Justicia procumbens suppresses high-fat diet-induced weight gain in mice and adipogenesis in 3T3-L1 cells with inhibition of AKT and STAT3 phosphorylation

Obesity is a major public health concern, and the long-term use of current pharmacological therapies can be constrained by adverse effects. Therefore, natural products with potential applicability to obesity management are of growing interest. Here, we investigated the anti-obesity effects of an extract of Justicia procumbens (JE), a traditionally used medicinal plant, and its underlying mechanisms. Oral administration of JE in a high-fat diet-induced obese mouse model significantly reduced body weight gain, white adipose tissue mass, hepatic lipid accumulation, and circulating triglyceride levels. Chemical profiling of JE followed by chromatographic purification and structural characterization identified seven lignans and lignan glycosides, including two previously undescribed lignan glycosides. Network pharmacology analysis highlighted phosphorylation-related signaling pathways associated with adipogenesis, particularly PI3K-AKT and JAK-STAT signaling, as candidate mechanisms of JE action. Consistent with these predictions, JE suppressed adipogenic differentiation and attenuated AKT-p70S6K and STAT3 phosphorylation in 3T3-L1 preadipocytes and white adipose tissue. Functional screening further identified four lignan compounds with anti-adipogenic activity that differentially attenuated AKT or STAT3 phosphorylation. Collectively, our findings demonstrate that JE suppresses adipogenesis and attenuates obesity-associated metabolic abnormalities, highlighting its potential as a plant-derived candidate for obesity management.