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(-)-Epigallocatechin-3-gallate Ameliorates Intervertebral Disc Degeneration Through Reprogramming of the Circadian Clock
Ist Teil von
Frontiers in pharmacology, 2021-11, Vol.12, p.753548-753548
Ort / Verlag
Frontiers Media S.A
Erscheinungsjahr
2021
Link zum Volltext
Quelle
EZB Electronic Journals Library
Beschreibungen/Notizen
The circadian clock is vital in the management of our daily physiological as well as metabolic processes. Disturbances of the clock can cause degenerative and age-related diseases. Increasing evidence has indicated that the intervertebral discs contain an internal biological clock related to degeneration. However, to date, no bioactive compounds have been found that can ameliorate intervertebral disc degeneration (IDD) by restoring the circadian clock. (-)-Epigallocatechin-3-gallate (EGCG) is a nutritious food with powerful antioxidant properties, as well as entraining biological clock to improve health. The purpose of this study was to determine whether the protective effects of EGCG on nucleus pulposus (NPCs) under oxidative stress is related to the circadian clock. First, we found that EGCG attenuated H
2
O
2
-induced extracellular matrix degradation in NPCs and inhibited H
2
O
2
-induced NPC apoptosis. Our
in vivo
experiments also confirmed this finding. Furthermore, EGCG attenuated H
2
O
2
-triggered dampening of phase shifts and daily oscillations in circadian clock gene transcription as well as protein expression levels. Intriguingly, core clock gene (Bmal1) knockdown notably blocked the protective effects of EGCG. To our knowledge, this study provides the first convincing evidence that EGCG prevents IDD in a Bmal1-dependent manner. In general, EGCG supplementation can be used as a nutritional prevention strategy for the rehabilitation of degenerative diseases related to the circadian clock.