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Molecules 2020, 25, 4613 6 of 36 Polyphenol Chrysin Cancer Type/ Cell Line HCT-116; HepG2; Hep 3B A549 Table 2. Cont. Major Outcomes References The combination of chrysin and cisplatin promoted apoptosis of HepG2 cells in both dose- and time- dependent manners Reinforce the therapeutic efficacy of DTX and mitigate [108] edema [107] 2.4. Neuroprotective Activity With the continuous improvement of medical standards, the average life span of humans has been significantly extended, but correspondingly, diseases related to brain aging caused by an aging population have also increased significantly, such as cognitive and neurodegenerative diseases [109]. Neurodegenerative diseases, characterized by the progressive loss of functions of a large number of neurons and neural stem cells, leading to sensory deficits and cognitive impairments, are a type of progressive, disabling and severely fatal complex disease [110]. Studies have found that all neurodegenerative diseases share a common cellular and molecular mechanism, that is, oxidative stress accumulation, inflammation, protein misfolding and aggregation, neurotoxicity, etc. [111–113]. In addition to genetic and environmental factors, the increase of oxidative stress in cells is considered to be the main cause of neurodegenerative diseases [114,115]. A large number of studies have shown that polyphenols can inhibit the increase of oxidative stress through many mechanisms. For example, polyphenols can enhance the activity of detoxification and antioxidant enzymes by activating the Nrf2 pathway [116–118]. They can also regulate the activity of reactive oxygen generation enzymes and modify the structural integrity and metabolic efficiency of mitochondria [119,120]. Inflammation is also the cause of such diseases. Polyphenols can regulate the expression of pro-inflammatory genes such as nitric oxide, lipoxygenase, cyclooxygenase (COX) and chemokines [115,121]. In addition, the neuroprotective effect of polyphenol compounds is also attributed to the reduction of amyloid aggregation and/or the formation of precursors. Curcumin has been shown to have anti-amyloidosis activity, and can not only inhibit the formation of new β-aggregates, but also decompose already formed aggregates [122]. Pomegranate polyphenols, myricetin, luteolin and honokiol variably altered the morphology of Aβ aggregation, the flavonoids all bound in a similar hydrophobic region of the amyloid pentamer and exhibited the most obvious inhibitory effect on Aβ1-42 aggregation [123]. 3. Nanoformulations for Loading and Delivery of Polyphenols As mentioned earlier, polyphenols have been widely concerned and applied in many fields due to various beneficial functions, but some of their restrictive factors have greatly hindered their applications, in vivo and in clinic. These factors mainly include low solubility, permeability, and bioavailability. In order to overcome the limitations, nanocarriers have been developed extensively [124]. The unique physicochemical properties of nanocarriers, such as high loading, drug protection and tumor cell penetration, provide preconditions for the delivery of polyphenols and other drugs [125,126]. At present, the delivery systems like phytosomes, liposomes, niosomes, protein-based nanoparticles, polymer nanoparticles, microspheres and emulsions have emerged as attractive options for controlled bioactive systems [127,128]. 3.1. Phytosome Phytosome is a relatively stable complex formed by electrostatic interaction between phospholipids, (mainly phosphatidylcholine), and plant extracts (mainly polyphenols) (Figure 2) [129]. This electrostatic effect mainly includes ion-dipole, dipole-dipole and hydrogen bonding [130].PDF Image | Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols
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