Promotion of mitochondrial biogenesis by synthetic 1,2‐ or 1,3‐digallates through activation of an energy sensing network

Abstract

Based on the observations suggesting that a digallate functionality might serve as a novel scaffold for inducers of mitochondrial biogenesis, we prepared a series of digallates and evaluated their activity in an in vitro model widely used in PD research (SH-SY5Y cells). Flow cytometry-based approach revealed stimulation of mitochondrial biogenesis by the gallates, particularly by those with the gallate substituted at the 1,2-or 1,3-positions. The relative mitochondrial mass calculated after taking cell sizes into account also confirmed the 1,2-or 1,3-digallates as stimulators of mitochondrial biogenesis. Finally, energy sensing network including AMPK, SIRT1, and PGC-1α was shown to be affected by 1,2-or 1,3-digallates to stimulate mitochondrial biogenesis. Taken together, this study presents a 1,2-or 1,3-digallate as a novel scaffold for stimulators of mitochondrial biogenesis. As inducers of mitochondrial biogenesis remain scarce, the current findings provide a valuable tool in the battle against neurodegenerative diseases.

Promoting effects of cannabidiol on neurite growth and neuronal development in neuron‐astrocyte sandwich coculture

“…(−)‐Cannabidiol (2‐[(1 R ,6 R )‐3‐methyl‐6‐prop‐1‐en‐2‐ylcyclohex‐2‐en‐1‐yl]‐5‐pentylbenzene‐1,3‐diol, CBD) is one of the major phytocannabinoids extracted from the Cannabis genus. Its nonpsychoactiveness, coupled with the potential therapeutic advantages in addressing neurodegenerative conditions such as epilepsy, schizophrenia, Parkinson's disease, Huntington's disease, and Alzheimer's disease, have recently garnered noticeable attention in neuroscience research 1–5 . In addition, there have been researches suggesting that CBD may even facilitate the proliferation of neural stem cells and induce their differentiation into distinct lineages within the central nervous system (CNS), notably neurogenesis 2,6,7 .…”

“…Its nonpsychoactiveness, coupled with the potential therapeutic advantages in addressing neurodegenerative conditions such as epilepsy, schizophrenia, Parkinson's disease, Huntington's disease, and Alzheimer's disease, have recently garnered noticeable attention in neuroscience research. [1][2][3][4][5] In addition, there have been researches suggesting that CBD may even facilitate the proliferation of neural stem cells and induce their differentiation into distinct lineages within the central nervous system (CNS), notably neurogenesis. 2,6,7 For instance, a study has demonstrated that the sustained administration of CBD to mice through injection leads to an increase in the population of newly generated neurons, including immature neurons expressing an early-stage neuronal marker-doublecortin-and mature neurons responding to the marker of neuronal maturity-NeuN-in the subventricular and subgranular zones.…”