Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties

Molecules. 2021 Oct 8;26(19):6087. doi: 10.3390/molecules26196087.


This work aims to assess the recently established anti-inflammatory and antioxidant potential of melatonin of plant origin extracted from the plant matrix as a phytomelatonin complex (PHT-MLT), and compare its activity with synthetic melatonin (SNT-MLT) when used on its own or with vitamin C. For this purpose, a COX-2 enzyme inhibitory activity test, an antiradical activity in vitro and on cell lines assays, was performed on both PHT-MLT and SNT-MLT products. COX-2 inhibitory activity of PHT-MLT was found to be ca. 6.5 times stronger than that of SNT-MLT (43.3% and 6.7% enzyme inhibition, equivalent to the activity of acetylsalicylic acid in conc. 30.3 ± 0.2 and 12.0 ± 0.3 mg/mL, respectively). Higher antiradical potential and COX-2 inhibitory properties of PHT-MLT could be explained by the presence of additional naturally occurring constituents in alfalfa, chlorella, and rice, which were clearly visible on the HPLC-ESI-QTOF-MS fingerprint. The antiradical properties of PHT-MLT determined in the DPPH test (IC50 of 21.6 ± 1 mg of powder/mL) were found to originate from the presence of other metabolites in the 50% EtOH extract while SNT-MLT was found to be inactive under the applied testing conditions. However, the antioxidant studies on HaCaT keratinocytes stimulated with H2O2 revealed a noticeable activity in all samples. The presence of PHT-MLT (12.5, 25 and 50 µg/mL) and vitamin C (12.5, 25 and 50 µg/mL) in the H2O2-pretreated HaCaT keratinocytes protected the cells from generating reactive oxygen species. This observation confirms that MLT-containing samples affect the intracellular production of enzymes and neutralize the free radicals. Presented results indicated that MLT-containing products in combination with Vitamin C dosage are worth to be considered as a preventive alternative in the therapy of various diseases in the etiopathogenesis, of which radical and inflammatory mechanisms play an important role.

Keywords: COX-2 inhibition; Chlorella vulgaris; DPPH; HaCaT cells; Medicago sativa; Oryza sativa; antiradical potential; phytomelatonin complex; synthetic melatonin.

Publication types

  • Comparative Study

MeSH terms

  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Ascorbic Acid / pharmacology
  • Cell Line
  • Cyclooxygenase 2 / metabolism*
  • Down-Regulation
  • Drug Synergism
  • Free Radicals / metabolism
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrogen Peroxide / adverse effects
  • Keratinocytes / cytology*
  • Keratinocytes / drug effects
  • Keratinocytes / metabolism
  • Melatonin / chemical synthesis
  • Melatonin / chemistry
  • Melatonin / pharmacology*
  • Phytochemicals / chemistry
  • Phytochemicals / pharmacology


  • Anti-Inflammatory Agents
  • Antioxidants
  • Free Radicals
  • Phytochemicals
  • Hydrogen Peroxide
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Melatonin
  • Ascorbic Acid