Hubby is doing really well at the moment and I think one of the things that has helped has been the introduction of 1/2 a entacapone tablet taken at the same time as his madopar/ mucuna doses. According to his genetic report his COMT appeared to be one thing that was functioning normally so I was a bit reluctant to try it but he does seem better on it.
Another contributing factor to him feeling better has been our 20 year old son turning a corner on his poor behaviour (drinking too much, taking drugs, not eating or sleeping properly and being on social media all day). He is now off all the bad stuff and has implemented his own healthy living protocol. Phew!
Also hubby has had a week with his older 2 kids looking after while I went away to a family wedding which he was dreading as he didn’t want them to see him in his state. It turned out to be the best time for them all. He had felt very guilty about leaving them with their mother when they were kids and moving to a different city for work. Their mother was not fit to look after them but they wouldn’t go with him. But they told him how much they cherished memories of him, no blame. All and all it was very cathartic for him.
So maybe it isn’t the entacapone but the relief from guilt, and anxiety?
anyway back to the COMT inhibitors. I looked up natural ones and oleanolic acid is in olives.
ncbi.nlm.nih.gov/pmc/articl...
“Go to:4. Conclusion
In summary, our research led to the discovery of novel COMT inhibitors with a chemical scaffold of pentacyclic triterpene, which is distinct from previously reported ones. Using a combination of the inhibition kinetic assay and molecular docking, we tried and explained the inhibition mechanism and the binding site of the pentacyclic triterpene to COMT. Furthermore, oleanic acid and betulinic acid displayed potent COMT inhibition and significantly less toxicity on the mitochondria membrane potential (MMP) of a human normal liver cell line, serving as an ideal lead compound to develop pentacyclic triterpene-type COMT inhibitors. It was possible that these novel COMT inhibitors can provide a starting point for synthetic efforts to generating related derivatives for further preclinical testing and new drugs used for the treatment of Parkinson’s disease, as adjuncts in L-dopa based therapy, or for the treatment of schizophrenia.”
“The most important sources of oleanolic acid in human diet are olives (Olea europaea L.), from which the compound derives its name, and their products, such as olive oil [27]. It is estimated that in the Mediterranean diet, containing olives and olive oils, total daily intake of oleanolic acid is around 25 mg [28”
“Practical applications. Betulinic acid (BA) isolated from natural plants such as fenugreek, eucalyptus bulb and mulberry has been reported with many biological activities”
Celastrol:
ncbi.nlm.nih.gov/pmc/articl...
“Neurodegenerative disordersThe effects of celastrol on MS, a neurological disease of autoimmune origin, have been described above. For other neurological diseases such as Parkinson’s disease, Alzheimer’s disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), celastrol has been shown to modulate pro-inflammatory cytokine production, to prevent the generation of reactive oxygen species (ROS), to limit oxidative damage, to protect against cell death, and to regulate heat-shock proteins (Hsps), as observed in mouse models and in vitro models of these diseases (Table 1B) [30–34,12,35–37]. For Gaucher disease (GD), celastrol modulates molecular chaperones and increases glucocerebrosidase activity in the GD fibroblasts model [38]. Celastrol is also known to modulate age-related macular degeneration [39].”
“CONCLUDING REMARKSCelastrol, a natural triterpene, has anti-inflammatory, anti-oxidant, and anti-cancer activities. Besides targeting multiple cell signaling pathways, celastrol modulates several other pathophysiological processes involved in chronic inflammatory diseases, autoimmune diseases, and cancer. Most of this information on celastrol is based on in vitro model systems in the laboratory and preclinical studies in animal models of human diseases. These studies have also offered mechanistic insights into the use of celastrol-containing herbal extracts from celastraceae family of plants for the treatment of some of these disorders in the traditional systems of medicine. Taken together, this knowledge has encouraged the clinical testing of T. wilfordii and related herbal preparations. In particular, the testing of T. wilfordii in RA patients has shown promising results. It is hoped that in the near future, T. wilfordii and similar other natural products might be approved for use in mainstream therapy as adjuncts for, or in place of, conventional allopathic drugs for RA and some other chronic diseases. This would be a significant contribution to the therapeutic arsenal against several chronic debilitating human diseases.”
