Frankincense-Functionalized Selenium Nanoparticles Provide Multimechanical Renal Protection against Aluminum Exposure

Introduction: Aluminum toxicity is a severe public health problem that affects the environment worldwide and causes nephrotoxicity via oxidative stress, inflammation, and apoptotic pathways. Frankincense extract (FE) has well-established bioactivity but a poor pharmacokinetic profile, limiting its therapeutic potential. Herein, the present work was designed to synthesize and characterize Frankincense-coated selenium nanoparticles (FE-SeNPs) as a better delivery vehicle and to investigate their protective effects against aluminum chloride (AlCl₃)-induced renal toxicity. Methods: This study extracted the Frankincense resin with water, and its total phenolic and flavonoid contents were determined by the Folin-Ciocalteu and aluminum chloride colorimetric assays, respectively. Preparation of FE-SeNPs was carried out by reacting the extract with sodium selenite under optimized conditions (60°C, pH 7.0). The synthesized particles were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Zeta potential, UV-Vis spectroscopy, and Fourier transform infrared spectrophotometry (FTIR). Acute oral toxicity was determined in accordance with OECD Guideline 423. In vivo efficacy was investigated in mice, and six groups were formed: Control, FE-SeNPs alone, AlCl₃ alone, AlCl₃ + FE, and two dosages of AlCl₃ + FE-SeNPs (53.9 and 134.75 mg/kg), all administered orally for 28 days. Biochemical observations included renal function (creatinine, urea) and lipid profile. This study analyzed parameters related to oxidative stress (MDA, SOD, GR, GSH), inflammatory cytokines (IL-1β, IL-6, and NF-κB), and apoptotic gene expression (COX-2 and caspase-9). Histological examination of renal tissue confirmed the diagnosis. results: Phytochemical profiling revealed FE contained 38.75 mg GAE/g phenolics and 8.64 mg QE/g flavonoids. FE-SeNPs were spherical (18–29 nm), monodisperse (PDI < 0.3), and stable (Zeta potential -25.6 mV), with spectroscopic data confirming Se⁰ formation and phytochemical capping. The LD₅₀ was 1500 mg/kg. In AlCl₃-intoxicated mice, high-dose FE-SeNPs markedly improved renal function (43% reduction in creatinine, 52% reduction in urea), corrected dyslipidemia, enhanced antioxidant defenses (188.5% increase in SOD, 148.7% increase in GSH), suppressed inflammation (52.4% reduction in IL-1β, 66.9% reduction in NF-κB), and downregulated COX-2 and caspase-9 expression. FE-SeNPs demonstrated 24–42% higher efficacy than native FE and preserved renal histoarchitecture. Results: Phytochemical screening indicated that the frankincense extract contained 21.42mg GAE/g of phenolics and 4.87mg QE /g of flavonoids. The FE-SeNPs were spherical (18-29nm), monodisperse with PDI < 0.3, and stable (zeta potential -25.6 mV). Spectroscopic studies also evidenced the production of selenium-element-capped plant phytochemicals. The LD₅₀ is 1500mg/kg. In the AlCl₃-induced renal mice, high dose of FE-SeNPs resulted in a significant improvement in kidney functions (decreased creatinine by 43%, urea by 52%), correction of dyslipidemia level, restoration of antioxidant defense system (increased SOD to 188.5%, GSH to 148.7%), abrogation of inflammation (reduced expression levels of IL-1β and NF-κB by 52.4% and 66.9% respectively) and also reduced expression levels of pro-apoptotic genes COX2 and caspase-9). The effects of FE-SeNPs were more pronounced than those of the crude extract, and the nanoparticles maintained normal renal architecture. Discussion: Evidence that increased selenium levels in FE-SeNPs enhanced their protective effects suggests a complementary interaction between elemental selenium and the bioactive components of frankincense. As a couple, they act against oxidative stress, inflammation, and apoptosis. Moreover, the FE-NP formulation improved the poor in vivo bioavailability of the crude extract, thereby encouraging its use. Conclusion: FE-SeNPs represent a safe and effective plant-derived nanotherapeutic approach for combating aluminum-induced nephrotoxicity. Future research will focus on efficacy assessment in chronic kidney disease models, aiming to provide a standardized natural product-based intervention for environmental heavy metal toxicity.