In Vitro Studies on Phytochemical Content, Antioxidant, Anticancer, Immunomodulatory, and Antigenotoxic Activities of Lemon, Grapefruit, and Mandarin Citrus Peels

Asian Pac J Cancer Prev. 2016;17(7):3559-67.


Background: In recent years, there has been considerable research on recycling of agroindustrial waste for production of bioactive compounds. The food processing industry produces large amounts of citrus peels that may be an inexpensive source of useful agents.

Objective: The present work aimed to explore the phytochemical content, antioxidant, anticancer, antiproliferation, and antigenotxic activities of lemon, grapefruit, and mandarin peels.

Materials and methods: Peels were extracted using 98% ethanol and the three crude extracts were assessed for their total polyphenol content (TPC), total flavonoid content (TFC), and antioxidant activity using DPPH (1, 1diphenyl2picrylhydrazyl). Their cytotoxic and mitogenic proliferation activities were also studied in human leukemia HL60 cells and mouse splenocytes by CCK8 assay. In addition, genotoxic/ antigenotoxic activity was explored in mouse splenocytes using chromosomal aberrations (CAs) assay.

Results: Lemon peels had the highest of TPC followed by grapefruit and mandarin. In contrast, mandarin peels contained the highest of TFC followed by lemon and grapefruit peels. Among the extracts, lemon peel possessed the strongest antioxidant activity as indicated by the highest DPPH radical scavenging, the lowest effective concentration 50% (EC50= 42.97 ?g extract/ mL), and the highest Trolox equivalent antioxidant capacity (TEAC=0.157). Mandarin peel exhibited moderate cytotoxic activity (IC50 = 77.8 ?g/mL) against HL60 cells, whereas grapefruit and lemon peels were ineffective antileukemia. Further, citrus peels possessed immunostimulation activity via augmentation of proliferation of mouse splenocytes (Tlymphocytes). Citrus extracts exerted noncytotoxic, and antigenotoxic activities through remarkable reduction of CAs induced by cisplatin in mouse splenocytes for 24 h.

Conclusions: The phytochemical constituents of the citrus peels may exert biological activities including anticancer, immunostimulation and antigenotoxic potential.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antioxidants / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Citrus / chemistry*
  • Citrus paradisi / chemistry*
  • Flavonoids / pharmacology
  • Fruit / chemistry*
  • HL-60 Cells
  • Humans
  • Immunization / methods
  • Mice
  • Phytochemicals / pharmacology*
  • Plant Extracts / pharmacology*
  • Polyphenols / pharmacology
  • T-Lymphocytes / drug effects


  • Antineoplastic Agents
  • Antioxidants
  • Flavonoids
  • Phytochemicals
  • Plant Extracts
  • Polyphenols