Friday Hope: Gastrodin: Protecting Against the Spike by Inhibiting Ang II, Inflammation and Amyloid Aggregation

This TCM powerhouse also protects mitochondria and disaggregates amyloid while polarizing M1 macrophages to M2 macrophages and preventing M1 macrophage polarization.

Gastrodin may alleviate the damage caused by SARS-CoV-2 by inhibiting Ang II. After SARS-CoV-2 infection, ACE2 expression is downregulated, but Ang II levels are increased. Ang II, combining with AT1R, induces oxidative stress by affecting NOX2 and SIRT3 and results in "cytokine storm” by initiating inflammatory reaction, eventually causing multiple organs damage. However, gastrodin can reduce the production of AngII by inhibiting the activation of ACE; gastrodin can also inhibit AT1R and PRRs activation but upregulate NRF2 expression. Ultimately, gastrodin reduces AngII-mediated inflammation, oxidative stress.

I find myself filled with wonder and awe. The more we look at Nature, the more we find that it supplies us with an immense bounty of healing. I hope the Big Pharma blinders placed on so many physicians are lifted and they may learn how much Nature can help in restoring health to their patients.

In my continuing search for therapeutics to prevent, treat and heal the damage caused by SARS-CoV-2 and its Spike Protein, I have found that Traditional Chinese Medicine (TCM) presents us, once again, with a stellar medicine. Please let me introduce you to Gastrodin.

Gastrodin (4-hydroxybenzyl alcohol-4-O-β-D-glucopyranoside) is the main bioactive component and an important marker for quality control of the famous Chinese herb Gastrodia elata Blume [1,2]. G. elata Blume is mainly distributed in China, Korea, Japan and other places, and has always been distinguished as a superior class of herbs. This herb is a traditional medicinal and food homology substance that has been used for thousands of years and is often used to treat headaches, dizziness, epilepsy and other diseases [3,4]. The pharmacological effects of G. elata Blume have been continuously studied, and a recent review comprehensively elaborated on its mechanisms and functions regarding the cardiovascular system [5]. As the main active ingredient of G. elata Blume, gastrodin has naturally received increasing attention and research. Gastrodin (Figure 1), which has the chemical formula C13H18O7 and a molecular weight of 286.278 Da, is easily soluble in methanol, ethanol and water but insoluble in chloroform and ether. Gastrodin has good stability in water, methanol, ethanol and phosphate-buffered saline (PBS) solutions, and the equilibrium solubility of gastrodin in an aqueous solution decreases as the pH increases, while in organic solvents, it decreases as the polarity decreases [6]. Gastrodin has a wide range of pharmacological activities, such as sedation and hypnosis [7,8], anti-epilepsy [9,10], anti-depression [11], anti-anxiety [12], analgesia [13], blood pressure reduction [14,15], heart protection [16] and osteonecrosis prevention [17]. Among these effects, gastrodin has an outstanding effect on the central nervous system (CNS) and can be used to treat or improve epilepsy, neurodegeneration, emotional disorders, cognitive impairment and other diseases [3,4,18]. At the same time, gastrodin can reduce inflammatory reactions, improve oxidative stress injury and promote the secretion of the brain-derived neurotrophic factor (BDNF) to help the recovery of nerve function and exert good neuroprotective effects.

Gastrodin, a Promising Natural Small Molecule for the Treatment of Central Nervous System Disorders, and Its Recent Progress in Synthesis, Pharmacology and Pharmacokinetics
https://pmc.ncbi.nlm.nih.gov/articles/PMC11394983/

First, Gastrodin can help alleviate the inflammation and oxidative stress associated with acute COVID, Long COVID and Spike Protein disease/injury. It’s ability to decrease Ang II (elevated because of the Spike’s interaction with ACE2) is its foundational mechanism in accomplishing this. Additionally, Gastrodin exercises the same abilities with the NRF2 pathway.

In the cell or animal models of neuroinflammation and cardiovascular inflammation, gastrodin can reduce the production of AngII by inhibiting ACE. And gastrodin can also inhibit the activation of AT1R. Ultimately, gastrodin reduces AngII-mediated inflammation and oxidative stress [30,[119], [120], [121]]. SARS-CoV-2 causes the downregulation of ACE2, resulting in the increase of AngII. However, we cannot casually increase the expression of ACE2, because ACE2 may increase the susceptibility to SARS-CoV-2 [115]. However, gastrodin reduces the source of AngII and inhibits the AT1R by which the AngII works. Therefore, gastrodin may inhibits the “cytokine storm” in COVID-19.

In addition, in various experimental models, gastrodin has shown excellent antioxidative capacity whether through the RAS-SIRT3/NOX2 pathway [30] or the NRF2 pathway [31]. The increased oxidative stress level in COVID-19 patients is related to the severity of disease [122]. Therefore, the antioxidative effect of gastrodin may alleviate the serious symptoms of COVID-19.

A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19
https://pmc.ncbi.nlm.nih.gov/articles/PMC10637887/

As we have been discovering, M1 macrophages are extremely deleterious in all things Spike related. Indeed, the Spike induces M1 macrophage polarization. Gastrodin prevents this polarization and induces M2 polarization.

It is well known that gastrodin induces M2 polarization but inhibits M1 polarization in macrophages. Gastrodin reprogrammed macrophages from M1 type to M2 type, resulting in higher expression of pro-regenerative cytokines and lower expression of pro-inflammatory cytokines.

A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19
https://pmc.ncbi.nlm.nih.gov/articles/PMC10637887/

Protecting mitochondria and improving their function is yet another way Gastrodin helps in combating the Spike Protein.

In a variety of cell and animal experimental models, gastrodin protected the structure and function of mitochondria. For example, via anti-inflammatory and antioxidant properties, gastrodin attenuated mitochondrial damage, maintained the structure and function of mitochondrial, and ensured ATP production in the injury models of nerve cells, cardiomyocytes and osteoblasts [[99], [100], [101]]. In addition, gastrodin enhanced autophagic flux to eliminate dysfunctional mitochondria, thus protecting neighboring mitochondria.

A review: Mechanism and prospect of gastrodin in prevention and treatment of T2DM and COVID-19
https://pmc.ncbi.nlm.nih.gov/articles/PMC10637887/

There is still more to gush about.

We know that the Spike Protein is amyloidogenic. This is where Gastrodin performs additional, beneficial functions in treating Spike Protein disease/injury. Gastrodin not only inhibits aggregation of amyloid beta, it also disaggregates it. Furthermore, Gastrodin alleviates the activation of microglial cells (CNS macrophages).

Our results showed that chronic gastrodin administration inhibits aggregation and disaggregate oligomeric and fibrillar species of Aβ42, prevents Aβ42 induced neurotoxicity in cell SH-SY5Y, decreases the levels of Aβ plaques and hyperphosphorylated tau, alleviates activation of glial cells and proinflammatory cytokines, attenuates oxidative stress in the APP/PS1 transgenic mice.

Gastrodin as a multi-target protective compound reverses learning memory deficits and AD-like pathology in APP/PS1 transgenic mice
https://www.sciencedirect.com/science/article/pii/S175646462030548X

Once again, it is my hope that this research will help guide physicians in the treatment of their patients and encourage research institutes to conduct relevant studies using Gastrodin. Indeed, all that we have discussed today is greatly encouraging. Of course, as with any medicine or supplement, always consult your Primary Care Provider before use.

It has been hazy thanks to the wildfire smoke from our northerly neighbors this week. However, today the skies seem to be clearing, welcoming abundant wall-to-wall summer sunshine. I wish all a blessed, hopeful and especially peaceful weekend. Thank you, as always, for your readership, dialogue and support.