Licoisoflavone B: Multifunctional Prenylated Isoflavone Blocks MAPK Pathway and Protects Gut Barrier

1. Description

Licoisoflavone B is a natural isoflavone compound isolated from plants such as licorice (Glycyrrhiza uralensis). Its molecular formula is C₂₀H₁₆O₆, and its molecular weight is approximately 352.34 Da. It appears as a white to yellow solid powder with a melting point of 180–183°C. In terms of solubility, it is soluble in DMSO (solubility approximately 40 mg/mL). It should be stored at –20°C in a sealed container, protected from light and moisture; in powder form, it has a shelf life of 3 years. This compound inhibits lipid peroxidation and the activity of cytochrome P450 enzymes (CYP2C8, CYP2C9).

2. Application

(1) Oxidative stress research: Used to investigate mechanisms for inhibiting lipid peroxidation and to evaluate antioxidant activity in copper-induced protein oxidation modification models.

(2) Drug metabolism research: As an inhibitor of cytochrome P450 enzymes (CYP2C8 and CYP2C9), it is used to study drug interactions and metabolic pathways.

(3) Phytochemical Research: As a characteristic component of plants such as licorice, it is used for quality control of traditional Chinese medicinal materials, fingerprint analysis, and screening of bioactive compounds.

(4) Antifungal Research: Used in studies to inhibit the growth of hyphae in arbuscular mycorrhizal fungi (such as Gigaspora margarita), exploring its potential role in plant-fungus interactions.

3. Main Efficacy

(1) Anti-psoriatic effects: By targeting stearoyl-CoA desaturase 1 to regulate lipid metabolic reprogramming, it inhibits the IL-17-induced upregulation of stearoyl-CoA desaturase 1 and lipid droplet accumulation in keratinocytes; it also suppresses the expression of keratin 17 and Ki67, markers of excessive keratinocyte proliferation; In a mouse model of imiquimod-induced psoriasis, it reduces Th17 cell differentiation and IL-17 production, exerting dual antiproliferative and immunomodulatory effects.

(2) Inhibition of cytochrome P450 enzyme activity: It inhibits human CYP2C8, CYP2C9, and CYP2B6. The strongest inhibitory effect is observed for CYP2C9 (IC₅₀ = 4.9 μM), exhibiting a mixed inhibition mechanism (Ki = 1.2 μM); competitive inhibition is observed for CYP2C8 (IC₅₀ = 7.4 μM, Ki = 7.0 μM); It exerts moderate inhibition on CYP2B6 via a dual mechanism of irreversible and reversible inhibition (IC₅₀ = 16.0 μM, time-dependent inhibition of 34.8%, with 76.4% residual activity after washing). It also exhibits weak inhibition of CYP3A4 (IC₅₀ = 26.7 μM).

(3) Inhibition of lipid peroxidation: It effectively inhibits lipid peroxidation reactions with a half-maximal inhibitory concentration (IC₅₀) of 2.7 μM, protecting cell membranes and proteins from oxidative damage. Its inhibitory activity is associated with the compound’s hydroxyl groups and benzopyran structure, but is weaker than that of genistein and mannitol.

(4) Potential antiviral activity: Computational simulations indicate that Licoisoflavone B exhibits strong binding affinity for the Lassa virus nucleoprotein, maintaining conformational stability during 100 ns molecular dynamics simulations. Principal component analysis further confirms this conformational stability, while density functional theory analysis reveals favorable electronic properties, and pharmacokinetic and toxicity predictions show excellent characteristics.

(5) Antifungal activity: At a concentration of 0.63 μg/well, it strongly inhibits the growth of hyphae in arbuscular mycorrhizal fungi.