Marina N. Makarova

Anti-inflammatory activity of a HPLC-fingerprinted aqueous infusion of aerial part of Bidens tripartita L.

The anti-inflammatory potential of three doses of an aqueous infusion of aerial parts Bidens tripartita L. against carrageenan-induced acute paw edema in rats was investigated. A phytochemical study and qualitative-quantitative analyses revealed the presence of flavonoids, tannins, polysaccharides, phenols, amino acids, ascorbic acid, organic acids and polyacetylenes. Infusion doses of 20ml/kgbody wt. exhibited significant anti-inflammatory activity in rats, as compared with indomethacin. In addition, the infusion showed analgesic properties in a hot-plate test and antipyretic properties in carrageenan-induced local hyperthermia, both in rats. The effects were dose-dependent. Our results provide evidence for the potential usefulness of B. tripartita infusion in the treatment of inflammatory disorders.

Determination and pharmacokinetic study of taxifolin in rabbit plasma by high-performance liquid chromatography.

Taxifolin has been widely used in the treatment of cerebral infarction and sequelae, cerebral thrombus, coronary heart disease and angina pectoris. A reliable sensitive reversed-phase high-performance liquid chromatography (RP-HPLC) method with UV detection for the pharmacokinetic study of taxifolin in rabbit plasma after enzymatic hydrolysis was developed and validated for the first time. Taxifolin, with biochanin A as the internal standard, was extracted from plasma samples by liquid/liquid extraction after hydrolysis with beta-glucuronidase and sulfatase. Chromatographic separation was conducted on a Luna C18 column (4.6 mm x 150 mm, 5 microm particle size) and pre-column (2.0 mm, the same sorbent). Two-step linear gradient elution with acetonitrile and 0.03% water solution of trifluoroacetic acid as mobile phase at a flow rate of 1.0 ml/min was used. The UV detector is set at 290 nm. The elution time for taxifolin and biochanin A was approximately 7.9 and 18.3 min, respectively. The calibration curve of taxifolin was linear (r > 0.9997) over the range of 0.03-5.0 microg/ml in rabbit plasma. The limit of detection (LOD) and limit of quantification (LOQ) for taxifolin were 0.03 and 0.11 microg/ml, respectively. The present method was successfully applied for the estimation of the pharmacokinetic parameters of taxifolin following intravenous and oral administration of lipid solution to rabbits. The absolute bioavailability of taxifolin after oral administration of lipid solution was 36%.

Antiallergic effects of pigments isolated from green sea urchin (Strongylocentrotus droebachiensis) shells.

This study was undertaken to evaluate possible antiallergic effects of an extract of pigments from green sea urchin (Strongylocentrotus droebachiensis) shells. Effects were studied on animal models - guinea pig ileum contraction, rabbit eyes allergic conjunctivitis, and rabbit local skin irritation. The extract significantly reduced, in a dose-dependent manner, the histamine-induced contractions of the isolated guinea pig ileum with ID50 =1.2 µg/mL (in equivalents of spinochrome B), had an inhibitory effect on the model of ocular allergic inflammation surpassing the reference drug olopatadine, and did not show any irritating effect in rabbits. The extract predominantly contained polyhydroxy-1,4-naphthoquinone which would be responsible for the pharmacological activity. The active compounds of the extract were evaluated in silico with molecular docking. Molecular docking into H1R receptor structures obtained from molecular dynamic simulations showed that all spinochrome derivatives bind to the receptor active site, but spinochrome monomers fit better to it. The results of the present study suggest possibilities for the development of new agents for treating allergic diseases on the base of pigments from sea urchins shells.

Effect of Bergenia crassifolia L. extracts on weight gain and feeding behavior of rats with high-caloric diet-induced obesity

The objective of this study was to evaluate the feeding behavior and weight gain in rats with high-calorie diet-induced obesity that are treated with Bergenia crassifolia black and fermented leaves extracts. The daily dietary intake of all treated animals was reduced to 40% compared with the control group on day 22 of the experiment. A significant improvement in glucose tolerance was noted after 7 days of treatment with the Bergenia extracts. In rats treated with an extract of black leaves for 7 days, a significant reduction in the serum triglyceride level, 45% (p<0.05), compared with the control group was observed. However, the treatment did not affect the cholesterol level. Our results provide evidence for the potential use of B. crassifolia as an appetite and energy intake suppressant.

Bergenia crassifolia (L.) Fritsch - Pharmacology and phytochemistry

PURPOSE Bergenia crassifolia (L.) Fritsch, a species in the Bergenia genus belongs to the family Saxifragaceae, is valuated for its medicinal application. The review focuses on the medicinal uses, phytochemistry, and the biological activities of B. crassifolia to explore its benefits and potential uses. METHODS In this review, we summarized data, published in Russia and in other countries related to B. crassifolia. RESULTS Rhizomes and leaves of this plant are in use as traditional remedies for the treatment of different disorders in the folk medicine systems of Russia and Asia. The plant is a potential source of tannins, benzanoids, flavonoids, polysaccharides and other active compounds. Due to the presence of a multitude of bioactives, a wide array of pharmacological activities have been ascribed to different parts of this herb and individual compounds, which include adaptogenic, antiinflammatory, antihypertensive, antimicrobial, antioxidant, antiobesity, antitussive, cerebro-protective, hepatoprotective, immunomodulating, and diuretic. CONCLUSION The review highlights the potential of B. crassifolia for further development of herbal medicines on its base.

Determination of icariin in rat plasma by reverse-phase high-performance liquid chromatography after oral administration of a lipid-based suspension of Epimedium koreanum extract.

A simple, specific and sensitive method for quantitative determination of icariin in rat plasma using reverse-phase high-performance liquid chromatography with UV-detection was developed and applied to an animal study of a lipid-based suspension of the Epimedium koreanum extract in rats. Rutin was selected as the internal standard and methanol was found to be the best solvent for extraction of icariin from the plasma. Linearity was observed between 0.030 and 100 microg/mL (r > 0.99). The extraction recoveries of icariin and rutin were approximately 75 and 80%, respectively, in plasma. The intra- and inter-day coefficients of variation were less than 5%. The limit of detection was 6 ng/mL and the limit of quantification was 18 ng/mL.

Pharmacological evaluation of Potentilla alba L. in mice: adaptogenic and central nervous system effects.

Context: Potentilla alba L. (Rosaceae) rhizomes have anti-inflammatory, antioxidant, and adaptogenic effects and are used for the treatment of diarrhea and intestinal colic. However, the data concerning the adaptogenic and central nervous system activities of P. alba are fragmentary. Objectives: To determine the effect of oral administration of dried P. alba extract on the swimming endurance, light/dark exploration, and open-field tests for mice. Materials and methods: The mice were orally administered Rhodiola rosea extract (RR group); dry extract of P. alba at doses of 12, 36, or 72 mg/kg (groups: PA12, PA36, and PA72); or distilled water (control group) for 7 consecutive days. Results: The swimming times of the RR, PA36, and PA72 groups were significantly longer than those of the control group. The administration of P. alba significantly increased the light time, latency time, and the number of rearings in a dose-dependent manner. In the open-field test, the P. alba extract at a dose of 12 mg/kg produced a significant increase in the frequency of head dipping and the number of squares crossed and a significant decrease in grooming compared with the control treatment. Conclusion: The current findings demonstrate that P. alba extracts significantly increased swimming endurance time and have anxiolytic-like action with a predominant locomotor component.

A new tridecapeptide with an octaarginine vector has analgesic therapeutic potential and prevents morphine-induced tolerance

HighlightsThe efficiency in various pain animal models.The absence of tolerance to analgesic effect during 7‐day therapy with oral administration.The absence of cross‐tolerance to morphine.Candidate for use in the treatment of chronic pain. ABSTRACT A growing body of evidence suggests that peptides may possess analgesic effects without tolerance development. The synthetic tetrapeptide Tyr‐d‐Arg‐Phe‐Gly‐NH2 was modified with the inclusion of a (d‐Arg)8 vector to prevent the action of endopeptidase and to increase the duration of the analgesic action of the tetrapeptide when administered orally. The aim of this study was to estimate the analgesic efficacy of the tetrapeptide with (d‐Arg)8 (tridecapeptide, TDP) in experimental models of acute and chronic pain. The analgesic effects of TDP were estimated using a model of acute visceral pain in mice (writhing test) and a model of chronic neuropathic pain (chronic constriction injury (CCI) of the sciatic nerve) in rats. The intravenous administration of morphine (0.32–1 mg/kg) and TDP (0.32–1.8 mg/kg) produced significant dose‐related antinociceptive effects in the writhing test. The potency of TDP after i.g. administration was lower than that after i.v. administration but comparable with that of i.g. morphine. In the CCI model, TDP (0.1, 1 and 10 mg/kg, i.g.) induced marked analgesia with repeated administration without any signs of tolerance. The single administration of TDP after morphine treatment (7 days) produced a significant analgesic effect in morphine‐tolerant rats, indicating the absence of cross‐tolerance between these two drugs. The combined administration of TDP and morphine resulted in the reduction of analgesic tolerance to morphine. The absence of cross‐tolerance to morphine and the ability to prevent morphine tolerance allows this compound to be a prospective candidate for chronic pain therapy. In order to find the target receptors for TDP, a docking study was performed. It was found that the molecule can bind to the NMDA receptor using electrostatic, hydrogen bonding and hydrophobic interactions.

Chemical Profiling and Bioactivity of Body Wall Lipids from Strongylocentrotus droebachiensis

The lipids from gonads and polyhydroxynaphthoquinone pigments from body walls of sea urchins are intensively studied. However, little is known about the body wall (BW) lipids. Ethanol extract (55 °C) contained about equal amounts of saturated (SaFA) and monounsaturated fatty acids (MUFA) representing 60% of total fatty acids, with myristic, palmitic and eicosenoic acids as major SaFAs and MUFAs, respectively. Non-methylene-interrupted dienes (13%) were composed of eicosadienoic and docosadienoic acids. Long-chain polyunsaturated fatty acids (LC-PUFA) included two main components, n6 arachidonic and n3 eicosapentaenoic acids, even with equal concentrations (15 μg/mg) and a balanced n6/n3 PUFA ratio (0.86). The UPLC-ELSD analysis showed that a great majority of the lipids (80%) in the ethanolic extract were phosphatidylcholine (60 μg/mg) and phosphatidylethanolamine (40 μg/mg), while the proportion of neutral lipids remained lower than 20%. In addition, alkoxyglycerol derivatives—chimyl, selachyl, and batyl alcohols—were quantified. We have assumed that the mechanism of action of body wall lipids in the present study is via the inhibition of MAPK p38, COX-1, and COX-2. Our findings open the prospective to utilize this lipid fraction as a source for the development of drugs with anti-inflammatory activity.

THE ULCEROGENIC EFFECT OF NON-STEROID ANTI-INFLAMMATORy DRUGS AND HEPATOTOXICITy OF NIMESULIDE IN EXPERIMENT ON RATS

In animal experimental model the ulcerogenic effect of non-selective and selective inhibitors of cyclooxigenase has been estimated. The all tested remedies influenced morphology of liver and mucosa of stomach. Meanwhile the reaction of each animal on non-steroidal anti-inflammatory drugs was individual. It has been elucidated that ketorolac significantly down-regulated prostaglandin E2 production in gut mucosa. Nimesulide (selective non-steroidal anti-inflammatory drug) significantly up-regulated the activity of aspartat-aminotransferase in serum of experimental rats. The mechanism of nimesulide hepatotoxicity is being discussed.