Valorization of Citrus Wastes into Medicinally Active Anti-acne Pharmaceutical Preparation (RSPG 2.2)

Abstract

In order to protect the planet and achieve sustainability, several approaches are suggested to reduce waste production and avoid too many different faces of pollution such as recycling and valorization. Valorization is to try to enhance the price, value, or status of products by organized and usually governmental action and our aim in this project is to valorize citrus waste and produce a pharmaceutical product for the treatment of acne. Citrus waste is estimated to be about15 million tons annually worldwide, including peels, seeds and fruit pulps. With Egypt producing around three million ton of citrus waste annually, valorization of citrus wastes into pharmaceutical product is considered a great tool to initiate and achieve sustainable production in the pharmaceutical field. Acne is an inflammatory skin disorder. The most common bacteria causing acne is Propionibacterium acne which triggers the inflammatory response in the skin causing swelling and redness, so the key route for treating acne is to inhibit the growth of this bacteria and treat inflammation. Many plants are known to have anti inflammatory such as Citrus fruits. Objective: The aim of the study is the valorization of the waste products of various Citrus fruits, exploring their chemical composition and evaluates their use in treatment of acne. Methods: The anti-inflammatory effects of the ethanolic extract of different citrus peels were tested in vitro on lipopolysaccharide(LPS)- induced inflammation in raw 264.7 cell model. The antimicrobial effect was evaluated against Propionibacterium acne and the metabolic profiling of the active extracts was performed using UPLC-MS/MS analysis. The ethanolic extract of Bitter orange is accordingly was chosen to be formulated as nano preparation to be tested in vivo. Results: It was found that bitter orange (Citrus aurantium), sweet orange (Citrus sinensis) and lemon (Citrus limon) peels extracts were the most effective as they inhibit NO and PEG2 production. Also, RT-PCR showed that the three extracts had down regulated the gene expression of COX2 and iNOS. These results were confirmed by the Western blotting assay. Thus, the three extracts were chosen for further study of the antibacterial activity against Propionibacterium acne, where the bitter orange extract showed the lowest MIC 1.875 mg/ml, while lemon and orange extracts had higher MIC (30 and 15 mg/ml). The metabolic profiling of bitter orange extract showed the VI identification of many flavonoids such as hesperidin and vicenin II. Bitter orange in-vivo testing shows promising results where the medicated nano-micelles in the mice of group four showed comparable activity to the Erythromycin. Conclusion: Bitter Orange (Citrus aurantium) shows promising in-vivo anti acne activity