Introduction to Bioactive Polyphenols

Polyphenols are the secondary metabolites produced by plants through shikimic acid (phenylpropanoids) and acetic acid (phenols) pathways. They are classified as flavonoids and non-flavonoids. They possess strong antioxidant and metal chelating properties, which make them effective therapeutic candidates for the treatment of neurodegenerative conditions, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, vascular dementia, etc. They are also effective therapeutic candidates for diseases such as endometriosis, cancer, cardiovascular disorders, respiratory ailments, diabetes, prostate disease, and autoimmune disorders. Their emerging popularity is due to the efficacy in modulating the molecular targets of a disease. They can specifically target several pathways, such as SIRT1/PGC-1, AMPK/NF-kB, PI3K/Akt/GSK-3β, MAPK/PI3K/AKT, ERK/CREB/BDNF, FAK/MAPK/HIF-1α axis, Nrf2/Keap1/HO1 axis, etc. Different polyphenols of therapeutic significance include apigenin, anthocyanins, genistein, resveratrol, curcumin, demethoxycurcumin, naringenin, kaempferol, ellagic acid, carnosic acid, quercetin, rosmarinic acid, licochalcone-A, luteolin, etc. They can target several microRNAs (miRNAs), such as miR-95, miR-103, miRNA 138, miRNA 155, miR-183, miR-223, etc. They are also capable of targeting other molecular messengers, such as long non-coding RNA (lncRNA), vascular endothelial growth factor (VEGF), CD31, Tie2, Ve-cadherin, Ang-1 mRNA, and protein, Ang-2 mRNA, matrix metalloproteinase (MMP-1, MMP-2, MMP-3, MMP-9), interleukin/cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-15, IL-16, IL-17A, IL-18, IL-27, IL-33, IL-37, TNF-α, NF-kB, IFN-γ, MCP-1), and receptors (COX-2, PGE2, EP4, leptin, progesterone receptor B, ER-α, ER-β). Expression of proteins such as COX-2 and leptin is also regulated. Polyphenols also target hepatocyte growth factor (HGF), urokinase-type plasminogen activator, insulin-like growth factor 1 (IGF-1), fibrinogen alpha chain, and expression of genes such as MKNK1 , TOP3A , etc. With this wide range of molecular targeting and crosstalk pathways, polyphenols are capable of controlling inflammation, pain, invasion and pathological proliferation of cells, angiogenesis, apoptosis, fibrosis, infertility, and many other pathological conditions. This envisages the scope of polyphenols in pathological conditions where allopathic medicine or surgery has limited success or shows a relapse or imposes a huge economic burden. Findings related to therapeutic efficiency encourage the synthesis of polyphenols and their enrollment in clinical trials for the development of novel therapeutic regimen against pathological conditions.