vitisin-a and epsilon-viniferin

Resveratrol was shown to exert anti-inflammatory effects in experimental models of psoriasis. Several natural oligomers of resveratrol have been extracted from plants. We investigated the antipsoriatic activity of topical administration of resveratrol oligomers and explored the effect of the number of resveratrol subunits on skin absorption to establish the structure-permeation relationship (SPR). Three oligomers, ε-viniferin (dimer), ampelopsin C (trimer) and vitisin A (tetramer), extracted from Vitis thunbergii root were compared to the resveratrol glycoside polydatin. Delivery to porcine skin was assessed in vitro using the Franz cell. Keratinocytes activated with imiquimod (IMQ) were utilized to evaluate cytokine/chemokine inhibition. Topical application of resveratrol and oligomers was characterized in vivo by assessing cutaneous absorption, skin physiology, proinflammatory mediator expression, and histopathology in IMQ-treated mice. Skin deposition decreased as the molecular size and lipophilicity of the permeants increased. Resveratrol exhibited highest absorption, followed by ε-viniferin. The monomers resveratrol and polydatin exhibited higher flux across skin than the larger oligomers. In silico modeling revealed the permeants that strongly interacted with stratum corneum (SC) lipids exhibited lower transport to viable skin and the receptor compartment. In vitro, resveratrol and its derivatives had comparable ability to inhibit IMQ-induced IL-1β, IL-6, and CXCL8 secretion in activated keratinocytes. In vivo, topically applied ε-viniferin accumulated at higher levels than resveratrol (0.067 versus 0.029 nmol/mg) in psoriasis-like mouse skin with impaired barrier capacity. Topical ε-viniferin alleviated psoriasiform symptoms and reduced IL-23 secretion (by 58% vs. 37%) more effectively than resveratrol. ε-Viniferin has potential as an anti-inflammatory agent to prevent or treat psoriasis.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Benzofurans; Chemistry, Pharmaceutical; Chemokines; Cytokines; Flavonoids; Glucosides; Inflammation Mediators; Keratinocytes; Mice; Phenols; Plant Extracts; Psoriasis; Resveratrol; Skin Absorption; Stilbenes; Swine

Hepatitis C virus (HCV) infection is responsible for various chronic inflammatory liver diseases. Here, we have identified a naturally occurring compound with anti-HCV activity and have elucidated its mode of antiviral action.. Luciferase reporter and real-time RT-PCR assays were used to measure HCV replication. Western blot, fluorescence-labelled HCV replicons and infectious clones were employed to quantitate expression levels of viral proteins. Resistant HCV mutant mapping, in vitro NS3 protease, helicase, NS5B polymerase and drug affinity responsive target stability assays were also used to study the antiviral mechanism.. A resveratrol tetramer, vitisin B from grapevine root extract showed high potency against HCV replication (EC50 = 6 nM) with relatively low cytotoxicity (EC50 >10 μM). Combined treatment of vitisin B with an NS5B polymerase inhibitor (sofosbuvir) exhibited a synergistic or at least additive antiviral activity. Analysis of a number of vitisin B-resistant HCV variants suggested an NS3 helicase as its potential target. We confirmed a direct binding between vitisin B and a purified NS3 helicase in vitro. Vitisin B was a potent inhibitor of a HCV NS3 helicase (IC50 = 3 nM). In vivo, Finally, we observed a preferred tissue distribution of vitisin B in the liver after i.p. injection in rats, at clinically attainable concentrations. Conclusion and Implications Vitisin B is one of the most potent HCV helicase inhibitors identified so far. Vitisin B is thus a prime candidate to be developed as the first HCV drug derived from natural products.

Topics: Animals; Benzofurans; Biological Products; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Drug Synergism; Flavonoids; Hepacivirus; Humans; Phenols; Protein Binding; Rats; Resveratrol; RNA Helicases; Sofosbuvir; Stilbenes; Tissue Distribution; Viral Nonstructural Proteins; Virus Replication

Biofilm formation is closely related to bacterial infection and is also a mechanism of antimicrobial resistance. Hence, the antibiofilm approach provides an alternative to an antibiotic strategy. In this study, the antibiofilm activities of resveratrol (1) and five of its oligomers, namely, ε-viniferin (2), suffruticosol A (3), suffruticosol B (4), vitisin A (5), and vitisin B (6), were investigated against enterohemorrhagic Escherichia coli O157:H7 and Pseudomonas aeruginosa PA14. Vitisin B (6), a stilbenoid tetramer, was found to inhibit biofilm formation by the two bacteria the most effectively and at 5 μg/mL inhibited E. coli O157:H7 biofilm formation by more than 90%.

Topics: Anti-Bacterial Agents; Benzofurans; Biofilms; Escherichia coli O157; Molecular Structure; Phenols; Pseudomonas aeruginosa; Resveratrol; Stilbenes

This study aimed to investigate the antihypertensive effects of ethanolic extracts (EE) and compounds isolated from the small-leaf grape (Vitis thunbergii var. taiwaniana, VTT). The highest antiangiotensin-converting enzyme (anti-ACE) was found in stem-EE (IC50 was 69.5 μg/mL). In spontaneously hypertensive rats (SHRs), stem-EE effectively reduced blood pressure 24 h after administration of a single oral dose or when administered daily for 4 weeks. The isolated compounds, including (+)-vitisin A, ampelopsin C, and (+)-ε-viniferin, were shown to have anti-ACE and vasodilating effects against phenylephrine-induced tensions in an endothelium-intact aortic ring, with (+)-vitisin A being the most effective compound. Compared to control rats, SHRs showed significantly reduced systolic and diastolic blood pressures 24 h after a single oral dose of (+)-vitisin A (10 mg/kg) or captopril (2 mg/kg). These results suggest that the development of functional foods with VTT extracts may be beneficial for regulating blood pressure.

Topics: Administration, Oral; Angiotensins; Animals; Antihypertensive Agents; Benzofurans; Blood Pressure; Captopril; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Ethanol; Flavonoids; Male; Phenols; Plant Extracts; Plant Leaves; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Sprague-Dawley; Stilbenes; Vitis

To study the chemical constituents of oligostilbenes from Vitis davidii.. Compounds were isolated with polystyrene resin RA, silica gel and C18 column chromatography. The structures were elucidated by means of spectroscopic evidence.. Seven compounds were obtained and identified as resveratrol, heyneanol A, ampelopsin E, amurensin B, (+)-epsilon-viniferin, vitisin A and amurensin G.. All the compounds were isolated from this plant for the first time.

Topics: Benzofurans; Phenols; Plants, Medicinal; Resveratrol; Stilbenes; Vitis