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Arg1 - Important for Clearing Arginine and Ammonia...Brain Fog

This article is not intended to be medical or healthcare advice. Before starting any health related regimen, speak to your Primary Care Physician or an M.D. first.


If you experience, brain fog, fatigue, difficulty clearing ammonia, low glutathione, high Urea/BUN/orotic acid markers on Organic Acids or Comprehensive Metabolic tests this article may be of interest. A list of compounds and herbs listed in the below article have research showing they inhibit ARG1 which may result in the build up of arginine and ammonia even without genetic mutations in play. Many are common herbs taken for their anti oxidant and anti inflammatory effects, and on the list are .....coffee and herbal teas:)


The urea cycle processes excess nitrogen, which is generated when proteins and their building blocks (amino acids) are used by the body. Through the urea cycle, excess nitrogen is made into a compound called urea that is excreted by the kidneys. Excreting the excess nitrogen prevents it from accumulating in the form of ammonia, which is toxic. Arginase controls the last step of the urea cycle, a reaction in which nitrogen is removed from the amino acid arginine and processed into urea for excretion from the body. A compound called ornithine is also produced in this reaction; it is needed for the urea cycle to repeat.[1]


If you your diet is mainly carnivore, this may be worthwhile to explore. A mutated ARG1 gene may result in an arginase enzyme that is unstable. Inhibition of the Arg1 gene from consuming certain herbs and compounds can also limit its ability. Either of these could cause an accumulation of excess ammonia and arginine in the body. Failure to break down nitrogen results in the abnormal accumulation of nitrogen, in the form of ammonia, in the blood.[3]


ARG1 also functions as a tumor suppressor in breast cancer and other cancers as well. Luckily from this, Arg1 has received extension research of late. Defective arginine metabolism also impairs mitochondrial homeostasis in Caenorhabditiselegans. [2]


ARG1 - Has A Role To Play In Colorectal Cancer

Inhibition of arginase activity significantly suppressed the proliferation and migration ability of CT26 murine colon cancer cells in vitro. Overexpression of ARG1 in CT26 cells reduced intracellular L-arginine levels, enhanced cell migration, and promoted epithelial-mesenchymal transition. Metastatic colonization of CT26 cells in lung and liver tissues was significantly augmented by ARG1 overexpression in vivo. ARG1 gene expression was higher in the tumor tissues of liver metastasis than those of primary tumor, and arginase inhibition suppressed the migration ability of HCT116 human colon cancer cells. Activation of ARG1 is related to the migration ability and metastatic colonization of colon cancer cells, and blockade of this process may be a novel strategy for controlling cancer malignancy. [4]


Herbs that Inhibit Arg1 - Licorice (TFRG), Panax Ginsing, Ginger, Tumeric/Circumin

"TFRG and ethanol extract of RS showed the strong inhibition of Arg-1 mRNA expression (above 90% at 100μg/mL). The inhibition of total saponins of RS, ethanol extract of DCXC, ethanol extract of CWJ, and ethanol extract of HQ reached above 50% at 100μg/mL. The inhibition of ingredients including glabridin, isoliquiritin apioside, lysionotin, cordycepin, astragaloside IV, and calycosin reached above 50% at 50μM."[5]


"However, both ginger and turmeric (2% and 4%) caused significant (p < 0.05) decreases in arginase activity and the atherogenic index, and prevented hypercholesterolemia by decreasing the TC, TGs, and LDL-C while increasing the HDL-C when compared with the controls. In conclusion, dietary supplementation with both types of rhizomes (ginger and turmeric) inhibited arginase activity and prevented hypercholesterolemia in rats that received a high-cholesterol diet. Therefore, these activities of ginger and turmeric represent possible mechanisms underlying its use in herbal medicine to treat several cardiovascular diseases."[6]


Piceatannol (Phenolic) and Chloregenic Acid (Think Coffee)

"There are two common natural arginase inhibitors, PIC (piceatannol) and CA, that have been extensively investigated for cancer therapy. PIC, a phenolic compound, shows potential arginase inhibition with inhibitory effect on mammalian arginase with IC50 of 12.1 μM . It has been reported to exhibit antitumor effects in a variety of cancers, including lung cancer , breast cancer, bladder cancer , etc. In lung cancer, in vitro and in vivo studies demonstrated that PIC used in a single agent or combined with gemcitabine led to an inhibitory effect on cell proliferation and metastasis . PIC is also capable of effectively reducing breast cancer growth and metastasis, and induces apoptosis via mediating p38, c-Myc, p-STAT3, NF-ĸB, and HIF-1α related signaling pathways. In bladder cancer cells, PIC significantly reduced the cell proliferative activity, augmented the cell cycle arrest at G0/G1 phase and induced apoptosis through the inhibition of cyclin-dependent kinase (CDK) activity . The other compound, CA (Chloregenic Acid), a major component of coffee polyphenols, could also inhibit mammalian arginase with IC50 of 10.6 μM . It has also been reported to exert antitumor and antimetastasis effect through antioxidant properties, anti-angiogenesis and inducing cancer apoptosis and differentiation . Although these natural products exhibited inhibitory effects on arginase activity and also showed their antitumor capacities, their inhibitory activities remained slightly lower than BEC (IC50 = 3.3 µM). Nevertheless, PIC and CA offers two potential core structures for the design of new arginase inhibitors."[8]


Inducers of Arg1:

LPS, TNFα, hyperglycemia, nitric oxide, AII, IL-1, and glucocorticoids.[9]


Other Inhibitors of Arg1:

Rutin, Luteolin (also inhibits NrF2), Ellagic Acid, Pomegranate, Resveratrol, Querectin, Hawthorne, Suamc, White broom, Saffron / Red Ginger, Herbal Teas, Coffee, Berries


If you would like to explore this in more detail, i encourage you to explore the references below. If you would like to review your genetics in detail regarding this pathway, and explore options, please schedule an appointment.


References


  1. National Library of Medicine 8600 Rockville Pike, Bethesda, MD 20894 U.S. Department of Health and Human Services National Institutes of Health

  2. NIH: National Center for Biotechnology Information, Gene ID: 383, updated on 3-Dec-2023

  3. www.rarediseases.org; Arginase-1 Deficiency. Print. Last updated: 04/11/2023. NORD gratefully acknowledges Stephen Cederbaum, MD, University of California Los Angeles Medical Center, for assistance in the preparation of this report.

  4. Arginase-1 inhibition reduces migration ability and metastatic colonization of colon cancer cells. Xiangdong Wang, Huihui Xiang, et al. Published: 13 January 2023. Cancer & Metabolism volume 11, Article number: 1 (2023) Cite this article

  5. NIH: Screening Five Qi-Tonifying Herbs on M2 Phenotype Macrophages

  6. Effect of Two Ginger Varieties on Arginase Activity in Hypercholesterolemic Rats

  7. Phytochemical screening and arginase inhibitory activity of extracts from several Tunisian medicinal plants. R. Attia , C. Messaoud et. al. South African Journal of Botany

  8. Phytochemical screening and arginase inhibitory activity of extracts from several Tunisian medicinal plants. R. Attia a b, C. Messaoud. et. a. South African Journal of Botany

  9. ReviewArginase: An emerging and promising therapeutic target for cancer treatment

  10. Thieme: Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment. Minozzo BR et al. Phenolic Compounds as… Planta Med 2018; 84: 277–295.

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