Molecular Effects of Baicalein in Hct116 Cells and Caenorhabditis elegans: Activation of the Nrf2 Signaling Pathway and Prolongation of Lifespan

Abstract

Baicalein is a major compound of extracts derived from Scutellaria baicalensis Lamiaceae, which are used as food supplements. Baicalein possesses a high radical scavenging activity and decreases intracellular reactive oxygen species in Hct116 human colon carcinoma cells and in Caenorhabditis elegans . It activates Nrf2, a key transcription factor that binds to the antioxidant responsive element (ARE): Baicalein causes a nuclear accumulation of Nrf2, increases ARE-dependent luciferase activity, and enhances the expression of heme oxygenase-1 in Hct116 cells. Additionally, accumulation of the Nrf2 homologue SKN-1 in nuclei of intestinal cells of C. elegans was observed. Lifespan analysis revealed that baicalein extends the mean, median, and maximum lifespans of the nematode by 45, 57 and 24%, respectively. Because SKN-1 activation is associated with prolongation of lifespan, the results suggest that baicalein increases the lifespan of C. elegans by activation of the Nrf2/SKN-1 signaling pathway.

Baicalein Inhibits Proliferation Activity of Human Colorectal Cancer Cells HCT116 Through Downregulation of Ezrin

“…Other compounds derived from the Chinese herb, such as wogonin [24], luteolin [25] and negletein [26], can have a synergistic effect on prevention and suppression of CRC as well. Signaling pathways are involved in its function of anti-CRC, including activation of the Nrf2 signaling pathway [27] and attenuation of the MAPKs and PI3K-Akt activation [28]. As for other common malignant tumors, several reports have revealed various kinds of signal paths mediated by baicalein [8,29,30].…”

Synthesis and biological evaluation of a novel baicalein glycoside as an anti-inflammatory agent

“…It has been reported that baicalein activates Nrf2, a key transcription factor that regulates inflammation, and enhances the expression of HO-1 in Hct116 human colon carcinoma cells (Havermann et al, 2013). To examine the effect of BG on Nrf2 activation, we took RAW 264.7-derived reporter cells that harbors a 1-kb long NQO-1 proximal promoter fused with the firefly luciferase gene, and treated them with BG (5-40 mM) for 8 h. Total cell lysate prepared for a luciferase reporter assay showed increased luciferase activity in a dose-dependent manner, suggesting the possibility that BG activates Nrf2 (data not shown).…”

Caenorhabditis elegansas Model System in Pharmacology and Toxicology: Effects of Flavonoids on Redox-Sensitive Signalling Pathways and Ageing

“…Baicalein, containing an additional OH group in the A ring, showed the most powerful effects. This flavonoid (100  μ M) increased mean, median, and maximum life span by 45, 57, and 24% [39]. …”

“…Various types of flavonoids were able to diminish oxidative stress levels induced by heat [37–39, 48, 61, 70]. For example, epicatechin treatment decreased intracellular levels of ROS by 24 to 28% [61].…”