A Standardized Composition Comprised of Extracts from Rosmarinus officinalis, Annona squamosa and Zanthoxylum clava-herculis for Cellulite

Background: Cellulite, characterized by changes in the skin morphology presented as dimpled or puckered skin appearance, is highly prevalent among postadolescent women. Cellulite management ranges from topical cream applications to invasive procedures. While some interventions showed improvements in physical appearances of affected areas, so far, none have reversed the condition to a full recovery. These unsuccessful measures signify the intricate nature of cellulite etiology highlighting its complexity leading to the possibility for a combination treatment approach to target multiple mechanisms. Materials and Methods: We screened our plant library for extracts that reduce cellular lipid accumulation, improve microcirculation, possess high total antioxidant capacity, significant anti-platelet aggregation, and anti-inflammatory activities using lipid accumulation assay in 3T3-L1 cells, Croton oil-induced hemorrhoid test in rats as a model for microcirculation, anti-platelet aggregation assay, nitric oxide (NO) inhibition assay, and 1,1-diphenyl-2-picrylhydrazyl assay. Results: Three known botanicals such as Rosemary officinalis, Annona squamosa and Zanthoxylum clava-herculis were identified as lead extracts in these tests. Treatment of 3T3 cell with A. squamosa at 1 μg/ml resulted in 68.8% reduction in lipid accumulation. In croton oil-induced hemorrhoid study, Z. clava-herculis reduced the recto-anus coefficient by 79.6% at 6 mg/kg indicating improvement in microcirculations. Similarly, R. officinalis caused inhibition of 82%, 71.8%, and 91.8% in platelet aggregation, NO production and free radical generation at 31.25 μg/ml, 6.2 μg/ml, and 40 μg/ml concentrations suggesting its anti-oxidant, and anti-inflammatory activities. Conclusions: Data depicted here suggest that formulation of these well-known botanicals at a specific ratio perhaps may yield a composition with a much wider spectrum of mechanisms of actions to impact the multiple pathways involved in cellulite onset, continuation, or exacerbations. Abbreviations Used: GMP: Good Manufacturing Practice; CA: Carnosic acid; NF-kB: nuclear factor-kB; HPLC: high-performance liquid chromatography; EtOH: Ethanol; DMEM: Dulbecco's modified Eagle's medium; FBS: fetal bovine serum; SD: Sprague Dawley; RAC: recto-anus coefficient; LPS: Lipopolysaccharide; DPPH: 1,1-diphenyl-2-picryl-hydrazyl; TNF-α: tumor necrosis factor; NO: Nitric oxide