Is Phytomelatonin Complex Better Than Synthetic Melatonin? The Assessment of the Antiradical and Anti-Inflammatory Properties
Open accessAbstract
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.
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In human cell line assays, phytomelatonin had 646% stronger COX-2 inhibition than synthetic melatonin.
“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
In a human skin cell line, phytomelatonin had 100% greater efficacy in reducing cellular ROS than synthetic melatonin.
“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
In human cell line assays, phytomelatonin had 267-470% more potent free-radical scavenging ability than synthetic melatonin.
“Phytomelatonin was found to have 646% stronger COX-2 inhibition (see Figure 3), 267–470% more potent free-radical scavenging ability (see Figure 4), and 100% greater efficacy in reducing cellular ROS in a human skin cell line (see Figure 5) when compared to synthetic melatonin”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
The superior effects of phytomelatonin compared to synthetic melatonin are most likely due to other constituents found in phytomelatonin such as chlorophyll, beta-carotene, lutein, and other protective, antioxidant phytonutrients.
“most likely due to the other constituents found in phytomelatonin such as chlorophyll, beta-carotene, lutein, and other protective, antioxidant phytonutrients [values derived from the original data presented in [34].”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
A proprietary phytomelatonin made from alfalfa, chlorella powder, and rice powders contains additional phytonutrients including chlorophyll, beta-carotene, isoflavones, phytates, and saponins.
“A particular proprietary form of phytomelatonin made from alfalfa (Medicago sativa), chlorella powder (Chlorella vulgaris), and rice (Oryza sativa) powders have been shown to contain other phytonutrients in addition to phytomelatonin such as chlorophyll, beta-carotene, isoflavones, phytates, and saponins, all of which are naturally occurring in the plant matrix concentrate [34]”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
Additional constituents of phytomelatonin may completely or partially explain why it outperformed synthetic melatonin in cellular assays for inflammation and free radical scavenging.
“In fact, those additional constituents may completely or partially explain why this phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation (using COX-2 inhibition) and free radical scavenging [34]”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
The proprietary phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation using COX-2 inhibition and free radical scavenging.
“In fact, those additional constituents may completely or partially explain why this phytomelatonin outperformed synthetic melatonin in cellular assays for inflammation (using COX-2 inhibition) and free radical scavenging [34]”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
In a cell assay, vitamin C and phytomelatonin demonstrated significant increases in free radical scavenging activity compared to either by themselves.
“In a cell assay, vitamin C and phytomelatonin have been shown to demonstrate significant increases in free radical scavenging activity compared to either by themselves [34]; however, those results need to be tested in a clinical trial to be able to extrapolate those findings to humans.”
From Is Melatonin the “Next Vitamin D”?: A Review of Emerging Science, Clinical Uses, Safety, and Dietary Supplements (2022) · cites this paper as [34]
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- Authors
- Kukula-Koch, W., Szwajgier, D., Gaweł-Bęben, K., Strzępek-Gomółka, M., Głowniak, K., & Meissner, H. O.
- Affiliations
- Medical University of Lublin (PL)
- University of Life Sciences in Lublin (PL)
- Department of Cosmetology, University of Information Technology and Management in Rzeszów, 2 Sucharskiego Str., 35-225 Rzeszów, Poland
- University of Information Technology and Management in Rzeszow (PL)
- Therapeutic Research, TTD International Pty Ltd., 39 Leopard Ave., Gold Coast 4221, Australia
- Corresponding author
- Kukula-Koch, Wirginia
- ORCID
- Venue
- Molecules
- Publisher
- MDPI AG
- Published
- 2021-10-08
- Volume
- 26
- Issue
- 19
- Pages
- 6087
- ISSN
- 1420-3049 (ISSN-L)
- PMC
- PMC8512846
- OpenAlex
- W3203720000
- Cited by
- 24
- References
- 45
- Citations by year
- 2026: 6 · 2025: 6 · 2024: 8 · 2023: 2 · 2022: 2
- FWCI
- 1.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Molecules (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- TTD International (-)
- Medical University of Lublin (DS 24)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Biochemistry › Phytochemicals and Antioxidant Activities
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
- Keywords
- antioxidant activity, anti-inflammatory activity, COX-2 inhibition, free radical scavenging, vitamin C, alfalfa, Chlorella, rice, reactive oxygen species, HaCaT keratinocytes, DPPH radical scavenging, H2O2-induced oxidative stress, natural product metabolites
- MeSH terms
- Anti-Inflammatory Agents, Antioxidants, Ascorbic Acid, Cell Line, Drug Synergism, Free Radicals, Gene Expression Regulation, Humans, Hydrogen Peroxide, Melatonin, Down-Regulation, Keratinocytes, Cyclooxygenase 2, Phytochemicals
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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