Connective Tissue Disorders/Ehler Danlos, the ECM and Chronic Issues - MCAS, CIRS, POTS, CFS, IBS, Dystonias, Pain, Proprioceptive Disorders, ETC.!

[Gaby]

@Gaby It was doxy that made me feel better! I checked my old forum post in private forum and I said that I felt better on two antibiotics (doxycycline and roxytromicin) and not the third one. And roxytromicin appears to also have anti-inflammatory properties:

Great combo. It's part of the macrolide antibiotics: azithromycin et al. Its anti-inflammatory properties has been noted many years before COVID-19, both in the literature and in the clinical practice. Practitioners were fond of prescribing it in viral respiratory infections, because it shortened the disease. In Spain, we were told (unofficially) to prescribe it to reduce sick leave days in the population.

Then mainstream guidelines said: "don't prescribe antibiotics in viral infections, because bad!" Then all this research of how good it is became common knowledge in the alternative community (anti COVID Vax peeps), and how those who had early treatment did better. We always knew it had immunomodulatory effects, though. You went to a medical practice to the remotest village long before COVID-19, and this was already known and normal for daily practice.

 

[Persej]

Then mainstream guidelines said: "don't prescribe antibiotics in viral infections, because bad!" Then all this research of how good it is became common knowledge in the alternative community (anti COVID Vax peeps), and how those who had early treatment did better. We always knew it had immunomodulatory effects, though. You went to a medical practice to the remotest village long before COVID-19, and this was already known and normal for daily practice.

Yes, it was fun watching the TV during COVID where all kinds of experts were warning people to not take antibiotics for this viral disease, while at the same time all the doctors were giving COVID infected people the antibiotics! It was such an obvious gaslighting of the people.

But even before COVID, like you say, antibiotics were part of the cultural heritage in my country because everybody knew that they work, even for things like flu. But somehow that common knowledge never became part of the official mainstream medical knowledge. It's like, everybody knows it works and uses it, you just can't put it on paper that it works.

 

[Persej]

Here is another way to increase PEA in the body:

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition of NAAA activity is a potential therapeutic strategy for inflammation-related diseases. Fucoxanthinol (FXOH) is a marine carotenoid from brown seaweeds with various beneficial effects. However, the anti-inflammatory effects and mechanism of action of FXOH in lipopolysaccharide (LPS)-stimulated macrophages remain unclear. This study aimed to explore the role of FXOH in the NAAA-PEA pathway and the anti-inflammatory effects based on this mechanism. In vitro results showed that FXOH can directly bind to the active site of NAAA protein and specifically inhibit the activity of NAAA enzyme. In an LPS-induced inflammatory model in macrophages, FXOH pretreatment significantly reversed the LPS-induced downregulation of PEA levels. FXOH also substantially attenuated the mRNA expression of inflammatory factors, including inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), and markedly reduced the production of TNF-α, IL-6, IL-1β, and nitric oxide (NO). Moreover, the inhibitory effect of FXOH on NO induction was significantly abolished by the peroxisome proliferator-activated receptor α (PPAR-α) inhibitor GW6471. All these findings demonstrated that FXOH can prevent LPS-induced inflammation in macrophages, and its mechanisms may be associated with the regulation of the NAAA-PEA-PPAR-α pathway.

Anti-Inflammatory Effects of Fucoxanthinol in LPS-Induced RAW264.7 Cells through the NAAA-PEA Pathway - PubMed

Palmitoylethanolamide (PEA) is an endogenous lipid mediator with powerful anti-inflammatory and analgesic functions. PEA can be hydrolyzed by a lysosomal enzyme N-acylethanolamine acid amidase (NAAA), which is highly expressed in macrophages and other immune cells. The pharmacological inhibition...

pubmed.ncbi.nlm.nih.gov

Fucoxanthinol is the primary active metabolite of fucoxanthin, a powerful antioxidant carotenoid pigment found abundantly in edible brown seaweeds and kelp, such as Wakame (Undaria pinnatifida), Kombu (Laminaria japonica), and Hijiki.

When ingested, fucoxanthin is rapidly hydrolyzed in the gastrointestinal tract by digestive enzymes into fucoxanthinol, which is generally considered more bioavailable and efficient in vivo than fucoxanthin itself.

N-Palmitoylethanolamine or palmitoylethanolamide (PEA) is an anti-inflammatory compound that was recently shown to exert peroxisome proliferator-activated receptor-α-dependent beneficial effects on colon inflammation. The actions of PEA are terminated following hydrolysis by 2 enzymes: fatty acid amide hydrolase (FAAH), and the less-studied N-acylethanolamine-hydrolyzing acid amidase (NAAA). This study aims to investigate the effects of inhibiting the enzymes responsible for PEA hydrolysis in colon inflammation in order to propose a potential therapeutic target for inflammatory bowel diseases (IBDs). Two murine models of IBD were used to assess the effects of NAAA inhibition, FAAH inhibition, and PEA on macroscopic signs of colon inflammation, macrophage/neutrophil infiltration, and the expression of proinflammatory mediators in the colon, as well as on the colitis-related systemic inflammation. NAAA inhibition increases PEA levels in the colon and reduces colon inflammation and systemic inflammation, similarly to PEA. FAAH inhibition, however, does not increase PEA levels in the colon and does not affect the macroscopic signs of colon inflammation or immune cell infiltration. This is the first report of an anti-inflammatory effect of a systemically administered NAAA inhibitor. Because NAAA is the enzyme responsible for the control of PEA levels in the colon, we put forth this enzyme as a potential therapeutic target in chronic inflammation in general and IBD in particular.

N-Acylethanolamine-hydrolyzing acid amidase inhibition increases colon N-palmitoylethanolamine levels and counteracts murine colitis - PubMed

N-Palmitoylethanolamine or palmitoylethanolamide (PEA) is an anti-inflammatory compound that was recently shown to exert peroxisome proliferator-activated receptor-α-dependent beneficial effects on colon inflammation. The actions of PEA are terminated following hydrolysis by 2 enzymes: fatty...

pubmed.ncbi.nlm.nih.gov

N-Acylethanolamine-Hydrolyzing Acid Amidase Inhibition, but Not Fatty Acid Amide Hydrolase Inhibition, Prevents the Development of Experimental Autoimmune Encephalomyelitis in Mice - PubMed

N-acylethanolamines (NAEs) are endogenous bioactive lipids reported to exert anti-inflammatory and neuroprotective effects mediated by cannabinoid receptors and peroxisome proliferator-activated receptors (PPARs), among others. Therefore, interfering with NAE signaling could be a promising...

pubmed.ncbi.nlm.nih.gov

Ramulus Cinnamomi essential oil exerts an anti-inflammatory effect on RAW264.7 cells through N-acylethanolamine acid amidase inhibition - PubMed

RCEO showed anti-inflammatory effects by inhibiting NAAA activity and elevating cellular PEA and OEA levels in NAAA-overexpressing HEK293 cells. (E)-cinnamaldehyde and O-methoxycinnamaldehyde, two components in RCEO, were identified as the main contributors of the anti-inflammatory effects of...

pubmed.ncbi.nlm.nih.gov

Natural Potent NAAA Inhibitor Atractylodin Counteracts LPS-Induced Microglial Activation - PubMed

<span><i>N</i>-acylethanolamine-hydrolyzing acid amidase (NAAA) is a lysosomal enzyme that inhibits the degradation of palmitoylethanolamide (PEA), an endogenous lipid that induces analgesic, anti-inflammation, and anti-multiple sclerosis through PPARα activation. Only a few potent NAAA...

pubmed.ncbi.nlm.nih.gov