Friday Hope: Maackia Amurensis Seed Lectin (MASL): Spike, Inflammatory and Oncogenic Inhibition

This seed lectin has the remarkable ability to not only bind Spike, but to also decrease the activity of inflammatory and oncogenic signaling pathways.

d) Cells were incubated with 2 μM Alexa 555 labeled spike protein for 1 h with and without 1.4 μM MASL. Fluorescent, DIC, and merged images are shown as indicated (bar = 200 μm). (e) Fluorescence from a 15000 μm2 area of cells incubated with spike protein with and without MASL was quantitated with quadruple asterisks indicating p < 0.0001 by t-test and indicated (mean + SEM, n = 4). 

There are days I wonder if we have exhausted what therapeutics Nature has to offer us. Fortunately, that moment has not arrived, and Nature never fails to offer us ever more benefits. Indeed, if all the hours spent toiling over new drug creation was spent examining combinations of nutraceuticals for disease treatment, one can only imagine what might now be curable. 

Given that the Spike must be prevented from entering cells and that it and the SARS-CoV-2 virus activate oncogenic pathways, I have always been on the hunt for natural solutions to these, and other Spike-related issues. This week I present a nutraceutical which, remarkably, both inhibits the Spike from entering cells and mutes oncogenic pathway signaling. This nutraceutical is Maackia Amurensis Seed Lectin (MASL). 

Amur maackia is a small, deciduous tree with a broad, rounded habit. Typically grows in cultivation at a slow-to-moderate rate to a height of 20-30' (to 60' in the wild). Features erect, narrow, spike-like clusters (4-6" long) of fragrant, dull white, pea-like flowers which appear in late spring. Flowers are followed by flat seed pods (2-3" long). Compound, odd-pinnate, dark olive green leaves (7-13 leaflets each) are attractive in summer but produce no fall color. Coppery-bronze bark exfoliates on mature trees. Karlovich Maack, a 19th century Siberian explorer, discovered the tree growing in the region of the Amur River which serves as the border between Siberia and China. This member of the pea family is both closely related and similar in appearance to yellowwood (Cladrastis). Yellowwood is slightly larger, has more attractive flowers, and exhibits excellent fall color. 

Maackia amurensis 
https://www.missouribotanicalgarden.org/PlantFinder/PlantFinderDetails.aspx?kempercode=a630 

However, it is the seed lectin (lectins are proteins found in most plants that can bind to carbohydrates) of this plant which has highly beneficial properties. For example, it is known to be antineoplastic (antitumor).  

A preparation of lectin extracted from the seeds of Maackia amurensis, with potential antineoplastic activity. Upon administration, Maackia amurensis seed lectin (MASL) may target and bind to podoplanin (PDPN), thereby blocking the activation of PDPN by endogenous ligands. This may inhibit tumor cell growth, migration and metastasis that result from PDPN activation. PDPN, a transmembrane receptor glycoprotein that is overexpressed in some cancer types, promotes tumor cell migration, invasion, and metastasis upon activation by various endogenous ligands. 

Maackia amurensis seed lectin 
https://www.cancer.gov/publications/dictionaries/cancer-drug/def/maackia-amurensis-seed-lectin 

MASL also decreases the activity of half of the oncogenic signaling pathways that SARS-CoV-2 activates. 

Taken together, results from this study indicate that MASL decreases activity of JAK-STAT, TGFβ-SMAD, and Wnt-βCTN signaling pathways to inhibit oral squamous cell carcinoma  (OSCC) growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer. 

Effects of Maackia amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855468/ 

These actions of MASL are, clearly, extremely beneficial in and of themselves. However, in the presence of the Spike Protein, MASL becomes an even more formidable weapon. 

MASL affects NFκB and STAT3 transcriptional activation pathways and SARS-CoV-2 infection. (a) HeLa cells transfected with Luciferase reporter constructs to detect NFκB and STAT3 activity were incubated with 0, 3.08, 5.16, or 7.70 μM MASL for 4–6 h as indicated. Luminescence values were normalized to untreated nontransfected control cells and are shown as percent control (mean + SEM, n = 2) with p values by ANOVA as indicated. (b) Vero E6 cells were incubated SARS-COV-2 virus for 72 h in 0, 770, and 2310 nM MASL. Cell viability was measured and shown as percent control (mean + SEM, n = 4) with quadruple asterisk indicating p < 0.0001by ANOVA as indicated. (c) Diagram illustrating how MASL reduces ACE2, ADAM17, and furin expression, and decreases inflammatory signaling events that would otherwise lead to activation of the IL6 amplifier implicated in COVID-19 induced ARDS. 

So, not only does MASL bind the Spike, preventing its entry, it also downregulates ACE2, denying the Spike a docking port. And, it ameliorates the major components of Spike/SARS-CoV-2 inflammation cascade, which can lead to the now infamous Cytokine Storm. 

Unlike antibodies, lectins can be taken orally to treat diseases [[65], [66], [67]] including cancer [65] and viral infections [16]. MASL targets sialic acid modified receptors to inhibit cancer progression and inflammation [18,19,21]. Results from this study indicate that MASL inhibits ACE2 expression, SARS-CoV-2 spike binding, and major components of the IL6 amplifier including STAT3, IL6, and NFκB as illustrated in Fig. 4d. In addition to viral lung inflammation, IL6 signaling also triggers contact dermatitis and psoriasis in keratinocytes [43], as well as arthritic inflammation in chondrocytes [39]. COVID-19 inflammation shares inflammatory mechanisms with arthritis [12]. Indeed, COVID-19 infection causes arthralgia and myalgia in 15% and 44% of patients, respectively [68,69]. It should therefore be noted that MASL has been found to attenuate inflammatory NFκB signaling and inflammation in chondrocyte cell culture, and can be administered orally to alleviate arthritis progression in mice [21]. In addition, MASL has also been reported to suppress interleukin induced psoriatic inflammation in reconstituted epidermis [70]. Taken together, data suggest that MASL has the potential to be used alone or in combination with other antiviral and anti-inflammatory agents for COVID-19 treatment. 

Evidence that Maackia amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells with potential to inhibit SARS-CoV-2 infection and COVID-19 disease progression 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019238/ 

After studying MASL over the past week, it is my belief that clinicians may wish to use MASL in treating those with Long COVID/Spike Protein injury. It may also be extremely beneficial to those exposed to the Spike Protein. It is my hope that more studies are conducted using MASL as a therapeutic for COVID, Long COVID and Spike Protein diseases/pathologies. 

There is definitely an Autumn chill in the air now in Vermont. However, it is fitting for the colors of Fall and the very pleasant aroma of fireplaces being lit up for the first time of the season. Please remember that the above is a work of medical research and not medical advice. Please consult your Primary Care Provider before using any supplement or medication. 

Your readership, support and dialogue are appreciated every day. Thank you and please have a blessed weekend.