Salicornia europaea L. Ethyl Acetate Fraction Induces Adipocyte Browning and Exhibits Anti-Obesity Effect in 3T3-L1 Preadipocytes.

Obesity is a widespread health issue, closely associated with metabolic conditions like Type 2 diabetes and heart disease. Salicornia europaea L. (SE), a halophytic coastal herb, has gained attention for its potential as a natural therapeutic agent. The anti-obesity activity of SE-ETAC was examined in vitro in 3T3-L1 cells treated during adipocyte differentiation. Lipid accumulation, cholesterol, triglycerides, and glycerol release were measured, while protein markers for adipogenesis and browning were analyzed by Western blot. ROS and cytokine levels were assessed using fluorescence microscopy and ELISA. Mechanistic insights were further examined using zinc protoporphyrin (ZnPP), CoPP, and compound C, and GC-MS was conducted to identify active constituents. SE-ETAC significantly inhibited adipogenesis and promoted lipolysis, reducing lipid accumulation, cholesterol, and triglyceride levels while increasing free glycerol. It also lowered reactive oxygen species (ROS) and suppressed proinflammatory cytokines (IL-6, IL-1β, and TNF-α). Mechanistically, SE-ETAC exerted its effects primarily through upregulation of the heme oxygenase-1 (HO-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, with ZnPP-mediated HO-1 inhibition nearly abolishing its efficacy. In contrast, AMP-activated protein kinase (AMPK) inhibition with compound C only partially reduced its effects. Furthermore, SE-ETAC induced adipose browning by upregulating AMPK, PRDM16, UCP1, and PGC-1α, facilitating the conversion of white adipocytes into metabolically active beige cells and enhancing energy expenditure. SE-ETAC demonstrates strong anti-obesity potential by targeting multiple mechanisms, including suppression of adipogenesis, enhancement of lipolysis, reduction of oxidative stress and inflammation, and promotion of adipose browning. These effects are mainly mediated by the HO-1/Nrf2 pathway, which showed a stronger influence on SE-ETAC's anti-obesity actions than AMPK signaling. Overall, these findings support the development of S. europaea L. as a functional, plant-based intervention for obesity and metabolic health.