Citrus sinensis Peel as a Sustainable Source of Bioactive Phytochemicals: A Comprehensive Review of Pharmacognosy, Phytochemistry, Anti-inflammatory Mechanisms, and Therapeutic Potential

Abstract

Citrus sinensis (sweet orange) peel, a major agricultural by-product of the juice processing industry, represents an underutilized source of bioactive phytochemicals with significant therapeutic potential. This comprehensive review critically examines the pharmacognostic characteristics, phytochemical composition, traditional medicinal applications, molecular mechanisms of anti-inflammatory activity, pharmacological properties, extraction technologies, and circular bioeconomy applications of orange peel. The peel contains diverse bioactive compounds including flavonoids (hesperidin, naringin, narirutin), polymethoxyflavones (nobiletin, tangeretin, sinensetin), phenolic acids, essential oils (primarily D-limonene), carotenoids, and limonoids. These phytochemicals exert potent anti-inflammatory effects through modulation of NF-κB, MAPK, COX/LOX, and NLRP3 inflammasome pathways, while simultaneously demonstrating antioxidant, antimicrobial, anticancer, cardioprotective, hepatoprotective, neuroprotective, antidiabetic, and gastroprotective activities. Recent advances in green extraction technologies, metabolomics, and systems pharmacology have facilitated comprehensive characterization of orange peel phytochemistry. Furthermore, valorization of citrus processing waste aligns with circular bioeconomy principles and sustainable development goals. Despite extensive preclinical evidence, challenges including limited clinical validation, poor bioavailability of key flavonoids, lack of standardized extracts, and insufficient long-term safety data must be addressed before large-scale therapeutic implementation. This review identifies critical research gaps and proposes future directions for translating citrus peel bioactives into evidence-based phytopharmaceuticals, nutraceuticals, and functional health products.