Chemistry, Biosynthesis and Pharmacology of Viniferin: Potential Resveratrol-Derived Molecules for New Drug Discovery, Development and Therapy

Abstract

Viniferin is a resveratrol derivative. Resveratrol is the most prominent stilbenoid synthesized by plants as a defense mechanism in response to microbial attack, toxins, infections or UV radiation. Different forms of viniferin exist, including alpha-viniferin (α-viniferin), beta-viniferin (β-viniferin), delta-viniferin (δ-viniferin), epsilon-viniferin (ε-viniferin), gamma-viniferin (γ-viniferin), R-viniferin (vitisin A), and R2-viniferin (vitisin B). All of these forms exhibit a range of important biological activities and, therefore, have several possible applications in clinical research and future drug development. In this review, we present a comprehensive literature search on the chemistry and biosynthesis of and the diverse studies conducted on viniferin, especially with regards to its anti-inflammatory, antipsoriasis, antidiabetic, antiplasmodic, anticancer, anti-angiogenic, antioxidant, anti-melanogenic, neurodegenerative effects, antiviral, antimicrobial, antifungal, antidiarrhea, anti-obesity and anthelminthic activities. In addition to highlighting its important chemical and biological activities, coherent and environmentally acceptable methods for establishing vinferin on a large scale are highlighted to allow the development of further research that can help to exploit its properties and develop new phyto-pharmaceuticals. Overall, viniferin and its derivatives have the potential to be the most effective nutritional supplement and supplementary medication, especially as a therapeutic approach. More researchers will be aware of viniferin as a pharmaceutical drug as a consequence of this review, and they will be encouraged to investigate viniferin and its derivatives as pharmaceutical drugs to prevent future health catastrophes caused by a variety of serious illnesses.

Keywords: biosynthesis; chemistry; drug discovery; oligostilbenoid; pharmacology; viniferin.

Figure 1

Different types of viniferin.

Figure 2

Chemical structures of ε-viniferin (A), δ-viniferin (B), and α-viniferin (C).

Scheme 1

Biosynthesis pathway for viniferin.

Scheme 2

Hypothesis to explain the biosynthetic process involved in oligomerization of resveratrol. Resveratrol’s (S1) oligomerization occurs via radical intermediates, S1a–c, to afford the C3–C8′ and C8–C10′ bond connections to form δ-viniferin (S2) and (+)-ε-viniferin (S3), respectively.

Figure 3

Biological attributes of viniferin against multiple conditions.

Figure 4

R2-viniferin apoptosis and inflammation-suppression mechanisms. R2-viniferin causes an increase in intracellular reactive oxygen species (ROS), thereby inhibiting the p38/ERK MAPK signaling pathway, arrests the cell cycle in G2/M and elevates the ratio of Bax/Bcl-2 proteins, predictive of apoptosis. Furthermore, the bioactive compound can also aid in lowering the level of pro-inflammatory cytokines, such as TNFα and IL-6. Abbreviations: ROS, Reactive oxygen species; MAPK, Mitogen-activated protein kinase; ERK, Extracellular signal-regulated kinase; JNK, Jun N-terminal Kinase; GSH, Glutathione; LPO, Lipid peroxides; GPx, Glutathione Peroxidase; SOD, Superoxide dismutase; CAT, Catalase; c-Myc, Cellular Homologue of Avian Myelocytomatosis Virus; NF-kB, Nuclear factor kappa B; TNFα, Tumor necrosis factor alpha; IL-6, Interleukin 6; Bcl-2, B-cell lymphoma-2; Cyt-c, Cytochrome complex; Bax, Bcl-2-associated X Protein.

Figure 5

Anti-adipogenesis activity of ε-viniferin. The ε-viniferin suppressed PPAR-γ and HMG-CoA, which resulted in an anabolic process that stimulated adipogenesis and reduced body weight, liver triglycerides, total cholesterol and blood glucose. Abbreviations: HMG-CoA, β-Hydroxy β-methylglutaryl-CoA; PCSK9, Proprotein convertase subtilisin/kexin type 9; LDLR, Low-density lipoprotein receptor; LPL, Lipoprotein lipase; VLDL, Very Low Density Lipoprotein Receptor; LDL, Low-density lipoprotein; ApoB, Apolipoprotein B.

Figure 6

The bite of a female Anopheles mosquito carrying the plasmodium parasite transmits malaria to humans. When Sporozoites are injected into the bloodstream, they travel to the hepatocytes of the liver, where they mature into schizonts that rupture and release merozoites. Merozoites invade erythrocytes in order to multiply asexually. It was found that α-viniferin inhibited plasmodium in vitro; consequently, it has the potential to be exploited and enhanced for the control of plasmodium.