Isoflavone biochanin A, a novel nuclear factor erythroid 2‐related factor 2 (Nrf2)‐antioxidant response element activator, protects against oxidative damage in HepG2 cells

Abstract

Isoflavones are one group of the major flavonoids and possess multiple biological activities due to their antioxidant properties. However, a clear antioxidant mechanism of dietary isoflavones is still remained to be answered. In this study, the effects of isoflavones on the nuclear factor E2‐related factor 2 (Nrf2)–antioxidant response element (ARE) signaling pathway and the underlying molecular mechanisms were investigated. Results showed that isoflavones are potential Nrf2–ARE activators while their activities were structure dependent. Biochanin A (BCA), an O‐methylated isoflavone with low direct antioxidant activity, can effectively protect HepG2 cells against tert‐butyl hydroperoxide (t‐BHP)‐induced oxidative damage via activation of the Nrf2 signaling, and thereby the induction of downstream cytoprotective enzymes including NAD(P)H quinone oxidoreductase‐1, heme oxygenasae‐1, and glutamate‐cysteine ligase catalytic subunit. A molecular docking study revealed that BCA could directly bind into the pocket of Kelch‐like erythroid cell‐derived protein with CNC homology (ECH)‐associated protein 1 (Keap1), a cytoplasmic suppressor of Nrf2, to facilitate Nrf2 activation. The upstream mitogen‐activated protein kinase (MAPK) pathways were also involved in the activation of Nrf2 signaling. These findings indicate that the protective actions of dietary isoflavones against oxidative damage may be at least partly due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2−ARE signaling pathway.

Biochanin A alleviates gingival inflammation and alveolar bone loss in rats with experimental periodontitis

“…The current study revealed that BA treatment significantly improved the number of Nrf2-positive cells in the alveolar bone. These results are consistent with a recent study by Liang et al (39), where BA was an effective Nfr2 activator. In addition, BA has the capability to counteract oxidative damages induced by LPS (33,40), high-fat diet (12) and D-galactosamine (41).…”

Antibacterial mechanism of Biochanin A and its efficacy for the control of Xanthomonas axonopodispv.glycines in soybean

“…10,11 Although soybean has been reported to produce Biochanin A, the concentration of this isoflavonoid is under the quantification limits, indicating that soybean can synthesize Biochanin A only in very low concentration. 12 Biochanin A has recently emerged as a multi-target and multi-functional compound to human cell, 13 with anti-inflammatory, 14 anticancer, 15 neuroprotective, 16 antioxidant, 17 hepatoprotective 18 and anti-COVID-19 19 properties. Despite these important advances, the role of Biochanin A in plant defence and its potential applications in plant disease management remain almost unexplored.…”

Perspectives Regarding the Role of Biochanin A in Humans

“…BCA may occur as an aglycon and can also be used as a hormone alternative therapy. BCA plays complex roles in the regulation of multiple biological functions by binding DNA and some specific proteins or acting as a competitive substrate for some enzymes (Roberts et al, 2004; Křížová et al, 2019; Liang et al, 2019; Luo et al, 2019). BCA is the methylated precursor of the isoflavone genistein (GEN), which is another well-studied isoflavone.…”