Tyrosinase Inhibitory Peptides from Enzyme Hydrolyzed Royal Jelly: Production, Separation, Identification and Docking Analysis

Abstract

Tyrosinase is inextricably related to the development of Alzheimer’s disease. The effects of natural tyrosinase inhibitors on human health have attracted widespread attention. This study aimed to isolate and analyze the tyrosinase (TYR) inhibitory peptides in the enzymatic digestion products of royal jelly. We first analyzed optimal process conditions for the enzymatic digestion of royal jelly by single-factor and orthogonal experiments and then used gel filtration chromatography to obtain five fractions (D1~D5) with molecular weights ranging from 600 to 1100 Da. LC-MS/MS was applied to identify the fractions with the highest activity, and the obtained peptides were screened and molecularly docked using AutoDock Vina. The results showed that the optimal enzymatic conditions for tyrosinase inhibition rate were acid protease, enzyme addition 10,000 U/g, initial pH 4, feed-to-liquid ratio 1:4, enzymatic temperature 55 °C, and enzymatic time 4 h. The D4 fraction had the most significant TYR inhibitory activity. The IC50 values of the three new peptides with the strongest TYR inhibitory activity, TIPPPT, IIPFIF, and ILFTLL, were obtained as 7.59 mg/mL, 6.16 mg/mL, and 9.25 mg/mL, respectively. The molecular docking results showed that aromatic and hydrophobic amino acids were more favorable to occupy the catalytic center of TYR. In conclusion, the new peptide extracted from royal jelly has the potential to be used as a natural TYR inhibitory peptide in food products with health-promoting properties.

Royal Jelly: Biological Action and Health Benefits

“…According to papers [58,[138][139][140][141][142][143][144][145][146][147][148][149][150][151][152], RJ has many beneficial effects on cognition and AD pathology, including the improvement of memory, neuroprotection and regulation of neurotrophins, regulation of neurotransmission, regulation of brain energy metabolism, protection against oxidative stress and neuroinflammation, reduction of apoptosis, attenuation of Aβ-induced neurotoxicity, and improvement of hormonal and metabolic abnormalities associated with cognitive impairment (see Figure 3). Many studies have highlighted the important role of neurotropic factors in the etiology and/or development of AD and other age-related diseases, suggesting that the increased synthesis of neuropeptide factors can be a promising avenue in the prevention of these diseases.…”

“…According to papers [ 58 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 ], RJ has many beneficial effects on cognition and AD pathology, including the improvement of memory, neuroprotection and regulation of neurotrophins, regulation of neurotransmission, regulation of brain energy metabolism, protection against oxidative stress and neuroinflammation, reduction of apoptosis, attenuation of Aβ-induced neurotoxicity, and improvement of hormonal and metabolic abnormalities associated with cognitive impairment (see Figure 3 ).…”

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

“…In the melanin process, tyrosinase monophenolase firstly catalyzes the hydroxylation of L-tyrosine to yield L-DOPA, which is further oxidized into o -dopaquinone by tyrosinase diphenolase ( Figure 1 ) [ 9 , 10 , 11 , 12 ]. The produced melanin is distributed in the keratinocytes of human skin and hair; it is very important for human health [ 13 , 14 , 15 , 16 , 17 ], due to the effects of melanin in protecting human skin and eyes from damage against UV light [ 18 , 19 ]. However, overproduction of melanin results in epidermal pigmentation, thereby causing skin hyperpigmentation disorders, including melasma, age spots, and freckles [ 20 , 21 , 22 ].…”