Tetracyclines are anti-PUFA

[Mauritio]

"Three important kinds of enzymes that are activated by stress and radiation are phospholipases (that release fatty acids), tryptophan hydroxylase (that controls the conversion of tryptophan to serotonin), and aromatase (estrogen synthetase, that converts androgens to estrogen). The products of these enzymes stimulate cell division, and produce features of the inflammatory process, including the leakiness of capillaries. "
-Ray Peat


Here are a two studies adding another mechanism to tetracyclines anti-inflammatory effects. Not only do they lower endotoxin, serotonin and MMPs, they also inhibit an enzyme called phospholipase A2.

This enzyme is responsible for the conversion of phospholipids to arachidonic acid, which is the precursor for the infamous prostaglandins and other inflammatory molecules.
So by inhibiting this conversion you should be able to reduce the amount of prostaglandins synthesized and thus antagonize PUFA and inflammation in a very fundamental way.

This study summarizes the dangers of phospholipase A2 quite well:

"Phospholipases A2 (PLA2) are a diverse group of enzymes that hydrolyze membrane phospholipids into arachidonic acid and lysophospholipids. Arachidonic acid is metabolized to eicosanoids (prostaglandins, leukotrienes, thromboxanes), and lysophospholipids are converted to platelet-activating factors. These lipid mediators play critical roles in the initiation, maintenance, and modulation of neuroinflammation and oxidative stress. Neurological disorders including excitotoxicity; traumatic nerve and brain injury; cerebral ischemia; Alzheimer’s disease; Parkinson’s disease; multiple sclerosis; experimental allergic encephalitis; pain; depression; bipolar disorder; schizophrenia; and autism are characterized by oxidative stress, inflammatory reactions, alterations in phospholipid metabolism, accumulation of lipid peroxides, and increased activities of brain phospholipase A2 isoforms. "

https://pubs.acs.org/doi/pdf/10.1021/acschemneuro.5b00073

So the main point of this thread is that several tetracyclines can lower phospholipase A2:

"MinoTc interferes with the conformation of the active-site Ca(2+)-binding loop, preventing Ca(2)(+) binding, and shields the active site from substrate entrance, resulting in inhibition of the enzyme. "

Nonantibiotic properties of tetracyclines: structural basis for inhibition of secretory phospholipase A2 - PubMed

Secretory phospholipase A(2) is involved in inflammatory processes and was previously shown to be inhibited by lipophilic tetracyclines such as minocycline (minoTc) and doxycycline. Lipophilic tetracyclines might be a new lead compound for the design of specific inhibitors of secretory...

pubmed.ncbi.nlm.nih.gov

"We found that minocycline and to a lesser degree doxycycline were markedly inhibitory to both pancreatic and non-pancreatic PLA2. "

Inhibition of enzymatic activity of phospholipases A2 by minocycline and doxycycline - PubMed

Extracellular phospholipases A2 play an important role in articular and extra-articular inflammatory processes. Secretory non-pancreatic phospholipase A2 (PLA2) has been implicated in the pathogenesis of articular inflammation in rheumatoid arthritis, whereas pancreatic PLA2 contributes to the...

pubmed.ncbi.nlm.nih.gov

 

[Mauritio]

I asked ray about this:
Do you know if subantimicrobial doses of the tetracyclines are enough to lower prostaglandin synthesis and phospholipase A2?


A:"The tetracyclines and macrolides such as azithromycin are antiinflammatory; aspirin has similar inhibitory effects."