Improvement of Oxidative Stress and Mitochondrial Dysfunction by β-Caryophyllene: A Focus on the Nervous System

Abstract

Mitochondrial dysfunction results in a series of defective cellular events, including decreased adenosine triphosphate (ATP) production, enhanced reactive oxygen species (ROS) output, and altered proteastasis and cellular quality control. An enhanced output of ROS may damage mitochondrial components, such as mitochondrial DNA and elements of the electron transport chain, resulting in the loss of proper electrochemical gradient across the mitochondrial inner membrane and an ensuing shutdown of mitochondrial energy production. Neurons have an increased demand for ATP and oxygen, and thus are more prone to damage induced by mitochondrial dysfunction. Mitochondrial dysfunction, damaged electron transport chains, altered membrane permeability and Ca2+ homeostasis, and impaired mitochondrial defense systems induced by oxidative stress, are pathological changes involved in neurodegenerative disorders. A growing body of evidence suggests that the use of antioxidants could stabilize mitochondria and thus may be suitable for preventing neuronal loss. Numerous natural products exhibit the potential to counter oxidative stress and mitochondrial dysfunction; however, science is still looking for a breakthrough in the treatment of neurodegenerative disorders. β-caryophyllene is a bicyclic sesquiterpene, and an active principle of essential oils derived from a large number of spices and food plants. As a selective cannabinoid receptor 2 (CB2) agonist, several studies have reported it as possessing numerous pharmacological activities such as antibacterial (e.g., Helicobacter pylori), antioxidant, anti-inflammatory, analgesic (e.g., neuropathic pain), anti-neurodegenerative and anticancer properties. The present review mainly focuses on the potential of β-caryophyllene in reducing oxidative stress and mitochondrial dysfunction, and its possible links with neuroprotection.

Influence of Seasonal Variation on the Chemical Composition and Biological Activities of Essential Oil from Eugenia pohliana DC Leaves

“…β-caryophyllene is known for its antiinflammatory, [14][15][16] antineoplastic, [17 -19] antimicrobial [20][21][22] and in combating neurodegenerative diseases [23][24][25] activities. δ-cadinene has been reported to have antineoplastic [26] and insecticidal [27] activities.…”

Role of Bioactive Compounds in the Regulation of Mitochondrial Dysfunctions in Brain and Age-Related Neurodegenerative Diseases

“…As a result, the highly reactive hydroxyl radical can damage macromolecules within mitochondria, such as lipids, proteins, and DNA [ 75 ], and unrepaired mitochondrial DNA damage can cause poor complex I and/or III function and produce a high production of superoxide [ 76 , 77 ]. In the synthesis of adenosine triphosphate, hydrogen ions derived from nicotinamide adenine dinucleotide and reduced flavin adenine dinucleotide in intermediary metabolism are transported along the complexes to molecular oxygen, resulting in the production of water [ 78 ], and protons are pumped across the mitochondrial inner membrane by complexes I, III, and IV [ 79 ]. The flow of these protons back into the mitochondrial matrix via complex V produces adenosine triphosphate [ 79 ].…”

“…In the synthesis of adenosine triphosphate, hydrogen ions derived from nicotinamide adenine dinucleotide and reduced flavin adenine dinucleotide in intermediary metabolism are transported along the complexes to molecular oxygen, resulting in the production of water [ 78 ], and protons are pumped across the mitochondrial inner membrane by complexes I, III, and IV [ 79 ]. The flow of these protons back into the mitochondrial matrix via complex V produces adenosine triphosphate [ 79 ]. Under typical physiological settings, 1–5% of the oxygen consumed is transformed to ROS [ 80 ].…”

Mitochondria‐targeted nanoparticles in treatment of neurodegenerative diseases

“…[ 50 ] In addition, mitochondrial dysfunction due to high ROS levels induces protein misfolding in HD, leads to aggregation of inclusion bodies in the axons and dendrites of neurons, and inhibits neurotransmitter delivery. [ 51 ] Moreover, in vivo studies of ALS confirm that mitochondrial dysfunction and deficient oxidative phosphorylation occur before the disease onset. [ 44,52 ] Additionally, mitochondrial dysfunction results in activation of caspase‐3 and neuronal apoptosis in NDs.…”