Development of a Phytomelatonin-Rich Extract from Cultured Plants with Excellent Biochemical and Functional Properties as an Alternative to Synthetic Melatonin

Abstract

Melatonin is a pleiotropic molecule with multiple and various functions. In recent years, there has been a considerable increase in the consumption of melatonin supplements for reasons other than those related with sleep (as an antioxidant, for anti-aging, and as a hunger regulator). Although the chemical synthesis of melatonin has recently been improved, several unwanted by-products of the chemical reactions involved occur as contaminants. Phytomelatonin, melatonin of plant origin, was discovered in several plants in 1995, and the possibility of using raw plant material as a source to obtain dietary supplements rich in phytomelatonin instead of synthetic melatonin, with its corresponding chemical by-products was raised. This work characterizes the phytomelatonin-rich extract obtained from selected plant material and determines the contents in phytomelatonin, phenols, flavonoids, and carotenoids. Additionally, the antioxidant activity was measured. Finally, a melatonin-specific bioassay in fish was carried out to demonstrate the excellent biological properties of the natural phytomelatonin-rich extract obtained.Antioxidants 2020, 9, 158 2 of 18 melatonin in in vivo and in vitro experimental models have appeared [12,[20][21][22]. Thus, the roles of melatonin in many tumors, both in growth, proliferation, apoptosis, and metastasis have been demonstrated [23,24]. The treatments of melatonin with chemo-and radiotherapy improves the sensitivity of tumors to nonproliferation by drugs, acting as a synergistic molecule in the control of cancer cells. Additionally, melatonin mitigates acute damage in normal cells, protecting them against drug toxicity, possibly enhancing immunomodulation [25][26][27][28]. More recently, the use of electrophile-melatonin derivatives as chemopreventive agents on cancer cells has been demonstrated, calling them new "intelligent" molecules [29]. However, without a doubt, the most known and well-studied roles of melatonin are those related with sleep regulation and circadian rhythms. In this sense, melatonin is produced by the pineal gland in the night, increasing blood melatonin levels during the first period of sleep to around 150-220 pmoles/mL, acting on sleep initiation, reducing sleep latency and fragmentation and increasing sleep duration and sleep quality [30][31][32]. Additionally, melatonin, being a powerful chronobiological molecule that contributes to the correct circadian behavior of physiological functions, acts as an internal synchronizer of the circadian sleep-wake cycle and seasonal rhythmicity. In this sense, many sleep disorders have been treated with melatonin, including delayed sleep phase syndrome, night shift-work sleep disorder, seasonal affective disorder, sleep disorders in the blind and aging, and patho-physiological disorders of children, with notable improvements in sleep quality [9,[32][33][34][35][36]. The most widespread disorder treated with melatonin is jet-lag, a de-phasing in the sleep-wake rhythms following trans-oceanic flights [37][38][39].

The Role of Adaptogens in Prophylaxis and Treatment of Viral Respiratory Infections

“…While the content of melatonin in the plants studied ranged from 0.01 to 6500 ng/g dry weight [ 283 , 286 , 287 , 288 , 289 ], assuming a therapeutic daily dose in the range from 1 to 10 g of dry herbal substance, the consumed melatonin (<0.065 mg) would be significantly lower than its therapeutic daily dose of 3–10 mg. However, these contents are in the range of daily amount (30 μg) of melatonin synthesized in adult humans.…”

Melatonin-Induced Water Stress Tolerance in Plants: Recent Advances

“…The relationship between melatonin and multiple stressor combinations is a topic to be taken into account in future research due to the complexity of the interaction of plants with diverse environmental agents. Lastly, the use of synthetic melatonin, a relatively cheap compound, or phytomelatonin-rich extracts should be an interesting approach to improving plant tolerance [ 120 , 121 ].…”

Melatonin as a plant biostimulant in crops and during post‐harvest: a new approach is needed

“…As a possible alternative, naturally obtained plant extracts rich in phytomelatonin and with a promising prospects for use as biostimulants of plant growth and development, as well as for use as a plant protector, have been proposed. 50 • Whatever the case, before melatonin can be approved by the relevant authorities for use in the improvement of agricultural production and post-harvest preservation, exhaustive studies will be required to establish the maximum levels of safety, both in plants for human use and in those intended for animal feed. • Such studies will throw light on the action mechanisms of melatonin not only in model plant species, but also in those intended as foodstuffs regarding its possible future use to minimize, to the greatest possible extent, damage to crops as a result of climate change.…”