(-)-Epigallocatechin-3-gallate Ameliorates Intervertebral Disc Degeneration Through Reprogramming of the Circadian Clock

Abstract

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 H2O2-induced extracellular matrix degradation in NPCs and inhibited H2O2-induced NPC apoptosis. Our in vivo experiments also confirmed this finding. Furthermore, EGCG attenuated H2O2-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.

Omics Analyses of Intestinal Microbiota and Hypothalamus Clock Genes in Circadian Disturbance Model Mice Fed with Green Tea Polyphenols

“…31 Existing studies have shown that tea catechins can effectively alleviate the circadian rhythm disorder induced by the external environment and significantly improve the health status by regulating the host circadian clock. 32 EGCG treatment changed the diurnal oscillatory expression patterns of major appetite regulation genes and circadian rhythm key genes Clock and Bmal1 in the hypothalamus of diet-induced obese mice, indicating the central role of EGCG in food intake regulation. 33 Moreover, another result showed that, compared with the control group, the high-fructose diet treatment group showed poorer diurnal oscillations of core clock genes and clock-controlling genes in the liver and fat.…”

“…It has been confirmed that circadian dysregulation is closely related to metabolic homeostasis, and circadian disorders can lead to diseases such as glucose tolerance, obesity, diabetes, hyperglycemia, and cancer . Existing studies have shown that tea catechins can effectively alleviate the circadian rhythm disorder induced by the external environment and significantly improve the health status by regulating the host circadian clock . EGCG treatment changed the diurnal oscillatory expression patterns of major appetite regulation genes and circadian rhythm key genes Clock and Bmal1 in the hypothalamus of diet-induced obese mice, indicating the central role of EGCG in food intake regulation .…”

Optineurin-mediated mitophagy as a potential therapeutic target for intervertebral disc degeneration

“…We first examined changes in OPTN expression in human and rat NP tissues. Next, we used a model of H 2 O 2 -induced cellular oxidative stress, which is widely used in the intervertebral disc field ( Wang Y et al, 2018 ; Xia et al, 2019 ; Mei et al, 2021 ; Shi et al, 2021 ). We identified differences in the expression of OPTN during the development of IVDD and changes in the expression of OPTN in NPCs subjected to oxidative stress and explored the impact of changes in OPTN expression on NPCs and the potential for OPTN as a therapeutic target for IVDD.…”

Pulsed Electromagnetic Field Alleviates Intervertebral Disc Degeneration by Activating Sirt1-Autophagy Signaling Network

“…All rats were intraperitoneally anesthetized with pentobarbital solution (1%, 40 mg/kg). As described in previous studies, following tail skin disinfection with iodophor and alcohol, a 20-gauge needle was used to fully puncture the tail disc from Co6-Co8 levels, including two IVDs (Co6-Co7 and Co7-Co8) ( Sun et al, 2020 ; Mei et al, 2021 ). The needle was then rotated 180 and left for 1 min before removal.…”