"Barberry is one of the biggest threats to wheat crops worldwide which is why it is illegal to plant in many countries."
Mitochondria, Yeast, and Barberry Leaves
When scientists get confused about human mitochondria, they sometimes refer back to it's more efficient and dynamic ancestor within Saccharomyces Cerevisiae(S. Cerevisiae). In response to extreme oxidative stress and/or infection, human mitochondria undergo changes. Those changes are rarely as favorable to the host as those imparted on our favorite foods by S. Cerevisiae and a slow ferment.
Since yeast are obligate parasites, the mitochondria within yeast have to adapt rapidly to changes in environmental conditions for host survival. Stressors during fermentation are what make yeast more resilient, more adaptable, more dynamic microcosms of organic matter.
In order to make penicillin, for instance, fungus must undergo stress during fermentation. A subsequent lysine molecule inhibits the process which then leads to more lysine molecules. The secondary metabolite, penicillin, ensures the integrity of a slower ferment by killing any jealous microbes while the other metabolite, lysine, continually stresses and slows fermentation. Penicillin is effectively a byproduct of adaptation allowing mitochondria within fungus to continue functioning under stressful conditions.
Secondary metabolites of mitochondria and fermentation alike are written off as non-essential for growth but the hardiest plants and ferments tell a different evolutionary story through secondary metabolites that sustain growth through protection.
Common secondary metabolites in plants include tannins, flavanoids, and polyphenols. What would simply appear to be non-essential waste doubles as a deterrent to other microbes, pests and small animals. Fortunately for humans, these plant toxins at safe doses trigger adaptive responses to oxidative stress within the body. These waste products are bitter and toxic but can add complexity to fruits, vegetables, breads, drinks and our own body's resilience to oxidative stress.
Barberry, one of the oldest most prolific sources of Berberine, is a shrub that seems to have no problem deterring mammals like deer. Even in full sun, Barberry's dense foliage creates a moist and protective canopy for insects and small rodents. Lyme carrying deer ticks are known to seek refuge in barberry shrubs for their ideal microclimate, feeding on and infecting small rodents. Lyme carrying ticks occasionally hitch a ride on deer but do not actually infect deer with the Lyme causing agents(a common misconception). Birds seem to love Barberry fruit which is, in part, how the plant is propagated. Barberry's seemingly extreme hardiness lends itself to numerous phenomenon that have, unfortunately, given it a bad wrap.
Barberry is one of the biggest threats to wheat crops worldwide which is why it is illegal to plant in many countries. The reason is that a unique heteroecious yeast occurs when barberry grows near wheat. Puccinia graminis which causes "wheat stem rust" can silence the DNA of an entire wheat crop if it is able to hop back and forth between the wheat and a barberry plant. Some wheat species were considered resistant to "stem rust" until new puccinia graminis mutations were discovered. Barberry and it's unique traits are a masterclass in reactive oxygen species, microbial resiliance, and permaculture.
An interesting theory in relation to SARS-Cov-2 is that "super-tasters" are less prone to SARS-Cov-2 infection because they cannot tolerate these bitter plant compounds. The theory is that folks who cannot tolerate strong bitter flavors have fewer receptor sites in the nasopharynx to which for SARS-Cov-2 to initially bind. Another theory somewhat unrelated to SARS-Cov-2 is that super-tasters, because of their aversion to bitter foods, may be more prone to neoplasms because they do not consume as many tannins, flavanoids, and polyphenols. There may be an inverse relationship between one's own Host Defense Peptides and their conditional aversion to tolerating more.
Polypermeability Theory
"Polypermeability Theory posits that less obvious endogenous Host Defense Peptides are more reliable than others at preventing and treating infections."
Polypermeability Theory is a framework for understanding the strengths and weaknesses of antimicrobial systems in the body. Host Defense Peptides(HDPs) exist organically throughout the body and may play a significant role in disease threshhold and pathogenesis. This theory and all related recommendations are not a replacement for mold remediation and mold avoidance in one's environment. Visit www.exposingmold.org for more resources.
From humans to jellyfish, the most resilient animals on the planet have something in common: they all produce antimicrobial and photoprotective waste particulate(plants as well!). They also rely on enzymes like Superoxide Dismutase to protect mitochondria from their own toxic waste(Reactive Oxygen Species or "ROS").
Unfortunately, mitochondria rely on the same enzymes(Superoxide Dismutase...) as do toxic molds and fungus for survival. In epithelial and endothelial squamous tissue that has already destroyed it's own mitochondria and nuclei[displaced by their own endogenous host defense peptides(HDRs)], mold and fungi burrow to deeper and deeper metabolically active layers causing rapid oxidation and cell turnover down to the endothelium.
How does mold get inside endothelial and epithelial cells? Leukocytes can "Trojan Horse" the problematic microbes into the host cytoplasm, or microbes can wiggle in through permeable tight junctions likely damaged by oxidative stress. My Polypermeability Theory posits that some less obvious endogenous HDRs are more reliable than others at preventing and treating infection. Certain plant pigments, for example, are a safe way to upregulate these defenses.
I believe that a more nuanced understanding of the evolutionary significance of Reactive Oxygen Species and HDRs can help us understand and develop novel therapeutics for disease and disease prevention complicated by chronic immune dysregulation, autoimmunity, mitochondrial dysfunction, dysbiosis, opportunistic infection and neurocognitive dysfunction.
Dr. Michael is an acupuncturist and herbalist from Chicago, practicing in New Orleans with a special interest in autoimmune and neurodegenerative diseases.
IACI Support is the fruit of a decade of clinical experience and tireless research into the aforementioned.
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Dr. Michael considers this his life's work and intends to focus on refining delivery and access to this and similar medicines while continuing to practice in New Orleans.
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Mehmood, Amber; Adil, Sadia. "Polyenes and SARS-COV-2." Researchgate, www.researchgate.net/publication/364951514_Polyenes_and_SARS-CoV-2
Petrison, Lisa. “Paul Cheney Seminar on Oxygen Toxicity (2013).” Paradigm Change, paradigmchange.me/wp/cheney/
​
Sheppard, Donald C, and Scott G Filler. “Host Cell Invasion by Medically Important Fungi.” Cold Spring Harbor Perspectives in Medicine, 3 Nov. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4292075/
Wolkenstein, Klaus; Burkhard, Schmidt C.. "Polyene-Based Colouration Preserved in 12 Million-Year-Old Gastropod Shells.", www.researchgate.net/publication/370929084_Polyene-based_colouration_preserved_in_12_million-year-old_gastropod_shells
​
Delattin, Nicolas; Cammue, Bruno PA; Thevissen, Karin. "Reactive Oxygen Species-Inducing Antifungal Agents and Their Activity Against Fungal Biofilms." www.future-science.com/doi/10.4155/fmc.13.189
Tanaka J; Kadekaru T; Ogawa K; Hitoe S; Shimoda H; Hara H; “Maqui Berry (Aristotelia Chilensis) and the Constituent Delphinidin Glycoside Inhibit Photoreceptor Cell Death Induced by Visible Light.” Food Chemistry, pubmed.ncbi.nlm.nih.gov/23561088/
​
El-Obeid A; Al-Harbi S; Al-Jomah N; Hassib. “Herbal Melanin Modulates Tumor Necrosis Factor Alpha (TNF-Alpha), Interleukin 6 (IL-6) and Vascular Endothelial Growth Factor (VEGF) Production.” Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, pubmed.ncbi.nlm.nih.gov/16635740/
​
López-Hernández, Yamilé, et al. “The Plasma Metabolome of Long COVID-19 Patients Two Years after Infection.” medRxiv, 1 Jan. 2023, www.medrxiv.org/content/10.1101/2023.05.03.23289456v1
Davis, Hannah E., et al. “Long Covid: Major Findings, Mechanisms and Recommendations.” Nature News, 13 Jan. 2023, www.nature.com/articles/s41579-022-00846-2
​
Babalghith, Ahmad O., et al. “The Role of Berberine in Covid-19: Potential Adjunct Therapy - Inflammopharmacology.” SpringerLink, 2 Oct. 2022, link.springer.com/article/10.1007/s10787-022-01080-1
​
Schaffer, Stephen, and Ha Won Kim. “Effects and Mechanisms of Taurine as a Therapeutic Agent.” Biomolecules & Therapeutics, 1
May 2018, www.ncbi.nlm.nih.gov/pmc/articles/PMC5933890/
Schaffer, Stephen W., et al. “Differences between Physiological and Pharmacological Actions of Taurine.” Advances in Experimental edicine and Biology, July 2022, link.springer.com/chapter/10.1007/978-3-030-93337-1_30
Seidel, Huebbe, and Rimbach. “Taurine: A Regulator of Cellular Redox Homeostasis and Skeletal Muscle Function.” Molecular Nutrition & Food Research, August 2019, pubmed.ncbi.nlm.nih.gov/30211983/
Jong, Sandal, and Schaffer. “The Role of Taurine in Mitochondria Health: More than Just an Antioxidant.” Molecules (Basel, Switzerland), August 2021, pubmed.ncbi.nlm.nih.gov/34443494/
​
Michalk, Wingenfeld, et al. “The Mechanisms of Taurine Mediated Protection against Cell Damage Induced by Hypoxia and Reoxygenation.” Advances in Experimental Medicine and Biology, pubmed.ncbi.nlm.nih.gov/8915359/. Accessed 21 May 2023.
​
Anis, and Zaky. "Glutamine and Taurine: No Longer Supplementary Nutrients." Journal of Anaesthesiology, January 2013, www.researchgate.net/publication/343323133_Glutamine_and_taurine_no_longer_supplementary_nutrients
​
Zhang, Pengcheng, et al. “Berberine Inhibits Growth of Liver Cancer Cells by Suppressing Glutamine Uptake.” OncoTargets and Therapy, 31 Dec. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6978679/
Combs, McClurg. “Sarcosine Dehydrogenase.” Sarcosine Dehydrogenase - an Overview | ScienceDirect Topics, The Vitamins(Sixth Edition), 2022, www.sciencedirect.com/topics/nursing-and-health-professions/sarcosine-dehydrogenase
​
Walter, Fruzsina R., et al. “Blood–Brain Barrier Dysfunction in L-Ornithine Induced Acute Pancreatitis in Rats and the Direct Effect of L-Ornithine on Cultured Brain Endothelial Cells - Fluids and Barriers of the CNS.” BioMed Central, 17 Feb. 2022, fluidsbarrierscns.biomedcentral.com/articles/10.1186/s12987-022-00308-0
​
​
Ou, Xiaofeng, et al. “Cognitive Impairments Induced by Severe Acute Pancreatitis Are Attenuated by Berberine Treatment in Rats.” Molecular Medicine Reports, 1 Sept. 2018, www.spandidos-publications.com/10.3892/mmr.2018.9313
​
Li, Jie, et al. “Berberine Inhibits the Warburg Effect through Tet3/Mir-145/HK2 Pathways in Ovarian Cancer Cells.” Journal of Cancer, 1 Jan. 2021, www.jcancer.org/v12p0207.htm
​
Almani, Suhail Ahmed, et al. “Berberine Protects against Metformin-Associated Lactic Acidosis in Induced Diabetes Mellitus.” Iranian Journal of Basic Medical Sciences, May 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5478779/
​
Aiyun Li a, et al. “Berberine Reduces Pyruvate-Driven Hepatic Glucose Production by Limiting Mitochondrial Import of Pyruvate through Mitochondrial Pyruvate Carrier 1.” EBioMedicine, 6 Aug. 2018, www.sciencedirect.com/science/article/pii/S2352396418302858
​
Guo, Wei, et al. “Glutamic-Pyruvic Transaminase 1 Facilitates Alternative Fuels for Hepatocellular Carcinoma Growth-a Small Molecule Inhibitor, Berberine.” MDPI, 9 July 2020, www.mdpi.com/2072-6694/12/7/1854
​
Ishikura, Keisuke, et al. “Effect of Taurine Supplementation on the Alterations in Amino Acid Content in Skeletal Muscle with Exercise in Rat.” Journal of Sports Science & Medicine, 1 June 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3761861/
Sun, Runbin, et al. “The Hypoglycemic Effect of Berberine and Berberrubine Involves Modulation of Intestinal Farnesoid X Receptor Signaling Pathway and Inhibition of Hepatic Gluconeogenesis.” Drug Metabolism & Disposition, 1 Mar. 2021, dmd.aspetjournals.org/content/49/3/276.abstract
​
Yu, Y., et al. “Berberine Improves Cognitive Deficiency and Muscular Dysfunction via Activation of the AMPK/SIRT1/PGC-1A Pathway in Skeletal Muscle from Naturally Aging Rats - The Journal of Nutrition, Health & Aging.” SpringerLink, 6 Mar. 2018, link.springer.com/article/10.1007/s12603-018-1015-7
​
​
Kosalec, Ivan, et al. “The Spectrum of Berberine Antibacterial and Antifungal Activities.” SpringerLink, 3 Feb. 2022, link.springer.com/chapter/10.1007/978-3-030-83504-0_7
​
Li, Jiaojiao, Pin Meng, et al. “Effect of Berberine Hydrochloride on the Diversity of Intestinal Flora in Parkinson’s Disease Patients.” Contrast Media & Molecular Imaging, 30 May 2022, www.ncbi.nlm.nih.gov/pmc/articles/PMC9170458
​
Duszka, Kalina. “Versatile Triad Alliance: Bile Acid, Taurine and Microbiota.” MDPI, 29 July 2022, www.mdpi.com/2073-4409/11/15/2337
​
Fu, Ni, Wang, Fu, and Hong. “Berberine Suppresses Mast Cell-Mediated Allergic Responses via Regulating FcÉ›ri-Mediated and MAPK Signaling.” International Immunopharmacology, March 2019, pubmed.ncbi.nlm.nih.gov/30861392/
McCarty, Mark F, et al. “Nutraceutical Aid for Allergies - Strategies for down-Regulating Mast Cell Degranulation.” Journal of Asthma and Allergy, 27 Oct. 2021, www.ncbi.nlm.nih.gov/pmc/articles/PMC8558634/
​
Tanikawa, Kiba, Yu, et al. “Degradative Effect of Nattokinase on Spike Protein of SARS-COV-2.” Molecules (Basel, Switzerland), August 2022, pubmed.ncbi.nlm.nih.gov/36080170/
​
Bhat, Mujtaba Aamir, et al. “Expedition into Taurine Biology: Structural Insights and Therapeutic Perspective of Taurine in Neurodegenerative Diseases.” Biomolecules, 5 June 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7355587/
​
Tavaf, Soltanmohammadi, et al. "Berberine promotes immunological outcomes and decreases neuroinflammation in the experimental model of multiple sclerosis through the expansion of Treg and Th2 cells." - Wiley Online Library, January 2023, onlinelibrary.wiley.com/doi/10.1002/iid3.766
​
​
Warowicka, Alicja, et al. “Antiviral Activity of Berberine.” Archives of Virology, Sept. 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7320912/
​
Šudomová, Miroslava, et al. “Berberine in Human Oncogenic Herpesvirus Infections and Their Linked Cancers.” Viruses, 28 May 2021, www.ncbi.nlm.nih.gov/pmc/articles/PMC8229678/
​
Wang, Kening, et al. “Glutamine Supplementation Suppresses Herpes Simplex Virus Reactivation.” The Journal of Clinical Investigation, 30 June 2017, www.ncbi.nlm.nih.gov/pmc/articles/PMC5490748/
​
Huang, Kaipeng, et al. “Berberine Reduces Fibronectin Expression by Suppressing the S1P-S1P2 Receptor Pathway in Experimental Diabetic Nephropathy Models.” PLOS ONE, journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0043874
​
Ciszewski, Lu-Nguyen, Slater, et al. “G-Quadruplex Ligands Mediate Downregulation of DUX4 Expression.” Nucleic Acids Research, pubmed.ncbi.nlm.nih.gov/32182342/
​
Ma, Shu-Rong, et al. “Berberine Treats Atherosclerosis via a Vitamine-like Effect down-Regulating Choline-TMA-TMAO Production Pathway in Gut Microbiota.” Nature News, 7 July 2022, www.nature.com/articles/s41392-022-01027-6
​
Zheng, Zhihua, et al. “Identification of Berberine as a Potential Therapeutic Strategy for Kidney Clear Cell Carcinoma and COVID-19 Based on Analysis of Large-Scale Datasets.” Frontiers in Immunology, 23 Mar. 2023, www.ncbi.nlm.nih.gov/pmc/articles/PMC10076552/
​
Gibellini, Lara, et al. “Altered Bioenergetics and Mitochondrial Dysfunction of Monocytes in Patients with Covid-19 Pneumonia.” EMBO Molecular Medicine, 7 Dec. 2020, www.ncbi.nlm.nih.gov/pmc/articles/PMC7645870/
​
Wang, Zhao, et al. "Effect of Taurine on Leucocyte Function" - European Journal of Pharmacology, June 2009, www.researchgate.net/publication/223078816_Effect_of_taurine_on_leucocyte_function
​
Yuhan Zhang, et al. “Berberine for Bone Regeneration: Therapeutic Potential and Molecular Mechanisms.” Journal of Ethnopharmacology, 29 May 2021, www.sciencedirect.com/science/article/abs/pii/S0378874121004761#:~:text=Berberine%20promotes%20osteogenesis,mineralization%20to%20promote%20bone%20formation
​
Zhu, Xiaofei, et al. “The Mitohormetic Response as Part of the Cytoprotection Mechanism of Berberine - Molecular Medicine.” BioMed Central, 23 Jan. 2020, molmed.biomedcentral.com/articles/10.1186/s10020-020-0136-8