic activity in all behavioral tests, with the strongest activity in the SI and the CER paradigms. In an in vitro GABAA competitive binding assay, a 66.5µg/mL concentration of P. amalago ethanol extract displaced 50% of the GABAA-BZD receptor ligand [(3)H]-Flunitrazepam. Bioassay-guided fractionation identified a furofuran lignan, a molecule with structural similarity to yangambin, with high affinity for the GABAA-BZD receptor as the principle bioactive. CONCLUSION: The results suggest that the ethnobotanical use of this plant may have a pharmacological basis in its anxiolytic activity, as demonstrated in animal behaviour tests.

Quality of life and exercise rehabilitation in end stage renal disease.

Using a qualitative approach, this study explored the perceptions of individuals with end stage renal disease (ESRD) regarding their physical, emotional, and social well-being after having participated in an eight-week hospital-based intra-dialytic exercise program. Individual semi-structured interviews (approximately 60 min. duration) were conducted with hemodialysis (HD) patients (n= 7) during their regular dialysis sessions, two weeks immediately following the completion of the exercise program. Interviews were audio-taped, transcribed verbatim, and content analysis was used to identify emerging themes. Data management was assisted by NVivo software. Using the interpretive paradigm, three primary themes emerged: improved performance in activities of daily living (ADL), positive change in HD experience, and enhanced sense of control. Participants reported an overall positive experience with the intra-dialytic exercise program and felt that their quality of life was enhanced to such an extent that they would choose to continue exercising while on HD.

Identification of a novel angiotensin-I-converting enzyme inhibitory peptide corresponding to a tryptic fragment of bovine beta-lactoglobulin.

The angiotensin-I-converting enzyme (ACE) inhibitory activity of a tryptic digest of bovine beta-lactoglobulin (beta-lg) was investigated. Intact beta-lg essentially did not inhibit ACE while the tryptic digest gave an 84.3% inhibition of ACE. Peptide material eluting between 20 and 25% acetonitrile during C18 solid-phase extraction of the beta-lg tryptic digest inhibited ACE by 93.6%. This solid-phase extraction fraction was shown by mass spectroscopy to contain beta-lg f(142-148). This peptide had an ACE IC50 value of 42.6 micromol/l. The peptide was resistant to further digestion with pepsin and was hydrolysed to a very low extent with chymotrypsin. The contribution of specific amino acid residues within the peptide to ACE inhibitory activity and the potential application of this peptide as a nutraceutical is discussed.

Synthetic peptides corresponding to alpha-lactalbumin and beta-lactoglobulin sequences with angiotensin-I-converting enzyme inhibitory activity.

Novel angiotensin-I-converting enzyme (ACE) inhibitory activities were detected in synthetic peptides corresponding to sequences of beta-lactoglobulin and alpha-lactalbumin and which are known to possess opioid activity. Using hippuryl-histidyl-leucine as substrate, the tetrapeptides beta-lactorphin (Tyr-Leu-Leu-Phe), alpha-lactorphin (Tyr-Gly-Leu-Phe) and beta-lactotensin (His-Ile-Arg-Leu) were shown to have IC50 values of 171.8, 733.3 and 1153.2 microM, respectively. Related dipeptides also inhibited ACE, with Tyr-Leu being the most potent, having an IC50 value of 122.1 microM.

Macquarimicins, microbial metabolites from Micromonospora. II. Isolation and structural elucidation.

A novel series of carbocyclic compounds has been isolated from two related Micromonospora cultures. The C-19 and C-22 macquarimicins represent different end products on a similar biosynthetic scheme. 1-D and 2-D homonuclear and heteronuclear NMR experiments allowed assignment of the basic structures of the macquarimicins. An X-ray structure of macquarimicin B suggested the stereochemistry for the series which was not discernible from spectroscopic data alone.

Aminopeptidases from Plasmodium falciparum, Plasmodium chabaudi chabaudi and Plasmodium berghei.

Using fluorogenic substrates and polyacrylamide gels we detected in cell-free extracts of Plasmodium falciparum, Plasmodium chabaudi chabaudi and Plasmodium berghei only a single aminopeptidase. A comparative study of the aminopeptidase activity in each extract revealed that the enzymes have similar specificities and kinetics, a near-neutral pH optima of 7.2 and are moderately thermophilic. Each has an apparent molecular weight of 80,000 +/- 10,000, determined by high performance liquid chromatography on a calibrated SW500 column. Whilst the P. c. chabaudi and P. berghei activity co-migrate in native polyacrylamide gels, that of P. falciparum migrates more slowly. The three enzymes can be selectively inhibited by ortho-phenanthroline and are thus metallo-aminopeptidases; however, in contrast to other aminopeptidases the metal co-factor does not appear to be Zn2+.

MLR-52, (4'-demethylamino-4',5'-dihydroxystaurosporine), a new inhibitor of protein kinase C with immunosuppressive activity.

In the course of screening with the mixed lymphocyte reaction, a new inhibitor of protein kinase C with immunosuppressive activity was isolated from the fermentation broth and mycelia of Streptomyces sp. AB 1869R-359. Although certain similarities exist, this strain is morphologically and physiologically distinct from other reported producers of staurosporine-related compounds. We have found that this strain produces relatively high levels of staurosporine and the new minor compound MLR-52, which possesses the indolo[2,3-a]carbazole chromophore of staurosporine, but differs in the substitution pattern of the sugar moiety. Their structures have been elucidated by mass and NMR spectra. MLR-52 has been shown to inhibit the enzymatic activity of protein kinase C and the murine mixed lymphocyte reaction.

5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. II. Isolation and elucidation of the structure of 5-N-acetylardeemin and two congeners.

A family of novel compounds has been detected and isolated following an assay for the attenuation of multiple drug resistance in tumor cells from the fermentation broth and mycelia of a strain of Aspergillus fischeri which we have designated var. brasiliensis. The structures of three components were determined employing 1-D and 2-D homonuclear and heteronuclear NMR spectroscopy and mass spectrometry. The structure of 5-N-acetylardeemin was confirmed by single crystal X-ray diffraction. These compounds are most closely structurally related to asperlicin E1).

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. II. Isolation and elucidation of structures.

A novel complex of antifungal and immunosuppressant compounds has been isolated from the fermentation broth and mycelia of two strains of Streptomyces diastatochromogenes. The structures of eight related components were determined employing 1D and 2D homonuclear and the heteronuclear NMR spectroscopy and mass spectrometry. These structures represent the first reported spiroketal 24-membered macrolide natural products related to the common 26-membered oligomycins.