Alternative Approach for Specific Tyrosinase Inhibitor Screening: Uncompetitive Inhibition of Tyrosinase by Moringa oleifera

Abstract

Tyrosinase (TYR) is a type III copper oxidase present in fungi, plants and animals. The inhibitor of human TYR plays a vital role in pharmaceutical and cosmetic fields by preventing synthesis of melanin in the skin. To search for an effective TYR inhibitor from various plant extracts, a kinetic study of TYR inhibition was performed with mushroom TYR. Among Panax ginseng, Alpinia galanga, Vitis vinifera and Moringa oleifera, the extracts of V. vinifera seed, A. galanga rhizome and M. oleifera leaf reversibly inhibited TYR diphenolase activity with IC50 values of 94.8 ± 0.2 µg/mL, 105.4 ± 0.2 µg/mL and 121.3 ± 0.4 µg/mL, respectively. Under the same conditions, the IC50 values of the representative TYR inhibitors of ascorbic acid and kojic acid were found at 235.7 ± 1.0 and 192.3 ± 0.4 µg/mL, respectively. An inhibition kinetics study demonstrated mixed-type inhibition of TYR diphenolase by A. galanga and V. vinifera, whereas a rare uncompetitive inhibition pattern was found from M. oleifera with an inhibition constant of Kii 73 µg/mL. Phytochemical investigation by HPLC-MS proposed luteolin as a specific TYR diphenolase ES complex inhibitor, which was confirmed by the inhibition kinetics of luteolin. The results clearly showed that studying TYR inhibition kinetics with plant extract mixtures can be utilized for the screening of specific TYR inhibitors.

Preventive Effects of Anthocyanins from Lyciumruthenicum Murray in High-Fat Diet-Induced Obese Mice Are Related to the Regulation of Intestinal Microbiota and Inhibition of Pancreatic Lipase Activity

“…The Lineweaver–Burk curve of inhibition kinetics of pancreatic lipase is shown in Figure 6 c. The kinetic parameters of the K m and V max values for the samples are listed in Table 3 . In the presence of the main compound and crude extract of anthocyanins, the K m values increased while the V max remained unchanged, indicating their enzymatic inhibitory type was competitive [ 18 ].…”

The Relationship between the IC50 Values and the Apparent Inhibition Constant in the Study of Inhibitors of Tyrosinase Diphenolase Activity Helps Confirm the Mechanism of Inhibition

“…Inhibition of tyrosinase by a component of Moringa oleifera extract ( Figure S12 ) has been described [ 35 ]. The type of inhibition described is uncompetitive, with an IC 50 = 121.3 ± 0.4 µg/mL and = 73 µg/mL.…”

Mechanism of skin whitening through San-Bai decoction-induced tyrosinase inhibition and discovery of natural products targeting tyrosinase

“…[2] TYR is a key rate-limiting enzyme in melanin synthesis and plays an important role in maintaining the stability of TYR on the melanosomal membrane, thus inhibiting the death of immature melanocytes. [38][39][40] Currently, common chemical-based skin-whitening products can destroy melanocytes directly but exhibit some cytotoxicity, [41,42] whereas biological skin-whitening agents are safer, yet generally have longer production cycles and are more expensive. [43] Meanwhile, natural skin-whitening products are safe, abundant, and economical [8,42,43] ; therefore, TCM formulations hold great potential in skin-whitening research.…”

“…[38][39][40] Currently, common chemical-based skin-whitening products can destroy melanocytes directly but exhibit some cytotoxicity, [41,42] whereas biological skin-whitening agents are safer, yet generally have longer production cycles and are more expensive. [43] Meanwhile, natural skin-whitening products are safe, abundant, and economical [8,42,43] ; therefore, TCM formulations hold great potential in skin-whitening research. Based on the TCM theory, the search for safe, nontoxic, and efficient TYR inhibitors derived from Chinese herbs is becoming a popular research topic with promising market prospects.…”