Opioid Analgesic as a Positive Allosteric Modulator of Acid-Sensing Ion Channels.

Tafalgin (Taf) is a tetrapeptide opioid used in clinical practice in Russia as an analgesic drug for subcutaneous administration as a solution (4 mg/mL; concentration of 9 mM). We found that the acid-sensing ion channels (ASICs) are another molecular target for this molecule. ASICs are proton-gated sodium channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system.

Natural Inhibitors of Mammalian α-Amylases as Promising Drugs for the Treatment of Metabolic Diseases.

α-Amylase is a generally acknowledged molecular target of a distinct class of antidiabetic drugs named α-glucosidase inhibitors. This class of medications is scarce and rather underutilized, and treatment with current commercial drugs is accompanied by unpleasant adverse effects. However, mammalian α-amylase inhibitors are abundant in nature and form an extensive pool of high-affinity ligands that are available for drug discovery.

Control of postprandial hyperglycemia by oral administration of the sea anemone mucus-derived α-amylase inhibitor (magnificamide).

Diabetes mellitus is a serious threat to human health in both developed and developing countries. Optimal disease control requires the use of a diet and a combination of several medications, including oral hypoglycemic agents such as α-glucosidase inhibitors. Currently, the arsenal of available drugs is insufficient, which determines the relevance of studying new potent α-amylase inhibitors.

Dual Modulator of ASIC Channels and GABA Receptors from Thyme Alters Fear-Related Hippocampal Activity.

Acid-sensing ion channels (ASICs) are proton-gated ion channels that mediate nociception in the peripheral nervous system and contribute to fear and learning in the central nervous system. Sevanol was reported previously as a naturally-occurring ASIC inhibitor from thyme with favorable analgesic and anti-inflammatory activity. Using electrophysiological methods, we found that in the high micromolar range, the compound effectively inhibited homomeric ASIC1a and, in sub- and low-micromolar ranges, positively modulated the currents of α1β2γ2 GABA receptors.

TRPV3 Ion Channel: From Gene to Pharmacology.

Transient receptor potential vanilloid subtype 3 (TRPV3) is an ion channel with a sensory function that is most abundantly expressed in keratinocytes and peripheral neurons. TRPV3 plays a role in Ca homeostasis due to non-selective ionic conductivity and participates in signaling pathways associated with itch, dermatitis, hair growth, and skin regeneration. TRPV3 is a marker of pathological dysfunctions, and its expression is increased in conditions of injury and inflammation.

Retinoic Acid-Differentiated Neuroblastoma SH-SY5Y Is an Accessible In Vitro Model to Study Native Human Acid-Sensing Ion Channels 1a (ASIC1a).

Human neuroblastoma SH-SY5Y is a prominent neurobiological tool used for studying neuropathophysiological processes. We investigated acid-sensing (ASIC) and transient receptor potential vanilloid-1 (TRPV1) and ankyrin-1 (TRPA1) ion channels present in untreated and differentiated neuroblastoma SH-SY5Y to propose a new means for their study in neuronal-like cells. Using a quantitative real-time PCR and a whole-cell patch-clamp technique, ion channel expression profiles, functionality, and the pharmacological actions of their ligands were characterized.

Magnificamide Is a New Effective Mammalian α-Amylase Inhibitor.

Recombinant analogue of the sea anemone Heteractismagnifica peptide was obtained, and the kinetic parameters of its interaction with mammalian α-amylases were determined. Magnificamide inhibits α-amylases significantly stronger than the medical drug acarbose (Precose or Glucobay). Magnificamide is assumed to find application as a drug for prevention and treatment of metabolic disorders and type 2 diabetes mellitus.

Magnificamide, a β-Defensin-Like Peptide from the Mucus of the Sea Anemone , Is a Strong Inhibitor of Mammalian α-Amylases.

Sea anemones' venom is rich in peptides acting on different biological targets, mainly on cytoplasmic membranes and ion channels. These animals are also a source of pancreatic α-amylase inhibitors, which have the ability to control the glucose level in the blood and can be used for the treatment of prediabetes and type 2 diabetes mellitus. Recently we have isolated and characterized magnificamide (44 aa, 4770 Da), the major α-amylase inhibitor of the sea anemone mucus, which shares 84% sequence identity with helianthamide from .

[Steroidal compounds from the Pacific starfish Mithrodia clavigera and their toxic properties against human melanoma cells].

The new sulfated polyhydroxysteroid has been isolated from the Pacific starfish Mithrodia clavigera, collected from Maldives Islands and named as mitrotriol (I, Na-salt of (20S)-3beta,6alpha,20-trihydroxy-5alpha-cholest-9(11)-ene 3-O-sulfate). In addition six previously known compounds, including glycosides: echinasteroside B, granulatoside A, linckoside K, forbeside L and thornasterol sulfate A and cholesterol sulfate were isolated and identified. The structure of mitrotriol was elucidated by spectroscopic methods (mainly 2D NMR: 1H, 13C, DEPT, COSY-45, NOESY, HSQC and HMBC) and mass-spectrometry.

[Two new asterosaponins from the antarctic starfish Diplasterias brucei. Structures and cytotoxic activities].

Two new asterosaponins, diplasteriosides A and B, with the same oligosaccharide chains beta-D-Fucp-(1-->2)-beta-D-Galp-(1-->4)-[beta-D-Quip-(1-->2)]-beta-D-Quip-(1-->3)-beta-D-Quip-(1-->, linked to C6 of known genins, 3-O-sulfates of thornasterols A and B, respectively, were isolated along with the previously known asteriidoside A from the Antarctic starfish Diplasterias brucei. The structures of new compounds were elucidated by spectroscopic methods (mainly 2D NMR and mass spectrometry). The cytotoxicity of isolated asterosaponins against human colon cancer cell line HCT-116, human breast cancer cell line T-47D, and human melanoma cancer cell line RPMI-7951 was investigated.

[Three new polyhydroxysteroids from the tropical starfish Asteropsis carinifera].

Thirteen steroidal compounds including three new polyhydroxysteroids, (24R,25S)-24-methyl-5α-cholestane-3β,6α,8,15β,16β,26-hexaol, (22E,24R,25S)-24-methyl-5α-cholest-22-ene-3β,6α,8,15β,16β,26-hexaol and (22E,24R,25S)-24-methyl-5α-cholest-22-ene-3β,4β,6α,8,15β,16β,26-heptaol, have been isolated along with the previously known ten polyhydroxysteroids from the tropical starfish Asteropsis carinifera collected near the coast of Vietnam. The structures of new compounds were elucidated by spectroscopic methods (mainly 2D NMR and ESI-mass-spectrometry).

[Polar steroids from Solaster endeca starfish and the physiological activity of polar steroids from three starfish species].

Four polyhydroxylated steroids, new (20R)-5alpha-cholestan-3beta,6alpha,8,15alpha,24,26-hexaol (I) and known (20R,25S)-5alpha-cholestan-3beta6alpha,8,15beta,16beta,26-hexaol, (20R,25S)-5alpha-cholestan-3beta,6alpha,15beta,16beta,26-pentaol, and marthasterone sulfate were isolated from the Solaster endeca starfish inhabiting the Sea of Okhotsk and characterized. Steroid (I) contains a 24,26-dihydroxylated side chain, which is uncommon for starfish polyols. The isolated steroids and related metabolites from two starfish species of the Evasterias genus (in total, 15 compounds) were weakly cytotoxic in a human HeLa cell culture and some of them were inhibitors of nonspecific esterase from mouse Ehrlich carcinoma.

[Two new steroid glycosides from the Far East starfish Hippasteria kurilensis].

Two new steroid glycosides were isolated from the Far East starfish Hippasteria kurilensis collected in the Sea of Okhotsk. They were characterized as (22E,24R)-3-O-(2-O-methyl-beta-D-xylopyranosyl)-24-O-[2-O-methyl-beta-D-xylopyranosyl-(1-->5)-alpha-L-arabinofuranosyl]-5alpha-cholest-22-ene-3beta,4beta,6alpha,7alpha,8,15beta,24-heptaol (kurilensosid I) and (24S)-3-O-(2-O-methyl-beta-D-xylopyranosyl)-24-O-(alpha-L-arabinofuranosyl)-5alpha-cholestan-3beta,4beta,6beta,15alpha,24-pentaol (kurilensosid J). In addition, the earlier known glycosides linkosides F and L1, levisculoside G, forbeside L, desulfated echinasteroside A, and granulatoside A were isolated and identified.

[Steroid compounds from two pacific starfish of the genus Evasterias].

Three new steroid glycosides (evasteriosides C, D, and E), along with six known compounds, were isolated from two Pacific starfish of the genus Evasterias. Evasterioside C from E. retifera collected from the Sea of Japan was identified as (20R,22E)-3-O-(beta-D-xylopyranosyl)-24-nor-5alpha-cholest-22-ene-3beta,6beta,8,15alpha,26-pentaol 26-sulfate sodium salt.

[Steroid compounds from the Far East starfish Pteraster obscurus and the ophiura Asteronyx loveni].

Seven sulfated polyhydroxysteroids were isolated from the Far East starfish Pteraster obscurus and the ophiura (snake star) Asteronyx loveni (collected in the Sea of Okhotsk) and characterized: disodium and sodium salts of (20R)-24-methyl-2beta-hydroxycholesta-5,24(28)-diene-3alpha,21-diyl disulfate, (20R)-5alpha-cholestane-3beta,21-diyl disulfate, (20R)-3beta-hydroxy-5alpha-cholestan-21-yl sulfate, (20R)-cholest-5-ene-3beta,21-diyl disulfate, (20R)-2beta-hydroxycholest-5-ene-3alpha,21-diyl disulfate, (20R)-cholest-5-en-3beta-yl sulfate, and (20R)-5alpha-cholestan-3beta-yl sulfate. The first four compounds turned out to be new, whereas the others were identical to the known compounds. Structures of the isolated steroids were identified by two-dimensional NMR spectroscopy and other physicochemical methods.

[Trofosides A and B and other cytostatic steroid-derived compounds from the Far East starfish Trofodiscus über].

Three new polar steroids identified as trofoside A, (20R,24S)-24-O-(3-O-methyl-beta-D-xylopyranosyl)-3beta,6alpha,8,15beta,24-pentahydroxy-5alpha-cholestane, its 22(23)-dehydro derivative (trofoside B), and 15-sulfoxy-(20R,24S)-5alpha-cholestane-3beta,6beta,8,15alpha,24-pentaol sodium salt, were isolated from Trofodiscus uber starfish extracts collected in the Sea of Okhotsk. Two known compounds, trofoside A aglycone, (20R,24S)-3beta,6alpha,8,15beta,24-pentahydroxy-5alpha-cholestane, and triseramide, (20R,24R,25S,22E)-24-methyl-3beta,6alpha,8,15beta-tetrahydroxy-5alpha-cholest-22-en-27-oic acid (2-sulfoethyl)amide sodium salt, were also found. The structures of the isolated polyoxysteroids were established from their spectra.

[Monosulfated triterpene glycosides from Cucumaria okhotensis Levin et Stepanov, a new species of sea cucumbers from Sea of Okhotsk].

Three compounds were isolated from the fraction of monosulfated triterpene glycosides from Cucumaria okhotensis, a new sea cucumber species, and their structures were elucidated. First of them, okhotoside A1-1, is a new glycoside containing tetrasaccharide sugar moiety; the second, okhotoside A2-1, is a new pentaoside with a glucose residue in the second position of sugar moiety (such a structural peculiarity has been found in holothurians of the genus Cucumaria for the first time); and the third is a previously known pentaoside cucumarioside A0-1 from C. japonica.

[New steroid glycosides from the starfish Fromia milleporella].

Two new steroid glycosides from the starfish Fromia milleporella collected in the Seychelles were isolated and characterized: milleporoside A, (20R, 24R)-29-O-[3-O-methyl-beta-D-xylopyranosyl-(1-->4)-3-O-methyl-beta-D-xylopyranosyl]-24-ethyl-5alpha-cholestane-3beta,4beta,6alpha,8,15beta,16beta,29-heptaol, and milleporoside B, (20R, 24R)-(22E)-28-O-[3-O-methyl-beta-D-xylopyranosyl-(1-->4)-3-O-methyl-beta-D-xylopyranosyl]-24-methyl-5alpha-cholest-22-ene-3beta,4beta,6alpha,8,15beta,16beta,28-heptaol. The structures of the glycosides were determined from their spectra and a comparison with spectral characteristics of known compounds. These compounds exhibit a moderate cytostatic activity toward the embryos of the sea urchin Strongylocentrotus intermedius.

[Steroid compounds from far Eastern starfishes Henricia aspera and H. tumida].

Six new natural compounds were isolated from two Far Eastern starfish species, Henricia aspera and H. tumida, collected in the Sea of Okhotsk. Two new glycosylated steroid polyols were obtained from H.

[Steroidal polyols from Far Eastern starfish Henricia sanguinolenta and H. leviuscula leviuscula].

Two new asterosaponins, (20R)-3-O-beta-D-(2-O-methylxylopyranosyl)-24-propylcholest-4-ene-3 beta,6 beta, 8, 15 alpha, 16 beta, 29-hexaol (sanguinoside A) and (20R,24S)-3-O-beta-D-(2,3,4-tri-O-methylxylopyranosyl)-5 alpha-cholestane-3 beta, 4 beta, 6 beta, 8, 15 alpha, 24-hexaol (sanguinoside B), were isolated from two species of Pacific Far Eastern Starfish Henricia sanguinolenta and H. leviuscula leviuscula, collected in the Sea of Okhotsk. Both glycosides contain aglycones with pentahy-droxysteroid nuclei of similar structures, which are substituted at the 3-hydroxy group with differently methylated beta-D-xylosyl residues.

[Dot immunoassay with colloidal silver particles as a marker of specific antigen for testing human sera for brucellosis].

Whether the dot immunoassay is suitable for the detection of Brucella antibodies in human sera by using a colloidal silver-labeled Brucella specific antigen as a diagnostic tool is assessed. The antigen was the B. abortus 19BA protein polysaccharide complex isolated by Brucella acetic acid hydrolysis.