Trans-fused iridoid glycosides from Penstemon mucronatus

Two new trans-fused iridoid glycosides (5 alpha H)-6 alpha-8-epidihydrocornin and (5 alpha H)-6 alpha-8-hydroxy-8-epiloganin, were isolated from Penstemon mucronatus, along with cornin, penstemoside and three hastatosides. The trans-fused iridoids are only the second and third known among over 900 described cis-fused iridoid glycosides. Two pairs of iridoids, identical except for the stereochemistry at C-8, were found. Structures were determined by spectroscopic methods.     

Hypoglycemic activity and structure-activity relationship of iridoidal glycosides

Four iridoidal glycosides, deacetylasperulosidic acid methyl ester (DE), scandoside methyl ester (SC), geniposide (GE) and gardenoside (GA) isolated from Gardenia jasminoides Ellis grandiflora Makino leaves, were tested hypoglycemic activity in mice. DE lowered the blood glucose level in normal mice. However, SC, GE and GA did not affect the blood glucose level in normal mice, indicating that the absolute configuration of 6 position hydroxy based (OH) should be essential for the biological activity.     

Triterpenoid glycosides from Anagallis arvensis

From the herb of Anagallis arvensis, we have isolated four novel oleanane glycosides, anagallosaponins VI-IX, and two artifact saponins, apoanagallosaponins III and IV, formed from anagallosaponins III and IV. The structures were elucidated by chemical and spectral methods, 2D NMR techniques being particularly helpful. The structures of anagallosaponins VI and VII were characterized as priverogenin B 3-O-beta-D-xylopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->4)-alpha-L-arabinopyranoside and 3-O-(beta-D-glucopyranosyl (1-->4)-[beta-D-xylopyranosyl (1-->2)]beta-D-glucopyranosyl (1-->4)-alpha-L-arabinopyranoside), respectively. The structures of anagallosaponins VIII and IX were characterized as 23-hydroxypriverogenin B 22-acetate 3-O-(beta-D-xylopyranosyl (1-->2)-O-beta-D-glucopyranosyl (1-->4)[beta-D-glucopyranosyl (1-->2)]-alpha-L-arabinopyranoside), 3-O-(beta-D-glucopyranosyl (1-->4)-[beta-D-xylopyranosyl (1-->2)]beta-D-glucopyranosyl (1-->4)[beta-D-glucopyranosyl (1-->2)]- alpha-L-arabinopyranoside), respectively. The structures of apoanagallosaponins III and IV were characterized as camelliagenin A 16-acetate 3-O-beta-D-xylopyranosyl (1-->2)-beta-D-glucopyranosyl (1-->4)-alpha-L-arabnopyranoside, 3-O-(beta-D-xylopyranosyl (1-->2)-O-beta-D-glucopyranosyl (1-->4)[beta-D-glucopyranosyl (1-->2)]-alpha-L-arabinopyranoside), respectively.     

Flavonol glycosides from Epimedium koreanum

A novel flavonol glycoside named caohuoside-B was isolated from the aerial parts of Epimedium koreanum, along with a known flavonol glycoside, epimedokoreanoside-I. Their structures were established by spectroscopic methods. The new compound was elucidated as anhydroicaritin 3-O-beta-D-(4,6-O- diacetyl)glucopyranosyl-(1-->3)-alpha-L-(4"-O-acetylrhamnopyranoside+ ++)-7-O-beta- D-glucopyranoside.     

Complement-inhibiting cucurbitacin glycosides from Picria fel-terrae

Effect of high larval density in Drosophila melanogaster cultures on the phenotypic and genetic variation of morphological traits (thorax length, wing length, and number of stempoleural bristles) and on the stability of development (estimated as the fluctuating asymmetry of bilateral traits) was studied. The fluctuating asymmetry of both bilateral traits was higher at high than at low larval density. An increase in phenotypic variation at a high as compared to low density was demonstrated. However, no increase in genetic variation at a high density was revealed.     

Flavonol and chalcone ester glycosides from Bidens andicola

OBJECTIVES: To examine the effect of black race and acute (negative life events) and chronic (lack of social support) psychological stress on the risk of herpes zoster in late life. DESIGN: A population-based, prospective cohort study. SETTING: Central North Carolina. PARTICIPANTS: Duke Established Populations for Epidemiological Studies of the Elderly, a stratified probability sample of community-dwelling persons more than 65 years of age. MEASUREMENTS: Interviewers administered a comprehensive health survey to the participants in 1986-1987 (P1, n = 4162), 1989-1990 (P2, n = 3336), and 1992-1994 (P3, n = 2568). Incident cases of zoster between P1 and P2 and P2 and P3 served as the dependent variable. Hypothesis-testing variables included race, negative life events, and five measures of social support. Control variables included age, sex, education, cancer, chronic diseases, basic ADLs, instrumental ADLs, depression, self-rated health, hospitalization, and cigarette smoking. Statistical analyses employed chi-square tests and proportional hazards model. RESULTS: At baseline, the sample had a mean age of 73.6 years and was 55% black, 45% white, and 65% female. There were 65 cases of zoster between P1 and P2 and 102 cases of zoster between P2 and P3. From P1 to P2, 1.4% of blacks and 3.4% of whites developed zoster (P < .001). From P2 to P3, 2.9% of blacks and 7.5% of whites developed zoster (P < .001). After controlling for the above variables, blacks were significantly less likely to develop zoster (adjusted risk ratio = 0.35; 95% confidence interval (CI), 0.24-0.51; P < .001). Negative life events increased the risk of zoster, but the result was borderline for statistical significance (adjusted RR = 1.38, 95% CI 0.96-1.97; P = .078). No measures of social support were significantly associated with zoster. CONCLUSION: Black race decreased the risk of zoster in late life significantly. Measures of stress were not significantly related to zoster, but study limitations preclude definitive conclusions. Future research should focus on these factors in larger samples and different populations.     

Steroidal glycosides from Allium albopilosum and A. ostrowskianum

Chemical studies of the bulbs of Allium albopilosum and A. ostrowskianum have led to the isolation of two new steroidal saponins and four new cholestane glycosides together with several known compounds. The structures of the new compounds were established by the spectroscopic data, hydrolysis and chemical correlations as (25 R and S)-5 alpha-spirostane-2 alpha,3 beta,6 beta-triol 3-O-(O-beta-D-glucopyranosyl-(1-->2)-O-[3-O-acetyl-beta-D-xylopyranosyl- (1-->3)]-O-beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside), (25R)-2-O-[(S)-3-hydroxy-3-methylglutaroyl]-5 alpha-spirostane-2 alpha, 3 beta, 6 beta-triol 3-O-(O-beta-D-glucopyranosyl-(1-->2)-O-[beta-D-xylopyranosyl-(1-->3)]-O- beta-D-glucopyranosyl-(1-->4)-beta-D-galactopyranoside), (22S)-cholest-5-ene-1 beta,3 beta,16 beta,22-tetraol 1-O-alpha-L-rhamnopyranoside 16-O-(O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside), 1 beta,3 beta,16 beta-trihydroxycholest-5-en-22-one 1-O-alpha-L-rhamnopyranoside 16-O-(O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside), 1 beta,3 beta,16 beta-trihydroxy-5 alpha-cholestan-22-one 1-O-alpha-L-rhamnopyranoside 16-O-(O-alpha-L-rhamnopyranosyl-(1-->3)-beta-D-glucopyranoside) and (22S)-cholest-5-ene-1 beta,3 beta,16 beta,22-tetraol 16-O-(O-beta-D-glucopyranosyl-(1-->3)-beta-D-glucopyranoside).     

Flavonol glycosides and flavonol glucoside gallates from Peltophorum africanum

In this study of interactions occurring within the heart, isolated superfused strips of rabbit atria, containing the sinoatrial (s.a.) node, were subjected to sinusoidal subthreshold current pulses of varied frequencies and intensities. A.C. current from an R.C. oscillator was applied through a Grass stimulation isolation unit, push-pull connection, and non-polarizing (Ag-AgCl-KCl-Tyrode Agar-Agar) electrodes. A Grass polygraph and tachometer were used to record the applied pulses and nodal firing rates; simultaneous magnetic tape recordings were obtained and used for data analysis. Suction electrode recordings and oscilloscope displays were used to determine how the cyclic impulses affected cellular activity. The s.a. nodal rhythm was modified by subthreshold A.C. current applications; when frequencies were low, firing rates of the node were modulated by the A.C. and mean rates were reduced. As frequencies were progressively increased, slow waxings and wanings in heart rate were produced. These periodic fluctuations were not readily correlated with either the A.C. frequency nor the intrinsic nodal rate, but were representative of the difference between the two. As applied current frequency neared the pacemaker's intrinsic rate, a synchronization occurred and the discharges locked in at a specific phase of the applied current alternation. This synchronization maintained during slight further increases in A.C. frequency but above a critical rate this relationship broke down and the waxing and wanings in frequency of pacemaker rate again developed. It was concluded that pacemaker action of the s.a. node is effected by integration of cellular activity through electron coupling.     

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.     

Three phenylethanoid glycosides and an iridoid glycoside from Picrorhiza scrophulariiflora

To identify risk factors associated with death in traumatized children, we prospectively studied 507 consecutive patients (7+/-4 yr) admitted to a level I pediatric trauma center over a 3-yr period. Pediatric Trauma Score (PTS), Glasgow Coma Scale (GCS) score, and Injury Severity Score (ISS) were calculated. Age, injury mechanism, injury pattern, and initial critical care were recorded. Univariate and multivariate analyses were performed for potential risk factors associated with mortality. Receiver operating characteristic curves were used to determine threshold values of variables identified by univariate analysis. Most children suffered from blunt trauma (99.6%), and head trauma was noted in 85%. Median values (range) of GCS scores, PTS, and ISS were 10 (3-15), 7 (-4 to 12), and 16 (3-75), respectively. The mortality rate was 12%. Using multivariate analysis, death was significantly associated with an ISS > or = 25 (odds ratio [OR] 22.2, 95% confidence interval 2.8-174.9), GCS score < or = 7 (OR 4.77, 1.8-12.7), emergency blood transfusion > or = 20 mL/kg (OR 4.3, 2.1-9.1), and PTS < or = 4 (OR 3.7, 1.4-9.7). An ISS > or = 25, GCS score < or = 7, immediate blood transfusion > or = 20 mL/kg, and PTS < or = 4 were significant and independent risk factors of death in an homogenous population of severely injured children. The probability of traumatic death was therefore 0 (95% confidence interval 0-0.0135) in children with no one of these threshold values in the four predictive factors and 0.63 (95% confidence interval 0.47-0.76) in those children with all the threshold values. IMPLICATIONS: Methods used for evaluating outcome of trauma patients have essentially been derived from adult series, and attempts to apply them to children have usually been inaccurate. Univariate and multivariate analyses were performed to identify risk factors associated with death in severely traumatized children, and Receiver operating characteristic curves were used to determine threshold values.     

Acylated C-21 steroidal bisdesmosidic glycosides from Caraluma umbellata

From the whole plant of Caraluma umbellata, three new C-21 steroidal glycosides, named as carumbellosides III-V, were isolated and their structures elucidated by extensive spectroscopic experiments, devoid of any derivatisation, as caralumagenin 3-O-beta-D-glucopyranosyl(1-->4)-beta-D-digitalopyranoside-20-O-be ta- D-glucopyranoside, caralumagenin 3-O-beta-D-glucopyranosy(1-->4)- beta-D-digitalopyranoside-20-O-(2-O- benzoyl)-beta-D-glucopyranoside and caralumagenin 3-O-[6-O-benzoyl-beta-D-glucopyranosyl(1-->4)]-beta-D- digitalopyranoside-20-O-(2-O-benzoyl)-beta-D-glucopyranoside. The determination of the absolute configuration of the aglycone as (20 R), the conformations of the sugars and the unambiguous assignments of their NMR spectroscopic signals were achieved by a combination of 2D-NMR techniques. The isolates were devoid of significant cytotoxity in the UIC human cancer cell panel.     

Bioactive anthraquinone glycosides from Picramnia antidesma spp. fessonia

A bioactivity guided fractionation, using KB cells and brine shrimp assays, of the methanolic extract from the leaves of Picramnia antidesma yielded two known anthraquinones, aloe-emodin and aloe-emodin anthrone, and three new aloe-emodin C-glycosides, named picramnioside A, picramnioside B and picramnioside C. Structures were established by spectroscopic methods (UV, IR, mass spectrometry, 1H and 13C and 2D NMR including COSY 45, HMQC, HMBC and ROESY). CD was used to establish the absolute configuration of the picramniosides.     

Two new 7-dehydroaporphine alkaloids and antiplatelet action aporphines from the leaves of Annona purpurea

Bioactivity-directed fractionation led to the isolation of two new 7-dehydroaporphine alkaloids, 7-hydroxy-dehydrothalicsimidine (1) and 7-formyl-dehydrothalicsimidine (2), along with the five known alkaloids, thalicsimidine (3), norpurpureine (4), N-methyllaurotetanine (5), lirinidine (6) and N-methylasimilobine (7), from the leaves of Annona purpurea. Structural elucidation of these compounds was established by mass and spectroscopic analyses. Among them, 1, 3, 4, 6 and 7 exhibited significant inhibition of collagen, arachidonic acid and platelet activating factor-induced platelet aggregation; 1 also showed inhibition against thrombin-induced platelet aggregation.     

Cycloartane triterpene glycosides from the roots of Astragalus brachypterus and Astragalus microcephalus

Three new cycloartane-type triterpene glycosides, brachyosides A (1), B (3), and C (2), from the roots of Astragalus brachypterus and one new glycoside, cyclocephaloside II (4), from the roots of Astragalusmicrocephalus have been isolated together with five known saponins, astragalosides I, II, and IV, cyclocanthoside E, and cycloastragenol. The structures of the new compounds were established as 3-O-[beta-D-xylopyranosyl(1-->3)-beta-D-xylopyranosyl-6-O-beta-D-gluc opyranosyl-3beta,6alpha,16beta,24(S),25-pentahydrox ycycloartane (1), 3-O-beta-D-xylopyranosyl-6-O-beta-D-glucopyranosyl-24-O-beta-D-glucop yranosyl-3beta,6alpha,16beta,24(S),25-pentahydroxyc ycloartane (2), 20(R),24(S)-epoxy-6-O-beta-D-glucopyranosyl-3beta,6alpha,16beta , 25-tetrahydroxycycloartane (3), and 20(R), 24(S)-epoxy-3-O-(4'-O-acetyl)-beta-D-xylopyranosyl-6-O-beta-D-glucopy ranosyl-3beta,6alpha,16beta,25-tetrahydroxycycloart ane (4). For the structure elucidations, 1D- and 2D-NMR experiments and FABMS were used.     

Digitalis, diuretic and vasodilator treatment of cardiac failure

Angiotensin-converting-enzyme inhibitors increase life expectancy in congestive heart failure, and they have thus changed the therapeutic strategy. The well tolerated highest daily dosage has to be used. Diuretics are often associated with vasodilators; however, they have to be administered at a minimal chronic daily dosage, in order to avoid deleterious neurohormonal effects. Digoxin keeps a great interest, as the unique positive inotropic agent without surmortality. Nitrates associated or not with hydralazine may show an additional interesting benefit. The role of other vasodilators, namely amlodipine and losartan, in the treatment of chronic heart failure remains to be defined. New vasodilators are in development and might further increase our therapeutic possibilities against congestive heart failure.     

Antidiabetic principles of natural medicines. III. Structure-related inhibitory activity and action mode of oleanolic acid glycosides on hypoglycemic activity

We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.     

Karsoside and scropolioside D, two new iridoid glycosides from Scrophularia ilwensis

Two new iridoid glycosides, karsoside [1] and scropolioside D [2], were isolated from the aerial parts of Scrophularia ilwensis. Their structures were elucidated on the basis of chemical and spectral data as 6'-O-(beta-D-xylopyranosyl)-methylcatalpol and 6-O-[(2",4"-di-O-acetyl-3"-O-trans-cinnamoyl)-alpha-L-rhamnopyranosyl]- catalpol, respectively. Additionally, four known iridoids (aucubin, harpagide, 8-O-acetylharpagide, and ajugol), a phenylpropanoid glycoside (angoroside C), and two flavonoids (quercetin-3-O-rutinoside and kaempferol-3-O-rutinoside) were isolated and identified.     

Synthesis and antitumor activity of new glycosides of epipodophyllotoxin, analogues of etoposide, and NK 611

A series of 3-amino- and 3-alkylamino-2-deoxy-beta-D-ribo- and beta-D-arabino-glycosides of 4'-demethylepipodophyllotoxin have been synthesized by means of an improved trimethylsilyliodide procedure for the podophyllotoxin-4'-demethylepipodophyllotoxin conversion, an efficient and high yielding synthesis of silyl glycoside donors of 3-azido-2,3-dideoxy-beta-D-ribo- and beta-D-arabino-hexopyranosides and stereoselective glycosylations. In vitro evaluation of cytotoxic effects against murine L1210 leukemia critically demonstrates the essential role played by a 4,6-acetal for biological activity. Among the most cytotoxic compounds, 3-amino-2,3-dideoxy- and 3-N, N-(dimethylamino)-2,3-dideoxy etoposide analogues, 17 and 27-29 are at least as potent as etoposide on the in vivo P388 (iv/ip) murine leukemia models. However, surprisingly enough, none of these compounds inhibits the human DNA topoisomerases I or II or binds to tubulin to prevent its polymerization and microtubule assembly. Therefore, their mechanism of action remains to be cleared up.