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The Hydroxychloroquine Hype


Photo: Adam Ringham


DNA Diligence – Connect the Dots – Reverse Engineer


The antimalarial drugs chloroquine, hydroxychloroquine, and quinacrine are derivatives of quinine, a natural alkaloid isolated from the South American cinchona bark tree[1].


So right out of the gate, we see that Hydroxychloroquine is literally derived from cinchona bark!


Just recently, within 20 minutes of doctors sharing a live video of their experience treating COVID19 with hydroxychloroquine- Facebook, YouTube, and Google pulled the video.


Watch the censored video here:

https://www.bitchute.com/video/HeC0tHZDX7dk/


So what makes hydroxychloroquine work?


Recent studies demonstrated that these compounds function as inhibitors of TLR7, TLR8, and TLR9.


We will discuss Toll-Like receptor 9 (TLR9) below in detail.


Hydroxychloroquine[2] was approved for medical use in the United States in 1955. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.


It is a medication used to prevent and treat malaria in areas where malaria remains sensitive to chloroquine. Other uses include treatment of rheumatoid arthritis, lupus, and porphyria cutanea tarda.


Let’s dissect how Hydroxychloroquine works in order to unearth other possible natural remedies, as opposed to the use of pharmaceuticals, which often times are riddled with side effects.


Common side effects of Hydroxychloroquine may include vomiting, headache, changes in vision, and muscle weakness. Severe side effects may include allergic reactions, vision problems, and heart problems.


Serious reported neuropsychiatric adverse effects of hydroxychloroquine use include agitation, mania, difficulty sleeping, hallucinations, psychosis, catatonia, paranoia, depression, and suicidal thoughts.


Pharmacology & Mechanism of action of Hydroxychloroquine


Hydroxychloroquine inhibits stimulation of the toll-like receptor (TLR) 9 family receptors.


TLRs are cellular receptors for microbial products that induce inflammatory responses through activation of the innate immune system.


Hydroxychloroquine has similar pharmacokinetics to chloroquine, with rapid gastrointestinal absorption, large distribution volume, and elimination by the kidneys. Cytochrome P450 enzymes (CYP2D6, 2C8, 3A4 and 3A5) metabolize hydroxychloroquine to N-desethylhydroxychloroquine.


Both agents also inhibit CYP2D6 activity and may interact with other medications that depend on this enzyme.


Hydroxychloroquine increases lysosomal pH in antigen-presenting cells. In inflammatory conditions, it blocks toll-like receptors on plasmacytoid dendritic cells (PDCs).


Toll-like receptor 9 (TLR 9), which recognizes DNA-containing immune complexes, leads to the production of interferon and causes the dendritic cells to mature and present antigen to T cells.


Hydroxychloroquine, by decreasing TLR signaling, reduces the activation of dendritic cells and the inflammatory process.


Pathogens commonly utilize endocytic (clathrin) pathways to gain cellular access.


The endosomal pattern recognition receptors TLR7 and TLR9 detect pathogen-encoded nucleic acids to initiate MyD88- dependent proinflammatory responses to infection.[3]


Hydroxychloroquine has been suggested to be a zinc ionophore and may derive an anti-cancer action from increasing intracellular zinc uptake.


CYP2D6 & Toll-like receptor 9 (TLR 9) seem to be the two main genes involved with the Pharmacology & Mechanism of action behind Hydroxychloroquine.


CYP2D6 Gene


Cytochrome P450 2D6 (CYP2D6)[4] is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.


CYP2D6, a member of the cytochrome P450 mixed-function oxidase system, is one of the most important enzymes involved in the metabolism of xenobiotics in the body.


In particular, CYP2D6 is responsible for the metabolism and elimination of approximately 25% of clinically used drugs.


Hydroxychloroquine inhibits CYP2D6 so this will be the main focus for natural discovery.


Natural Inhibitors of CYP2D6[5]:


· Cannabidiol (STRONG)

· St. John’s Wort

· Vitamin B3

· Sesame (seeds, oil)


CYP2D6 cytochrome P450[6] is involved in the metabolism of fatty acids, steroids and retinoids. Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase).


Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling.


Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis. Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (Vitamin A).


Compounds for CYP2D6 Gene[7]:


· Galantamine

· Vinpocetine

· Yohimbine

· Niacin

· Cannabidiol

· Curcumin

· St. John's Wort

· Berberine

· Linoleic acid

· Rutin

· Vitamin A

· Vitamin D3

· Black cohosh

· Rhubarb (Rhein)

· Arachidonic acid

· Stinging Nettle (Formic acid)

· Artemisinin

· Calcium


CBD Daily Broad Spectrum - BioCx + CBD and Curcumin



Toll-like receptor 9 (TLR 9)


TLR9[8] is an important receptor expressed in immune system cells including dendritic cells, macrophages, natural killer cells, and other antigen-presenting cells.


TLR9 preferentially binds DNA present in bacteria and viruses and triggers signaling cascades that lead to a pro-inflammatory cytokine response.


Cancer, infection, and tissue damage can all modulate TLR9 expression and activation.


TLR9 is also an important factor in autoimmune diseases, and there is active research into synthetic TLR9 agonists and antagonists that help regulate autoimmune inflammation.


The TLR family plays a fundamental role in pathogen recognition and activation of innate immunity.


TLR9 is preferentially expressed in immune cell-rich tissues, such as spleen, lymph node, bone marrow and peripheral blood leukocytes. Studies in mice and humans indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response.


TLR9 interacts with MyD88, the primary protein in its signaling pathway.


TLR9 can work through MyD88, an adaptor molecule that increases the expression of NF-κB.


Therefore, NF-κB inhibition is also vital!


https://www.frontiersin.org/files/Articles/103002/fimmu-05-00367-HTML/image_m/fimmu-05-00367-g002.jpg

Compounds for NFKB1 Gene[9]: