Mechanistic Insights into Systemic Targets of Magnolia Mediating Beneficial Effects in Metabolic Syndrome through Biochemical and In Situ Analyses.

Abstract

Metabolic syndrome (MetS) is characterized by a cluster of biochemical and physiological abnormalities. Healthy eating, including the consumption of natural products, holds promise for promoting health and preventing disease. Among these, Magnolia officinalis bark extract (MAGBE) is widely used as a dietary supplement due to its potent antioxidant, anti-inflammatory, and neuroprotective properties. In this study, we aimed to investigate the therapeutic potential of MAGBE in a rat model of MetS and to identify its target proteins. One group of 2-month-old male Wistar rats was supplemented with MAGBE (400 mg/kg/day, administered intragastrically) for 16 weeks alongside a high-carbohydrate diet (containing 32% sucrose) (MetS + MAGBE group). A second group received only the high-carbohydrate diet for the same period (MetS group), while a third group was maintained under standard conditions (Control group). Following confirmation of MetS induction in experimental animals, MAGBE treatment significantly improved elevated systolic and diastolic blood pressure, as well as heart rate. It also provided significant benefits in terms of oxidative stress/antioxidant balance and anti-inflammatory status, along with improved plasma levels of leptin, IL-6, IL-10, TNF-α, and leukotriene B4 (LTB₄), a product of arachidonate 5-lipoxygenase (ALOX5). Furthermore, in silico molecular docking approaches identified several potential protein targets of MAGBE, including the cannabinoid receptors CB₁ and CB₂. These receptors play central roles in regulating appetite and energy balance by modulating metabolic processes, as well as in immune function by suppressing cytokine production. Additionally, our analysis revealed strong interactions between MAGBE and the active site of ALOX5, which catalyzes the conversion of arachidonic acid into proinflammatory molecules such as LTB₄, a key mediator of inflammation and immune response. Overall, our findings highlight the beneficial antioxidant and anti-inflammatory effects of MAGBE in the prevention of MetS-associated disorders, potentially through interactions with receptors such as cannabinoid CB₁/CB₂ and ALOX5.Impact StatementIncreasing evidence supports the rapid rise in the prevalence of metabolic syndrome (MetS) across populations, contributing to the development of various organ dysfunctions and type 2 diabetes. Given the importance of healthy nutrition with natural compounds, we demonstrated the beneficial effects of Magnolia officinalis bark extract (MAGBE) even under a high-carbohydrate diet by analyzing systemic physiological parameters. MAGBE treatment restored heart function as well as plasma biomarkers related to oxidative stress/antioxidant balance and anti-inflammatory status, despite elevated blood glucose and plasma insulin levels. Using in silico molecular docking approaches, we identified several protein targets through which MAGBE may exert its effects, including cannabinoid receptors CB₁ and CB₂, central regulators of appetite, energy balance, and immune response via cytokine suppression, and the active site of ALOX5, which catalyzes the production of leukotriene B₄ (LTB₄), a key proinflammatory mediator in immune responses.