Recent Trends in Potential Therapeutic Applications of the Dietary Flavonoid Didymin

Qing Yao, Meng-Ting Lin, Yin-Di Zhu, He-Lin Xu, Ying-Zheng Zhao, Qing Yao, Meng-Ting Lin, Yin-Di Zhu, He-Lin Xu, Ying-Zheng Zhao

Abstract

Didymin (isosakuranetin 7-O-rutinoside) is an orally bioactive dietary flavonoid glycoside first found in citrus fruits. Traditionally, this flavonoid has long been used in Asian countries as a dietary antioxidant. Recent studies have provided newer insights into this pleiotropic compound, which could regulate multiple biological activities of many important signaling molecules in health and disease. Emerging data also presented the potential therapeutic application of dietary flavonoid glycoside didymin against cancer, neurological diseases, liver diseases, cardiovascular diseases, and other diseases. In this review, we briefly introduce the source and extraction methods of didymin, and summarize its potential therapeutic application in the treatment of various diseases, with an emphasis on molecular targets and mechanism that contributes to the observed therapeutic effects. The dietary flavonoid didymin can be used to affect health and disease with multiple therapeutic targets, and it is anticipated that this review will stimulate the future development of this potential dietary medicine.

Keywords: cancer; didymin; dietary flavonoid glycoside; neurodegenerative disorders; therapeutic effects.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure and basic properties of didymin. (A) The chemical structure of didymin. (B) Major physical and chemical properties.
Figure 2
Figure 2
Therapeutic application of didymin in promoting the health. The green arrow indicates the promoted effect of didymin. The red arrow indicates the inhibitory effect of didymin.
Figure 3
Figure 3
Didymin is involved in lung cancer cell signaling pathways. The main pathway of apoptosis of A549 and H460 cells induced by didymin is the Fas/Fas ligand apoptotic system. Fas is a cell surface receptor when its ligand (FasL) recognizes and activates Fas; it leads to oligomerization of the intracellular death domain and recruitment of the intracellular adaptor Fas-associated death domain (FADD). After binding, FADD can activate procaspase-8 and procaspase-10 in the death-inducing signaling complex, causing A549 and H460 cells apoptosis or death without the mediation of p53 and p21/WAF1.
Figure 4
Figure 4
Didymin affects neuroblastoma signaling pathways. Stimulating the expression of RKIP is a key role for didymin to exert its efficacy. Also, didymin inhibits N-Myc transcription, on the other hand, didymin decreases the expression levels of PI3K, Akt, vimentin, and down-regulates cyclin D1, B1, and CDK4. By staining the pathological sections of the tumor tissue, didymin not only reduced the expression of the angiogenesis marker CD31 in vivo but also inhibited the expression of the proliferation markers Ki67 and N-Myc. The blue arrow indicates normal signal transduction, the green arrow indicates enhancement, and the red arrow represents inhibition.

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