The flavonoid myricetin reduces nocturnal melatonin levels in the blood through the inhibition of serotonin N-acetyltransferase.
Melatonin is secreted during the hours of darkness and is thought to influence the circadian and seasonal timing of a variety of physiological processes. AANAT, which is expressed in the pineal gland, retina, and various other tissues, catalyzes the conversion of serotonin to N-acetylserotonin and is the rate-limiting enzyme in the biosynthetic pathway of melatonin. The compounds that modulate the activity of AANAT can be used to treat patients with circadian rhythm disorders that are associated with specific circadian rhythm alterations, such as shift work disorder. In the present study, we screened modulators of AANAT activity from the water extracts of medicinal plants. Among the 267 tested medicinal plant extracts, Myricae Cortex (Myrica rubra), Perillae Herba (Perilla sikokiana), and Eriobotryae Folium (Eriobotrya japonica) showed potent inhibition of AANAT activity. Myricetin (5,7,3',4',5'-pentahydroxyflavonol), a main component of the Myricae Cortex, strongly inhibited the activity of AANAT and probably block the access to the substrate by docking to the catalytic residues that are important for AANAT activity. Myricetin significantly decreased the nocturnal serum melatonin levels in rats. In addition, the locomotor activity of rats treated with myricetin decreased during the nighttime and slightly increased throughout the day. These results suggest that myricetin could be used as a therapy to increase nighttime alertness by changing the circadian rhythm of serum melatonin and locomotor activity.
Pohang Center for Evaluation of Biomaterials, Pohang Technopark, Jigok-dong, Pohang, Gyeongbuk, South Korea; The College of Veterinary Medicine, Kyungpook National University, Sangyeok-dong, Daegu, South Korea.
Jae-Cheon
JC
Shin
Hoe-Yune
HY
Jung
Amaravadhi
A
Harikishore
Oh-Deog
OD
Kwon
Ho Sup
HS
Yoon
Kyong-Tai
KT
Kim
Bo-Hwa
BH
Choi
D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects*; D003624:Darkness; D005419:Flavonoids / Q000378:metabolism / Q000494:pharmacology*; D008297:Male; D008550:Melatonin / Q000097:blood*; D009043:Motor Activity / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D051381:Rats
D005419:Flavonoids; D010936:Plant Extracts; C040015:myricetin; D047068:Arylalkylamine N-Acetyltransferase; D008550:Melatonin
Circadian rhythm; Locomotor activity; Melatonin; Myricetin; Serotonin N-acetyltransferase