Therapeutic Potential and Mechanisms of Novel Simple O-Substituted Isoflavones against Cerebral Ischemia Reperfusion

Abstract

Isoflavones have been widely studied and have attracted extensive attention in fields ranging from chemotaxonomy and plant physiology to human nutrition and medicine. Isoflavones are often divided into three subgroups: simple O-substituted derivatives, prenylated derivatives, and glycosides. Simple O-substituted isoflavones and their glycosides, such as daidzein (daidzin), genistein (genistin), glycitein (glycitin), biochanin A (astroside), and formononetin (ononin), are the most common ingredients in legumes and are considered as phytoestrogens for daily dietary hormone replacement therapy due to their structural similarity to 17-β-estradiol. On the basis of the known estrogen-like potency, these above isoflavones possess multiple pharmacological activities such as antioxidant, anti-inflammatory, anticancer, anti-angiogenetic, hepatoprotective, antidiabetic, antilipidemic, anti-osteoporotic, and neuroprotective activities. However, there are very few review studies on the protective effects of these novel isoflavones and their related compounds in cerebral ischemia reperfusion. This review primarily focuses on the biosynthesis, metabolism, and neuroprotective mechanism of these aforementioned novel isoflavones in cerebral ischemia reperfusion. From these published works in in vitro and in vivo studies, simple O-substituted isoflavones could serve as promising therapeutic compounds for the prevention and treatment of cerebral ischemia reperfusion via their estrogenic receptor properties and neuron-modulatory, antioxidant, anti-inflammatory, and anti-apoptotic effects. The detailed mechanism of the protective effects of simple O-substituted isoflavones against cerebral ischemia reperfusion might be related to the PI3K/AKT/ERK/mTOR or GSK-3β pathway, eNOS/Keap1/Nrf-2/HO-1 pathway, TLRs/TIRAP/MyD88/NFκ-B pathway, and Bcl-2-regulated anti-apoptotic pathway. However, clinical trials are needed to verify their potential on cerebral ischemia reperfusion because past studies were conducted with rodents and prophylactic administration.

Bioinformatics-Based Analysis of Key Genes in Steroid-Induced Osteonecrosis of the Femoral Head That Are Associated with Copper Metabolism

“…Among the drugs predicted to target the key genes in this study and thus to affect SLC2A1, genistein (genistein) may be one of the most promising drugs. Genistein is an isoflavone that is also known as genistein, and it is an estrogen-like compound that is widely found in legumes [ 64 ]. It can prevent bone loss in human and rat models of osteoporosis directly by acting through estrogen receptors (ERs) on bone cells and indirectly by affecting thyroid follicular cell activity [ 65 ].…”

The Contribution of Isoflavones in Menopausal Symptomatic as Alternative Treatment Option

“…In women with aromatase inhibitors, what is the action of phytoestrogens? In America they are not recommended to consume large amounts, as in Asia, but there is no concern about the usual diets [29][30][31][32].…”

Non-Volatile Compounds Involved in Bitterness and Astringency of Pulses: A Review

“…In addition, malonyl-β-glucosides such as malonyl daidzein, malonyl glycitin and malonyl genistein have been identified in soybean flakes [81]. These are derived from the malonylation of β-glucosides [121]. These malonyl-β-glucosides should contribute as much to soybean bitterness and astringency as DDMP saponin and more than the other saponins and isoflavones [81].…”