Innovative Anti-Obesity Strategy: Moringa peregrina Seed Extract-Stabilized Selenium Nanoparticles for Comprehensive Metabolic Health Improvement
The obesity epidemic poses a global challenge that requires safer, natural- based therapeutic alternatives. Here, we present a nanobiotechnology strategy by employing Moringa peregrina (MP) seed extract for the energy-efficient synthesis of stabilized selenium nanoparticles (MPS-SeNPs) and demonstrate their anti-obesity efficacy. MPS-SeNPs were biosynthesized using Moringa peregrina seed extract and characterised by UV-Vis spectroscopy, FT-IR, TEM, and DLS techniques. Phytochemical profiling was performed by HPLC. The LD₂⁽ for acute oral toxicity was determined in mice. For the efficacy studies, male albino mice were fed a high-fat diet (HFD) for 8 weeks and treated with MPS-SeNPs (44.60 or 111.50 mg/kg), metformin (500 mg/kg), or vehicle, respectively. Body weight, hepatic lipids (NEFA, TC, TG), liver enzymes (ALT, AST), inflammatory markers (MCP- 1, COX-2), insulin signaling proteins (PI3K, GLUT2), as well as lipogenic enzymes (FAS, ACC) were also determined. Liver histopathology and gut microbiota composition were also assessed. MPS-SeNPs exhibited uniform size (49.30 ± 2.26 nm), while successful conjugation of phytochemicals was confirmed using FT-IR. High concentrations of quercetin (14.54 mg/g), kaempferol (9.43 mg/g), chlorogenic acid (6.89 mg/g), rutin (6.18 mg/g), and β-sitosterol (4.86 mg/g) were detected by HPLC. Acute toxicity was low (LD₂⁽ > 2000 mg/kg). High-dose MPSSeNPs (111.50 mg/kg) significantly decreased body weight gain in HFD-fed mice by 34.1% (p <0.001), corrected the hepatic lipids (NEFA ↓52.5%; TC ↓50.0%; TG ↓62.5%), and restored liver enzyme levels to those of controls (ALT, AST). Mechanistically, MPS-SeNPs suppressed lipogenic enzymes (FAS ↓57%, ACC ↑39% normalization), restored insulin signaling (PI3K/Akt, GLUT2), and inhibited inflammation (MCP-1 ↓47%, COX-2 fully normalized). These effects were comparable to metformin. The excellent activity of MPS-SeNPs is likely due to the synergistic effects of the bioactive phytoconstituents of M. peregrina, including flavonoids and the selenium core. This synergy concurrently modulates three cardinal pathogenic cascades: de novo lipogenesis, insulin resistance, and chronic low-grade inflammation. Moreover, the green synthesis process enhances the stability, bioavailability, and intrinsic antioxidant properties of the formulation. These results position plant-stabilized nanoparticles as an intriguing avenue for the formation of natural product-based therapeutics against metabolic disorders. MPS-SeNPs represent a promising multitargeted nanotherapeutic against obesity, with lipid metabolism modulations, enhanced insulin sensitivity, and reduced inflammation and gut microbiota representing target processes to exert their anti-obesity effects. This study suggests that the combined action of selenium and Moringa phytochemicals, as well as a favorable safety profile, provides a basis for further development of MPS-SeNPs for clinical use in metabolic diseases.