Effect of plant flavonoids on the volume regulation of rat thymocytes under hypoosmotic stress

BackgroundCell volume regulation and volume-regulated anion channels are critical for cell survival in non-isosmotic conditions, and dysregulation of this system is detrimental. Although genes and proteins underlying this basic cellular machinery were recently identified, the pharmacology remains poorly explored.MethodsWe examined effects of 16 flavonoids on the regulatory volume decrease (RVD) of thymocytes under hypoosmotic stress assessed by light transmittance and on the activity of volume-sensitive chloride channel by patch-clamp technique.ResultsComparison of effects of flavonoids on RVD revealed a group of four active substances with lehmannin being the strongest inhibitor (IC₅₀ = 8.8 μM). Structure-functional comparison suggested that hydrophobicity brought about by methoxy, prenyl or lavandulyl groups as well as by the absence of glucosyl fragment together with localization of the phenyl ring B at the position C2 (which is at C3 in totally inactive isoflavones) are important structural determinants for the flavonoids activity as volume regulation inhibitors. All active flavonoids suppressed RVD under Gramicidin D-NMDG hypotonic stress conditions when cationic permeability was increased by an ionophore, gramicidin D, with all extracellular monovalent cations replaced with bulky NMDG⁺ suggesting that they target volume-sensitive anionic permeability. While effects of hispidulin and pulicarin were only partial, lehmannin and pinocembrin completely abolished RVD under Gramicidin D-NMDG conditions. In direct patch-clamp experiments, lehmannin and pinocembrin produced a strong inhibiting effect on the swelling-induced whole-cell chloride conductance in a voltage-independent manner.ConclusionLehmannin, pinocembrin, and possibly hispidulin and pulicarin may serve as leads for developing effective low-toxic immunomodulators.     

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In order to maximise revenue in a nurse clinic, certain steps and considerations should be taken into account. It is important to determine what it is hoped is going to be achieved and how this is to be done. A veterinary nurse embarking on a nurse clinic should give consideration to the market at which she is aiming and what sales skills she requires in order to achieve her objectives.     

Action of phytoecdysteroids on the bile-secretory function of the normal liver and in experimental hepatitis

Phytoecdysteroids from Rhaponticum carthemoides (Willd) Iljin and Ajuga turkestanica (Rgl.) Brig in a dose of 5 mg/kg per os markedly stimulate the bile secretion in normal rats treated with single (cyasterone) and 7-day-long (ecdysterone, cyasterone) administration. The chemical composition of the bile is significantly improved because of increased levels of bile acids and bilirubin and a decreased cholesterol content. Phytoecdysteroids (ecdysterone) exert more beneficial effect on the parameters under study in rats with toxic hepatitis induced by heliotrine.     

The relation between myosin adenosinetriphosphatase activity and inactivation of myosin under alkaline conditions of heart muscles in mammals of different size

Summary ATPase activity of myosin in the heart muscle of the mouse, rat, guinea-pig, rabbit and pig was studied at neutral pH and under mild alkaline conditions. At neutral pH the ATPase activity of myosin is inversely related to body size of the animal species. The decrease of ATPase activity of myosin after alkaline preincubation depends on the degree of ATPase activity of intact myosin, i.e. myosin from the heart of the mouse exhibits high ATPase activity and a small loss of ATPase activity after preincubation at pH 10.0, myosin from the heart of the pig exhibits a low ATPase activity and is very labile at pH 10.0. The same relationship was found, when comparing myosin of new-born and adult heart muscle. It is concluded that the rate of alkaline inactivation of heart myosin is directly related to the degree of ATPase activity of intact myosin in all animals.     

Melatonin and colon carcinogenesis: I. Inhibitory effect of melatonin on development of intestinal tumors induced by 1,2-dimethylhydrazine in rats

The effect of pineal indole hormone melatonin on colon carcinogenesis was firstly studied in rats. Two-month-old outbred female LIO rats were weekly exposed to 15 (experiment 1, groups 1 and 2) or to five (experiment 2, groups 1 and 2) s.c. injections of 1,2-dimethylhydrazine (DMH) at a single dose of 21 mg/kg of body weight. From the day of the first injection of the carcinogen DMH, the rats from groups 2 (experiments 1 and 2) were given melatonin five days a week during the night-time (from 18:00 h to 8:00 h), dissolved in tap water at 20 mg/l. The experiment was finalized in 6 months after the first injection of DMH. In both experiments the majority of tumors were localized in the descending colon. Tumors of the small intestines developed only in rats from experiment 1. Total incidence of colon tumors as well as tumors in different parts of the colon and the mean number of tumors per rat were much higher in rats from both groups in experiment 1 than that in rats from experiment 2. In experiment 1 melatonin failed to influence the total incidence of colon tumors. However, incidence of carcinomas in the ascending colon was significantly reduced (P < 0.01). The multiplicity of total colon tumors per rat, as well as the mean number of tumors, ascending and descending colon per rat, was also decreased under the influence of melatonin (group 2 vs group 1, P < 0.01). In the same experiment, melatonin slightly decreased the depth of tumor invasion and increased number of highly differentiated colon carcinomas induced by DMH. The percentage of small tumours in the descending colon among rats from group 2 was higher than that of group 1. Treatment with melatonin was also followed by a decrease in the multiplicity of DMH- induced tumors of the duodenum (group 2 vs group 1, P < 0.05) and by a decrease in the incidence of jejunum and ileum tumors (group 2 vs group 1, P < 0.05). In experiment 2, the inhibitory effect of melatonin on DMH-induced colon carcinogenesis was much more expressed than that in experiment 1. Thus, in group 1 the incidence of total colon tumors, ascending and descending colon tumors, was significantly decreased in comparison with group 2; also melatonin reduced the number of tumors per rat in the ascending and descending colon. The number of colon tumors that invaded only mucosa was significantly higher in group 2 than in group 1, P < 0.05. The ratio of highly differentiated tumors was increased (P < 0.05) and the ratio of low-differentiated tumors was decreased (P < 0.05) in rats exposed to melatonin (group 4) as compared with group 3. The number of large size tumors in the ascending and descending colon was decreased whereas the number of small size tumors (<10 mm2) was increased in those parts of the colon that were under the influence of melatonin in experiment 2. Thus, our results demonstrate the inhibitory effect of melatonin on intestinal carcinogenesis induced by DMH in rats.      

Chemical composition and biological activity of total bufadienolides from the Central-Asian <Emphasis Type="Italic">Bufo viridis</Emphasis> toad venom

The chemical composition of bufadienolides isolated from the venom of Bufo viridis green toad occurring in Central Asia was determined and their biological properties were studied. Six individual bufadienolides were isolated by reverse-phase chromatography on a Lichrosorb RP-8 (10 μ) column in amounts sufficient for qualitative analysis. Two of these were previously identified as arenobufagin and gamabufotalin by NMR spectroscopy and x-ray diffraction methods. The chemical structures of four other bufadienolides are now established by NMR spectroscopy and HPLC. These compounds have been identified as telocinobufagin (3β,5β,14β-trihydroxybufa-20,22-dienolide), marinobufagin (3β, 5β-hydroxy-14,15β-epoxybufa-20,22-dienolide), bufarenogin (3β,12β,14β-hydroxybufa-20,22-dienolide), and bufalin (3β,14β-hydroxybufa-20,22-dienolide). __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 11, pp. 33–37, November, 2007.     

Technology for Preparation of Pure Total Flavonoid Fraction from Roots of <Emphasis Type="Italic">Pseudophora alopecuroides</Emphasis> and Evaluation of Its Hepatoprotector and Biligenic Activity

The optimal regime for extraction of the total flavonoid fraction from the roots of Pseudosophora alopecuroides has been found and the corresponding technological scheme for the isolation of flavonoids from this medicinal plant has been developed. Acomparative pharmacological investigation showed that both the total flavonoid extract obtained using a semicommercial apparatus according to the proposed technology and a laboratory preparation are comparable in activity with the well-known drug tanacechol based on common tansy flowers. This result shows that Pseudosophora alopecuroides offers an important source of biologically active flavonoids possessing hepatoprotector and biligenic activity. The annular natural resource of roots of this medicinal plant has been evaluated. The qualitative composition of the flavonoids and their total content in various extracts have been compared.__________Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 39, No. 2, pp. 25 – 27, February, 2005.     

Experimental study of the anabolic activity of 6-ketoderivatives of certain natural sapogenins]

It is shown that 6-ketoderivatives of natural sapogenins, viz. agigenin, diosgenin and alliogenin, display the anabolic activity and do not manifest any androgenic properties. The compoud IV/(25 R)-5alpha-spirostan-2alpha, 3beta, 5alpha-triol-6-OH/produces an accelerated gain of weight in rats, and also an increase in the weight of the liver, heart, kidneys, musculus tibiliasis anterior and augments the total amount of protein therein. All of the above-mentioned changes become more pronounced with the study substance introduced to young animals. Castration of sexually immature rats greatly mitigates the anabolic effect of the compound IV.