Soybean isoflavones ameliorate ischemic cardiomyopathy by activating Nrf2-mediated antioxidant responses

Abstract

Ischemic cardiomyopathy (IC) is the major cause of heart failure. Conventional medicine has been proved ineffective with adverse effects. Soybean presents exciting adjunctive therapies and shows protective benefits for IC. However, the molecular mechanisms remain unclear. Isoflavones are the main bioactive components of soybean and may be protective against heart disease. Isoflavones were extracted by using an acidic-ethanol method and analyzed by HPLC. All patients with ischemic stroke were randomly and evenly assigned to two groups: the isoflavone group (80 mg day, n = 100) and control group (80 mg day placebo, n = 100), and the whole period of the experiment was 24 weeks. The effects of soybean isoflavone on brachial flow-mediated dilatation (FMD) were measured. HPLC fractionation shows that isoflavone extracts are mainly composed of 55% genistein, 23% daidzein, and 14% glycitein. Isoflavone therapy reduced more levels of triglyceride and LDL-c in females than in males. FMD was higher in the isoflavone group than in the control group after 24-week therapy (treatment effect 2.0%, 95% CI 0.18-3.0, P = 0.01). The baseline differences were adjusted in FMD and the isoflavone therapies were closely associated with the reduction of FMD impairment at 24 weeks (odds ratio 0.30, 95% CI 0.14-0.85, P = 0.01). The effects of isoflavone on brachial FMD were negatively associated with base FMD (r = -0.65, P < 0.01). Furthermore, isoflavone therapy caused a significant increase in the levels of erythroid-derived 2-like 2 (Nrf2), superoxide dismutase (SOD) and a significant decrease in serum levels of C-reactive protein, 8-isoprostane, malondialdehyde, interleukin-6 and tumor necrosis factor alpha. In contrast, the isoflavones had no effects on the levels of oxidation-related molecules when Nrf2 was silenced. These results suggest that soybean isoflavones ameliorate IC patients by improving their antioxidant capacities via the upregulation of Nrf2.

Effect of whole soy and isoflavones daidzein on bone turnover and inflammatory markers: a 6-month double-blind, randomized controlled trial in Chinese postmenopausal women who are equol producers

“…The non-significant findings in inflammatory markers in our trial could be due to the relatively healthy status of our participants, although they presented with slightly increased BPs. The clinical trials conducted among patients with ischemic stroke, 46 overweight and obese menopausal women, 47 or menopausal women with metabolic syndromes 48 all reported improved anti-inflammatory effects. Inflammatory status may interfere with isoflavone metabolism.…”

NRF2 as a Therapeutic Target in Neurodegenerative Diseases

“…Supplementation resulted in increased brachial flow-mediated dilation and NRF2 and SOD expression along with decreased circulating levels of C-reactive protein, 8-isoprostane, malondialdehdye, IL-6, and TNFa. The effects on circulating oxidative stress markers were lost when NRF2 was silenced (Li and Zhang, 2017; Table 2).…”

Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis

“…Nrf2 is a potential target for therapeutic purposes to treat vascular disorders induced by oxidative stress, through the overexpression of Nrf2 or its dissociation from the Keap1-Nrf2 complex, protecting against CVD (Cuadrado et al 2019;Chen and Maltagliati 2018;Ge et al 2019). Food antioxidants have been considered as adjuvants for the treatment of cardiovascular diseases due to the activation exerted on Nrf2 and antioxidant response elements (ARE) (Ooi et al 2018;Matzinger, Fischhuber, and Heiss 2018;Li and Zhang 2017).…”