Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon. Production of interleukins (IL) 1β, tumor necrosis factors (TNF) α, nuclear factor (NF) κB, activator protein (AP) 1, macrophage inflammatory protein (MIP), toll-like receptor (TLR) 4, and several other harmful cytokines are often evaluated for clinical significance in hepatic complications as recommended by much evidence. On the other hand, transforming growth factors (TGF) β, matrix metalloproteinases, and extracellular matrix- (ECM-) mediated hepatic fibrosis have been identified as major targets. However, modern medicines rely not only on synthetic compounds but also on herbal sources. Traditional therapies are gradually being acknowledged due to having fewer ADRs and other complications. Citrus fruits are generally seen all over the world and offer a great value as seasonal fruit. Several important biologically active components such as polyphenols, flavonols, carbohydrates, amino acids, and oils have been isolated from this family. Evidence suggests that polyphenol-based therapies have already proved their high potency against the production of inflammatory cytokines and profibrogenic factors. Along with the prevention of oxidative stress, these molecules hinder the generation of free radicals. Furthermore, polyphenols induce several defensive genes such as Nrf2, AMPK, superoxide dismutase, catalase, heme oxygenase (HO), Sirt1, and other important functional proteins to serve mitochondrial biogenesis. Therefore, this review will try to establish some molecular theories between citrus polyphenols and liver dysfunctions.
