Flavonoids for treatment of Alzheimer's disease: An up to date review.



Flavonoids, an omnipresent class of polyphenolic compounds, are commonly present in fruits, vegetables, and plant-derived beverages (Panche et al., 2016[36]). To date, more than 9000 structural variants of flavonoids have been identified (Williams et al., 2004[50]), most of which are important pigments that impart color to flowers to attract animal pollinators. Flavonoids protect against ultraviolet radiation, organisms that cause plant diseases, and herbivores. In addition, flavonoids play a role as physiological regulators, chemical messengers, and cell cycle inhibitors (Yonekura-Sakakibara et al., 2019[54]).

Flavonoids are chemically composed of two aromatic ring systems (A and B rings) and a heterocyclic ring (C), forming a 15-carbon skeleton structure. This carbon structure can be abbreviated as C6-C3-C6 (Kumar and Pandey, 2013[26]). Based on the degree of unsaturation and substitution pattern, flavonoids can be divided into different subgroups, including anthocyanins, chalcone flavanols or catechins, flavanones, flavanonols, flavones, flavonols, and isoflavonoids (Santos-Buelga and Feliciano, 2017[38]).

Owing to the numerous inevitable biotic properties of flavonoids, they might act as anticancer, antioxidant, anti-inflammatory, antimicrobial, and antiviral agents. In addition, flavonoids have shown neuroprotective and cardioprotective effects in many clinical trials (Ullah et al., 2020[45]; Terahara, 2015[42]; Nijveldt et al., 2001[33]). Natural substances are considered to have robust protective effects against several unidentified diseases. Recently, it has been proven that they are most effective for the treatment of neurodegenerative diseases, including Alzheimer's disease (AD). Among the different natural compounds, flavonoids are used for their neuroprotective effects. In this review, we highlight the therapeutic potential of flavonoids, especially for AD. We report the current findings on the biological and pharmacological activities of flavonoids for the treatment of AD (Table 1(Tab. 1); References in Table 1: Ali et al., 2018[1]; Ano et al., 2019[2]; Bao et al., 2020[3]; Bortolotto et al., 2020[4]; Chakraborty et al., 2016[5]; Chen et al., 2020[6][7]; Currais et al., 2018[8]; Daily et al., 2020[9]; Diaz et al., 2019[10]; Dourado et al., 2020[11]; Guo, et al., 2017[12]; Hajizadeh Moghaddam et al., 2020[13]; He et al., 2018[14]; Heysieattalab and Sadeghi, 2020[15]; Hofmann et al., 2020[16]; Huang et al., 2018[17], 2019[18], 2020[19]; Ide et al., 2018[20]; Iida et al., 2015[21]; Inoue et al., 2019[22]; Jin et al., 2019[23]; Khan et al., 2019[24]; Kouhestani et al., 2018[25]; Li et al., 2019[27], 2020[28]; Lu et al., 2018[29]; Masood et al., 2020[30]; Meng et al., 2018[31]; Nakagawa and Ohta, 2019[32]; Oladapo et al., 2021[34]; Pacheco et al., 2018[35]; Ramezani et al., 2016[37]; Sohanaki et al., 2016[39]; Soleimani Asl et al., 2019[40]; Sonawane et al., 2019[41]; Thummayot et al., 2018[43]; Uddin and Kabir, 2019[44]; Wang et al., 2015[47], 2016[48], 2017[46]; Wei et al., 2019[49]; Xia et al., 2019[51]; Xian et al., 2012[52]; Yan et al., 2019[53]; Yu et al., 2015[56], 2019[55]; Zhao et al., 2019[57]; Zhong et al., 2019[58]; Zhou et al., 2020[59]; Zhu and Wang, 2015[60]).

Table 1

Pharmacological and biochemical activities of flavonoids for the treatment of Alzheimer's disease reported recently

Acknowledgements

This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3A9A5919548).

Conflict of interest

The authors declare no conflict of interest.