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The present study reports a cost-effective, environmentally friendly method to increase the bioavailability and bio-efficacy of <i>B. rufescens</i> stem bark extract in the biological system via functional modification as <i>B. rufescens</i> stem bark nanoparticles (BR-TO₂-NPs). The biosynthesis of BR- -NPs was confirmed by UV-visible (UV-vis) and Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and X-ray diffraction analyses. The shifts in FT-IR stretching vibrations of carboxylic and nitro groups (1615 cm⁻¹), the O–H of phenolics or carboxylic acids (3405 cm⁻¹), alkanes, and alkyne groups (2925 and 2224 cm⁻¹) of the plant extract and lattice (455) indicated successful biosynthesis of BR- -NPs. Compared with the stem bark extract, 40 ng/dL dose of BR- -NPs led to a reduction in adipogenesis and an increase in mitochondrial biogenesis-related gene expressions, <i>adiponectin-R1</i>, <i>PPARγC1α</i>, <i>UCP-1</i>, and <i>PRDM16</i>, in maturing-adipocytes. This confirmed the intracellular uptake, bioavailability, and bio-efficiency of BR-TiO₂-NPs. The lipid-lowering capacity of BR-TiO₂-NPs effectively inhibited the metabolic inflammation-related gene markers, <i>IL-6</i>, <i>TNF-α</i>, <i>LTB4-R</i>, and <i>Nf-κb</i>. Further, BR-TiO₂-NPs stimulating mitochondrial thermogenesis capacity was proven by the significantly enhanced CREB-1 and AMPK protein levels in adipocytes. In conclusion, BR-TiO₂-NPs effectively inhibited lipid accumulation and proinflammatory adipokine levels in maturing adipocytes; it may help to overcome obesity-associated comorbidities.