Can Cannbidiol (or CBD) Support Your DNA?
A wealth of previously unknown health benefits show that the phytocannabinoid known as cannabidiol (CBD) holds massive potential as therapeutically useful for treating a variety of ailments. To date, CBD has been found to possess anti-seizure, antioxidant, neuroprotective, anti-inflammatory, analgesic, anti-tumor, anti-psychotic, and anti-anxiety properties.
As research into this powerful drug continues, studies have also been conducted on CBD’s mechanisms of action on the body. CBD has been shown to act as an inhibitor, an antagonist but also as an agonist as well.
An agonist is a chemical that binds to a receptor and activates it – therefore stimulating an action. In the case of CBD, the cannabinoid binds with and activates TRPA1 receptors which may play a potential role in CBD’s analgesic effects. It is also an agonist of TRPV1 (which may be responsible for CBD’s antipsychotic and analgesic effects), TRPV2 (may mediate a peptide that plays an integral role in migraines), and 5-HT1A (a subtype of the serotonin receptor involved in CBD’s anti ischemic and anxiolytic effects).
In addition, CBD is an agonist (or stimulant) of peroxisome proliferator-activated receptors or PPARs.
More specifically, CBD binds to and stimulates PPAR Gamma or PPARγ. This mechanism of action has become a particular area of interest for researchers because of its potential as a therapeutic target. For example, recent studies suggest that the PPARγ agonists may serve as good candidates for the treatment of several neurodegenerative disorders including Parkinson’s disease (PD), Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis, even though multiple etiological factors contribute to the development of these disorders.
In this article we dive into some of the latest research into CBD’s mechanism of action on PPARγ and its potential for therapeutic uses.
What are PPARs?
In the field of molecular biology, the peroxisome proliferator-activated receptors (PPARs) are ligand-inducible transcription factors that belong to the hormone nuclear receptor superfamily. These receptors are involved in regulating the expression of genes that control numerous physiological processes including lipid homeostasis, glucose metabolism, inflammatory responses, cellular differentiation and proliferation. A growing body of evidence suggests PPARs as drug targets for treating several dysmetabolic conditions and inflammatory degenerative diseases, as well.
PPARs act mainly as lipid sensors. In response to dietary lipid intake, they regulate metabolism and direct the subsequent metabolism and storage of lipids. Three types of PPARs have been identified: PPAR alpha (PPAR), PPAR beta/delta (PPARβ/δ), and PPAR gamma (PPARγ).
PPARα is known to regulate energy homeostasis and is activated under conditions of energy deprivation. It stimulates fatty acid and cholesterol breakdown of fatty acids and drives gluconeogenesis and reduced triglyceride levels. This receptor in particular acts as a lipid sensor, binding fatty acids and initiating their subsequent metabolism. PPARα is a major regulator of lipid metabolism in the liver and also has high expression in the intestine, heart, and kidney.
The PPARβ/δ receptors are expressed in many tissues but markedly in brain, adipose tissue, and skin and play an important role in metabolic adaptation of several tissues to environmental changes. They’re involved in the normalization of metabolic parameters and reduction of adiposity for obese animals. They’ve also been implicated in the regulation of fatty acid burning capacities of skeletal muscle and adipose tissue. PPARδ may also be responsible for the adaptive metabolic response of skeletal muscle to endurance exercise. These receptors bind and respond to VLDL-derived fatty acids, eicosanoids, including prostaglandin A1, and are involved in fatty acid oxidation.
PPARγ regulates fatty acid storage and glucose metabolism by stimulating adipocyte (fat cell) differentiation and lipid metabolism. It operates in the metabolism of lipid and carbohydrate metabolism and its activation is related to reduction of glucose levels.
When activated, these receptors also antagonize the action of NFkappaB or NF-κB (a protein that converts DNA to RNA involved in immune, inflammatory, and stress responses and neuronal survival). This reduces the expression of pro-inflammatory enzymes (i.e. iNOS, COX-2) and pro-inflammatory cytokines (messengers that stimulate the movement of cells towards sites of inflammation, infection and trauma).
Several studies have looked into how CBD and PPARγ interact in neurodegenerative disorders, irritable bowel diseases, and in cancer.
CBD and PPARγ for neurodegenerative disorders, inflammatory bowel diseases, and cancer
PPARγ has been reported to play a role in regulating the pathophysiological features of Alzheimer’s disease (AD).
Meanwhile, CBD has been shown to have promising neuroprotective properties in rat AD models as well (although researchers still don’t know the mechanisms responsible). But since we know that CBD binds to and activates PPARγ, does that mean they work together to produce CBD’s anti-inflammatory and neuroprotective effects?
In a study published in 2011 in the journal PLOS ONE, Italian researchers looked at whether CBD’s neuroprotective effects depend on its activity on PPARγ receptors. Using in vitro (cell culture) and in vivo (rat AD model) studies, the researchers either administered or didn’t administer PPAR antagonists (or blockers) to see if CBD’s neuroprotective effects were affected.
Their results showed that CBD activated PPARγ to reduce neuroinflammation and promote growth of nervous tissue in the hippocampal region of the brain. However, when PPARγ was blocked, CBD’s neuroprotective functions were almost completely abolished. Their findings demonstrated the crucial role this receptor plays in mediating CBD actions in AD.
In another study by Italian researchers published in 2014 in Phytotherapy Research, the team looked into how CBD might beneficially interfere with beta amyloid (Aβ) peptide-triggered neurodegeneration. Build up of amyloid plaques between nerve cells in the brain are one of the hallmarks of Alzheimer’s disease. It messes with neuronal homeostasis and leads to oxidative injury which provokes tangle formation with consequent neuronal loss. Aβ’s precursor molecule is the amyloid precursor protein (APP).
In this study, the role of CBD was investigated as a possible modulating compound of APP processing in neurons (specifically, SHSY5Y(APP+ neurons). The researchers also looked at the involvement of PPARγ as a potential site responsible for CBD’s actions.
Results showed that CBD caused a substantial decrease in APP levels which led to a decrease in Aβ production. CBD also promoted an increased survival of SHSY5Y(APP+) neurons, by reducing their long-term apoptotic (programmed cell death) rate. Finally, the results also showed that CBD’s effects were dependent on the selective activation of PPARγ.
But while CBD (through PPARγ interactions) looks promising for AD, CBD (through PPARγ interactions) could help with inflammatory bowel diseases (IBD) as well.
In yet another study by Italian researchers published in 2012 in Phytotherapy Research, the authors reviewed the scientific literature in regards to CBD and IBD. They found that CBD may reduce intestinal inflammation severity because of its capability to activate PPARγ. This might better explain the potent anti-inflammatory action of CBD during intestinal inflammation.
In fact, the authors found that CBD’s effects on PPARγ activation may be a beneficial approach in the management of ulcerative colitis or Crohn’s disease and also in reducing the risk of persistent inflammation of the colon – making it a potential chemopreventive tool for combating colon cancer.
Finally, in a 2013 study by the American Association for Cancer Research published in Molecular Cancer Therapeutics, researchers looked into the roles of COX-2 (an enzyme responsible for inflammation and pain) and PPARγ in CBD’s tumor-regressive action in vivo and CBD’s proapoptotic action in human lung cancer cells in vitro.
They found that CBD unregulated expression levels of COX-2 and PPARγ and led to the activation of PPAR-γ by COX-2–dependent prostaglandins (prostaglandins are lipids that aid in recovery at sites of tissue damage or infection). They concluded that activation of PPAR-γ may present a promising target for lung cancer therapy and that CBD may represent a promising anticancer drug.
As you can see, from neurodegenerative disorders to inflammatory bowel diseases to cancer, researchers are increasingly looking into the relationship between CBD and PPARγ as a potential therapeutic target. Although more research is required, CBD is a promising compound that may be useful for more effective treatments of these conditions in the near future.
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